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2. Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure

Author

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

Published
2022
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8. 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

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

Author

Kozakova, M., Gastaldelli, A., Morizzo, C., Hojlund, 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., Bohles, 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., Sanchez, E. M., Carraro, R., Friera, A., Novella, B., Nilssone, 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., 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., Ciociaro, D., Mari, A., Pacini, Giovanni, Cavaggion, C., Mingrone, Geltrude, Guidone, C., Favuzzi, Angela Maria Rita, Di Rocco, P., Anderwald, C., Bischof, M., Promintzer, M., Krebs, M., Mandl, M., Hofer, A., Luger, A., Waldhausl, W., Roden, M., Palombo, C., Pacini G., Mingrone G. (ORCID:0000-0003-2021-528X), Favuzzi A., Kozakova, M., Gastaldelli, A., Morizzo, C., Hojlund, 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., Bohles, 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., Sanchez, E. M., Carraro, R., Friera, A., Novella, B., Nilssone, 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., 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., Ciociaro, D., Mari, A., Pacini, Giovanni, Cavaggion, C., Mingrone, Geltrude, Guidone, C., Favuzzi, Angela Maria Rita, Di Rocco, P., Anderwald, C., Bischof, M., Promintzer, M., Krebs, M., Mandl, M., Hofer, A., Luger, A., Waldhausl, W., Roden, M., Palombo, C., Pacini G., Mingrone G. (ORCID:0000-0003-2021-528X), and Favuzzi A.

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 <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.

Published
2020

16. 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

21. 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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23. Insulin sensitivity and beta-cell function in the offspring of type 2 diabetic patients: impact of line of inheritance

Author

Natali, A., Muscelli, E., Mari, A., Balkau, B., Walker, M., Tura, A., Anderwald, C., Golay, A., Ferrannini, E., Dekker, J.M., Nijpels, G., Epidemiology and Data Science, General practice, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adult, Male, medicine.medical_specialty, Offspring, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Inheritance Patterns, Context (language use), Type 2 diabetes, Carbohydrate metabolism, Biochemistry, Endocrinology, Child of Impaired Parents, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, medicine, Humans, Child, Pancreatic hormone, Family Health, business.industry, Insulin, Biochemistry (medical), Glucose Tolerance Test, Middle Aged, medicine.disease, Actigraphy, Diabetes Mellitus, Type 2, Adult Children, Female, Insulin Resistance, business, Dyslipidemia
Abstract

What defects in glucose metabolism are present in offspring of type 2 diabetic patients (FHD(+) with a positive family history of diabetes) and to what extent they depend on line of inheritance are uncertain.The objective of this study was to assess clinical phenotype, insulin sensitivity, and β-cell function in FHD(+) by line of inheritance.The subjects included 1221 nondiabetic men and women aged 30-60 yr, of whom 343 were FHD(+), who participated to the Relationship between Insulin Sensitivity and Cardiovascular Disease Investigators study, a multicenter European collaboration.The main outcome measures included the following: insulin sensitivity by the euglycemic clamp; total insulin secretion, β-cell glucose sensitivity, rate sensitivity, and potentiation by C-peptide deconvolution and oral glucose tolerance test modeling; and acute insulin response to i.v. glucose.Older age, increased adiposity, and dyslipidemia were the dominant features of FHD(+) clinical phenotype. FHD(+) subjects had a 13% reduction in insulin sensitivity [95% confidence interval (CI) of 6,19], which in males was more pronounced (17%, CI: 5,24 vs. 10%, CI: 2,20) and influenced by maternal inheritance (21%, CI: 5,38 vs. 14%, CI: 0,28 paternal). After adjusting for confounders, β-cell glucose sensitivity and rate sensitivity were reduced by 13% (CI: 3,20) and 18% (CI: 5,35), respectively (P0.01 for both); the former defect was more severe with maternal (16%, CI: 4,26) than paternal (9%, CI: -2,22) transmission. Independently of line of inheritance, both fasting and total oral glucose tolerance test insulin secretion were increased in proportion to the insulin resistance, whereas acute insulin response and rate sensitivity were not.Diabetic inheritance is expressed as a characteristic clinical phenotype associated with defects in insulin sensitivity and β-cell glucose sensitivity, which are accentuated along maternal inheritance. β-Cell rate sensitivity is reduced and β-cell dynamic responses to insulin resistance are lost independently of the line of inheritance.

Published
2010
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24. 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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25. 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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26. 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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27. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

Author

Muscelli, E. Kozàkovà, M. Flyvbjerg, A. Kyriakopoulou, K. Astiarraga, B.D. Glintborg, D. Konrad, T. Favuzzi, A. Petrie, J.R. 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. Hatunic, M. Konrad, T. Böhles, H. Fuellert, S. Baer, F. Zuchhold, H. Golay, A. Harsch Bobbioni, E. Barthassat, V. Makoundou, V. Lehmann, T.N.O. Merminod, T. 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. 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. Nilsson, 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. Beck-Nielsen, H. Staehr, P. Hojlund, K. 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. 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. Coppack, S.W. Dekker, J.M. Ferrannini, E. Mari, A. Walker, M. Gaffney, P. Nolan, J. Boran, G. Olsen, C. Hansen, L. Beck-Nielsen, H. Kok, A. Dekker, J. Patel, S. Walker, M. Gastaldelli, A. Ciociaro, D. Kozakova, M. Guillanneuf, M.T. Balkau, B. Mhamdi, L. Mari, A. Pacini, G. Cavaggion, C. Hills, S.A. Landucci, L. Mota, L.

Subjects
cardiovascular system, cardiovascular diseases
Abstract

Background: The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unexplained. The aim of this cross-sectional study was to evaluate the associations between early menopause, established cardiovascular (c-v) risk factors, metabolic parameters (insulin secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. Methods: In 74 menopausal women (mean age = 51 ± 3 years, mean duration of menopause = 2.9 ± 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed by mathematical modeling. Results: CCA diameter (5.55 ± 0.46 vs. 5.21± 0.51 mm, P < 0.001), CCA IMT (608 ± 78 vs. 576 ± 74 νm, P < 0.01) and systolic blood pressure (BP) (117 ± 12 vs. 113 ± 11 mm Hg, P < 0.05) were higher in menopausal women, whereas CCA IMT/diameter ratio and IMT in other carotid segments did not differ between the groups. By multivariate models, independent predictors of CCA diameter were menopause and body weight (cumulative R2= 0.37) and independent correlates of CCA IMT were luminal diameter, systolic BP and low-density lipoprotein (LDL) cholesterol (cumulative R2= 0.48). Fasting insulin, insulin secretion, and sensitivity and plasma adiponectin were similar in the two groups and were not related to carotid IMT. Conclusions: Early menopause is associated with CCA remodeling, characterized by a proportional increase in luminal diameter and wall thickness, independent of atherosclerotic risk factors and metabolic variables. © 2009 American Journal of Hypertension, Ltd.

Published
2009

29. 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

33. 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

34. 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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35. 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

37. 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

38. 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

40. 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

43. Body weight, not insulin sensitivity or secretion, may predict spontaneous weight changes in nondiabetic and prediabetic subjects: the RISC study

Author

Rebelos, E, Muscelli, E, Natali, A, Balkau, B, Mingrone, G, Piatti, P, Konrad, T, Mari, A, Ferrannini, E, 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, 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, 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, Beck Nielsen, H, 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, 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

Published
2011

44. Effect of sedentary behaviour and vigorous physical activity on segment-specific carotid wall thickness and its progression in a healthy population

Author

Kozàkovà, M, Palombo, C, Morizzo, C, Nolan, Jj, Konrad, T, 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, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, 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, 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, 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, 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, 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, Waldhausl, W, Roden, M, Dekker, Jm, Mari, A, 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, and Mota, L.

Published
2010

46. Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults

Author

Anderwald, C, Stadler, M, Golay, A, Krebs, M, Petrie, J, Luger, 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, Hatunic, M, Konrad, T, Bönles, H, Franke, 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 Kuopio, 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, 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, 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, Gb, 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, Bischof, M, Promintzer, M, Mandl, M, Hofer, 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.

Published
2010

47. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

Author

Muscelli, E., Kozakova, M., Flyvbjerg, A., Kyriakopoulou, K., Astiarraga, B. D., Glintborg, D., Konrad, T., Favuzzi, A., Petrie, J., Heine, R. J., Dekker, J., De Rooij, S., Nijpels, G., Boorsma, W., Mitrakou, A., Tournis, S., 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., 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., 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., 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., Hojlund, K., Vestergaard, V., Olsen, C., Hansen, L., Bolli, G. B., Porcellati, F., Fanelli, C., Lucidi, P., Calcinaro, F., Saturni, A., Ferrannini, E., Natali, A., Pinnola, S., Mingrone, G., Guidone, C., Di Rocco, P., Anderwald, C., Bischof, M., Promintzer, M., Krebs, M., Mandl, M., Hofer, A., Luger, A., Waldhausl, W., Roden, M., Balkau, B., Dekker, J. M., Mari, A., Gaffney, P., Boran, G., Kok, A., Patel, S., Gastaldelli, A., Ciociaro, D., Guillanneuf, M. T., Mhamdi, L., Pacini, G., Cavaggion, C., Hills, S. A., Landucci, L., and Mota, L.

Subjects
Blood Glucose, medicine.medical_specialty, Carotid Artery, Common, medicine.medical_treatment, Blood Pressure, Insulin resistance, Risk Factors, medicine.artery, Internal medicine, Insulin Secretion, Internal Medicine, Medicine, Humans, Insulin, Common carotid artery, cardiovascular diseases, Ultrasonography, Adiponectin, Cardiovascular Diseases, Cross-Sectional Studies, Female, Insulin Resistance, Menopause, Middle Aged, Tunica Intima, Tunica Media, business.industry, medicine.disease, Common, Endocrinology, Blood pressure, Intima-media thickness, cardiovascular system, Carotid Artery, business, Body mass index
Abstract

BACKGROUND The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unexplained. The aim of this cross-sectional study was to evaluate the associations between early menopause, established cardiovascular (c-v) risk factors, metabolic parameters (insulin secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. METHODS In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed by mathematical modeling. RESULTS CCA diameter (5.55 +/- 0.46 vs. 5.21 +/- 0.51 mm, P less than 0.001), CCA IMT (608 +/- 78 vs. 576 +/- 74 mu m, P less than 0.01) and systolic blood pressure (BP) 0 17 +/- 12 vs. 113 +/- 11 mm Hg, P less than 0.05) were higher in menopausal women, whereas CCA IMT/diameter ratio and IMT in other carotid segments did not differ between the groups. By multivariate models, independent predictors of CCA diameter were menopause and body weight (cumulative R-2 = 0.37) and independent correlates of CCA IMT were luminal diameter, systolic BP and low-density lipoprotein (LDL) cholesterol (cumulative R-2 = 0.48). Fasting insulin, insulin secretion, and sensitivity and plasma adiponectin were similar in the two groups and were not related to carotid IMT. CONCLUSIONS Early menopause is associated with CCA remodeling, characterized by a proportional increase in luminal diameter and wall thickness, independent of atherosclerotic risk factors and metabolic variables.

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

Author

De Rooij, S.R. Dekker, J.M. Kozakova, M. Mitrakou, A. Melander, O. Gabriel, R. Guidone, C. Højlund, K. Murphy, M.S. Nijpels, G. 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. Hatunic, M. Konrad, T. Böhles, 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. 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, M.E. Carraro, R. Friera, A. Perez, S. Nilsson, 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. Beck-Nielsen, H. Staehr, P. Hojlund, K. 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. 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. Coppack, S.W. Dekker, J.M. Ferrannini, E. Mari, A. Walker, M. Gaffney, P. Nolan, J. Boran, G. Olsen, C. Hansen, L. Beck-Nielsen, H. Kok, A. Dekker, J. Patel, S. Walker, M. Gastaldelli, A. Ciociaro, D. Kozakova, M. Guillanneuf, M.T. Balkau, B. Mhamdi, L. Balkau, B. Balkau, B. Mari, A. Mhamdi, L. Landucci, L. Hills, S. Mota, L. Mari, A. Pacini, G. Cavaggion, C. Hills, S.A. Landucci, L. Mota, L.

Abstract

Objective: Fasting 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 methods: The 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. Results: Fasting 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. Conclusions: Fasting 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. © 2009 European Society of Endocrinology.

Published
2009

50. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

Author

Muscelli, E, Kozàkovà, M, Flyvbjerg, A, Kyriakopoulou, K, Astiarraga, Bd, Glintborg, D, Konrad, T, Favuzzi, A, Petrie, J, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, 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, 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, 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, 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, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, 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.

Published
2009

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