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Aim This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetic population. Methods A total of 446 people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) who participated in the Da Qing Diabetes Study, were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response. Results Over 30 years, the rates of all cause death were 9.94, 14.81, 15.02, and 17.58 per 1000 person-years across the four groups respectively. The rate for cardiovascular disease (CVD) death was 5.14, 6.50, 6.80 and 10.47 per 1000 person-years. Compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR = 2.14, 95% CI 1.34–3.42), Q3 (HR = 1.94, 95% CI 1.20–3.14), and Q2 group (HR = 1.70, 95% CI 1.06–2.74). In the Fine-Gray model with non-CVD death as competing risk, the increased insulin AUC were also significantly associated with the CVD death (Q4 vs Q1, HR = 2.04, 95% CI 1.10–3.79). In the fractional polynomial regression analysis, a nonlinear association between insulin AUC and all-cause and CVD death was demonstrated. In addition, insulin AUC was associated with a progressively higher risk of all-cause death and CVD death (fractional power 3, P Conclusion A higher post-load insulin response was significantly associated with a long-term increased risk of all-cause and CVD deaths in the Chinese non-diabetic population. It suggests that people featured by this phenotype is a potential important target for further intervention.

Insufficient insulin release plays a crucial role in the development of unhealthy status in patients with obesity; the present study aimed to classify these patients by the indices for insulin resistance and insulin release. After the indices from OGTT were assessed to achieve high differentiability and low redundancy in classifying patients, HOMA-IR and IGI30min were chosen to classify the patients using K-means clustering method. A total of 249 non-diabetic patients with obesity were classified into four groups. In Group 1, 19 patients were characteristic of high insulin resistance and high insulin release, as well as well-controlled glucose levels, the highest BMI, the youngest age, and the highest early phase release of insulin. In Group 2, 38 patients were unhealthiest in terms of high insulin resistance, reduced insulin release and IGT status. Group 3 consisted of 63 patients that were healthiest with low insulin resistance and high insulin release. In Group 4, 46 IGT patients and 14 IFG patients were identified among 129 patients that showed low insulin resistance, low insulin release, moderate obesity and older age. These concurrent impotent insulin release, older age, and moderate obesity indicated decreasing obesity with increasing age and reduced insulin release. The classification of patients with obesity using K-means clustering method by HOMA-IR and IGI30min provides more information about the development of obesity and unhealthy status. The patients with distinct insulin resistance and insulin release should be followed up, especially for those with reduced or even absent insulin response to glucose stimulation.

Background This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetes population.Methods A total of 446 non-diabetes who participated in the Da Qing Diabetes Study were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The insulin AUC increased drastically from 75.23, 129.61, 179.06 to 309.85mU/L across the four groups. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response.Results The rates of all-cause death in participants who were assigned in the highest (Q4) and lowest (Q1) quartiles of insulin AUC groups were 17.58/1000 and 9.94/1000 person years during a 30-year period, respectively. Multiple Cox analyses with adjustment for baseline age, sex, smoking, post load glucose and other potential confounders showed that the risks of all-cause death in the Group 4 was significantly higher than Group 1(HR 1.90, 95% CI:1.12-3.23). The CVD death rate across these subgroups showed a similar trend (10.47/1000 person years in Group 4 vs 5.14/1000 person years in Group 1) as all-cause death, but it was not significantly different after the same adjustment. Conclusions A higher post-load insulin response was significantly associated with a long-term increased risk of all-cause mortality in the Chinese non-diabetes population. Therefore, subjects featured by this phenotype was a potential important target for further intervention.

The purpose of this study was to examine the effects of a low-carbohydrate high-protein (LCHP) diet on the expression of glucose transporters and their relationships to glucose metabolism. Male C57BL/6 mice were fed a normal control or LCHP diet for 2 weeks. An oral glucose tolerance test and insulin tolerance test (ITT) were performed, and the expression of glucose transporters was determined in the gastrocnemius muscle, jejunum and pancreas. The increase in plasma insulin concentrations after glucose administration was reduced in the LCHP group. However, LCHP diet had no effects on peripheral insulin sensitivity or glucose transporters expression in the gastrocnemius and pancreas. Soluble glucose transporter (SGLT)-1 protein content in jejunum was lower in the LCHP group. Taken together, these results suggest that the blunted insulin response after glucose administration in LCHP diet-fed mice might be due to decreased SGLT-1 expression, but not to an increase in peripheral insulin sensitivity. Abbreviations: LCHP: low-carbohydrate high-protein; ITT: insulin tolerance test; GLUT: glucose transporter; SGLT: soluble glucose transporter; OGTT: oral glucose tolerance test; AUC: area under the curve.

Objective To determine the effects of varying doses of orally administered BPA on indices of glucose metabolism. Methods Eleven college students (21.0 ± 0.8 years; 24.2 ± 3.9 kg/m2) were randomized in a double-blinded, crossover fashion separated by >1 week to placebo (PL), deuterated BPA at 4 µg/kg body weight (BPA-4), and deuterated BPA at 50 µg/kg body weight (BPA-50). Total BPA, glucose, insulin, and C-peptide were assessed at baseline, minutes 15, 30, 45, 60, and every 30 minutes for 2 hours in response to a glucose tolerance test. Results There was a significant condition × time interaction for total BPA (P < 0.001) such that BPA increased more rapidly in BPA-50 than BPA-4 and PL (P = 0.003) and increased more rapidly in BPA-4 than PL (P < 0.001). There were no significant condition × time interactions on glucose, insulin, and C-peptide. Significant condition main effects were observed for glucose such that BPA-50 was significantly lower than PL (P = 0.036) and nearly lower for BPA-4 vs PL (P = 0.056). Significant condition main effects were observed such that insulin in BPA-50 was lower than BPA-4 (P = 0.021), and C-peptide in BPA-50 was lower than BPA-4 (t18 = 3.95; Tukey-adjusted P = 0.003). Glucose, insulin, and C-peptide areas under the curve for the 3-hour profile were significantly lower in BPA-50 vs PL (P < 0.05). Conclusion Orally administered BPA protocol appeared feasible and has immediate effects on glucose, insulin, and C-peptide concentrations.

Purpose Carbohydrate (CHO) ingestion 30 to 45 min before exercise results in transient hypoglycemia after starting the exercise in some, but not all, subjects. However, whether transient hypoglycemia is more likely to occur under fed or fasted condition remains unknown. This study aimed to directly compare the effects of fasting versus feeding on plasma glucose responses after preexercise CHO intake and to examine the relationship between insulin responses and onset of transient hypoglycemia. Methods Sixteen subjects performed 60-min cycle ergometer exercises at 75% maximal oxygen uptake (V˙O2max) under overnight fasted and fed (4 h after breakfast) conditions. In both conditions, they consumed 500 mL of beverage (150 g of glucose) 30 min before beginning exercise. Results The mean plasma glucose concentrations 15 min after starting the exercise did not fall below 4.0 mmol·L−1 (criteria for hypoglycemia) in both states; however, individual differences in the occurrence of transient hypoglycemia were noted. In the fasted state, plasma glucose levels transiently dropped below 4.0 mmol·L−1 in five subjects, who had substantially higher serum insulin levels at the start of exercise, compared with those who did not develop hypoglycemia. Although seven subjects developed transient hypoglycemia in the fed state, no relationship was observed between insulin responses and hypoglycemia. Three subjects developed hypoglycemia in both fasted and fed states. Conclusions These results suggest that transient hypoglycemia after preexercise CHO ingestion occurs in some, but not all, subjects, under both conditions. Furthermore, subjects with enhanced insulin responses seem to be more prone to transient hypoglycemia in the fasted condition.

Purpose: Variations in specific oral processing behaviours may contribute to differences in glucose, insulin and satiety responses to a standardised test meal. This study tested how natural variations in oral processing between slower and faster eaters contribute to differences in post-prandial glucose (PP glucose), insulin response (PP insulin) and post-meal satiety for a standardised test meal. Methods: Thirty-three participants with higher risk for type 2 diabetes consumed a standardised test-meal while being video recorded to derive specific oral processing behaviours. Plasma glucose, insulin and satiety measures were collected at baseline, during and post meal. Participants were split into slower and faster eaters using median split based on their eating rates and individual bolus properties were analysed at the point of swallow. Results: There were large variations in eating rate (p < 0.001). While there was no significant difference in PP glucose response (p > 0.05), slower eaters showed significantly higher PP insulin between 45 and 60 min (p < 0.001). Slower eaters had longer oro-sensory exposure and increased bolus saliva uptake which was associated with higher PP glucose iAUC. Faster eating rate and larger bolus particle size at swallow correlated with lower PP glucose iAUC. A slower eating rate with greater chews per bite significantly increased insulin iAUC. Faster eaters also consistently rated their hunger and desire to eat higher than slower eaters (p < 0.05). Conclusions: Natural variations in eating rate and the associated oral processing contributed to differences in PP glucose, PP insulin and satiety responses. Encouraging increased chewing and longer oral-exposure time during consumption, may promote early glucose absorption and greater insulin and satiety responses, and help support euglycaemia. Trial Registration: ClinicalTrials.gov identifier: NCT04522063.

Background: We previously showed that insulin response to an IV glucose load increases in early pregnancy, independent of changes in insulin sensitivity. It is unknown whether oral glucose tolerance test (OGTT)-based measures of insulin secretory response (ISR) capture the same phenomenon. Methods: This is a secondary analysis of a longitudinal study. Participants (N=31) were studied pre-pregnancy and in early (12-14 wks) and late (34-36 wks) gestation. On separate days, after overnight fasts, an OGTT (75g pre-pregnancy/100g in pregnancy) and an hyperinsulinemic-euglycemic clamp were performed. We calculated Insulinogenic index (IGI), Corrected insulin response (CIR), insulin/glucose area under the curve (AUCins/AUCglu), and Stumvoll 1st Phase Estimate (Stumvoll) from OGTT insulin and glucose levels. Linear mixed effects models examined ISR in early as compared to pre- and late pregnancy; we adjusted p-values for 2 comparisons. Adjusted models included insulin sensitivity, measured with the clamp, as a time-dependent covariate. Results: IGI (adjusted mean ± SEM) increased between pre- and early pregnancy (1.25 ± 0.13 vs. 1.52 ± 0.15, P0.99). The results for Stumvoll were similar. Conclusion: OGTT-based ISR indices capture an insulin sensitivity-independent augmentation of insulin secretion in early pregnancy. Disclosure C.E. Powe: None. J.J. Locascio: None. P. Catalano: None. Funding National Institutes of Health (K23DK113218); Robert Wood Johnson Foundation; Harold Amos Medical Faculty Development Award

We assessed whether OI slowed metabolic decline after 1 yr of treatment among highest risk relatives who participated in the Diabetes Prevention Trial-Type 1 (DPT1) and TrialNet (TN) T1D prevention trials for OI. As published, with a diagnosis of T1D as the endpoint, both OI trials (7.5 mg/day) were negative overall. However, subgroup analyses suggested efficacy for those at high risk in each trial (DPT1: higher titer of insulin autoantibodies; TN: lower first-phase insulin response). Thus, we assessed whether OI slowed metabolic decline among the OI trial participants at highest risk, defined by DPT1 Risk Scores over a 6.75 threshold (DPTRS; OGTT C-peptide and glucose, age, and BMI), above which T1D risk increases sharply as DPTRS increases. Of 73% in DPT1 and 89% in TN with 1 yr OGTTs, 32% in DPT1 (90/282; age: 8.7±4.8 yrs) and 35% in TN (118/340; age: 6.9±3.3 yrs) were in the highest risk groups (3 yr risks: 56% in DPT-1; 55% in TN). In the analysis, area under curve (AUC) C-peptide increased from baseline to 1 yr in both OI groups (DPT1: p In conclusion, when DPTRS was >6.75 metabolic outcomes at 1 yr appeared similarly favorable for OI in the DPT1 and TN trials, suggesting OI slows insulin decline in those at high risk for T1D. Moreover, metabolic measures could be useful endpoints for T1D prevention trials. Disclosure J. Sosenko: None. J.P. Palmer: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. A. Pugliese: None. D. Schatz: None.

Background: Metabolic regulation of glucose can be altered by fasting periods. The aim of our study was to examine the glucose metabolism after an overnight fast (12 hours) as well as after prolonged fasting (36 hours of fasting) in non-obese people, people with obesity and people with type 2 diabetes (T2DM). Material and Methods: Glucose metabolism was assessed by a 75 g oral glucose tolerance test after 12 and 36 hours fasting, respectively. Area under the curve (AUC) was calculated according to the trapezoidal rule. Insulin sensitivity was estimated by using QUICKI and HOMA-IR. Results: In total 60 participants (age 43±16 years, 62% women) were included. Fasting levels of glucose, insulin and c-peptide were significantly lower in all cohorts after 36 hours vs. 12 hours of fasting (p Conclusion: Our data demonstrate higher glucose excursions and a reduced early insulin response after 36 hours of fasting compared to an overnight fasting period in participants with various glucose tolerance levels. Disclosure N.J. Tripolt: None. P.N. Pferschy: None. A. Obermayer: None. M.L. Eckstein: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis. H. Kojzar: None. C. Sourij: None. O. Moser: Other Relationship; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi. B.M. Obermayer-Pietsch: None. R. Riedl: None. H. Sourij: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi.

We previously showed that patients with A-β+ KPD (“obese ketosis-prone type 2 diabetes”) have diminished intracellular arginine availability that may impair their ability to generate an adequate beta cell response in the face of hyperglycemia, and thus make them vulnerable to develop ketoacidosis (Mulukutla et al, J Nutr 2018). To investigate further their β cell responsiveness to exogenous arginine, we studied 9 recently diagnosed, stable, near-normoglycemic A-β+ KPD patients and 10 age-, sex- and BMI-matched nondiabetic controls with dynamic measures of insulin and C-peptide responses to glucose or arginine bolus under two conditions: in the euglycemic, fasting (basal) state and after a 5h hyperglycemic clamp. In the basal state, total and first phase insulin areas under the curve (AUC) in response to glucose were significantly greater in controls than KPD (total AUC 1756 ± 298 vs. 857 ± 126 min·µU/mL; P = 0.05); after hyperglycemia, AUC insulin response to glucose remained significantly greater in controls (total AUC 2470 ± 296 vs. 1512 ± 316 min·µU/mL; P = 0.04), and KPD patients mounted only a non-significant increase in total AUC insulin compared to the basal state (P = 0.12). In contrast, total and first phase AUC insulin in response to arginine in the basal state was similar in controls and KPD (total AUC 544 ± 85 vs. 337 ± 50 min·µU/mL; P = 0.75). After hyperglycemia, although AUC insulin response to arginine was greater in controls (total AUC 1854 ± 2227 vs. 1149 ± 207 min·µU/mL; P = 0.002), the KPD patients mounted a significant 70% increase in total AUC insulin compared to the basal state (P = 0.002). C-peptide responses mirrored those of insulin under all conditions. Thus, KPD patients exhibit a robust β cell response to arginine but not to glucose, both during fasting euglycemia and after sustained hyperglycemia. Exogenous arginine could augment insulin secretion during hyperglycemia and prevent the episodes of ketoacidosis that characterize A-β+ KPD. Disclosure J.W. Hsu: None. A.J. Cardenas: None. R. Gaba: None. M. Tosur: None. N. Ram: None. A.D. Gutierrez: Speaker’s Bureau; Self; AstraZeneca. K.M. Bohren: None. E.I. Caducoy: None. F. Jahoor: None. A. Balasubramanyam: None. Funding National Institutes of Health (R01DK101411)

OBJECTIVES: Multiple studies have examined the effects of fresh watermelon, watermelon juice, or watermelon powder on satiety and skin health; however, few studies have addressed the effects of blenderized (flesh, rind, and seeds) watermelon juice. The objective of this study was to determine the effects of blenderized watermelon juice consumption on satiety, postprandial glucose, insulin response, and topical application on skin health in healthy adults. METHODS: In a crossover design, subjects (N = 20, 16 females, 4 males, age 22.8 ± 2.5 y, BMI 22.6 ± 2.80 kg/m(2)) consumed 8 fl oz of either blenderized watermelon juice or isocaloric sugar water. After an overnight fast, blood glucose and insulin levels were measured at baseline, and at 30 and 60 minutes after drink consumption. Measurements for satiety using a visual analogue scale and skin health using a moisture content test were conducted at baseline, right after, 15, 30, 45, and 60 minutes after consumption and topical application of the juices. RESULTS: Both blenderized watermelon and sugar water significantly increased satiety (P

A growing body of research over the last decades has shown that diets based on the low glycaemic index (GI) foods reduce the risk of developing diabetes and improve blood glucose control in people with diabetes. The range of inflexion on the glycaemic response of low GI (LGI) foods is an interesting observation that has not been studied by many. LGI 1 (GI 54 ± 3.3) biscuit was formulated using a basic formulation while the LGI 2 (23.8 ± 3.3) biscuits was a modification of LGI 1 recipe, formulated with the inclusion of functional ingredients. Biscuits were formulated to be iso-caloric (kcal/100 g: 521 ± 12). Each participant consumed identical standard meals for lunch and dinner. Biscuits were consumed as breakfast and mid-afternoon snack. Using a randomized, controlled, crossover study, 13 males [(means ± SD) age: 25.3 ± 1.0 years, BMI 21.6 ± 0.5 kg/m2, fasting blood glucose 4.7 ± 0.1 mmol/L] wore continuous glucose monitoring systems (CGMS™) for 3 days for each test session. The postprandial glycaemic response and insulin response were compared within participants. Total iAUC for breakfast and standard dinner were significantly lower for LGI 2 treatment (p p = 0.01). The postprandial glycaemic response of two types of biscuits that fall within the low GI classification (GI 24 and 54) differed with LGI 2 biscuits (GI 24) showing a more suppressed postprandial glycaemic response. Our study shows that even within the low GI range, the GI value matters in influencing postprandial glucose.

Background: We previously showed that 1st phase insulin response increases dramatically in pregnancy, independent of changes in insulin sensitivity. Measurement of 1st phase insulin response requires the use of hyperglycemic clamps or intravenous glucose tolerance tests (IVGTTs) which are rarely performed in pregnant women. Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy. Methods: In a secondary analysis of a longitudinal study of glucose metabolism in pregnancy, we examined Pearson correlations between OGTT-based insulin secretory response measures and 1st phase insulin response. Forty women were studied pre-pregnancy; 36 returned in early and late pregnancy (12–14 and 34–36 weeks gestation). At each time point, after overnight fasts, an IVGTT and an OGTT were performed on separate days. The 1st phase insulin response was calculated as the incremental area under the curve during the 1st 10 minutes after intravenous administration of a 0.5 g/kg glucose load (or 19g/m2 body surface area if weight >120% ideal body weight). Homeostatic Model Assessment (HOMAB), Insulinogenic index (IGI), Corrected insulin response (CIR), Insulin area under the curve/Glucose area under the curve (AUCins/AUCglu), and the Stumvoll 1st Phase Estimate (Stumvoll) were calculated from insulin and glucose levels measured fasting and 30, 60, 90, 120, and 180 minutes after an oral glucose load (75 grams pre-pregnancy, 100 grams in pregnancy). Results: The best OGTT-based measure for estimation of 1st phase insulin response differed across study timepoints. In early and late pregnancy, AUCins/AUCglu had the strongest correlation with 1st phase insulin response (early: R=0.79, P Conclusion: OGTT-based measures of insulin secretion do not have a consistent relationship with 1st phase insulin response across pre-, early, and late pregnancy. Our findings suggest that Stumvoll can be used in OGTT-based longitudinal studies of insulin secretory response that begin prior to pregnancy and span gestation. For cross-sectional studies in pregnancy, AUCins/AUCglu are the best estimates of 1st phase insulin response.

The aim of this retrospective study was to evaluate the effects of a treatment with α-lipoic acid (ALA) associated with two different doses of myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Eighty-eight women received the treatment, and 71 among them had complete clinical charts and were considered eligible for this study. All women were treated with 800 mg of ALA per day: 43 patients received 2000 mg of MI and 28 received 1000 mg of MI per day. Menstrual cyclicity, BMI, FSH, LH, estradiol, testosterone, androstenedione, fasting insulin, HOMA-IR, and insulin response to a 2 h OGTT were evaluated before and after 6 months of treatment. The presence of diabetic relatives (DRs) was investigated. Cycle regularity was improved in 71.2% of women. The improvement of menstrual cyclicity occurred regardless of the state of IR and the presence of DRs of the patients. Women with IR mainly showed a significant improvement of metabolic parameters, while those without IR had significant changes of reproductive hormones. Patients with DRs did not show significant changes after the treatment. 85.7% of women taking 2000 mg of MI reported a higher improvement of menstrual regularity than those taking 1000 mg of MI (50%; p<0.01). In conclusion, ALA + MI positively affects the menstrual regularity of women with PCOS, regardless of their metabolic phenotype, with a more evident effect with a higher dose of MI. This effect seems to be insulin independent. The presence of IR seems to be a predictor of responsivity to the treatment in terms of an improvement of the metabolic profile.

Objective The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. Methods Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. Results In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. Conclusions Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

OBJECTIVE To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α (HNF1A) found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3. RESEARCH DESIGN AND METHODS We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5–5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups. RESULTS Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes (P < 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P < 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes. CONCLUSIONS Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.

Moderate hyperglycaemic levels seem to be related to abnormal gastric motility in diabetes mellitus. However, experimental models designed to evaluate the relationship between motility and diabetes over time are not yet well established. Our objective was to investigate the long‐term effects of mild diabetes on gastric motility in rats. Newborn male rats received streptozotocin (mild diabetes groups – MD) or vehicle (control groups – C), and both groups were evaluated after 3 (C3 and MD3) and 6 months (C6 and MD6) postinduction. Mild diabetic animals (MD3 and MD6) showed moderately elevated blood glucose and decreased insulin levels compared with control (C3 and C6). Insulin secretion was enhanced in MD6 compared with MD3, most likely due to partial β‐cell regeneration indicated by HOMA‐β. In HOMA‐IR, it was noticed that MD6 animals had impaired insulin response compared with MD3. Gastric emptying was faster, amplitude of contraction was stronger in MD6 compared with MD3, and in both groups, the differences were significant when compared with control animals. A significant abnormal rhythmic index was calculated for the mild diabetic groups, despite unchanged mean frequency of contraction. In conclusion, despite increased insulin levels over time, constant levels of moderate hyperglycaemia are also related to abnormal gastric motility and impairment of gastric function.

Comprising of two experiments, this study assessed the metabolic, endocrine and appetite-related responses to acute and chronic milk consumption in adolescent males (15–18 y). Eleven adolescents [mean ± SD age: 16.5 ± 0.9 y; BMI: 23.3 ± 3.3 kg/m2] participated in the acute experiment and completed two laboratory visits (milk vs. fruit-juice) in a randomized crossover design, separated by 7-d. Seventeen adolescents [age: 16.1 ± 0.9 y; BMI: 21.8 ± 3.7 kg/m2] completed the chronic experiment. For the chronic experiment, a parallel design with two groups was used. Participants were randomly allocated and consumed milk (n = 9) or fruit-juice (n = 8) for 28-d, completing laboratory visits on the first (baseline, day-0) and last day (follow-up, day-28) of the intervention phase. On laboratory visits (for both experiments), measures of appetite, metabolism and endocrine responses were assessed at regular intervals. In addition, eating behavior was quantified by ad libitum assessment under laboratory conditions and in the free-living environment by weighed food record. Acute milk intake stimulated glucagon (P = 0.027 [16.8 pg mL; 95% CI: 2.4, 31.3]) and reduced ad libitum energy intake relative to fruit-juice (P = 0.048 [−651.3 kJ; 95% CI: −1294.1, −8.6]), but was comparable in the free-living environment. Chronic milk intake reduced free-living energy intake at the follow-up visit compared to baseline (P = 0.013 [-1910.9 kJ; 95% CI: −554.6, −3267.2]), whereas the opposite was apparent for fruit-juice. Relative to baseline, chronic milk intake increased the insulin response to both breakfast (P = 0.031) and mid-morning milk consumption (P = 0.050) whilst attenuating blood glucose (P = 0.025). Together, these findings suggest milk consumption impacts favorably on eating behavior in adolescent males, potentially through integrated endocrine responses.

Aims Black Africans are disproportionally affected by type 2 diabetes, but the pathophysiology is poorly understood. The study aimed to examine the effect of sex and age on insulin sensitivity and insulin response in black South African adults. Methods This cross-sectional study included a random sample of 179 men and 260 women aged 25–74years with normal glucose tolerance from 5 peri-urban townships in Cape Town, SA. Insulin sensitivity (insulin sensitivity index, ISI 0,120 ) and response (insulinogenic index, IGI), and the disposition index (DI, ISI 0,120 ×IGI), derived from an oral glucose tolerance test, were measured. Results Although men were older (median [interquartile range]: 39 [30–48] vs. 35 [29–44], P =0.021) and had significantly lower BMI than women (22.6 [20.0–25.3] vs. 31.0 [25.9–35.7] kg/m 2 , P =0.001), DI was not different ( P =0.740), but ISI 0,120 was higher ( P =0.007) and IGI was lower ( P =0.074) in men than women, adjusting for age and BMI. With increasing age, DI ( β (95%CI): −24.4 (−36.3 to −12.5), P β (95%CI): −4.9 (−7.5 to −2.2), P 0,120 did not change ( β (95%CI): 0.005 (−0.20 to 0.03), P =0.675). Conclusion Black South African women with normal glucose tolerance have lower insulin sensitivity than their male counterparts, but increase their insulin response to maintain normoglycemia. With increasing age, insulin sensitivity remains unchanged, but the insulin response decreases at a similar rate in men and women.

International audience; AbstractPurpose of reviewBecause arginine is the substrate for nitric oxide synthesis, which is pivotal to vascular homeostasis and linked to the insulin response, it has long been posited that supplemental arginine could benefit cardiometabolic health.Recent findingsRecent data have supported the view that supplemental arginine could alleviate the initiation and development of endothelial dysfunction and also shown that it may reduce the risk of type 2 diabetes. One important finding is that these effects may indeed vary as a function of the amount of arginine, its form and notably the metabolic status of the population. Some studies have shown that low doses of slow-release arginine are better used for nitric oxide synthesis and beneficial in individuals with abnormal arginine metabolism/bioavailability. Pathophysiological data in rodents have emphasized the importance of arginase activation during the development of cardiometabolic risk, which lends credence to a potential benefit for arginine supplements. Likewise, epidemiological evidence suggests that alterations to arginine bioavailability are important regarding the cardiometabolic risk. However, other metabolic mechanisms linked to the multiple pathways of arginine metabolism may also play a role.SummaryFurther studies are needed to confirm and analyze how and when supplemental arginine is beneficial to cardiometabolic health.

Type 1 diabetes is a heterogeneous disease with differences in β-cell dysfunction and rates of progression. We thus assessed whether there are differences in C-peptide and glucose responses during 2-hour oral (OGTTs) and intravenous (IVGTTs) glucose tolerance tests between children and adolescents at high risk for T1D. Data from the Diabetes Prevention Trial-type 1 (DPT-1) study participants who progressed to T1D was used for the analysis. We compared C-peptide and glucose responses between children ( In conclusion, the findings showed that despite a lower early insulin response in children, OGTT glucose levels were not higher. This suggests increased insulin sensitivity. The findings also showed that despite the lower early insulin response, the time to diagnosis did not differ. Other aspects of insulin responsiveness, and perhaps sensitivity, appear to also determine the progression rate to T1D. Disclosure H.M. Ismail: None. B.M. Nathan: None. J.P. Palmer: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None. Funding National Institutes of Health

Aims: Observational studies have suggested that beta cell functional mass inevitably decreases over time. We assessed this after 2 years in a geographically defined subgroup of DiRECT who achieved initial remission after diet-induced weight loss. Methods: A Stepped Insulin Secretion Test with Arginine (SISTA) was used to quantify functional beta cell mass (maximum insulin secretory response during hyperglycemia). Insulin secretion rates were estimated by de-convolution; 40 subjects initially achieved remission (HbA1c Results: In the responder group, median (IQ range) maximum rate of insulin secretion increased from 0.58 (0.48 to 0.81) at baseline to 0.74 (0.54 to 1.00) at 5 months, 0.94 (0.57 to 1.24) (p=0.017 from baseline) at 12 months, and 0.94(0.64 to 1.44) (p=0.030 from baseline) nmol/min/m2 at 24 months. This was comparable to NDC (1.02(0.86 to 1.51) nmol/min/m2) by 12 (p=0.064) and 24 months (p=0.244). Median first phase insulin response increased in responders from 0.042 (0.004 to 0.0637) at baseline to 0.108 (0.058 to 0.163) nmol/min/m2 (p Those who failed to maintain remission were characterized by more weight regain 5-24 months (11. 3±1.9 vs. 6.6±1.0 kg, p=0.036). In responders mean HBA1C was 6.0±0.0% at 24 months. Conclusion: Provided weight regain is minimized, remission of type 2 diabetes is durable over 2 years, with a gradual increase to normal beta cell functional mass. Disclosure S.V. Zhyzhneuskaya: None. A. Al-Mrabeh: None. A.C. Barnes: None. B. Aribisala: None. K.G. Hollingsworth: None. H. Pilkington: None. N. Sattar: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Consultant; Self; NAPP Pharmaceuticals Limited. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Amgen Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Roche Diagnostics France, Sanofi. M.E. Lean: Consultant; Self; Counterweight Ltd., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. R. Taylor: Advisory Panel; Self; Wilmington Healthcare. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG. Funding Diabetes UK

Aims: Short-term intensive insulin therapy (SIIT) reverses β cell dysfunction in early T2DM, but this effect vanes overtime. This study aimed to investigate the effects of metformin plus pioglitazone sequential therapy on maintenance of the effect of SIIT. Methods: SIIT were applied in 50 patients with newly diagnosed T2DM to normalize blood glucose for 2 weeks. Patients were then randomly assigned to receive either sequential therapy (metformin 0.5g bid plus pioglitazone 15mg bid) or lifestyle change alone for 3 months. OGTTs were performed with plasma glucose and insulin measured. Results: As showed in the figure, plasma glucose profiles and insulin response during OGTT were improved similarly by SIIT in both groups. At 3 months of follow-up, GHbA1c (6.2±0.6% vs. 6.5±0.4%, P=0.12) in the sequential treatment group was slightly lower though without statistical significance. In OGTT, blood glucose 30, 60 and 90 minutes was significantly lower in the sequential treatment group, which led to lower AUCglucose (1456.1±266.3 vs. 1644.8±184.5 mmol/L*min, P=0.03) and higher AUCinsulin to AUCglucose ratio (2.5±1.9 vs. 1±1.1, P=0.01). HOMA B, HOMA IR, Mesuda index and ISSI-2 were all similar between the two groups. Conclusion: Metformin plus pioglitazone as sequential therapy might improve glycemic control and β cell function after SIIT in newly diagnosed T2DM. Disclosure L. Liu: None. L. Hai: None. W. Ke: None. Y. Li: None. Funding National Key Research and Development Program of China (2018YFC1314102)

Background: The consumption of high-fructose beverages is associated with higher risk for T2D. Fructose can stimulate GLP-1 secretion in lean adults, in the absence of any inhibitory effect on appetite. We hypothesized that the ingestion of glucose (GLC) and fructose (FRU) may differentially stimulate GLP-1 and insulin response in lean and obese adolescents. Methods: We studied 14 lean (4F, 15.9±1.6y, 21.8±2.2 kg/m2) and 23 obese (5F, 15.1±1.6y, 34.5±4.6 kg/m2) adolescents. Participants received, in a double blinded cross-over study, 75g of GLC or FRU. Plasma was obtained every 10min for 60 minutes GLC was determined by YSI Analyzer; insulin and GLP-1 were measured by Millipore RIA; data were expressed as incremental values from baseline and compared by linear mixed effect model between lean and obese. Results: Obese adolescents exhibited greater insulin (p Conclusion: Fructose, but not glucose, ingestion elicits higher insulin and GLP-1 response in obese as compared to lean adolescents. High-fructose consumption may contribute to the hyperinsulinemic phenotype through a GLP-1 mediated mechanism. Disclosure A. Galderisi: None. M.A. Van Name: Research Support; Self; Novo Nordisk Inc. C. Giannini: None. M. Savoye: None. S. Caprio: None. Funding National Institutes of Health (1R01DK085577-01, R01HD40787, R01HD28016; P30DK045735, K12DK094714-02; R01DK111038-01A1; Pediatric Endocrine Society; Robert E. Leet and Clara Guthrie Patterson Trust; European Medical International Framework (EMIF115372)

Background: Hyperinsulinaemia is emerging as an independent risk factor for metabolic disease, but diagnostic measures are limited. It is plausible that insulin resistance measures, such as homeostatic model assessment (HOMA) type 2 variants, may model hyperinsulinaemia, but repeatability data are limited. Kraft and Hayashi insulin response patterns may not only add value in diagnosing hyperinsulinaemia, but also lack suitable repeatability data. Aim: The aim of this study was to investigate the repeatability of insulin response patterns, and fasting and dynamic measures of insulin resistance, and to determine whether these latter measures can predict the insulin response pattern. Setting: This study was conducted at Auckland University of Technology Millennium Institute’s sports performance laboratories. Methods: Oral glucose (100 g) tolerance tests were conducted weekly on eight people. Six people completed four tests, while two completed at least two tests. Each test assessed insulin resistance and response patterns. Insulin resistance measures included fasting tests (HOMA2, McAuley Index) and a dynamic test (oral glucose insulin sensitivity [OGIS]). The insulin response patterns were assessed with both Kraft and Hayashi methodologies. Repeatability characteristics of ordinal variables were assessed by Bland and Altman methods, while Fleiss’ κ was applied to categorical variables. Results: Fasting measures of insulin resistance recorded poor repeatability (HOMA2) or poor sensitivity (McAuley Index) compared to the dynamic measure (OGIS). Kraft insulin response patterns were more repeatable compared to Hayashi patterns, based on a combination of Fleiss’ κ (0.290 vs. 0.186,) p -value (0.15 vs. 0.798) and 95% confidence intervals. Conclusions: Both hyperinsulinaemia and insulin resistance should be dynamically assessed with a multi-sampled oral glucose tolerance test. Further investigations are required to confirm a preferred methodology.

Purpose We previously showed that short-term intervention with barley kernel bread (BKB) improved glucose tolerance. However, glucose tolerance was not improved in a subset of individuals (non-responders) who were characterized by a low Prevotella/Bacteroides ratio. The purpose of the present study was to investigate if the baseline Prevotella/Bacteroides ratio can be used to stratify metabolic responders and non-responders to barley dietary fiber (DF). Methods Fecal samples were collected from 99 healthy humans with BMI 2 between 50 and 70 years old. The abundance of fecal Prevotella and Bacteroides was quantified with 16S rRNA quantitative PCR. 33 subjects were grouped in three groups: subjects with highest Prevotella/Bacteroides ratios, “HP”, n = 12; subjects with lowest Prevotella/Bacteroides ratios, “LP”, n = 13; and subjects with high abundance of both measured bacteria, HPB, n = 8. A 3-day randomized crossover intervention with BKB and white wheat bread (control) was performed. Cardiometabolic test variables were analyzed the next day following a standardized breakfast. Results The BKB intervention lowered the blood glucose responses to the breakfast independently of Prevotella/Bacteroides ratios (P P P Conclusions Here we show that the abundance of gut Prevotella and Bacteroides at baseline did not stratify metabolic responders and non-responders to barley DF intervention. However, our results indicate the importance of gut microbiota in host metabolic regulation, further suggesting that higher Prevotella/Bacteroides ratio may be favorable. ClinicalTrials.gov ID NCT02427555

Aims/Introduction The severity of insulin resistance is higher in Japanese‐American people with American lifestyles than in native Japanese people with Japanese lifestyles. Recently, the role of gut microbiota in the control of host metabolic homeostasis and organ physiology has been recognized. In addition, gut microbiota alterations have been suggested to contribute to pathogenesis of insulin resistance. The principle aim of the present study was to evaluate the impact of a Westernized lifestyle on the gut microbiota of Japanese‐Americans versus native Japanese, and its correlation with insulin resistance. Materials and Methods A total of 14 native Japanese men living in Hiroshima, Japan, and 14 Japanese‐American men living in Los Angeles, USA, were included. A 75‐g oral glucose tolerance test was carried out for all participants to assess their glucose tolerance, and normal glucose tolerance was observed. We compared the insulin response with oral glucose load, the Matsuda Index, and the composition of the gut microbiota between the native Japanese and Japanese‐American men. Results Japanese‐American men showed higher area under the curve values for serum insulin concentrations during the oral glucose tolerance test and lower Matsuda Index than native Japanese men. Gut microbiota composition of the Japanese‐American men was different; in particular, they showed a relatively lower abundance of Odoribacter than native Japanese men. The ratio between relative abundance of Odoribacter and Matsuda Index was positively correlated between the two groups. Conclusions Our findings suggest that Westernized lifestyles alter gut microbiota, and its alteration might induce insulin resistance in non‐diabetic Japanese men.

It is recommended that the oral sugar test (OST) for insulin dysregulation (ID) be performed after an overnight fast, but fasting is impractical in ponies kept solely at pasture. There are few data on OST repeatability and reliability in ponies.To report 1) whether OST results obtained in the morning after an overnight fast or without fasting in the afternoon (FASTING/FED) can be used interchangeably, 2) time of highest insulin concentration TMethod comparison study.Oral sugar tests were performed on four occasions in 10 adult native British ponies, twice FASTING and twice FED. Insulin concentrations were measured by radioimmunoassay at 0-120 min (TSerum [insulin] was significantly (P≤0.05) higher at TOral sugar tests were performed on a small number of animals on one pasture during one season (spring).Clinicians should beware of interpreting changes in absolute OST results owing to poor repeatability. When stabling is unavailable, OSTs of ponies at pasture may yield similar dichotomous results without prior fasting.

Objective Premeal consumption of whey protein improves the postmeal glycemic profile, but little information exists on soy protein. The study aim was to examine the effect of consuming different amounts of a soy protein isolate (SPI) before a 75-g oral glucose tolerance test (OGTT) on subsequent glycemic control. Methods After overnight fasting, eight healthy young subjects consumed a 400-mL liquid meal containing 0 g (SP0), 20 g (SP20) or 40 g (SP40) SPI. Thirty minutes after SPI consumption, an OGTT was performed to evaluate the individual glycemic response. Blood glucose and plasma insulin concentrations were measured immediately before the SPI preload (i.e., 30 min before the start of the OGTT) and before (−10 min) and during the OGTT (15, 30, 45, 60, 90, and 120 min). Results The incremental area under the curve and peak blood glucose response were significantly less for SP40 than those for SP0 and SP20. Insulin secretion was significantly higher for SP20 and SP40 than that for SP0 before and at 15 min after oral glucose consumption. The incremental area under the curve of plasma insulin was significantly higher for SP20 and SP40 than that for SP0. Conclusions An SPI preload of 40 g, but not 20 g, improved glycemic control in young healthy subjects. Glycemic control appears to be attributed not only to the exaggerated insulin response to SPI preload, but also to non-insulin dependent mechanism(s), such as delayed gastric emptying.

It was believed that Type 2 diabetes (DM2) was a progressive condition, with gradual decrease in beta-cell function. Data from the United Kingdom Prospective Study indicate that approximately only 50% beta-cell function remains at the time of diagnosis which decreases to 30% within 6 years. 1 This reduction in betacell function is associated with treatment intensification including additional oral hypoglycaemic agents and ultimately insulin. 1 Due to the decrease in beta-cell function, the first phase insulin response (insulin secretion within the first 10 minutes after eating) is believed to be permanently lost in people with Type 2 diabetes. 2,3 Lim et al. (2011) challenged this view when the first phase insulin secretion normalised following a very low calorie diet (VLCD) (less than 600 kcal) for 8 weeks. 4 Subsequently, glycaemic control normalized and DM2 was in remission. It is not surprising that this study led researchers to question if DM2 could be reversed 3 and sparked mass interest in these diets from people living with DM2. 5

Hyperinsulinaemia is the precursor to numerous metabolic disorders. Early diagnosis and intervention could improve population health. Diagnosing hyperinsulinaemia is problematic because insulin has a very short half-life (2&ndash, 5minutes). It is theorised that c-peptide levels (half-life 20&ndash, 30minutes) would be a better proxy for insulin due to both hormones being released in equimolar amounts. However, the correlation between c-peptide and insulin levels is unknown. We aim to identify their correlation following a four-hour oral glucose tolerance test (OGTT). Data were obtained from records of routine medical care at St Joseph&rsquo, s Hospital, Chicago, IL, USA, during 1977. Two hundred and fifty-five male and female participants aged over 20 years undertook a fourhour OGTT with plasma glucose, insulin and c-peptide levels recorded. Correlation was assessed with Pearson&rsquo, s correlation. There was a weak correlation between insulin and c-peptide, which increased to moderate across the four-hour OGTT (r = 0.482&ndash, 0.680). There was no significant change in this relationship when data was subdivided according to either the WHO glucose status or Kraft insulin response. Although there was a correlation between insulin and c-peptide, it was too weak to recommend the use of c-peptide as an alternative biomarker for the diagnosis of hyperinsulinaemia.

Background: It is well known that the metabolic regulation of glucose can be influenced by dietary interventions, including alterations in meal timing. Aim of our analysis was to examine the glucose metabolism after an overnight fast (10 hours) and after prolonged fasting (36 hours of fasting). Material and Methods: Glucose metabolism was assessed by a 75 g oral glucose tolerance test after an overnight fasting period of 10 hours and a fasting period of 36h. Beta-cell function was quantified by 1st and 2nd phase insulin secretion indices. Results: We included 37 healthy subjects (mean age 48±10 years; 54% women) with a mean body mass index (BMI) of 25.2±3.4 kg/m2. After prolonged fasting mean 2h-glucose and AUC for glucose value were significantly higher than after 10h fasting (2h-glucose: 110±27 mg/dL vs. 89±24 mg/dL; p Conclusion: Our data demonstrate higher glucose excursions and a reduced insulin response after a 36 hour fasting period as compared to an overnight fasting period in healthy subjects.After 10h fastingAfter 36h fastingp-valueFasting c-peptide (ng/mL)1.39 ± 0.651.09 ± 1.030.025Fasting insulin (mU/L)7.9 ± 5.15.7 ± 5.80.042Fasting glucose (mg/dL)88 ± 988 ± 180.830Insulin after 60min (mU/L)87.6 ± 85.853.4 ± 51.80.0361st phase insulin secretion982 ± 573745 ± 5000.012HOMA-IR1.75 ± 1.181.39 ± 2.070.303Stumvoll index (ISI)0.10 ± 0.030.09 ± 0.03 0.230 Disclosure N.J. Tripolt: None. S. Stekovic: None. J. Url: None. F. Aberer: None. P.N. Pferschy: None. R. Riedl: None. B.M. Obermayer-Pietsch: None. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. F. Madeo: None. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc..

Context Postprandial hyperinsulinemia might be an important cardiometabolic risk determinant in black compared with white women. However, the contributions of insulin clearance and β-cell function to racial differences in postprandial insulin response are unknown. Objective To compare, by race and menopause, early insulin response to oral and intravenous glucose and to measure postprandial intact glucagon-like peptide 1 (GLP-1) concentrations, insulin clearance, and β-cell function. Design and Participants 119 federally employed women without diabetes [87 premenopausal (52 black, 35 white) and 32 postmenopausal (19 black, 13 white)] underwent an oral glucose tolerance test, insulin-modified frequently sampled intravenous glucose test (IM-FSIGT), and mixed meal tolerance test (MMTT). Outcome Measures Early insulin response was measured as follows: (i) insulinogenic index (oral glucose tolerance test); (ii) acute insulin response to glucose (IM-FSIGT); and (iii) ratio of incremental insulin/glucose area under the curve in the first 30 minutes of the MMTT. Insulin clearance was assessed during the IM-FSIGT and MMTT. During the MMTT, intact GLP-1 was measured and β-cell function assessed using the insulin secretion rate and β-cell responsivity indexes. Results Black pre-menopausal and postmenopausal women had a greater insulin response and lower insulin clearance and greater dynamic β-cell responsivity (P ≤ 0.05 for all). No differences were found in the total insulin secretion rates or intact GLP-1 concentrations. Conclusions Greater postprandial hyperinsulinemia in black pre-menopausal and postmenopausal women was associated with lower hepatic insulin clearance and heightened β-cell capacity to rapid changes in glucose, but not to higher insulin secretion. The relationship of increased β-cell secretory capacity, reduced insulin clearance, and ambient hyperinsulinemia to the development of cardiometabolic disease requires further investigation.

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous CLTC gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response., eLife digest When we eat carbohydrates, they are digested into sugars that circulate in the blood to provide energy for the brain and other parts of the body. But too much blood sugar can be poisonous. The body regulates blood sugar balance using the hormone insulin, which triggers the removal of sugar from the blood into muscle and fat cells. This removal process involves a pore in membranes at the surface of muscle and fat tissue, called a glucose transporter, through which the sugar molecules can pass. During fasting, the glucose transporter remains inside muscle and fat. But after a meal, insulin acts to release the transporter from its storage area to the surface of the tissue. How efficiently this process happens reflects how efficiently sugar can be removed from the blood. When this pathway breaks down, it can lead to diabetes. In humans, a protein called CHC22 is needed to deliver the glucose transporter to its storage area. In mice, CHC22 is absent. The question arises: do different animals' eating habits influence CHC22's role in controlling blood sugar? The evolutionary history of CHC22 in a number of different animals could reveal what is special about glucose transport after a meal in humans, and how it might fail in diabetes. By analyzing the genomes of several different species, Fumagalli et al. found that the gene encoding CHC22 first evolved around the time animals began developing a backbone and complex nervous systems. Afterwards, it was lost by some animals – including mice, sheep and pigs. Fumagalli et al. also discovered that CHC22 varies between individual people. A new form of CHC22, which first appeared in ancient humans, is less effective at holding the glucose transporter inside muscle and fat – leading to a tendency to reduce blood sugar levels. This new form became more common in humans over a period witnessing the introduction of cooking, and later farming; both of these technologies are associated with increased sugar in the diet. But not everyone has this new variant of the gene – both the old and newer variants are present in people today. The history of CHC22 suggests that it was useful for early humans to hold the glucose transporter inside muscle and fat, keeping blood sugar levels high, which contributed to the development of a large brain. But as humans became exposed to higher dietary levels of sugar the newer form of CHC22 allowed blood sugar to be lowered more readily. People with different forms of CHC22 are likely to differ in their ability to control blood sugar after a meal. In some cases, this could lead to heightened blood sugar levels, which in turn can lead to diabetes.

Individuals with cystic fibrosis and pancreatic insufficiency have a gradual decline in insulin secretion over time, which results in an increase in the prevalence of diabetes with age; up to 50% of adults with cystic fibrosis aged over 35 years have diabetes. Cystic fibrosis-related diabetes differs from Type 1 and Type 2 diabetes in several ways; there is a pattern of insulin deficiency with reduced and delayed insulin response to carbohydrates but a sparing of basal insulin that results in glucose abnormalities, which are frequently characterized by normal fasting glucose and postprandial hyperglycaemia. Insulin deficiency and hyperglycaemia, even at levels which do not reach the threshold for a diagnosis of diabetes, have an adverse impact on lung function and clinical status in people with cystic fibrosis. Although the risk of microvascular complications occurs as in other forms of diabetes, the main reason for treatment is to prevent deterioration in lung function and weight loss; treatment may therefore be required at an earlier stage than for other types of diabetes. Treatment is usually with insulin, but management needs to take into account all the other medical issues that arise in cystic fibrosis.

The article deals with the development of acute myocardial infarction with concomitant obesity and type 2 diabetes mellitus. The pathogenetic roles of FABP4 and CTRP3 - regulatory proteins involved in regulation of adipogenesis, insulin response, and the development of acute myocardial infarction with concomitant obesity and type 2 diabetes are presented. It is proposed to consider FABP4 and CTRP3 as new markers of development and the course of acute myocardial infarction with concomitant obesity and type 2 diabetes. Keywords : protein, humoral indicators, insulin resistance, cardiovascular diseases. кандидат медичних наук, Котелюх М. Ю. Вивчення FABP 4 та CTRP 3 в діагностиці гострого інфаркту міокарда з супутнім ожирінням і цукровим діабетом 2 типу / Харківський національний медичний університет, Україна, м. Харків У статті розглядаються питання розвитку гострого інфаркту міокарда з супутнім ожирінням і цукровим діабетом 2 типу. Наводяться патогенетичні ролі FABP4 та CTRP3 – регуляторних білків, які беруть участь у регулюванні адипогенезу, відповіді на інсулін та в розвитку гострого інфаркту міокарда з супутнім ожирінням і цукровим діабетом 2 типу. Пропонуються для розгляду FABP4 та CTRP3 в якості нових маркерів розвитку та перебігу гострого інфаркту міокарда з супутнім ожирінням і цукровим діабетом 2 типу. Ключові слова : білок, гуморальні показники, інсулінорезистентність, кардіо-васкулярні захворювання.

金沢大学附属病院代謝内科, Aim. To characterize subjects with a nonpositive insulinogenic index and longitudinally observe changes in their glucose tolerance. Subjects and Methods. A historical cohort study was conducted using data from the medical checkups of public school workers. Indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance test (OGTT) and the incidences of diabetes and impaired glucose tolerance (IGT) were compared among subgroups of subjects with different insulinogenic index (change in insulin/change in glucose over the first 30 min on the OGTT). Results. Of the 1464 nondiabetic subjects at baseline, 72 (4.9%) subjects had a nonpositive insulinogenic index: 42 of those subjects had a nonpositive glucose response (ΔGlu0–30 ≤ 0) and 30 had a nonpositive insulin response (ΔIns0–30 ≤ 0). Compared with subjects who had normal glucose tolerance (NGT) with insulinogenic index ≥ 0.4, subjects with a nonpositive glucose response had a higher first-phase Stumvoll and lower incidences of diabetes and IGT based on a log-rank test (), whereas subjects with a nonpositive insulin response had lower indices of insulin secretion and a higher incidence of diabetes (). Conclusions. These results demonstrate that in the first 30 min on the OGTT, subjects with a nonpositive insulinogenic index due to a nonpositive glucose response (ΔGlu0–30 ≤ 0) had a lower risk for future diabetes and that subjects with nonpositive insulin response (ΔIns0–30 ≤ 0) had a higher risk for future one.

Introduction: Non-caloric artificial sweeteners (NAS) consumption may not be safe for health. Several cohort studies have found a positive association between consumption of artificially sweetened beverages (ASB) with weight gain chronic non-communicable diseases. Therefore, it is of interest to study the effect of the consumption of NAS on glucose and insulin response in different conditions.Aim: To determine the effect of acute NAS consumption on blood glucose and insulin curves in healthy people.Methods: A randomized double-blind clinical trial was conducted in 9 apparently healthy subjects who were randomly assigned to drink one can of ASB and one can of sugar sweetened beverages (SSB) and repeated under identical conditions for 3 times each beverage. Blood glucose and insulin levels were measured in the fasted state and during 180 min after the ingestion of the beverage. Areas Under the Curve (AUC) for glucose and insulin were calculated for the values above baseline for the 3 hour period following the drink intake. Within and between coefficients of variation were calculated.Results: The ASB beverage induced a significantly lower area under the curve (AUC) for plasma glucose (87 ± 182 mg* min/dl) and plasma insulin (36 ± 50 μ UI * min/ml) compared with the SSB drink (glucose 954 ± 669 mg * min/dl and insulin 1738 ± 887 μ UI * min/ml) p

Glucosafe is a medical decision support system developed for glycaemic control in critically ill patients. The system recommends nutrition and insulin doses based on a physiological insulin–glucose model. This model assumes constant endogenous insulin release, in contrast to experimental data from healthy humans where a dual-phase insulin release (i.e. a phase-1 and phase-2 response) has been found along with evidence of a 2-pool insulin system. We included two different pancreas models in Glucosafe, one with a phase-2 response (Phase 2 model) and one with a phase-1 and phase-2 response (Phase 1 + 2 model) and studied the stability of Glucosafe with each applied model. The pancreas models were fitted to plasma glucose and insulin data from 14 healthy subjects receiving meals, and compared by calculating the respective loop gains (LG) for each model. The models were also compared by short perturbations of the simulated blood glucose with 1 mmol/l increases over 10 min and measuring the predicted subsequent oscillations of blood glucose and endogenous insulin production. In this second comparison, the time constant (τ) for the decay of the oscillations was used as stability marker of the models. When fitting the models to the pooled data, a better fit (p In conclusion, a pancreas model with both a phase-1 and phase-2 insulin response results in a Glucosafe model which is more stable than Glucosafe with a Phase 2 pancreas model. What remains to be investigated is to which extent the damped oscillations simulated by Glucosafe match the physiological response to a BG perturbation in normal subjects and in patients, and to investigate if a Phase-1 + 2 model improves accuracy of Glucosafe's BG predictions.