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1. Advancing the global public health agenda for NAFLD: a consensus statement

Author

Lazarus, J.V. Mark, H.E. Anstee, Q.M. Arab, J.P. Batterham, R.L. Castera, L. Cortez-Pinto, H. Crespo, J. Cusi, K. Dirac, M.A. Francque, S. George, J. Hagström, H. Huang, T.T.-K. Ismail, M.H. Kautz, A. Sarin, S.K. Loomba, R. Miller, V. Newsome, P.N. Ninburg, M. Ocama, P. Ratziu, V. Rinella, M. Romero, D. Romero-Gómez, M. Schattenberg, J.M. Tsochatzis, E.A. Valenti, L. Wong, V.W.-S. Yilmaz, Y. Younossi, Z.M. Zelber-Sagi, S. Åberg, F. Adams, L. Khatry, M.S.A. Naamani, K.A. Murillo, O.A. Allen, A.M. Alnaser, F. Alqahtani, S.A. Alswat, K. Alvaro, D. Andrade, R.J. Arrese, M. Awuku, Y.A. Ayesha, M. Baatarkhuu, O. Bakieva, S. Basu, R. Bataller, R. Bedri, S. Bosi, E. Bourliere, M. Bruha, R. Bugianesi, E. Burra, P. Buti, M. Byrne, C.D. Calleja, J.L. Carrieri, P. Carter, F. Fernandez, M.I.C. Castillo-Lopez, G. Castro-Narro, G.E. Chan, H.L.Y. Chan, W.-K. Chang, Y. Colombo, M. Coppell, K.J. Corey, K. Craxi, A. Cryer, D. Dassanayake, A. Martins, A.A.S. de Ledinghen, V. DelPrato, S. Demaio, A. Desalegn, H. Dillon, J. Duseja, A. Dorairaj, P. Ekstedt, M. El Kassas, M. Elsanousi, O.M. Esmat, G. Fan, J.-G. Farpour-Lambert, N. Flisiak, R. Fouad, Y. Fuchs, M. Gani, R.A. Gerber, L. Ghazinyan, H. Gheorghe, L. Goh, G.B.-B. Grønbæk, H. Gulnara, A. Hamid, S. Hebditch, V. Hickman, I.J. Hocking, S.L. Hunyady, B. Idilman, R. Isakov, V.A. Jamal, M.H. Jepsen, P. Iskandar, N.J. Song, M.J. Sudhamshu, K.C. Kakizaki, S. Kalamitsis, G. Kanwal, F. Kao, J.-H. Kaplan, L. Kawaguchi, T. Khader, Y. Kim, S.U. Kodjoh, N. Koek, G. Koike, K. Komas, N.P. Korenjak, M. Kugelmas, M. Labidi, A. Lange, N.F. Lavine, J.E. Lazo, M. Lee, N. Lesmana, C.R.A. Liu, C.-J. Long, M.T. Lopez-Jaramillo, P. Malekzadeh, R. Mahtab, M.A. Marchesini, G. Marinho, R. Vázquez, S.E.M. Mateva, L. Nlombi, C.M. Melin, P. Mikolasevic, I. Milovanovic, T. Musso, C. Nakajima, A. Nava, E. Nersesov, A.V. Nikolova, D. Norris, S. Novak, K. Oben, J. Ong, J.P. Onyekwere, C. Papatheodoridis, G. Paruk, I. Patel, K. Macedo, M.P. Penha-Gonçalves, C. Figueroa, M.P. Hofmann, W.P. Petta, S. de Oliveira, C.P.M.S. Puri, P. Pan, C.Q. Rac, M. Ralston, J. Ramji, A. Razavi, H. Alvares-da-Silva, M.R. Roberts, S. Roden, M. Rose, T. Rouabhia, S. Rovere-Querini, P. Rowe, I.A. Sadirova, S. Salupere, R. Saparbu, T. Sayegh, R. Sebastiani, G. Seki, Y. Selmo, J. Serme, A.K. Shaw, J.E. Shenoy, T. Sheron, N. Shibolet, O. Silva, M. Skrypnyk, I. Socha, P. Soriano, J. Spearman, C.W. Sridharan, K. Suárez, J.J. Sheriff, D.S. Sung, K.-C. Swain, M. Tacke, F. Taheri, S. Tan, S.-S. Tapper, E.B. Yki-Järvinen, H. Thiele, M. Shawa, I.T. Tolmane, I. Torres, E.A. Trauner, M. Treeprasertsuk, S. Turcanu, A. Valantinas, J. Vesterhus, M. Waked, I. Wild, S.H. Willemse, J. Wong, R.J. Xanthakos, S. Young, D.Y. Yu, M.-L. Zheng, K.I. Zeybel, M. Zheng, M.-H. the NAFLD Consensus Consortium

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD. © 2021, Springer Nature Limited.

Published
2022

2. Human myocardial mitochondrial oxidative capacity is impaired in mild acute heart transplant rejection

Author

Scheiber, D., Zweck, E., Albermann, S., Jelenik, T., Spieker, M., Bönner, F., Horn, P., Schultheiss, H.P., Aleshcheva, G., Escher, F., Boeken, U., Akhyari, P., Roden, M., Kelm, M., Szendroedi, J., and Westenfeld, R.

Subjects
Heart Diseases, Heart failure, Original Articles, Mitochondria, Heart, Acute cellular heart transplant rejection, Oxidative Stress, Diabetes Mellitus, Type 2, Myocardial inflammation, RC666-701, Diseases of the circulatory (Cardiovascular) system, Heart Transplantation, Humans, Original Article, Acute Cellular Heart Transplant Rejection, Heart Failure, Mitochondrial Respiration, Myocardial Inflammation, Mitochondrial respiration
Abstract

AIMS: Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long-term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high-resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction. METHODS AND RESULTS: We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high-resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P=0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P=0.57; chronic kidney disease stage 5: 8% vs. 9%, P>0.99; arterial hypertension: 59% vs. 30%, P=0.35), medications (tacrolimus: 100% vs. 91%, P=0.54; mycophenolate mofetil: 92% vs. 91%, P>0.99; prednisolone: 92% vs. 96%, P>0.99) and time post-transplantation (21.5±26.0months vs. 29.4±26.4months, P=0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8±23.0 vs. 128.0±33.0; P14 CD3+ -lymphocytes/mm2 (100% sensitivity, 82% specificity; P&nbsp

Published
2021
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3. A panel of six biomarkers significantly improves the prediction of type 2 diabetes in the MONICA/KORA study population

Author

Thorand, B., Zierer, A., Büyüközkan, M., Krumsiek, J., Bauer, A., Schederecker, F., Sudduth-Klinger, J., Meisinger, C., Grallert, H., Rathmann, W., Roden, M., Peters, A., Koenig, W., Herder, C., and Huth, C.

Subjects
Biomarkers, Cohort Analysis, Risk Prediction Model, Type 2
Abstract

CONTEXT: Improved strategies to identify persons at high risk of type 2 diabetes are important to target costly preventive efforts to those who will benefit most. OBJECTIVE: To assess whether novel biomarkers improve the prediction of type 2 diabetes beyond non-invasive standard clinical risk factors alone or in combination with HbA1c. DESIGN AND METHODS: We used a population-based case-cohort study for discovery (689 incident cases and 1,850 non-cases) and an independent cohort study (n=262 incident cases, 2,549 non-cases) for validation. An L1-penalized (lasso) Cox model was used to select the most predictive set among 47 serum biomarkers from multiple etiological pathways. All variables available from the non-invasive German Diabetes Risk Score (GDRSadapted) were forced into the models. The C-index and the category-free net reclassification index (cfNRI) were used to evaluate the predictive performance of the selected biomarkers beyond the GDRSadapted model (plus HbA1c). RESULTS: Interleukin-1 receptor antagonist, insulin growth factor binding protein-2, soluble E-selectin, decorin, adiponectin, and high density lipoprotein-cholesterol were selected as most relevant. The simultaneous addition of these six biomarkers significantly improved the predictive performance in both the discovery (C-index [95% CI]: 0.053 [0.039-0.066]; cfNRI [95% CI]: 67.4% [57.3%-79.5%]) and the validation study (0.034 [0.019-0.053]; 48.4% [35.6%-60.8%]). Significant improvements by these biomarkers were also seen on top of the GDRSadapted model plus HbA1c in both studies. CONCLUSION: The addition of six biomarkers significantly improved the prediction of type 2 diabetes when added to a non-invasive clinical model or to a clinical model plus HbA1c.

Published
2021

4. Different effects of lifestyle intervention in high- and low-risk prediabetes

Author

Fritsche, A., Wagner, R., Heni, M., Kantartzis, K., Machann, J., Schick, F., Lehmann, R., Peter, A., Dannecker, C., Fritsche, L., Valenta, V., Nawroth, P.P., Kopf, S., Pfeiffer, A.F., Kabisch, S., Dambeck, U., Stumvoll, M., Blüher, M., Birkenfeld, A.L., Schwarz, P., Hauner, H., Clavel, J., Seißler, J., Lechner, A., Müssig, K., Weber, K., Laxy, M., Bornstein, S., Schürmann, A., Roden, M., Hrabě de Angelis, M., Stefan, N., and Häring, H.-U.

Abstract

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit from conventional LI and individuals with high risk benefit from an intensification of LI in a multi-center randomized controlled intervention over 12 months with 2 years follow up. 1105 prediabetic individuals based on ADA glucose criteria were stratified into a high- and low-risk phenotype, based on previously described thresholds of insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI according to the DPP protocol or control (1:1), high-risk individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In high-risk individuals, the difference between conventional and intensified LI in post-challenge glucose change was -0.29 mmol/l [CI:-0.54;-0.04], p=0.025. Liver fat (-1.34 percentage points [CI:-2.17;-0.50], p=0.002) and cardiovascular risk (-1.82[CI:-3.13-0.50],p=0.007) underwent larger reductions with intensified than with conventional LI. During a follow up of 3 years, intensified compared to conventional LI had a higher probability to normalize glucose tolerance (p=0.008). In conclusion, it is possible in high-risk individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk-phenotype-based LI may be beneficial for the prevention of diabetes.

Published
2021

5. Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk

Author

Kozakova, M. Gastaldelli, A. Morizzo, C. Højlund, K. Nilssson, P.M. Ferrannini, E. Heine, R.J. Dekker, J. de Rooij, S. Nijpels, G. Boorsma, W. Kok, A. Mitrakou, A. Tournis, S. Kyriakopoulou, K. Thomakos, P. Lalic, N. Lalic, K. Jotic, A. Lukic, L. Civcic, M. Nolan, J. Yeow, T.P. Murphy, M. DeLong, C. Neary, G. Colgan, M.P. Hatunic, M. Gaffney, P. Boran, G. Konrad, T. Böhles, H. Fuellert, S. Baer, F. Zuchhold, H. Golay, A. Bobbioni, E.H. Barthassat, V. Makoundou, V. Lehmann, T.N.O. Merminod, T. Petrie (now Dundee), J.R. Perry, C. Neary, F. MacDougall, C. Shields, K. Malcolm, L. Laakso, M. Salmenniemi, U. Aura, A. Raisanen, R. Ruotsalainen, U. Sistonen, T. Laitinen, M. Saloranta, H. Coppack, S.W. McIntosh, N. Ross, J. Pettersson, L. Khadobaksh, P. Balkau, B. Mhamdi, L. Guillanneuf, M.T. Laville, M. Bonnet, F. Brac de la Perriere, A. Louche-Pelissier, C. Maitrepierre, C. Peyrat, J. Beltran, S. Serusclat, A. Gabriel, R. Sánchez, E.M. Carraro, R. Friera, A. Novella, B. Nilssone, P. Persson, M. Östling, G. Melander, O. Burri, P. Piatti, P.M. Monti, L.D. Setola, E. Galluccio, E. Minicucci, F. Colleluori, A. Walker, M. Ibrahim, I.M. Jayapaul, M. Carman, D. Ryan, C. Short, K. McGrady, Y. Richardson, D. Patel, S. Beck-Nielsen, H. Staehr, P. Hojlundd, K. Vestergaard, V. Olsen, C. Hansen, L. Bolli, G.B. Porcellati, F. Fanelli, C. Lucidi, P. Calcinaro, F. Saturni, A. Ferranninia, E. Natali, A. Muscelli, E. Pinnola, S. Kozakovaa, M. Hills, S.A. Landucci, L. Mota, L. Gastaldelli, A. Ciociaro, D. Mari, A. Pacini, G. Cavaggion, C. Mingrone, G. Guidone, C. Favuzzi, A. Di Rocco, P. Anderwald, C. Bischof, M. Promintzer, M. Krebs, M. Mandl, M. Hofer, A. Luger, A. Waldhäusl, W. Roden, M. Palombo, C. RISC Investigators

Abstract

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and

Published
2021

6. One hour post-load plasma glucose and 3 year risk of worsening fasting and 2 hour glucose tolerance in the RISC cohort

Author

Manco, Melania, Mari, Andrea, Petrie, John, Mingrone, Geltrude, Balkau, Beverley, Amsterdam, for the EGIR-RISC study group., Heine, Rj, Dekker, J, S de Rooij, Nijpels, G, W Boorsma Athens, Greece:, A Mitrakou, Tournis, S, Kyriakopoulou, K, P Thomakos Belgrade, Serbia:, N Lalic, Lalic, K, Jotic, A, Lukic, L, M Civcic Dublin, Ireland:, J Nolan, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, M Hatunic Frankfurt, Germany:, T Konrad, Böhles, H, Fuellert, S, Baer, F, H Zuchhold Geneva, Switzerland:, A Golay, E Harsch Bobbioni, Barthassat, V, Makoundou, V, Tno, Lehmann, T Merminod Glasgow, Scotland, UK: JR Petrie, Perry, C, Neary, F, Macdougall, C, Shields, K, L Malcolm Kuopio, Finland:, M Laakso, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, H Saloranta London, England, UK: SW Coppack, Mcintosh, N, Ross, J, Pettersson, L, P Khadobaksh Lyon, France:, M Laville, F Bonnet (now Rennes), A Brac de la Perriere, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, A Serusclat Madrid, Spain:, R Gabriel, Sánchez, Em, Carraro, R, Friera, A, B Novella Malmö, Sweden (1):, P Nilsson, Persson, M, G Östling (2):, O Melander, P Burri Milan, Italy: PM Piatti, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, A Colleluori Newcastle-upon-Tyne, Uk:, M Walker, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, D Richardson Odense, Denmark:, H Beck-Nielsen, Staehr, P, Højlund, K, Vestergaard, V, Olsen, C, L Hansen Perugia, Italy: GB Bolli, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, A Saturni Pisa, Italy:, E Ferrannini, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, BD Astiarraga Rome, Italy:, G Mingrone, Guidone, C, Favuzzi, A, P Di Rocco Vienna, Austria:, C Anderwald, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, and Roden, M

Subjects
Post-load glucose, Adult, Male, Blood Glucose, 0301 basic medicine, Diagnostic criteria, Endocrinology, Diabetes and Metabolism, Physiology, 030209 endocrinology & metabolism, Prediabetic State, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Research Letter, Internal Medicine, medicine, Humans, Prediabetes, Plasma glucose, Glucose tolerance test, Post-challenge glucose, Prediabetes phenotype, Progression, medicine.diagnostic_test, business.industry, Fasting, Female, Glucose Tolerance Test, Middle Aged, Settore MED/13 - ENDOCRINOLOGIA, Human physiology, medicine.disease, Diabetes and Metabolism, 030104 developmental biology, Cohort, business
Abstract

The affiliation details for Geltrude Mingrone are corrected below.

Published
2018
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7. Association between Biomarkers of Low-grade Inflammation and Sex Hormones in Women with Polycystic Ovary Syndrome

Author

Hatziagelaki, E. Pergialiotis, V. Kannenberg, J.M. Trakakis, E. Tsiavou, A. Markgraf, D.F. Carstensen-Kirberg, M. Pacini, G. Roden, M. Dimitriadis, G. Herder, C., Prof. Dr.

Abstract

Objective Women with polycystic ovary syndrome (PCOS) have higher circulating levels of C-reactive protein, but the relationship between inflammation and endocrine function in PCOS remains poorly understood. Thus, this study aimed to investigate the association between low-grade inflammation and sex hormones in women with PCOS. Design and Patients A comprehensive panel of biomarkers of inflammation was measured in serum of 63 women with PCOS using proximity extension assay technology. Associations of 65 biomarkers with sex hormones were assessed without and with adjustment for age and body mass index (BMI). Results In the unadjusted analysis, 20 biomarkers were positively correlated with 17-OH-progesterone (17-OH-P), 14 with prolactin and 6 with free testosterone, whereas inverse associations were found for 16 biomarkers with sex hormone-binding globulin (SHBG), 6 with luteinizing hormone (LH) and 6 with estrogen (all p

Published
2020

8. Mitochondrial respiratory states and rate

Author

Gnaiger, E., Aasander Frostner, E., Abdul Karim, N., Abumrad, NA., Acuna-Castroviejo, D., Adiele, RC., Ahn, B., Ali, SS., Alton, L., Alves, MG., Amati, F., Amoedo, ND., Andreadou, I., Arago, M., Aral, C., Arandarcikaite, O., Armand, AS., Arnould, T., Avram, VF., Bailey, DM., Bajpeyi, S., Bajzikova, M., Bakker, BM., Barlow, J., Bastos Sant'Anna Silva, AC., Batterson, P., Battino, M., Bazil, J., Beard, DA., Bednarczyk, P., Bello, F., Ben-Shachar, D., Bergdahl, A., Berge, RK., Bergmeister, L., Bernardi, P., Berridge, MV., Bettinazzi, S., Bishop, D., Blier, PU., Blindheim, DF., Boardman, NT., Boetker, HE., Borchard, S., Boros, M., Borsheim, E., Borutaite, V., Botella, J., Bouillaud, F., Bouitbir, J., Boushel, RC., Bovard, J., Breton, S., Brown, DA., Brown, GC., Brown, RA., Brozinick, JT., Buettner, GR., Burtscher, J., Calabria, E., Calbet, JA., Calzia, E., Cannon, DT., Cano Sanchez, M., Canto, AC., Cardoso, LHD., Carvalho, E., Casado Pinna, M., Cassar, S., Cassina, AM., Castelo, MP., Castro, L., Cavalcanti-de-Albuquerque, JP., Cervinkova, Z., Chabi, B., Chakrabarti, L., Chakrabarti, S., Chaurasia, B., Chen, Q., Chicco, AJ., Chinopoulos, C., Chowdhury, SK., Cizmarova, B., Clementi, E., Coen, PM., Cohen, BH., Coker, RH., Collin, A., Crisostomo, L., Dahdah, N., Dalgaard, LT., Dambrova, M., Danhelovska, T., Darveau, CA., Das, AM., Dash, RK., Davidova, E., Davis, MS., De Goede, P., De Palma, C., Dembinska-Kiec, A., Detraux, D., Devaux, Y., Di Marcello, M., Dias, TR., Distefano, G., Doermann, N., Doerrier, C., Dong, L., Donnelly, C., Drahota, Z., Duarte, FV., Dubouchaud, H., Duchen, MR., Dumas, JF., Durham, WJ., Dymkowska, D., Dyrstad, SE., Dyson, A., Dzialowski, EM., Eaton, S., Ehinger, J., Elmer, E., Endlicher, R., Engin, AB., Escames, G., Ezrova, Z., Falk, MJ., Fell, DA., Ferdinandy, P., Ferko, M., Ferreira, JCB., Ferreira, R., Ferri, A., Fessel, JP., Filipovska, A., Fisar, Z., Fischer, C., Fischer, M., Fisher, G., Fisher, JJ., Ford, E., Fornaro, M., Galina, A., Galkin, A., Gallee, L., Galli, GL., Gama Perez, P., Gan, Z., Ganetzky, R., Garcia-Rivas, G., Garcia-Roves, PM., Garcia-Souza, LF., Garipi, E., Garlid, KD., Garrabou, G., Garten, A., Gastaldelli, A., Gayen, J., Genders, AJ., Genova, ML., Giovarelli, M., Goncalo Teixeira da Silva, R., Goncalves, DF., Gonzalez-Armenta, JL., Gonzalez-Freire, M., Gonzalo, H., Goodpaster, BH., Gorr, TA., Gourlay, CW., Granata, C., Grefte, S., Guarch, ME., Gueguen, N., Gumeni, S., Haas, CB., Haavik, J., Haendeler, J., Haider, M., Hamann, A., Han, J., Han, WH., Hancock, CR., Hand, SC., Handl, J., Hargreaves, IP., Harper, ME., Harrison, DK., Hassan, H., Hausenloy, DJ., Heales, SJR., Heiestad, C., Hellgren, KT., Hepple, RT., Hernansanz-Agustin, P., Hewakapuge, S., Hickey, AJ., Ho, DH., Hoehn, KL., Hoel, F., Holland, OJ., Holloway, GP., Hoppel, CL., Hoppel, F., Houstek, J., Huete-Ortega, M., Hyrossova, P., Iglesias-Gonzalez, J., Irving, BA., Isola, R., Iyer, S., Jackson, CB., Jadiya, P., Jana, PF., Jang, DH., Jang, YC., Janowska, J., Jansen, K., Jansen-Duerr, P., Jansone, B., Jarmuszkiewicz, W., Jaskiewicz, A., Jedlicka, J., Jespersen, NR., Jha, RK., Jurczak, MJ., Jurk, D., Kaambre, T., Kaczor, JJ., Kainulainen, H., Kampa, RP., Kandel, SM., Kane, DA., Kapferer, W., Kappler, L., Karabatsiakis, A., Karavaeva, I., Karkucinska-Wieckowska, A., Kaur, S., Keijer, J., Keller, MA., Keppner, G., Khamoui, AV., Kidere, D., Kilbaugh, T., Kim, HK., Kim, JKS., Klepinin, A., Klepinina, L., Klingenspor, M., Klocker, H., Komlodi, T., Koopman, WJH., Kopitar-Jerala, N., Kowaltowski, AJ., Kozlov, AV., Krajcova, A., Krako Jakovljevic, N., Kristal, BS., Krycer, JR., Kuang, J., Kucera, O., Kuka, J., Kwak, HB., Kwast, K., Laasmaa, M., Labieniec-Watala, M., Lagarrigue, S., Lai, N., Land, JM., Lane, N., Laner, V., Lanza, IR., Laranjinha, J., Larsen, TS., Lavery, GG., Lazou, A., Lee, HK., Leeuwenburgh, C., Lehti, M., Lemieux, H., Lenaz, G., Lerfall, J., Li, PA., Li Puma, L., Liepins, E., Liu, J., Lopez, LC., Lucchinetti, E., Ma, T., Macedo, MP., Maciej, S., MacMillan-Crow, LA., Majtnerova, P., Makarova, E., Makrecka-Kuka, M., Malik, AN., Markova, M., Martin, DS., Martins, AD., Martins, JD., Maseko, TE., Maull, F., Mazat, JP., McKenna, HT., McKenzie, M., Menze, MA., Merz, T., Meszaros, AT., Methner, A., Michalak, S., Moellering, DR., Moisoi, N., Molina, AJA., Montaigne, D., Moore, AL., Moreau, K., Moreira, BP., Moreno-Sanchez, R., Mracek, T., Muccini, AM., Munro, D., Muntane, J., Muntean, DM., Murray, AJ., Musiol, E., Nabben, M., Nair, KS., Nehlin, JO., Nemec, M., Neufer, PD., Neuzil, J., Neviere, R., Newsom, SA., Nozickova, K., O'Brien, KA., O'Gorman, D., Olgar, Y., Oliveira, B., Oliveira, MF., Oliveira, MT., Oliveira, PF., Oliveira, PJ., Orynbayeva, Z., Osiewacz, HD., Pak, YK., Pallotta, ML., Palmeira, CM., Parajuli, N., Passos, JF., Passrugger, M., Patel, HH., Pavlova, N., Pecina, P., Pedersen, TM., Pereira da Silva Grilo da Silva, F., Pereira, SP., Perez Valencia, JA., Perks, KL., Pesta, D., Petit, PX., Pettersen, IKN., Pichaud, N., Pichler, I., Piel, S., Pietka, TA., Pino, MF., Pirkmajer, S., Plangger, M., Porter, C., Porter, RK., Procaccio, V., Prochownik, EV., Prola, A., Pulinilkunnil, T., Puskarich, MA., Puurand, M., Radenkovic, F., Ramzan, R., Rattan, SIS., Reboredo, P., Renner-Sattler, K., Rial, E., Robinson, MM., Roden, M., Rodriguez, E., Rodriguez-Enriquez, S., Roesland, GV., Rohlena, J., Rolo, AP., Ropelle, ER., Rossignol, R., Rossiter, HB., Rubelj, I., Rybacka-Mossakowska, J., Saada, A., Safaei, Z., Saharnaz, S., Salin, K., Salvadego, D., Sandi, C., Saner, N., Sanz, A., Sazanov, LA., Scatena, R., Schartner, M., Scheibye-Knudsen, M., Schilling, JM., Schlattner, U., Schoenfeld, P., Schots, PC., Schulz, R., Schwarzer, C., Scott, GR., Selman, C., Shabalina, IG., Sharma, P., Sharma, V., Shevchuk, I., Shirazi, R., Shiroma, JG., Siewiera, K., Silber, AM., Silva, AM., Sims, CA., Singer, D., Singh, BK., Skolik, R., Smenes, BT., Smith, J., Soares, FAA., Sobotka, O., Sokolova, I., Sonkar, VK., Sowton, AP., Sparagna, GC., Sparks, LM., Spinazzi, M., Stankova, P., Starr, J., Stary, C., Stelfa, G., Stepto, NK., Stiban, J., Stier, A., Stocker, R., Storder, J., Sumbalova, Z., Suomalainen, A., Suravajhala, P., Svalbe, B., Swerdlow, RH., Swiniuch, D., Szabo, I., Szewczyk, A., Szibor, M., Tanaka, M., Tandler, B., Tarnopolsky, MA., Tausan, D., Tavernarakis, N., Tepp, K., Thakkar, H., Thapa, M., Thyfault, JP., Tomar, D., Ton, R., Torp, MK., Towheed, A., Tretter, L., Trewin, AJ., Trifunovic, A., Trivigno, C., Tronstad, KJ., Trougakos, IP., Truu, L., Tuncay, E., Turan, B., Tyrrell, DJ., Urban, T., Valentine, JM., Van Bergen, NJ., Van Hove, J., Varricchio, F., Vella, J., Vendelin, M., Vercesi, AE., Victor, VM., Vieira Ligo Teixeira, C., Vidimce, J., Viel, C., Vieyra, A., Vilks, K., Villena, JA., Vincent, V., Vinogradov, AD., Viscomi, C., Vitorino, RMP., Vogt, S., Volani, C., Volska, K., Votion, DM., Vujacic-Mirski, K., Wagner, BA., Ward, ML., Warnsmann, V., Wasserman, DH., Watala, C., Wei, YH., Whitfield, J., Wickert, A., Wieckowski, MR., Wiesner, RJ., Williams, CM., Winwood-Smith, H., Wohlgemuth, SE., Wohlwend, M., Wolff, JN., Wrutniak-Cabello, C., Wuest, RCI., Yokota, T., Zablocki, K., Zanon, A., Zanou, N., Zaugg, K., Zaugg, M., Zdrazilova, L., Zhang, Y., Zhang, YZ., Zikova, A., Zischka, H., Zorzano, A., and Zvejniece, L.

Subjects
Mitochondrial respiratory control, coupling control, mitochondrial preparations, protonmotive force, uncoupling, oxidative phosphorylation, OXPHOS, efficiency, electron transfer, ET, proton leak, LEAK, residual oxygen consumption, ROX, State 2, State 3, State 4, normalization, flow, flux, O2
Abstract

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

Published
2019

9. Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

Author

Trico, D, Mengozzi, A, Nesti, L, Hatunic, M, Sanchez, Rg, Konrad, T, Lalic, K, Lalic, Nm, Mari, A, Natali, A, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Bohles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Lehmann, Tno, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere, Ab, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sanchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, I, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck-Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, Saturni, A, Ferrannini, E, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhausl, W, Roden, M, Balkau, B, Dekker, Jm, Petrie, J, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, and Mota, L.

Subjects
Adult, Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Subcutaneous adipose tissue, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030209 endocrinology & metabolism, Carbohydrate metabolism, Palmitate, NEFA, Fatty Acids, Monounsaturated, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Insulin-Secreting Cells, Internal medicine, Adipokine, Internal Medicine, medicine, Humans, Palmitoleic acid, Longitudinal Studies, Monounsaturated fatty acid, Lipokine, Beta cell function, Glucose tolerance, Metabolism, Glucose Tolerance Test, Middle Aged, medicine.disease, Insulin sensitivity, Cross-Sectional Studies, 030104 developmental biology, Endocrinology, chemistry, Body Composition, Female, Insulin Resistance, Hormone
Abstract

Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

Published
2019

10. Amino acid and fatty acid levels affect hepatic phosphorus metabolite content in metabolically healthy humans

Author

Kahl, S. Nowotny, B. Strassburger, K. Bierwagen, A. Klüppelholz, B. Hoffmann, B. Giani, G. Nowotny, P.J. Wallscheid, F. Hatziagelaki, E. Pacini, G. Hwang, J.-H. Roden, M.

Abstract

Objective: Hepatic energy metabolism negatively relates to insulin resistance and liver fat content in patients with type 2 diabetes, but its role inmetabolically healthy humans is unclear.Wehypothesized that intrahepatocellular g-Adenosine triphosphate (gATP) and inorganic phosphate (Pi) concentrations exhibit similar associations with insulin sensitivity in nondiabetic, nonobese volunteers. Design:Atotal of 76 participantsunderwent a four-point sampling, 75-goralglucose tolerance test (OGTT), as well as in vivo 31P/1Hmagnetic resonance spectroscopy. In 62 of them, targeted plasmametabolomic profiling was performed. Pearson correlation analyses were performed for the dependent variables gATP and Pi. Results: Adjusted for age, sex, and body mass index (BMI), hepatic gATP and Pi related to 2-hour OGTT glucose (r = 0.25 and r = 0.27, both P

Published
2018

11. Ldlr-/- and ApoE-/- mice better mimic the human metabolite signature of increased carotid intima media thickness compared to other animal models of cardiovascular disease

Author

Saulnier-Blache, J.S., Wilson, R., Klavins, K., Graham, D., Alesutan, I., Kastenmüller, G., Wang-Sattler, R., Adamski, J., Roden, M., Rathmann, W., Seissler, J., Meisinger, C., Koenig, W., Thiery, J., Suhre, K., Peters, A., Kuro-O, M., Lang, F., Dallmann, G., Delles, C., Voelkl, J., Waldenberger, M., Bascands, J.-L., Klein, J., and Schanstra, J.P.

Subjects
lipids (amino acids, peptides, and proteins), cardiovascular diseases
Abstract

Background and aims Preclinical experiments on animal models are essential to understand the mechanisms of cardiovascular disease (CVD). Metabolomics allows access to the metabolic perturbations associated with CVD in heart and vessels. Here we assessed which potential animal CVD model most closely mimics the serum metabolite signature of increased carotid intima-media thickness (cIMT) in humans, a clinical parameter widely accepted as a surrogate of CVD. Methods A targeted mass spectrometry assay was used to quantify and compare a series of blood metabolites between 1362 individuals (KORA F4 cohort) and 5 animal CVD models: ApoE−/−, Ldlr−/−, and klotho-hypomorphic mice (kl/kl) and SHRSP rats with or without salt feeding. The metabolite signatures were obtained using linear regressions adjusted for various co-variates. Results In human, increased cIMT [quartile Q4 vs. Q1] was associated with 26 metabolites (9 acylcarnitines, 2 lysophosphatidylcholines, 9 phosphatidylcholines and 6 sphingomyelins). Acylcarnitines correlated preferentially with serum glucose and creatinine. Phospholipids correlated preferentially with cholesterol (total and LDL). The human signature correlated positively and significantly with Ldlr−/− and ApoE−/− mice, while correlation with kl/kl mice and SHRP rats was either negative and non-significant. Human and Ldlr−/− mice shared 11 significant metabolites displaying the same direction of regulation: 5 phosphatidylcholines, 1 lysophosphatidylcholines, 5 sphingomyelins; ApoE−/− mice shared 10. Conclusions The human cIMT signature was partially mimicked by Ldlr−/− and ApoE−/− mice. These animal models might help better understand the biochemical and molecular mechanisms involved in the vessel metabolic perturbations associated with, and contributing to metabolic disorders in CVD. &nbsp

Published
2018

12. Meal-derived glucagon responses are related to lower hepatic phosphate concentrations in obesity and type 2 diabetes

Author

Weber, K. S. Strassburger, K. Fritsch, M. Bierwagen, A. and Koliaki, C. Phielix, E. Pacini, G. Hwang, J-H Markgraf, D. F. Burkart, V Muessig, K. Szendroedi, J. Roden, M.

Subjects
endocrine system, digestive, oral, and skin physiology
Abstract

Aim. - Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. Methods. - In this observational study, lean insulin-sensitive control subjects (BMI: 23.2 +/- 1.5 kg/m(2)), age-matched insulin-resistant obese subjects (BMI: 34.3 +/- 1.7 kg/m(2)) and similarly obese elderly T2D patients (BMI: 32.0 +/- 2.4 kg/m(2)) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic gamma ATP, inorganic phosphate (P-i) and lipids using P-31/H-1 magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. Results. - MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P < 0.001), while glucagon concentrations were comparable across all three groups. At 260 min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r = 0.60) and postprandial hepatocellular lipid levels (160 min: r= 0.51, 240 min: r = 0.59), and negatively with adipose tissue insulin sensitivity (r = -0.73). Higher meal-induced glucagon release (iAUC(0)(-260) (min)) correlated with lower fasting (r = -0.62) and postprandial P(i )levels (160 min: r = -0.43, 240 min: r = -0.42; all P < 0.05). Higher meal-induced release of GIP (iAUC(0-260) (min)) correlated positively with fasting (r = 0.54) and postprandial serum triglyceride concentrations (iAUC(0-260 min, )r = 0.54; all P < 0.01). Conclusion. - Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic P-i suggest a role for glucagon in hepatic energy metabolism. (C) 2018 Elsevier Masson SAS. All rights reserved.

Published
2018

13. Constant hepatic ATP concentrations during prolonged fasting and absence of effects of Cerbomed Nemos® on parasympathetic tone and hepatic energy metabolism

Author

Gancheva, S. Bierwagen, A. Markgraf, D.F. Bönhof, G.J. Murphy, K.G. Hatziagelaki, E. Lundbom, J. Ziegler, D. Roden, M.

Abstract

Objective Brain insulin-induced improvement in glucose homeostasis has been proposed to be mediated by the parasympathetic nervous system. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) activating afferent branches of the vagus nerve may prevent hyperglycemia in diabetes models. We examined the effects of 14-min taVNS vs sham stimulation by Cerbomed Nemos® on glucose metabolism, lipids, and hepatic energy homeostasis in fasted healthy humans (n = 10, age 51 ± 6 yrs, BMI 25.5 ± 2.7 kg/m2). Methods Heart rate variability (HRV), reflecting sympathetic and parasympathetic nerve activity, was measured before, during and after taVNS or sham stimulation. Endogenous glucose production was determined using [6,6-2H2]glucose, and hepatic concentrations of triglycerides (HCL), adenosine triphosphate (ATP), and inorganic phosphate (Pi) were quantified from 1H/31P magnetic resonance spectroscopy at baseline and for 180 min following stimulation. Results taVNS did not affect circulating glucose, free fatty acids, insulin, glucagon, or pancreatic polypeptide. Rates of endogenous glucose production (P = 0.79), hepatic HCL, ATP, and Pi were also not different (P = 0.91, P = 0.48 and P = 0.24) between taVNS or sham stimulation. Hepatic HCL, ATP, and Pi remained constant during prolonged fasting for 3 h. No changes in heart rate or shift in cardiac autonomic function from HRV towards sympathetic or parasympathetic predominance were detected. Conclusion Non-invasive vagus stimulation by Cerbomed Nemos® does not acutely modulate the autonomic tone to the visceral organs and thereby does not affect hepatic glucose and energy metabolism. This technique is therefore unable to mimic brain insulin-mediated effects on peripheral homeostasis in humans. © 2017 The Authors

Published
2018

14. Informationsbedürfnisse von Menschen mit kürzlich diagnostiziertem Diabetes mellitus: Ergebnisse der Deutschen Diabetes-Studie

Author

Grobosch, S., Kuske, S., Linnenkamp, U., Ernstmann, N., Stephan, A., Genz, J., Begun, A., Haastert, B., Szendroedi, J., Müssig, K., Burkart, V., Roden, M., and Icks, A.

Subjects
Diabetes mellitus, ddc: 610, Patientenzentrierte Versorgung, Informationsbedürfnisse, 610 Medical sciences, Medicine
Abstract

Hintergrund: Menschen mit Diabetes mellitus haben im Vergleich zu Menschen mit anderen chronischen Erkrankungen ein höheres Informationsbedürfnis. Dennoch sind ihre Informationsbedürfnisse bisher kaum untersucht. Fragestellung: Ziele dieser Studie sind (1) die Informationsbedürfnisse[zum vollständigen Text gelangen Sie über die oben angegebene URL], 51. Kongress für Allgemeinmedizin und Familienmedizin

Published
2017

15. Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study

Author

Markus, M.R.P., Ittermann, T., Baumeister, S.E., Huth, C., Thorand, B., Herder, C., Roden, M., Siewert-Markus, U., Rathmann, W., Koenig, W., Dörr, M., Völzke, H., Schipf, S., and Meisinger, C.

Subjects
Adult, Blood Glucose, Male, Time Factors, endocrine system diseases, Kidney, Risk Assessment, Prediabetic State, Risk Factors, Germany, Albuminuria, Humans, Insulin, Renal Insufficiency, Chronic, Aged, Aged, 80 and over, Glycated Hemoglobin, nutritional and metabolic diseases, Fasting, Glucose Tolerance Test, Middle Aged, Prognosis, Cross-Sectional Studies, Chronic Kidney Disease, Diabetes, Insulin Resistance, Microalbuminuria, Creatinine, Female, Biomarkers, Glomerular Filtration Rate
Abstract

Background and Aims: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Methods and Results: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. Conclusion: Our findings suggest that prediabetes might have harmful effects on the kidney.

Published
2017

16. Longitudinal associations of air pollution with biomarkers of inflammation and insulin resistance

Author

Kathrin Wolf, C Herder, Wolfgang Koenig, Alexander Schneider, Peters A, R. Pickford, Susanne Breitner, Mwiberi S, Roden M, and S. Zhang

Subjects
Global and Planetary Change, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Air pollution, Inflammation, medicine.disease, medicine.disease_cause, Pollution, Insulin resistance, Immunology, medicine, medicine.symptom, business
Published
2019
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17. HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confoundersin a meta-analysis of individual participant data from six cohort studies

Author

Schöttker, B., Rathmann, W., Herder, C., Thorand, B., Wilsgaard, T., Njølstad, I., Siganos, G., Mathiesen, E. B., Saum, K. U., Peasey, A., Feskens, E., Boffetta, P., Trichopoulou, A., Kuulasmaa, K., Kee, F., Brenner, H., Peters, A., Meisinger, C., Schneider, A., Lorbeer, R., Holleczek, B., Koenig, W., Roden, M., Alssema, M., Mostaza, J. M., Greenwood, D. C., Schöttker, B., Rathmann, W., Herder, C., Thorand, B., Wilsgaard, T., Njølstad, I., Siganos, G., Mathiesen, E.B., Saum, K.U., Peasey, A., Feskens, E., Boffetta, P., Trichopoulou, A., Kuulasmaa, K., Kee, F., Brenner, H., Peters, A., Meisinger, C., Schneider, A., Lorbeer, R., Holleczek, B., Koenig, W., Roden, M., Alssema, M., Mostaza, J.M., and Greenwood, D.C.

Subjects
Gerontology, Male, Aging, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Glycated hemoglobin, Risk Factors, Cause of Death, Medicine, Cause of death, Aged, 80 and over, Medicine(all), education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Research Support, Non-U.S. Gov't, Hazard ratio, Confounding, Confounding Factors, Epidemiologic, General Medicine, Middle Aged, Nutrition Surveys, Cardiovascular disease, 3. Good health, Europe, Stroke, Cardiovascular Diseases, Cohort, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, Population, HbA1c - cardiovascular outcomes, 030209 endocrinology & metabolism, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Myocardial infarction, Mortality, Meta-analysis, Journal Article, Humans, ddc:610, education, VLAG, Aged, Proportional Hazards Models, Hemoglobin A, Glycosylated, Global Nutrition, Wereldvoeding, business.industry, Proportional hazards model, Cardiovascular Disease, Cohort Study, Glycated Hemoglobin, Myocardial Infarction, Confounding Factors (Epidemiology), United States, Liver function, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Meta-Analysis
Abstract

Source: doi: 10.1186/s12916-016-0570-1 Background:To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. Methods: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as Results:Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50 % of the excess risk and attenuated hazard ratios (95 % confidence interval) for increased HbA1c to 1.14 (1.03–1.27), 1.17 (1.00–1.37) and 1.19 (1.04–1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders.Conclusions: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results. Keywords: Glycated hemoglobin, Cardiovascular disease, Myocardial infarction, Stroke, Mortality, Cohort study, Meta-analysis

Published
2016
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18. Das Gehirn als Schaltzentrale des Stoffwechsels

Author

Fritsche, A., Heni, M., Gancheva, S., Preissl, H., Kullmann, S., Lehnert, H., Tschöp, M.H., Brüning, J.C., Roden, M., and Häring, H.-U.

Abstract

Das Gehirn spielte in der Diabetesforschung lange keine Rolle, inzwischen ist es in den Fokus der Forscher gerückt. Denn Studien der vergangen Jahre belegen: Das Gehirn ist ein insulinsensitives Organ. So reagiert eine Reihe von Gehirngebieten auf Insulin – dazu zählen Areale, die für die Nahrungsaufnahme, den Stoffwechsel und das Gedächtnis wichtig sind. Vermutlich dämpft das Hormon im Gehirn den Hunger oder verstärkt die Sättigung nach dem Essen. Das Gehirninsulin verbessert auch die Wirkung des Hormons im übrigen Körper. Diese Arbeiten eröffnen neue Angriffspunkte in der Diabetestherapie. &nbsp

Published
2017

19. Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study

Author

Kozakova, M, Natali, A, Dekker, J, Beck Nielsen, H, Laakso, M, Nilsson, P, Balkau, B, Ferrannini, E, Heine, Rj, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie Dundee JR, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, Filippo, Saturni, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, Dekker, Ferrannini, Mari, A, Natali, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, Mota, L., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adult, Blood Glucose, Carotid Artery Diseases, Male, medicine.medical_specialty, Adipokine, Carotid Intima-Media Thickness, Risk Assessment, Sensitivity and Specificity, Cohort Studies, Insulin resistance, Age Distribution, Adipokines, Diabetes mellitus, Internal medicine, medicine.artery, medicine, Humans, Common carotid artery, cardiovascular diseases, Sex Distribution, Retrospective Studies, business.industry, Incidence, Fatty Acids, Insulin sensitivity, Cholesterol, LDL, Glucose Tolerance Test, Middle Aged, medicine.disease, Prognosis, Endocrinology, Intima-media thickness, Cardiovascular Diseases, Cohort, Glucose Clamp Technique, cardiovascular system, Female, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Dyslipidemia
Abstract

Objective— Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. Approach and Results— We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher ( P P Conclusions— In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.

Published
2013
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20. Frühe diabetische Neurodegeneration – Finden sich im SD-OCT nachweisbare retinale Schichtdickenunterschiede?

Author

Guthoff, R, Schröder, K, Ackermann, P, Steingrube, N, Benthin, A, Völcker, M, Szendrödi, J, Müssig, K, Nowotny, B, Kuß, O, and Roden, M

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Die diabetische Retinopathie wurde lange Zeit als mikrovaskuläre Erkrankung angesehen. In den letzten Jahren rückten jedoch zunehmend zusätzliche neurodegenerative Aspekte der Pathogenese in den Fokus. Analog zur Entstehung der diabetischen Polyneuropathie können retinologische[zum vollständigen Text gelangen Sie über die oben angegebene URL], 29. Jahrestagung der Retinologischen Gesellschaft

Published
2016
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21. Parental origin of sequence variants associated with complex diseases

Author

Voight, B.F., Raychaudhuri, S., Purcell, S., McCarroll, S.A., Segrè, A.V., Ardlie, K., Burtt, N.P., Crawford, G., Elliott, A.L., Green, T., Guiducci, C., Saxena, R., Daly, M.J., Florez, J.C., Altshuler, D., Meigs, J.B., Scott, L.J., Welch, R.P., Willer, C.J., Ganser, M., Jackson, A.U., Stringham, H.M., Abecasis, G.R., Boehnke, M., Steinthorsdottir, V., Thorleifsson, G., Kong, A., Walters, G.B., Thorsteinsdottir, U., Stefansson, K., Dina, C., Proença, C., Cauchi, S., Froguel, P., Zeggini, E., Bumpstead, S., Payne, F., Smith, N., Barroso, I., Ferreira, T., Elliott, K.S., Lindgren, C.M., Prokopenko, I., Rayner, N.W., Robertson, N.R., Morris, A.P., McCarthy, M.I., Huth, C., Grallert, H., Gieger, C., Klopp, N., Meitinger, T., Petersen, A.-K., Thorand, B., Wichmann, H.-E., Illig, T., Aulchenko, Y.S., Amin, N., Witteman, J., Hofman, A., Van Duijn, C.M., McCulloch, L.J., Bennett, A.J., Groves, C.J., Hassanali, N., Owen, K.R., Gloyn, A.L., Wu, G., Stein, L.D., Langenberg, C., Griffin, S., Wareham, N.J., Hoffmann, O.M., Hide, W.A., Dupuis, J., Qi, L., Kraft, P., Sun, Q., Hunter, D., Hu, F.B., Cornelis, M., VanDam, R., Van Hoek, M., Van Herpt, T., Sijbrands, E., Uitterlinden, A., Navarro, P., Balkau, B., Benediktsson, R., Sigurdsson, G., Blagieva, R., Boehm, B.O., Boerwinkle, E., Bonnycastle, L.L., Chines, P.S., Erdos, M.R., Morken, M.A., Narisu, N., Swift, A.J., Boström, K.B., Bravenboer, B., Charpentier, G., Couper, D.J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Fox, C.S., Franklin, C.S., Rudan, I., Grarup, N., Hadjadj, S., Thomas Sparsø, [No Value], Campbell, H., Wilson, J.F., Hansen, T., Pedersen, O., Herder, C., Roden, M., Isomaa, B., Tuomi, T., Johnson, P.R.V., Jørgensen, T., Kao, W.H.L., Kuusisto, J., Laakso, M., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Nilsson, P., Groop, L., Marre, M., Midthjell, K., Platou, C., Hveem, K., Perry, J.R.B., Shields, B.M., Weedon, M.N., Frayling, T.M., Hattersley, A.T., Rathmann, W., Strassburger, K., Rocheleau, G., Sladek, R., Sampson, M.J., Shrader, P., Tichet, J., Bergman, R.N., Collins, F.S., Gyllensten, U., Hitman, G.A., Mohlke, K.L., Pramstaller, P.P., Tuomilehto, J., Walker, M., Watanabe, R.M., Pankow, J.S., and deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland. kong@decode.is

Subjects
Male, CCCTC-Binding Factor, Iceland, Mothers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Fathers, Genomic Imprinting, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Humans, SNP, Genetic Predisposition to Disease, Allele, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, Binding Sites, Multidisciplinary, Genome, Human, Chromosomes, Human, Pair 11, Haplotype, DNA Methylation, Pedigree, Repressor Proteins, Diabetes Mellitus, Type 2, Haplotypes, Carcinoma, Basal Cell, DNA methylation, Female, Human genome, Genomic imprinting, Chromosomes, Human, Pair 7, 030217 neurology & neurosurgery
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071

Published
2009
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22. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

Author

de Rooij SR, Dekker, Jm, Kozakova, M, Mitrakou, A, Melander, O, Gabriel, R, Guidone, C, Højlund, K, Murphy, Ms, Nijpels, G, Dekker, J, de Rooij, S, Boorsma, P, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Raisanen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, S, Sánchez, Me, Carraro, R, Friera, A, Perez, S, Nilsson, P, Persson, M, Ostling, G, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Mingrone, G, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofe, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Mota, Epidemiology and Data Science, General practice, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Cohort Studies, Endocrinology, Insulin resistance, Internal medicine, Prevalence, medicine, Hyperinsulinemia, Humans, Insulin, Ultrasonography, Metabolic Syndrome, Glucose tolerance test, medicine.diagnostic_test, business.industry, Metabolic Syndrome X, Fasting, General Medicine, Odds ratio, Glucose Tolerance Test, Middle Aged, Glucose clamp technique, medicine.disease, Cardiovascular Diseases, Europe, Female, Glucose Clamp Technique, Insulin Resistance, Tunica Media, Intima-media thickness, Metabolic syndrome, business
Abstract

ObjectiveFasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.Design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.ResultsFasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.ConclusionsFasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.

Published
2009
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23. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population

Author

Gastaldelli, A., Kozakova, M., Hojlund, K., Flyvbjerg, A., Favuzzi, A., Mitrakou, A., Balkau, B., Heine, R. J., Dekker, J., Nijpels, G., Boorsma, W., Tournis, S., Kyriakopoulou, K., Thomakos, P., Lalic, N., Lalic, K., Jotic, A., Lukic, L., Civcic, M., Nolan, J., Yeow, T. P., Murphy, M., Delong, C., Neary, G., Colgan, M. P., Hatunic, M., Konrad, T., Bohles, H., Fuellert, S., Baer, F., Zuchhold, H., Golay, A., Harsch Bobbioni, E., Barthassat, V., Makoundou, V., Lehmann, T. N. O., Merminod, T., Petrie, J. R., Perry, C., Neary, F., Macdougall, C., Shields, K., Malcolm, L., Laakso, M., Salmenniemi, U., Aura, A., Raisanen, R., Ruotsalainen, U., Sistonen, T., Laitinen, M., Saloranta, H., Coppack, S. W., Mcintosh, N., Khadobaksh, P., Laville, M., Bonnet, F., Brac de la Perriere, A., Louche-Pelissier, C., Maitrepierre, C., Peyrat, J., Serusclat, A., Gabriel, R., Sanchez, E. M., Carraro, R., Friera, A., Novella, B., Nilsson, P., Persson, M., Oostling, G., Melander, O., Burri, P., Piatti, P. M., Monti, L. D., Setola, E., Galluccio, E., Minicucci, F., Colleluori, A., Walker, M., Ibrahim, I. M., Jayapaul, M., Carman, D., Short, K., Mcgrady, Y., Richardson, D., Beck-Nielsen, H., Staehr, P., Vestergaard, V., Olsen, C., Hansen, L., Bolli, G. B., Porcellati, F., Fanelli, C., Lucidi, P., Calcinaro, F., Saturni, A., Ferrannini, E., Natali, A., Muscelli, E., Pinnola, S., Mingrone, G., Guidone, C., Di Rocco, P., Anderwald, C., Bischof, M., Promintzer, M., Krebs, M., Mandl, M., Hofer, A., Luger, A., Waldhaausl, W., Roden, M., Dekker, J. M., Mari, A., Gaffney, P., Boran, G., Kok, A., Patel, S., Ciociaro, D., Guillanneuf, M. T., Mhamdi, L., Pacini, G., Cavaggion, C., Hills, S. A., Landucci, L., Mota, L., Epidemiology and Data Science, Internal medicine, General practice, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adult, Male, medicine.medical_specialty, Carotid Artery, Common, Coronary Disease, Impaired glucose tolerance, Framingham Heart Study, Insulin resistance, Risk Factors, Internal medicine, Diabetes mellitus, Humans, Medicine, Prospective Studies, Risk factor, Ultrasonography, Hepatology, Adiponectin, business.industry, Fatty liver, Middle Aged, Atherosclerosis, medicine.disease, Common, Europe, Fatty Liver, Endocrinology, Female, Insulin Resistance, Intima-media thickness, Carotid Artery, business
Abstract

Udgivelsesdato: 2009-May Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1,307 nondiabetic subjects (age 30-60 years) recruited at 19 centers, we evaluated liver enzymes, lipids, insulin sensitivity (by euglycemic-hyperinsulinemic clamp), glucose tolerance (by 75 g oral glucose tolerance test), carotid atherosclerosis as intima media thickness (IMT), CHD risk by the Framingham Heart study prediction score, and physical activity (by accelerometer). The presence of FL was estimated using the fatty liver index (FLI; >60, likelihood >78% presence FL; FLI 91% absence of FL). Subjects were divided into three groups: G1: FLI 60 (n = 234), G2: intermediate group (n = 465). Compared to G1, G3 included more men (70% versus 24%) and people with impaired glucose tolerance (23% versus 5%). IMT increased with FLI (G3 = 0.64 +/- 0.08 versus G1 = 0.58 +/- 0.08 mm, P < 0.0001). FLI was associated with increased CHD risk (r = 0.48), low-density lipoprotein cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r = -0.43), high-density lipoprotein cholesterol (r = -0.50), adiponectin (r = -0.42), and physical activity (r = -0.16, all P < 0.0001). The correlations hold also in multivariate analysis after adjusting for age, gender, and recruiting center. Conclusion: In middle-age nondiabetic subjects, increased IMT, CHD risk, and reduced insulin sensitivity are associated with high values of FLI.

Published
2009
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24. Sfrp5 associates with beta-cell function in humans

Author

Carstensen-Kirberg, M. Hatziagelaki, E. Tsiavou, A. Chounta, A. Nowotny, P. Pacini, G. Dimitriadis, G. Roden, M. Herder, C.

Abstract

Background: Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. Material and methods: This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT. Results: Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index. Conclusions: The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Published
2016

25. Obesity and carotid artery remodeling

Author

Kozakova, M., Palombo, C., Morizzo, C., Hojlund, K., Hatunic, M., Balkau, B., Nilsson, P. M., Ferrannini, E., Heine, R. J., Dekker, J., De Rooij, S., Nijpels, G., Boorsma, W., Mitrakou, A., Tournis, S., Kyriakopoulou, K., Thomakos, P., Lalic, N., Lalic, K., Jotic, A., Lukic, L., Civcic, M., Nolan, J., Yeow, T. P., Murphy, M., Delong, C., Neary, G., Colgan, M. P., Konrad, T., Bohles, H., Fuellert, S., Baer, F., Zuchhold, H., Golay, A., Bobbioni, E. H., Barthassat, V., Makoundou, V., Lehmann, T. N. O., Merminod, T., Petrie, J. R., Perry, C., Neary, F., Macdougall, C., Shields, K., Malcolm, L., Laakso, M., Salmenniemi, U., Aura, A., Raisanen, R., Ruotsalainen, U., Sistonen, T., Laitinen, M., Saloranta, H., Coppack, S. W., Mcintosh, N., Angel, ROSS JOHN, Pettersson, L., Khadobaksh, P., Laville, M., Bonnet, F., De La Perriere, A. B., Louche-Pelissier, C., Maitrepierre, C., Peyrat, J., Beltran, S., Serusclat, A., Gabriel, R., Sanchez, E. M., Carraro, R., Friera, A., Novella, B., Nilsson, P., Persson, M., Ostling, G., Melander, O., Burri, P., Piatti, P. M., Monti, L. D., Setola, E., Galluccio, E., Minicucci, F., Colleluori, A., Walker, M., Ibrahim, I. M., Jayapaul, M., Carman, D., Ryan, C., Short, K., Mcgrady, Y., Richardson, D., Beck-Nielsen, H., Staehr, P., Vestergaard, V., Olsen, C., Hansen, L., Bolli, G. B., Porcellati, F., Fanelli, C., Lucidi, P., Calcinaro, F., Saturni, A., Natali, A., Muscelli, E., Pinnola, S., Mingrone, G., Guidone, C., Favuzzi, A., Di Rocco, P., Anderwald, C., Bischof, M., Promintzer, M., Krebs, M., Mandl, M., Hofer, A., Luger, A., Waldhausl, W., Roden, M., Dekker, J. M., Mari, A., Gaffney, P., Boran, G., Kok, A., Patel, S., Gastaldelli, A., Ciociaro, D., Guillanneuf, M. T., Mhamdi, L., Mota, L., Pacini, G., Cavaggion, C., Hills, S. A., Landucci, L., Internal medicine, Dermatology, Epidemiology and Data Science, CCA - Immuno-pathogenesis, EMGO - Lifestyle, overweight and diabetes, and General practice

Subjects
Pathology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Carotid arteries, Carotid remodeling, Hemodynamics, Stroke volume, medicine.disease, Obesity, Obesity, Carotid remodeling, Ultrasound, Blood pressure, Diabetes mellitus, Ultrasound, Internal Medicine, medicine, cardiovascular system, Cardiac and Cardiovascular Systems, Original Article, cardiovascular diseases, Metabolic syndrome, business, Body mass index
Abstract

Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, PP=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, PPP=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). Conclusions: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could represent an additional biomarker, depicting the impact of altered hemodynamics on arterial wall.

Published
2015
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26. The Lin28/let-7 axis regulates glucose metabolism

Author

Zhu H, Shyh Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley G.Q. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Voight BF, Kanoni S, Cavalcanti Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Barroso I., PAOLISSO, Giuseppe, Zhu, H, Shyh Chang, N, Segrè, Av, Shinoda, G, Shah, Sp, Einhorn, W, Takeuchi, A, Engreitz, Jm, Hagan, Jp, Kharas, Mg, Urbach, A, Thornton, Je, Triboulet, R, Gregory, Ri, Diagram, Consortium, Magic, Investigator, Altshuler, D, Voight BF, Daley G. Q., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Voight, Bf, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, and Barroso, I.

Published
2011

27. A European evidence-based guideline for the prevention of type 2 diabetes

Author

Paulweber, B. Valensi, P. Lindström, J. Lalic, N.M. Greaves, C.J. McKee, M. Kissimova-Skarbek, K. Liatis, S. Cosson, E. Szendroedi, J. Sheppard, K.E. Charlesworth, K. Felton, A.-M. Hall, M. Rissanen, A. Tuomilehto, J. Schwarz, P.E. Roden, M. Paulweber, M. Stadlmayr, A. Kedenko, L. Katsilambros, N. Makrilakis, K. Kamenov, Z. Evans, P. Gilis-Januszewska, A. Lalic, K. Jotic, A. Djordevic, P. Dimitrijevic-Sreckovic, V. Hühmer, U. Kulzer, B. Puhl, S. Lee-Barkey, Y.H. Alkerwi, A. Abraham, C. Hardeman, W. Acosta, T. Adler, M. Barengo, N. Barengo, R. Boavida, J.M. Charlesworth, K. Christov, V. Claussen, B. Cos, X. Cosson, E. Deceukelier, S. Dimitrijevic-Sreckovic, V. Djordjevic, P. Evans, P. Felton, A.-M. Fischer, M. Gabriel-Sanchez, R. Gilis-Januszewska, A. Goldfracht, M. Gomez, J.L. Hall, M. Handke, U. Hauner, H. Herbst, J. Hermanns, N. Herrebrugh, L. Huber, C. Hühmer, U. Huttunen, J. Jotic, A. Kamenov, Z. Karadeniz, S. Katsilambros, N. Khalangot, M. Kissimova-Skarbek, K. Köhler, D. Kopp, V. Kronsbein, P. Kulzer, B. Kyne-Grzebalski, D. Lalic, K. Lalic, N. Landgraf, R. Lee-Barkey, Y.H. Liatis, S. Lindström, J. Makrilakis, K. McIntosh, C. McKee, M. Mesquita, A.C. Misina, D. Muylle, F. Neumann, A. Paiva, A.C. Pajunen, P. Paulweber, B. Peltonen, M. Perrenoud, L. Pfeiffer, A. Pölönen, A. Puhl, S. Raposo, F. Reinehr, T. Rissanen, A. Robinson, C. Roden, M. Rothe, U. Saaristo, T. Scholl, J. Schwarz, P.E. Sheppard, K.E. Spiers, S. Stemper, T. Stratmann, B. Szendroedi, J. Szybinski, Z. Tankova, T. Telle-Hjellset, V. Terry, G. Tolks, D. Toti, F. Tuomilehto, J. Undeutsch, A. Valadas, C. Valensi, P. Velickiene, D. Vermunt, P. Weiss, R. Wens, J. Yilmaz, T.

Abstract

Background: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. Aims: This guideline provides evidence-based recommendations for preventing T2DM. Methods: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. Results: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.84.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by 5% lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. Conclusions: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication. © Georg Thieme Verlag KG Stuttgart - New York.

Published
2010

28. A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

Author

Huan, T, Esko, T, Peters, MJ, Pilling, LC, Schramm, K, Schurmann, C, Chen, BH, Liu, C, Joehanes, R, Johnson, AD, Yao, C, Ying, SX, Courchesne, P, Milani, L, Raghavachari, N, Wang, R, Liu, P, Reinmaa, E, Dehghan, A, Hofman, A, Uitterlinden, AG, Hernandez, DG, Bandinelli, S, Singleton, A, Melzer, D, Metspalu, A, Carstensen, M, Grallert, H, Herder, C, Meitinger, T, Peters, A, Roden, M, Waldenberger, M, Dörr, M, Felix, SB, Zeller, T, Vasan, R, O'Donnell, CJ, Munson, PJ, Yang, X, Prokisch, H, Völker, U, van Meurs, JBJ, Ferrucci, L, Levy, D, Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Chasman, DI, Smith, AV, Tobin, MD, and Verwoert, GC

Subjects
International Consortium for Blood Pressure GWAS (ICBP)
Abstract

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p

Published
2015
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29. Serum chemerin concentrations associate with beta-cell function, but not with insulin resistance in individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)

Author

Hatziagelaki, E. Herder, C. Tsiavou, A. Teichert, T. Chounta, A. Nowotny, P. Pacini, G. Dimitriadis, G. Roden, M.

Subjects
nutritional and metabolic diseases
Abstract

The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI-cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI-ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD. © 2015 Hatziagelaki et al.

Published
2015

30. Metabolically healthy and unhealthy obese – the 2013 Stock Conference report

Author

Samocha-Bonet, D., Dixit, V. D., Kahn, C. R., Leibel, R. L., Lin, X., Nieuwdorp, M., Pietiläinen, K. H., Rabasa-Lhoret, R., Roden, M., Scherer, P. E., Klein, S., Ravussin, E., ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Vascular Medicine, and Experimental Vascular Medicine

Subjects
Blood Glucose, Metabolic Syndrome, Congresses as Topic, Reference Standards, Decision Support Systems, Clinical, Article, Body Mass Index, Phenotype, Cardiovascular Diseases, Non-alcoholic Fatty Liver Disease, Risk Factors, Humans, Gene-Environment Interaction, Obesity, Insulin Resistance
Abstract

Obesity is closely associated with cardiovascular diseases and type 2 diabetes, but some obese individuals, despite having excessive body fat, exhibit metabolic health that is comparable with that of lean individuals. The 'healthy obese' phenotype was described in the 1980s, but major advancements in its characterization were only made in the past five years. During this time, several new mechanisms that may be involved in health preservation in obesity were proposed through the use of transgenic animal models, use of sophisticated imaging techniques and in vivo measurements of insulin sensitivity. However, the main obstacle in advancing our understanding of the metabolically healthy obese phenotype and its related long-term health risks is the lack of a standardized definition. Here, we summarize the proceedings of the 13th Stock Conference of the International Association of the Study of Obesity. We describe the current research and highlight the unanswered questions and gaps in the field. Better understanding of metabolic health in obesity will assist in therapeutic decision-making and help identify therapeutic targets to improve metabolic health in obesity.

Published
2014

31. Änderungen retinaler Schichtdicken bei Typ-2-Diabetikern ohne diabetische Retinopathie

Author

Guthoff, Rainer, Steingrube, N., Ackermann, P., Ziegler, I., Brüggemann, J., Strom, A., Ziegler, D., and Roden, M.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Als frühe Diabetesauswirkung am Auge können subklinische Veränderungen wie verminderte Kontrastempfindlichkeit und elektrophysiologische Abweichungen als Zeichen einer retinalen Neurodegeneration auftreten. Die optische Kohärenztomographie (OCT) bietet die Möglichkeit,[for full text, please go to the a.m. URL], 27. Jahrestagung der Retinologischen Gesellschaft

Published
2014
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32. Blood cis-eQTL Analysis Fails to Identify Novel Association Signals among Sub-Threshold Candidates from Genome-Wide Association Studies in Restless Legs Syndrome Restless Legs Syndrome

Author

Schulte, E., Schramm, K., Schurmann, C., Lichtner, P., Herder, C., Roden, M., Gieger, C., Peters, A., Trenkwalder, C., Hoegl, B., Frauscher, B., Berger, K., Fietze, I., Gross, N., Stiasny-Kolster, K., Oertel, W., Bachmann, C., Paulus, W., Zimprich, A., Voelzke, H., Schminke, U., Nauck, M., Illig, T., Meitinger, T., Müller-Myhsok, B., Prokisch, H., and Winkelmann, J.

Subjects
mental disorders
Abstract

Restless legs syndrome (RLS) is a common neurologic disorder characterized by nightly dysesthesias affecting the legs primarily during periods of rest and relieved by movement. RLS is a complex genetic disease and susceptibility factors in six genomic regions have been identified by means of genome-wide association studies (GWAS). For some complex genetic traits, expression quantitative trait loci (eQTLs) are enriched among trait-associated single nucleotide polymorphisms (SNPs). With the aim of identifying new genetic susceptibility factors for RLS, we assessed the 332 best-associated SNPs from the genome-wide phase of the to date largest RLS GWAS for cis-eQTL effects in peripheral blood from individuals of European descent. In 740 individuals belonging to the KORA general population cohort, 52 cis-eQTLs with p(nominal) < 10(-3) were identified, while in 976 individuals belonging to the SHIP-TREND general population study 53 cis-eQTLs with p(nominal) < 10(-3) were present. 23 of these cis-eQTLs overlapped between the two cohorts. Subsequently, the twelve of the 23 cis-eQTL SNPs, which were not located at an already published RLS-associated locus, were tested for association in 2449 RLS cases and 1462 controls. The top SNP, located in the DET1 gene, was nominally significant (p < 0.05) but did not withstand correction for multiple testing (p = 0.42). Although a similar approach has been used successfully with regard to other complex diseases, we were unable to identify new genetic susceptibility factor for RLS by adding this novel level of functional assessment to RLS GWAS data.

Published
2014

36. Influence of Apolipoproteins on the Association Between Lipids and Insulin Sensitivity: A cross-sectional analysis of the RISC Study

Author

Baldi, S., Bonnet, F., Laville, M., Morgantini, C., Monti, L., Hojlund, K., Ferrannini, E., Natali, A., Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, Filippo, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Gaffney, P, Boran, G, Baldi, S, Balkau, B, Mhamdi, L, Mari, A, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, Dekker, Jm, and Walker, M.

Published
2013

37. Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

Author

Pham, M N, Kolb, H, Battelino, T, Ludvigsson, J, Pozzilli, P, Zivehe, F, Roden, M, Mandrup-Poulsen, T, Schloot, N C, University of Zurich, and Pham, M N

Subjects
2712 Endocrinology, Diabetes and Metabolism, 2724 Internal Medicine, 10265 Clinic for Endocrinology and Diabetology, 610 Medicine & health
Published
2013

38. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

Author

Stahl, E. A., Wegmann, D., Trynka, G., Gutierrez Achury, J., Do, R., Voight, B. F., Kraft, P., Chen, R., Kallberg, H. J., F. A. S., Replication, D. G., Consortium, M. a., Genetics, M. I., Kathiresan, S., Wijmenga, C., Gregersen, P. K., Alfredsson, L., Siminovitch, K. A., Worthington, J., P. I. W., Raychaudhuri, S., Plenge, R. M., Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Fox, Cs, Franklin, Cs, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam RM, van Haeften TW, van Herpt, T, van Vliet Ostaptchouk JV, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, Fs, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, Js, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn CM, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Kathiresan, S, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, Flavio Luciano, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, Ds, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, As, Peltonen, L, Melander, O, Berglund, G, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Purcell, S, Surti, A, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, Gabriel, Sb, Stahl, Ea, Wegmann, D, Trynka, G, Gutierrez achury, J, Do, R, Voight, Bf, Kraft, P, Che, R, Kallberg, H, Kurreeman, F, Diabetes Genetics Replication And Meta analysis Consortium: Myocardial Infarction Genetics, Consortium, Casari, GIORGIO NEVIO, Kathiresan, S, Wijmenga, C, Gregersen, Pk, Alfredsson, L, Siminovitch, Ka, Worthington, J, De Bakker, Pi, Raychaudhuri, S, Plenge, Rm, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Multifactorial Inheritance, SUSCEPTIBILITY LOCI, GENETIC SUSCEPTIBILITY, Genome-wide association study, Single-nucleotide polymorphism, Disease, HEART-DISEASE, Biology, VARIANTS, Polymorphism, Single Nucleotide, Article, Arthritis, Rheumatoid, COMMON SNPS, Missing heritability problem, MISSING HERITABILITY, Rheumatoid, Genetic model, Genetic predisposition, Diabetes Mellitus, Humans, genetics, Genetic Predisposition to Disease, Human height, Polymorphism, GENOME-WIDE ASSOCIATION, Arthritis, genetics, Bayes Theorem, Cardiovascular Diseases, genetics, Case-Control Studies, Celiac Disease, genetics, Diabetes Mellitus, Type 2, genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genetics, CELIAC-DISEASE, Bayes Theorem, RISK LOCI, Genetic architecture, Celiac Disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Genetic Loci, Case-Control Studies, HUMAN HEIGHT, Genome-Wide Association Study
Abstract

The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.

Published
2012

39. Comparison of measuring energy metabolism by different (31) P-magnetic resonance spectroscopy techniques in resting, ischemic, and exercising muscle

Author

Schmid, A.I., Schrauwen-Hinderling, V.B., Andreas, M., Wolzt, M., Moser, E., Roden, M., Beeldvorming, RS: NUTRIM - R1 - Metabolic Syndrome, and Humane Biologie

Subjects
MITOCHONDRIAL DYSFUNCTION, EXCHANGE-REACTIONS, magnetization transfer, exercise recovery, ATP SYNTHESIS, HUMAN SKELETAL-MUSCLE, RECOVERY, mitochondria, SACCHAROMYCES-CEREVISIAE, P-31, PHOSPHATE, skeletal muscle, NMR MAGNETIZATION-TRANSFER, IN-VIVO
Abstract

Alternate methods to quantify mitochondrial activity or function have been extensively used for studying insulin resistance and type 2 diabetes mellitus, namely saturation transfer and phosphocreatine (PCr) recovery. As these methods are in fact determining different parameters, this study aimed to compare saturation transfer results to PCr recovery measurements within the same group. Fifteen subjects underwent saturation transfer and ischemic exercise-recovery experiments. PCr decrease during ischemia (Q), induced by cuff inflation, served as an additional measure of resting ATP (adenosine triphosphate) production. ATP synthetic rate (fATP) measured by saturation transfer (0.234 +/- 0.043 mM/s) was greater than (Q = 0.0077 +/- 0.0011 mM/s), but correlated well with Q (r = 0.63 P = 0.013). Parameters of PCr recovery correlated well with fATP (Q(max,lin) : r = 0.71, P = 0.003, Q(max,ADP) : r = 0.66, P = 0.007) and Q (Q(max,lin) : r = 0.92, P = 0.000002, Q(max,ADP) : r = 0.76, P = 0.001). In conclusion, although saturation transfer yields higher ATP synthetic rates than PCr decrease during ischemia, their significant correlation indicates that fATP can be used as a marker of mitochondrial activity. The finding that both Q and fATP correlate with PCr recovery kinetics suggests that skeletal muscle with greater maximal aerobic ATP synthetic rates is also metabolically more active at rest. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc.

Published
2012

40. From metabolic normality to cardiometabolic risk factors in subjects with obesity

Author

Elisabetta Bobbioni Harsch, Zoltan, Pataky, Vincent, Makoundou, Martine, Laville, Emmanuel, Disse, Christian, Anderwald, Thomas, Konrad, Alain, Golay, Heine, Rj, Dekker, J, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Pataky, Z, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Subjects
Adult, Male, medicine.medical_specialty, Obesity, cardiometabolic risk factors, Carotid Artery, Common, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Blood Pressure, Overweight, Carotid Intima-Media Thickness, Body Mass Index, Impaired glucose tolerance, Young Adult, Endocrinology, Insulin resistance, Reference Values, Risk Factors, Internal medicine, Glucose Intolerance, medicine, Humans, Obesity, ddc:613, Nutrition and Dietetics, business.industry, Body Weight, Fasting, Middle Aged, medicine.disease, Impaired fasting glucose, Blood pressure, Cardiovascular Diseases, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Insulin Resistance, business, Lipoproteins, HDL, Body mass index, Weight gain
Abstract

The aim of the study was to evaluate the 3 years incidence of cardiometabolic risk factors, such as impaired fasting glucose, reduced high-density lipoprotein (HDL)-cholesterol, increased plasma triglycerides or blood pressure as well as impaired glucose tolerance in overweight or obese (ow/ob) and normal body weight (nbw) subjects metabolically normal at baseline. Subjects from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study were analyzed. We analyzed 284 nbw and 152 ow/ob subjects who, at baseline, did not show any of the above-mentioned cardiometabolic risk factors. At 3 years, these parameters were re-evaluated. Intima-media thickness (IMT) of the common carotid artery (CCA) was echographically measured. At follow-up, the incidence of one or more cardiometabolic risk factors was 57.2% in ow/ob vs. 31.7% in nbw (P < 0.0001). After adjustment for age, sex, menopause status, lifestyle parameters, insulin sensitivity, and fasting insulinemia, BMI remained significantly linked to the development of one or more cardiometabolic risk factors (P = 0.02). An increased BMI at follow-up was significantly associated with the development of cardiometabolic alterations, in both nbw and ow/ob groups (P = 0.04). Ow/ob subjects who, at 3 years follow-up, remained metabolically normal, showed a less favourable cardiometabolic profile, when compared to nbw counterparts. In ow/ob metabolically normal males and females, intima-media of the common carotid at follow-up was thicker than in nbw (P = 0.03 for males, P = 0.04 for females). In conclusion, metabolically normal obese subjects show a higher incidence of cardiometabolic risk factors, in a short follow-up period. Weight gain is significantly associated with the development of these factors, in both nbw and ow/ob subjects.

Published
2012

42. Fatty liver index, gamma-glutamyltransferase, and early carotid plaques

Author

Kozakova, M, Palombo, C, Eng, Mp, Dekker, J, Flyvbjerg, A, Mitrakou, A, Gastaldelli, A, Ferrannini, E, Heine, Rj, Dekker, Jm, de Rooij, S, Nijpels, G, Boorsma, W, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni Harsch, E, Barthassat, V, Makoundou, V, Lehmann, T, Merminod, T, Petrie, J, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere AB, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Me, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Natali, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Mari, A, Gaffney, P, Boran, G, Beck Nielsen, H, Kok, A, Patel, S, Ciociaro, D, Guillanneuf, Mt, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, Mota, L., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes

Subjects
Carotid Artery Diseases, Male, SMOOTH-MUSCLE-CELLS, Comorbidity, INTIMA-MEDIA THICKNESS, Severity of Illness Index, ADIPONECTIN, AMERICAN-HEART-ASSOCIATION, Prevalence, Gamma-glutamyltransferase, Ultrasonography, RISK, biology, INSULIN SENSITIVITY, Fatty liver, gamma-Glutamyltransferase, Middle Aged, Prognosis, Plaque, Atherosclerotic, Survival Rate, CARDIOVASCULAR-DISEASE, Hypertension, Female, Waist Circumference, Adult, medicine.medical_specialty, HEPATIC STEATOSIS, PLASMA-PROTEIN, ATHEROSCLEROSIS, Risk Assessment, Insulin resistance, Age Distribution, Internal medicine, Diabetes mellitus, medicine, Humans, Sex Distribution, Proportional Hazards Models, Hepatology, Adiponectin, business.industry, medicine.disease, Fatty Liver, Endocrinology, Cross-Sectional Studies, Logistic Models, Intima-media thickness, Multivariate Analysis, biology.protein, Metabolic syndrome, Insulin Resistance, business, Dyslipidemia
Abstract

An association between fatty liver and carotid atherosclerosis has been established; however, it is not clear whether this relationship is a consequence of shared conventional risk factors or whether it is determined by specific circulating factors originating from liver or adipose tissue. To identify the factors possibly linking fatty liver and atherosclerosis, we assessed, in 1,012 subjects free of confounding diseases (e.g., hypertension, diabetes, cardiovascular diseases, and dyslipidemia) and metabolic syndrome, the relationship between the presence of early plaques at carotid bifurcation and fatty liver index (FLI; a validated surrogate marker of fatty liver), as well as the associations between carotid plaque presence and established atherosclerotic risk factors, family history of cardiovascular disease (FH-CVD) or diabetes, insulin sensitivity, serum liver enzymes, adipokines, fatty free acids, and high-sensitivity C-reactive protein (hsCRP). A total of 55 of 1,012 subjects (5.4%) had small plaque at carotid bifurcation. Subjects with plaque were older and had higher prevalence of FLI ≥60 and FH-CVD, higher blood pressure, plasma low-density lipoprotein cholesterol, glucose, gamma-glutamyltransferase (GGT), and hsCRP, as compared to subjects without plaques (P < 0.05). In a logistic regression model, adjusted for sex, liver transaminase, and alcohol consumption, the independent predictors of plaque presence were age (P < 0.0005), FLI ≥60 (P < 0.0005), and current smoking (P < 0.05). When FLI in the model was replaced by variables used in its equation (e.g., body mass index, waist circumference, plasma triglycerides, and GGT), the independent determinants of plaque presence were age (P < 0.001), GGT (P = 0.001), and current smoking (P < 0.05). Conclusions: Our cross-sectional study suggests that subjects with FLI ≥60 are at higher risk of atherosclerotic lesions, independently of established risk factors, and that serum GGT may represent a link between fatty liver and the development of early atherosclerosis. (HEPATOLOGY 2012)

Published
2012
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43. Increased serum concentrations of adhesion molecules but not of chemokines in patients with Type 2 diabetes compared with patients with Type 1 diabetes and latent autoimmune diabetes in adult age: action LADA 5

Author

Pham, M. n., Hawa, M. i., Roden, M., Schernthaner, G., Pozzilli, P., Buzzetti, Raffaella, Scherbaum, W. a., Seissler, J., Hunter, S., Leslie, R. d. g., Kolb, H., and Schloot, N. c.

Subjects
Adult, Male, type2 diabetes, type 1 diabetes, adhesion molecules, type1 diabetes, chemokines, type 2 diabetes, latent autoimmune diabetes in adults, Vascular Cell Adhesion Molecule-1, Blood Pressure, Middle Aged, Body Mass Index, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Phenotype, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Humans, Female, Chemokines, Diabetic Angiopathies, Aged
Abstract

Systemic concentrations of adhesion molecules and chemokines are associated with increased risk of cardiovascular complications. We compared these factors between patients with Type 2 diabetes vs. Type 1 diabetes or latent autoimmune diabetes in adults.Serum concentrations of adhesion molecules sE-selectin, sICAM-1 and sVCAM-1, and chemokines CCL2, CCL3 and CCL4 were measured in 61 patients with latent autoimmune diabetes in adults, 90 with Type 1 diabetes, 465 with Type 2 diabetes and in 41 control subjects, using multiple regression models to adjust for possible confounders.Patients with Type 2 diabetes exhibited greater concentrations of adhesion molecules (P0.02) than those with Type 1 diabetes, latent autoimmune diabetes in adults and control subjects. These differences persisted upon adjustments for age, sex, BMI, blood pressure and diabetes duration (P0.04). Higher BMI positively correlated with concentrations of adhesion molecules in all subjects (P0.0001). Concentrations of sE-selectin positively related to diastolic (β = 0.31) and systolic (β = 0.28) blood pressure in the adjusted model (P0.04). Concentrations of the chemokines, CCL2 and CCL4, did not differ between groups, while CCL3 was higher in patients with latent autoimmune diabetes in adults and Type 1 diabetes than in those with Type 2 diabetes and control subjects (P0.05).Systemic concentrations of adhesion molecules, but not chemokines, relate to cardiovascular risk factors, but remain higher after adjustments in Type 2 diabetes, suggesting a diabetes-type specific effect without difference between latent autoimmune diabetes in adults and Type 1 diabetes, despite their dissimilar phenotype.

Published
2011

44. Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population

Author

Handberg, A, Højlund, K, Gastaldelli, A, Flyvbjerg, A, Dekker, Jm, Petrie, J, Piatti, P, Beck Nielsen, H, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere AB, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Dirocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Ciociaro, D, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, and Mota, L.

Subjects
Adult, CD36 Antigens, Male, Enzyme-Linked Immunosorbent Assay, Middle Aged, Atherosclerosis, Body Mass Index, Cohort Studies, Europe, Fatty Liver, Cross-Sectional Studies, Predictive Value of Tests, Diabetes Mellitus, Humans, Female, Prospective Studies, Insulin Resistance, Algorithms, Biomarkers
Abstract

Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects.In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity (M/I) by euglycaemic-hyperinsulinaemic clamp, carotid atherosclerosis as intima-media thickness (IMT) and two estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%).IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4), whereas adiponectin and M/I decreased (P ≤ 0.01). sCD36 was lower in women than in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log-normal distribution (log-normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation (P = 0.045), metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P0.001). sCD36 correlated significantly with insulin, triglycerides, M/I and FLI (P0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log-normal population, these relationships were stronger than in the total study population and, additionally, sCD36 was significantly associated with LF% and IMT (P0.05).In this cross-sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter-relationship between atherosclerosis, fatty liver and insulin resistance.

Published
2011

45. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
Male, Netherlands Twin Register (NTR), endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Genome-wide association study, Type 2 diabetes, CORONARY HEART-DISEASE, Fasting/blood, 0302 clinical medicine, Insulin, Glucose homeostasis, ddc:576.5, Genome-wide, Diabetes Mellitus, Type 2/blood/genetics/metabolism, CARDIoGRAM Consortium, POPULATION, Proinsulin, RISK, Genetics, 0303 health sciences, INSULIN SENSITIVITY, 11 Medical And Health Sciences, Fasting, Polymorphism, Single Nucleotide/genetics, OBESITY, Female, type 2 diabetes, Life Sciences & Biomedicine, hormones, hormone substitutes, and hormone antagonists, Insulin processing, Adult, medicine.medical_specialty, endocrine system, ENDOCRINOLOGY & METABOLISM, SUSCEPTIBILITY LOCI, Genotype, 030209 endocrinology & metabolism, DIAGRAM Consortium, Biology, C4D Consortium, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Insulin resistance, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, GIANT Consortium, Internal Medicine, medicine, Humans, METAANALYSIS, 030304 developmental biology, Science & Technology, Genome, Human, Hormonal regulation [IGMD 6], Genetic Variation, nutritional and metabolic diseases, proinsulin, medicine.disease, Proinsulin/blood, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, MuTHER Consortium, GLUCOSE-HOMEOSTASIS, Insulin/blood
Abstract

OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.

Published
2011
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46. Non-esterified fatty acid dynamics during oral glucose tolerance test in women with former gestational diabetes

Author

Tura, A., Pacini, G., Winhofer, Y., Bozkurt, L., Di Benedetto, G., Morbiducci, U., Roden, M., and Kautzky-Willer, A.

Subjects
ss-cell function, insulin sensitivity, free fatty acids, mathematical modelling, liver enzymes
Abstract

Aims Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). Methods We studied women with former gestational diabetes with normal glucose tolerance (n = 60) or impaired glucose metabolism (n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of beta-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. Results Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 +/- 0.52 vs. 1.06 +/- 0.20.10-2 ml/mu U). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. Conclusions Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes.

Published
2011
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47. Natural history and physiological determinants of changes in glucose tolerance in a non-diabetic population: the RISC Study

Author

Ferrannini, E, Natali, A, Muscelli, E, Nilsson, Pm, Golay, A, Laakso, M, Beck Nielsen, H, Mari, A, Dekker, Jm, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Tura, A, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, and Balkau, B.

Published
2011

48. A novel surrogate index for hepatic insulin resistance

Author

Vangipurapu, J, Stančáková, A, Kuulasmaa, T, Paananen, J, Kuusisto, J, EGIR RISC Study Group, Ferrannini, E, Laakso, M, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perrier, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Pacini, G, Cavaggion, C, Hills, Sa, and Mota

Published
2011

49. Serum 25-hydroxyvitamin D and risk of type 2 diabetes mellitus: Results from the MONICA/KORA Augsburg study

Author

Thorand, B, Zierer, A, Huth, C, Linseisen, J, Meisinger, C, Roden, M, Peters, A, Koenig, W, and Herder, C

Subjects
ddc: 610, endocrine system diseases, nutritional and metabolic diseases, vitamin D, type 2 diabetes, 610 Medical sciences, Medicine
Abstract

Background: It has been suggested that vitamin D reduces the risk of type 2 diabetes mellitus (T2DM). Also 25-hydroxyvitamin D (25[OH]D) may have immunomodulatory effects and it is well established that subclinical inflammation increases the risk of T2DM. Therefore, the aim was to assess the[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)

Published
2011
Full Text
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50. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women

Author

Bonnet, F, Ducluzeau, Ph, Gastaldelli, A, Laville, M, Anderwald, Ch, Konrad, T, Mari, A, Balkau, B, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Böhles, H, Fuellert, S, Ber, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Stehr, P, Hojlund, K, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Dekker, Jm, Petrie, J, Gaffney, P, Boran, G, Kok, A, Patel, S, Ciociaro, D, Flyvbjerg, A, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, and Mot

Published
2011

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