Search

Context The FTO gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by FTO has not been rigorously tested for in a uniformly obese study population comprising both sexes. Objective To test for associations of the rs9939609 FTO risk allele with NEFA suppression. Methods We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression. Results No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation (P >.7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression. Conclusion In a gender-mixed adult population of obese individuals, an FTO obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance. [ABSTRACT FROM AUTHOR]

Abstract Backgrounds Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. Methods This study was undertaken as a case–control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and

AIMS/HYPOTHESIS:In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing. METHODS:Forty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of SI, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB. RESULTS:Postoperatively, weight loss and SI-FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabetic participants and increased in the participants with type 2 diabetes. The resulting disposition indices (DIFSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and SI-MM and DIMM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups. CONCLUSIONS/INTERPRETATION:For up to 2 years following RYGB, obese participants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT00433810.

Backgrounds: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. Methods: This study was undertaken as a case–control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). Results: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. Conclusions: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM. [ABSTRACT FROM AUTHOR]

Despite multiple pharmacological options, including rapid-acting insulin analogs, postprandial hyperglycemia is still highly prevalent in patients with type 1 and type 2 diabetes. We hypothesize that the new rapid-acting insulin formulation, the so-called faster-acting Aspart, may have a different effect in controlling postprandial hyperglycemic burden according to the quality of the meal compared to the traditional Aspart. Twenty-five patients with type 1 diabetes were consecutively recruited at the diabetes care center of the University Hospital affiliate of the Magna Græcia University of Catanzaro. Each patient performed four meal tests one week apart, two with a predefined high glycemic index (HGI) food and two with a low glycemic index (LGI) food using insulin Aspart once and Faster Aspart the other time. The 0–30 min, 0–60 min, and 0–120 min glucose Area Under the Curve (AUC) of postprandial glycemic excursion, calculated from continuous glucose monitoring data, were significantly lower with Faster Aspart administered before the HGI test meal as compared to Aspart. A significant difference in favor of Faster Aspart was also found when comparing the 0–60 min and 0–120 min AUC after the LGI meal. Faster Aspart may provide better postprandial glucose control than Aspart regardless of the glycemic index of the meal. [ABSTRACT FROM AUTHOR]

Growth differentiating factor 15 (GDF15) is expressed in the intestine and is one of the most recently identified satiety peptides. The mechanisms controlling its secretion are unclear. The present study investigated whether plasma GDF15 concentrations are meal-related and if potential responses depend on macronutrient type or are affected by previous bariatric surgery. The study included 1) volunteers ingesting rapidly vs. slowly digested carbohydrates (sucrose vs. isomaltose; n = 10), 2) volunteers who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery and unoperated matched controls ingesting a liquid mixed meal (n = 9-10 in each group), and 3) individuals with previous RYGB compared with unoperated controls ingesting isocaloric glucose, fat, or protein (n = 6 in each group). Plasma was collected after an overnight fast and up to 6 h after ingestion (≥12 time points). In cohort 1, fasting GDF15 concentrations were ~480 pg/mL. Concentrations after sucrose or isomaltose intake did not differ from baseline (P = 0.26 to P > 0.99) and total area under the curves (tAUCs were similar between groups (P = 0.77). In cohort 2, fasting GDF15 concentrations were as follows (pg/mL): RYGB = 540 ± 41.4, SG = 477 ± 36.4, and controls = 590 ± 41.8, with no between-group differences (P = 0.73). Concentrations did not increase at any postprandial time point (over all time factor: P = 0.10) and tAUCs were similar between groups (P = 0.73). In cohort 3, fasting plasma GDF15 was similar among the groups (P > 0.99) and neither glucose, fat, nor protein intake consistently increased the concentrations. In conclusion, we find that plasma GDF15 was not stimulated by meal intake and that fasting concentrations did not differ between RYGB-, SG-, and body mass index (BMI)-matched controls when investigated during the weight stable phase after RYGB and SG. [ABSTRACT FROM AUTHOR]

Abstract Background Hyperinsulinemia aggravates insulin resistance and cardio-vascular disease. How the insulinotropic glucagon-like peptide-1 receptor agonist liraglutide in a physiologic post-prandial setting may act on pancreatic alpha and beta-cell function in patients with coronary artery disease (CAD) and type 2 diabetes (T2DM) is less clear. Methods Insulin resistant patients with established CAD and newly diagnosed well-controlled T2DM were recruited to a placebo-controlled, cross-over trial with two treatment periods of 12 weeks and a 2 weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6 mg q.d. to 1.8 mg q.d. within 4 weeks and metformin titrated from 500 mg b.i.d to 1000 mg b.i.d. within 4 weeks. Before and after intervention in both 12 weeks periods insulin, C-peptide, glucose, and glucagon were measured during a meal test. Beta-cell function derived from the oral glucose tolerance setting was calculated as changes in insulin secretion per unit changes in glucose concentration (Btotal) and whole-body insulin resistance using ISIcomposite. Results Liraglutide increased the disposition index [Btotal × ISIcomposite, by 40% (n = 24, p

Background: Breast cancer survivors are a growing population due to improved treatment. It is known that postmenopausal women treated for breast cancer may experience weight gain and increased insulin resistance, but detailed knowledge on how chemotherapy impact metabolic and endocrine mechanisms remain unknown., Objectives: We performed a thorough, preliminary study to elucidate the differing mechanisms of postprandial absorption and metabolism in postmenopausal early breast cancer (EBC) patients treated with adjuvant chemotherapy compared to healthy controls. We hypothesize that chemotherapy has a negative impact on metabolism in EBC patients., Methods: We examined four postmenopausal women shortly after treatment with chemotherapy for EBC and four age-matched healthy women who served as controls using isotopic tracers during a mixed meal-test. Blood was sampled during the 240 min meal-test to examine postprandial absorption and endogenous synthesis of lipid and carbohydrate metabolites., Results: We found that insulin concentrations were numerically higher before the meal-test in the EBC patients compared to controls (76.3 pmol/L vs 37.0 pmol/L; P = 0.06). Glucose kinetics was increased postprandial (most pronounced at 30 min, 9.46 mmol/L vs 7.33 mmol/L; P = 0.51), with no difference between the groups regarding liver glucose output. Fatty acid kinetics showed a numeric increase in oleic acid rate of appearance in BC patients, but only during the first hour after the mixed meal. There was no significant difference in VLDL-TAG synthesis between the two groups., Conclusions: This preliminary study is unique in using advanced tracer methods to investigate in vivo metabolism of EBC patients after chemotherapy although no statistical differences in glucose and fatty acid kinetics was seen compared to controls. However, during the first two postprandial hours, oral glucose and oleic acid appearance in the systematic circulation was elevated in the EBC patients. This could be due to changes in gastrointestinal uptake and further studies with altered set-up could provide valuable insights., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Schwarz reports financial support was provided by Greater Copenhagen Research Foundation. Peter Schwarz reports financial support was provided by MD Sofus Carl Emil and wife Olga Friis Scholarship. Linn Gillberg reports financial support was provided by Novo Nordisk Foundation. Linn Gillberg reports financial support was provided by The Danish Diabetes and Endocrine Academy. Gerrit van Hall reports financial support was provided by Arla Food for Health initiative. Peter Schwarz reports financial support was provided by Svend Andersen Fonden og Aase og Ejnar Danielsens Fond., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the associated effects of ambient temperature and inflammation caused by repeated administration of Escherichia coli lipopolysaccharide (LPS) on insulin, energy, and AA metabolism. Twenty-eight pigs were assigned to one of the two thermal conditions: thermoneutral (24 °C) or high ambient temperature (30 °C). The experimental period lasted 17 d, which was divided into a 7-d period without LPS (days −7 to −1), and a subsequent 10-d LPS period (days 1 to 10) in which pigs were administered 5 repeated injections of LPS at 2-d intervals. Postprandial profiles of plasma insulin and nutrients were evaluated through serial blood samples taken on days −4 (P0), 4 (P1), and 8 (P2). Before the LPS-challenge (P0), postprandial concentrations of glucose, lactate, Gln, Ile, Leu, Phe, Tyr, and Val were greater in pigs kept at 24 °C than at 30 °C (P < 0.05). In contrast, Arg, Asp, Gly, His, and Met postprandial concentrations at P0 were lower at 24 °C than at 30 °C (P < 0.05). At both 24 and 30 °C conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Compared with P0, postprandial concentrations of glucose were greater (P < 0.05) at P1 in pigs kept at 24 °C, and at P1 and P2 in pigs kept at 30 °C. At both ambient temperatures, pigs had lower (P < 0.05) postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at 24 °C (P < 0.05), whereas no difference was observed in pigs at 30 °C. Relative to P0, Gln and Tyr concentrations were lower at P1 and P2 in pigs kept at 24 °C (P < 0.01), whereas lower Gln concentration was observed only at P2 (P < 0.01) and lower Tyr only at P1 (P < 0.01) in pigs kept at 30 °C. Our study shows a hyperglycemic and hyperinsulinemic state in LPS-challenged pigs and a greater magnitude of this response in pigs kept at 30 °C. Furthermore, LPS caused important changes in BCAA, His, Thr, and Trp profiles, suggesting the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the associated effects of ambient temperature and inflammation caused by repeated administration of Escherichia coli lipopolysaccharide (LPS) on insulin, energy, and AA metabolism. Twenty-eight pigs were assigned to one of the two thermal conditions: thermoneutral (24 °C) or high ambient temperature (30 °C). The experimental period lasted 17 d, which was divided into a 7-d period without LPS (days −7 to −1), and a subsequent 10-d LPS period (days 1 to 10) in which pigs were administered 5 repeated injections of LPS at 2-d intervals. Postprandial profiles of plasma insulin and nutrients were evaluated through serial blood samples taken on days −4 (P0), 4 (P1), and 8 (P2). Before the LPS-challenge (P0), postprandial concentrations of glucose, lactate, Gln, Ile, Leu, Phe, Tyr, and Val were greater in pigs kept at 24 °C than at 30 °C (P < 0.05). In contrast, Arg, Asp, Gly, His, and Met postprandial concentrations at P0 were lower at 24 °C than at 30 °C (P < 0.05). At both 24 and 30 °C conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Compared with P0, postprandial concentrations of glucose were greater (P < 0.05) at P1 in pigs kept at 24 °C, and at P1 and P2 in pigs kept at 30 °C. At both ambient temperatures, pigs had lower (P < 0.05) postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at 24 °C (P < 0.05), whereas no difference was observed in pigs at 30 °C. Relative to P0, Gln and Tyr concentrations were lower at P1 and P2 in pigs kept at 24 °C (P < 0.01), whereas lower Gln concentration was observed only at P2 (P < 0.01) and lower Tyr only at P1 (P < 0.01) in pigs kept at 30 °C. Our study shows a hyperglycemic and hyperinsulinemic state in LPS-challenged pigs and a greater magnitude of this response in pigs kept at 30 °C. Furthermore, LPS caused important changes in BCAA, His, Thr, and Trp profiles, suggesting the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature. [ABSTRACT FROM AUTHOR]

Para peneliti mendapatkan bahwa pati beras cukup baik diabsorpsi di saluran cerna, bahkan lebih baik sebagai komposisi bersama elektrolit untuk mengatasi diare. Meskipun kecil, masih terdapat berbagai prevalensi malabsorpsi karbohidrat yang bervariasi, baik dengan pati beras maupun dengan pati lainnya. Khin Maung-U mendapatkan prevalensi malabsorpsi pati beras pada anak di Birma cukup besar (66,5%), sedangkan pati beras mudah didapat di negara-negara dengan beras sebagai makanan pokok sehingga perlu diteliti kemampuan absorpsi pati beras pada anak Indonesia. Telah dilakukan uji hidrogen napas pada 86 anak Indonesia usia 1-3 tahun di Kelurahan Pejaten Barat, Pasar Minggu, Jakarta Selatan. Di antara 86 anak yang di beri meal test dengan kue pati beras 80 g untuk setiap anak ternyata 82 anak (95,3%) masih mampu mengabsorpsi pati beras dengan baik, hanya 4 anak (4,7%) yang mengalami malabsorpsi pati beras. Belum diketahui pasti tipe malabsorpsi pada ke-empat anak ini. Pada penelitian ini terdapat 16 anak (18,6%) berasal dari keluarga sosial ekonomi tidak mampu, sebagian besar ibu berpendidikan SLTP ke bawah, dan sebagian besar pekerjaan orangtuanya di sektor swasta dan buruh. Tidak ditemukan hubungan bermakna (p>0,05) pengaruh diare pada 6 anak (7%), riwayat BBLR pada 13 anak (15,1%), status gizi kurang ataupun malnutrisi pada 35 anak (40,7%) dan infeksi cacing/jamur pada 17 anak (19,8%) terhadap malabsorpsi pati beras.

Background: Glucose homeostasis improves within days following Roux-en-Y gastric bypass (RYGB) surgery. The dynamic metabolic response to caloric intake following RYGB has been assessed using liquid mixed meal tolerance tests (MMTT). Few studies have evaluated the glycemic and hormonal response to a solid mixed meal in subjects with diabetes prior to, and within the first month following RYGB. Methods: Seventeen women with type 2 diabetes of less than 5 years duration participated. Fasting measures of glucose homeostasis, lipids and gut hormones were obtained pre- and post-surgery. MMTT utilizing a solid 4 oz chocolate pudding performed pre-, 2 and 4 weeks post-surgery. Metabolic response to 4 and 2 oz MMTT assessed in five diabetic subjects not undergoing surgery. Results: Significant reductions in fasting glucose and insulin at 3 days, and in fasting betatrophin, triglycerides and total cholesterol at 2 weeks post-surgery. Hepatic insulin clearance was greater at 3 days post-surgery. Subjects exhibited less hunger and greater feelings of fullness and satisfaction during the MMTT while consuming 52.9 ± 6. 5% and 51.0 ± 6.5% of the meal at 2 and 4 weeks post-surgery respectively. At 2 weeks post-surgery, glucose and insulin response to MMTT were improved, with greater GLP-1 and PYY secretion. Improved response to solid MMTT not replicated by consumption of smaller pudding volume in diabetic non-surgical subjects. Conclusions: With a test meal of size and composition representative of the routine diet of post-RYGB subjects, improved glycemic and gut hormone responses occur which cannot be replicated by reducing the size of the MMTT in diabetic subjects not undergoing surgery. [ABSTRACT FROM AUTHOR]

The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. Objective: To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks.Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (∼2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (∼80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch).After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet.A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects.

Introduction Secondary monotherapy failure in diabetes mellitus type 2 occurs early in the course of disease. Choosing the optimal combination therapy depends on the primary pathogenic mechanism. Evaluation of the residual beta cell function is of primary importance in deciding whether insulin should be included in the combination therapy. Objective To investigate the influence of standard meal test and homeostasis model assessment (HOMA-B) index, as markers of residual insulin secretion, on the efficacy of two different therapeutic strategies in secondary sulphonylurea (SU) failure. Methods In the group of thirty subjects with diabetes type 2, metabolic syndrome and secondary SU failure, metformin (MET) was added for the following six months. In the group of 30 subjects with diabetes type 2, secondary SU failure, with no metabolic syndrome, insulin (INS) was added for the same period. During the six-month follow-up period, fasting, postprandial, mean daily blood glucose and glycosylated haemoglobin (HbA1C) were evaluated. Fasting and meal stimulated C-peptide (CP) and insulin levels were measured at the beginning; absolute and relative increase of CP (delta CP, delta CP%), and HOMA-B were calculated. Correlation between CP secretion and HOMA-B at the beginning and glycaemic control after six months of therapy were evaluated by using Pearson correlation coefficient. Results Glycaemic control after six months was significantly improved in both therapeutic combinations (p

Background: Faster aspart is insulin aspart (IAsp) in a new formulation, which in continuous subcutaneous insulin infusion (CSII) in subjects with type 1 diabetes has shown a faster onset and offset of glucose-lowering effect than IAsp.Methods: This double-blind, randomized, crossover active-controlled trial compared 2-h postprandial plasma glucose (PPG) response, following 2 weeks of CSII with faster aspart or IAsp. Primary endpoint: mean change in PPG 2 h after a standardized meal test (ΔPGav,0-2h). Subjects (n = 43) had masked continuous glucose monitoring (CGM) throughout.Results: Faster aspart provided a statistically significantly greater glucose-lowering effect following the meal versus IAsp: ΔPGav,0-2h: 3.03 mmol/L versus 4.02 mmol/L (54.68 mg/dL vs. 72.52 mg/dL); estimated treatment difference (ETD) [95% CI]: -0.99 mmol/L [-1.95; -0.03] (-17.84 mg/dL [-35.21; -0.46]; P = 0.044). One hour postmeal, PG levels were -1.64 mmol/L (-29.47 mg/dL) lower with faster aspart versus IAsp (P = 0.006). Interstitial glucose (IG) profiles supported these findings; the largest differences were observed at breakfast: 9.08 versus 9.56 mmol/L (163.57 vs. 172.19 mg/dL; ETD [95% CI]: -0.48 mmol/L [-0.97; 0.01]; -8.62 mg/dL [-17.49; 0.24]; P = 0.057). Duration of low IG levels (≤3.9 mmol/L [70 mg/dL] per 24 h) was statistically significantly shorter for faster aspart versus IAsp (2.03 h vs. 2.45 h; ETD [95% CI]: -0.42 [-0.72; -0.11]; P = 0.008). No unexpected safety findings were observed.Conclusions: CSII delivery of faster aspart had a greater glucose-lowering effect than IAsp after a meal test. CGM results recorded throughout all meals supported this finding, with less time spent with low IG levels. [ABSTRACT FROM AUTHOR]

Objective: This study was performed to analyse the carbohydrate quantity of the non-standardised breakfast meal test consumed as part of a screening test for gestational diabetes. Design: A prospective descriptive design was utilised. Setting: Screening for gestational diabetes was performed in the High-Risk Antenatal Clinic at Tygerberg Academic Hospital, Cape Town, South Africa. Subjects: Fifty pregnant women who met the local selection criteria for diabetes screening. Outcome measures: The contents of the patient-provided breakfast meal tests were evaluated individually for total carbohydrate amount and compared with the 75 grams of carbohydrate provided by the oral glucose tolerance test (OGTT). Results: The median carbohydrate amount was 71 g but the range (55–145 g) was wide. Only seven meals (14%) fell within 10% of the 75 g carbohydrate target. Conclusion: The patient-provided breakfast meal showed wide variation in carbohydrate amount. If a meal test is to be used instead of the formal OGTT a carefully measured, prepared, palatable, readily available product would need to be sourced and provided. Layman’s summary: It is necessary to screen for the development of diabetes during pregnancy. The standard test with 75 g of glucose is unpalatable and is sometimes replaced by a meal test. However, when this meal test is provided by the women themselves without standardisation, the sugar and starch quantities are too variable. Careful consideration needs to be given to an alternative screening test if it is to be reliable. Strong lay message: Non-standardised screening meal tests for gestational diabetes should not be used. [ABSTRACT FROM PUBLISHER]

Background: The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin. Methods: In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA + DHA concentrate (5 g/day, containing ~2.8 g EPA + DHA; Omega-3), or (iv) pioglitazone and EPA + DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA + DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers. Results: Omega-3 and Pio& Omega-3 increased EPA + DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3. Conclusion: Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA + DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy. [ABSTRACT FROM AUTHOR]

A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M – 15 % protein and 65 % carbohydrate; (2) 6M – 15 % protein and 65 % carbohydrate; (3) 6MHP – 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P< 0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6MHP regimen (glucose: 3569 (se 83) mmol/l × min (64·3 (se 1·5) g/dl × min), insulin: 1·577 (se 0·146) pmol/l (22·7 (se 2·1) μIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (se 78) mmol/l × min (70·5 (se 1·4) g/dl × min), insulin: 2·195 (se 0·146) pmol/l × min (31·6 (se 2·1) μIU/dl × min) for 12 h) or the 6M regimen (glucose: 3902 (se 83) mmol/l × min (70·3 (se 1·5) g/dl × min), insulin: 1·861 (se 0·174) pmol/l × min (26·8 (se 2·5) μIU/dl × min) for 12 h; P< 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses. [ABSTRACT FROM PUBLISHER]

Background: Hyperinsulinemic hypoglycemia is a rare complication of Roux-en-Y gastric bypass (RYGB) surgery. Meals with a high carbohydrate (carb) content and high glycemic index (GI) may provoke these hypoglycemic attacks. The aim of this study is to assess the effects of reducing meal carb content and GI on glycemic responses in patients with post-RYGB hypoglycemia. Methods: Fourteen patients with post-RYGB hypoglycemia underwent two meal tests: a mixed meal test (MMT) with a carb content of 30 g and a meal test with the low GI supplement, Glucerna SR 1.5® (Glucerna meal test (GMT)). Plasma glucose and serum insulin levels were measured for a period of 6 h. Results: Peak glucose levels were reached at T during GMT and at T during MMT, and they were 1.5 ± 0.3 mmol/L lower during GMT than during MMT (7.5 ± 0.4 vs 9.0 ± 0.4 mmol/L, P < 0.005). GMT induced the most rapid rise in plasma insulin: at T plasma, insulin was 30.7 ± 8.5 mU/L higher during GMT than during MMT ( P < 0.005). None of the carb-restricted meals induced post-prandial hypoglycemia. Conclusion: A 30-g carb-restricted meal may help to prevent post-prandial hypoglycemia in patients with post-RYGB hypoglycemia. The use of a liquid, low GI, supplement offers no additional advantage. [ABSTRACT FROM AUTHOR]

Background Patients with end-stage renal disease (ESRD) have glucometabolic disturbances resulting in a high prevalence of prediabetes. The underlying pathophysiology remains unclear, but may prove important for the strategies employed to prevent progression to overt diabetes. Meal-induced release of the insulinotropic gut-derived incretin hormones and pancreatic hormones play a critical role in the maintenance of a normal postprandial glucose tolerance. Methods We studied patients with ESRD and either normal (n = 10) or impaired (n = 10) glucose tolerance, and control subjects (n = 11). Plasma concentrations of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured repeatedly during a standardized 4-h liquid meal including 1.5 g paracetamol (added for evaluation of gastric emptying). Results Fasting glucose and postprandial glucose responses were comparable between groups (P > 0.082). Patients with ESRD exhibited higher fasting levels of GIP and glucagon compared with controls (P < 0.001). Baseline-corrected GLP-1 and glucagon responses were enhanced (P < 0.002), baseline-corrected insulin responses and insulin excursions were reduced (P < 0.035), and paracetamol excursions were delayed (P < 0.024) in patients with ESRD compared with controls. None of the variables differed between the two ESRD subgroups. Conclusions Non-diabetic patients with ESRD were characterized by reduced postprandial insulin responses despite increased secretion of the insulinotropic incretin hormone GLP-1. Fasting levels and baseline-corrected responses of glucagon were elevated and gastric emptying was delayed in the ESRD patients. These perturbations seem to be caused by uraemia per se and may contribute to the disturbed glucose metabolism in ESRD patients. [ABSTRACT FROM PUBLISHER]

Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase- 4 suggests that endogenous GLP-1 may act locally before being degraded. Signaling via the vagus nerve was investigated in 20 truncally vagotomized subjects with pyloroplasty and 10 matched healthy controls. Subjects received GLP-1 (7-36 amide) or saline infusions during and after a standardized liquid mixed meal and a subsequent ad libitum meal. Despite no effect on appetite sensations, GLP-1 significantly reduced ad libitum food intake in the control group but had no effect in the vagotomized group. Gastric emptying was accelerated in vagotomized subjects and was decreased by GLP-1 in controls but not in vagotomized subjects. Postprandial glucose levels were reduced by the same percentage by GLP-1 in both groups. Peak postprandial GLP-1 levels were approximately fivefold higher in the vagotomized subjects. Insulin secretion was unaffected by exogenous GLP-1 in vagotomized subjects but was suppressed in controls. GLP-1 significantly reduced glucagon secretion in both groups, but levels were approximately twofold higher and were nonsuppressible in the early phase of the meal in vagotomized subjects. Our results demonstrate that vagotomy with pyloroplasty impairs the effects of exogenous GLP-1 on food intake, gastric emptying, and insulin and glucagon secretion, suggesting that intact vagal innervation may be important for GLP-1's actions. [ABSTRACT FROM AUTHOR]

Aberrant receptors have been implicated in the pathogenesis of several types of adrenal tumours. So far the presence of aberrant receptors has been investigated in patients with massively enlarged adrenals due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) and unilateral adrenal adenomas associated with overt or subclinical Cushing's syndrome. The likelihood of aberrant responses in patients presenting with bilateral adrenal incidentalomas (BI) presenting as discrete solitary bilateral adenomas has not been thoroughly addressed. This is an observational cross-sectional prospective study conducted in a secondary/tertiary care centre. We studied 33 patients; 28 with incidentally discovered bilateral discrete adrenal adenomas and five with massive bilateral adrenal macronodular hyperplasia. We probed responses to physiological stimuli, namely upright posture and meal; in a subgroup of menopausal women the presence of aberrant gonadotropin receptors was assessed by the LHRH test. Abnormal responses obtained in tests performed with no dexamethasone suppression were always repeated and confirmed under dexamethasone suppression. Aberrant cortisol responses were confirmed in 10 patients; 9 to posture, 1 to meal (along with a positive response to posture) and 1 to LHRH tests. Patients who responded to any test compared to those who tested negative had larger adenomas, higher post-LDDST and midnight cortisol and a trend for lower ACTH levels. Patients without subclinical hypercortisolism (SH) did not respond to any test while 50% of patients with SH had an aberrant response ( P = 0.002). A greater prevalence of aberrant responses was noted in patients with bilateral macronodular hyperplasia compared to those with solitary bilateral adenomas (80 vs. 21.4%, P = 0.02). Aberrant cortisol responses, primarily to posture testing, are present in a substantial proportion of patients with bilateral adrenal incidentalomas. Such cortisol responses are observed only in patients with subclinical hypercortisolism and especially in those patients with larger adrenal lesions. [ABSTRACT FROM AUTHOR]

A model able to simultaneously characterize and simulate 24-hour glucose and insulin profiles following multiple meal tests was developed, extending an integrated glucose—insulin model for oral glucose tolerance tests that was previously published. The analysis was based on glucose and insulin measurements from 59 placebo-treated patients with type 2 diabetes. Circadian variations in glucose homeostasis were assessed on relevant parameters based on literature review. They were best described by a nighttime dip in insulin secretion between approximately 9 p.m. and 5 a.m. using a modulator function. The integrated glucose—insulin model has thus been shown to be applicable to real-life situations determined by multiple meals over the course of a day. This provides the basis for the analysis and simulation of long-term glucose and insulin data. The model may also prove useful for understanding antidiabetic drug actions and requirements in the context of circadian changes in glucose—insulin regulation. [ABSTRACT FROM PUBLISHER]

Background: The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. Objective: To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks. Design: Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (~2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (~80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch). Results: After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet. Conclusion: A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects. [ABSTRACT FROM AUTHOR]

Objective. Mesenteric blood flow is believed to be influenced by digestion and absorption of ingested macronutrients. We hypothesized that the intestinotrophic hormone, GLP-2 (glucagons-like peptide 2), may be involved in the regulation of mesenteric blood flow. Changes in mesenteric blood flow were measured by Doppler ultrasound scanning of the superior mesenteric artery (SMA). The aim of the study was to demonstrate the influence of GLP-2 on this flow, expressed as changes in resistance index (RI). Material and methods. A homogeneous group of 10 fasting healthy volunteers completed a 2-day trial. On day 1, a standard meal was given, and RI measured in the SMA. On day 2, GLP-2 was infused intravenously (IV) at rates of 0.5, 1.0 and 2.0 pmol/kg/min over 3×45 min separated by a 15-20 min rest period. After a further 15-20 min of rest, 450 nmol synthetic GLP-2 was given subcutaneously (SC). RI in the SMA was measured before, during and after the meal and GLP-2 infusions. Results. After IV infusion of GLP-2, the following decreases in RI were observed: 0.5 pmol/kg/min: 2.7% (range 0-6.3%), 1.0 pmol/kg/min: 6.7% (range 0.4-15.9%), 2.0 pmol/kg/min: 15.3% (range 9.6-22.7%) p<0.00802. When given SC, GLP-2 elicited a maximum average change in RI of 15.6% (range 5.0-28.1%). The standard meal elicited a 14.7% (range 8.8-21.6%) change, p<0.020 There was a similar change in RI over time (0-90 min) after a standard meal and after subcutaneous GLP-2, p<0.005. Conclusions. Our study showed a significant association between IV and SC administration of synthetic GLP-2 and changes in mesenteric blood flow. An exponential dose-response relationship was observed after IV infusion. The meal-induced changes in mesenteric blood flow over time were similar to those obtained by SC GLP-2. Thus, our results support the hypothesis that GLP-2 is an important regulator of mesenteric blood flow. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cystic fibrosis (CF) patients present a high incidence of glucose tolerance abnormalities. Altered insulin secretion combined with recommended high-fat intake could be associated with dysregulation of glucose and lipid metabolism. We examined postprandial glucose and lipid profiles during an oral glucose tolerance test (OGTT) and following a standardized high-fat test meal (TM). Methods: Sixteen CF patients with normal glucose tolerance (NGT) or CF-related diabetes (CFRD) and 16 controls underwent a 4 h OGTT and a TM. We then measured plasma glucose, insulin, free fatty acid (FFA) and triglyceride (TG) concentrations. Results: CF patients presented higher glucose excursion compared to controls after the OGTT and TM. However, in CF patients, this excursion was significantly reduced in both amplitude and length after the TM. The TM provoked a comparable increase in TG levels in both groups whereas they remained stable during the OGTT. FFAs were suppressed similarly in both groups after both challenges. Conclusion: CF is associated with abnormal glucose excursion in the presence of relatively normal lipid excursion. The rapid normalization of glucose values after a mixed meal should be further explored and, if confirmed, might have significant implications for CFRD diagnostic. [Copyright &y& Elsevier]

The insulinotropic intestinal hormone GLP-1 is thought to exert one of its effects by direct action on the pancreatic β-cell receptors. GLP-1 is rapidly degraded in plasma, such that only a small amount of the active form reaches the pancreas, making it questionable whether this amount is sufficient to produce a direct incretin effect. The aim of our study was to assess, in a dog model, the putative incretin action of GLP-1 acting directly on the β-cell in the context of postprandial rises in GLP-1 and glucose. Conscious dogs were fed a high-fat, high-carbohydrate meal, and insulin response was measured. We also infused systemic glucose plus GLP-1, or glucose alone, to simulate the meal test values of these variables and measured insulin response. The results were as follows: during the meal, we measured a robust insulin response (52 ± 9 to 136 ± 14 pmol/1, P < 0.05 vs. basal) with increases in portal glucose and GLP-1 but only limited increases in systemic glucose (5.3 ± 0.1 to 5.7 ± 0.1 mmol/1, P = 0.1 vs. basal) and GLP-1 (6 ± 0 to 9 ± 1 pmol/1, P = 0.5 vs. basal). Exogenous infusion of systemic glucose and GLP-1 produced a moderate increase in insulin (43 ± 5 to 84 ± 15 pmol/l, 43% of the meal insulin). However, infusion of glucose alone, without GLP-1, produced a similar insulin response (37 ± 6 to 82 ± 14 pmol, 53% of the meal insulin, P = 0.7 vs. glucose and GLP-1 infusion). In conclusion, in dogs with postprandial rises in systemic glucose and GLP-1, the hormone might not have a direct insufinotropic effect and could regulate glycemia via indirect, portohepatic-initiated neural mechanisms. [ABSTRACT FROM AUTHOR]

Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The diagnostic value of the determination of the serum pancreatic polypeptide (PP) and gastrin concentrations after a standard meal for early diagnosis of patients with multiple endocrine neoplasia type 1 (MEN 1) is controversial. The aim of this study was to clarify this issue. Thirteen patients with MEN 1, seven healthy family members, and eight healthy controls were studied. Plasma PP and serum gastrin were measured before and after the ingestion of a standardized meal. The meal caused a statistically significant ( p<0.05) increase of both PP and gastrin in all three groups studied. Concerning PP, no statistically significant difference was observed between patients and controls. In family members, the values were significantly ( p<0.05) lower than in the other two groups. On the whole, no significant differences in gastrin levels were noted between patients and controls; in family members, the values were significantly ( p<0.05) lower than in patients. All patients who had abnormally high postprandial values of PP and gastrin also had abnormally high basal values of these two peptides. The determination of serum PP and gastrin levels after a meal stimulation test in patients with MEN 1 adds no information about the presence of pancreatic endocrine tumors over that provided by basal values of the two peptides. [ABSTRACT FROM AUTHOR]