Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

10.2337/figshare.17122142 ◽

2022 ◽

Author(s):

Marta Garaulet ◽

Jesus Lopez-Minguez ◽

Hassan S Dashti ◽

Céline Vetter ◽

Antonio Miguel Hernández-Martínez ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Area Under The Curve ◽

Serum Levels ◽

Postprandial Glucose ◽

Oral Glucose ◽

Elevated Concentration ◽

Endogenous Melatonin

Objective: We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (MTNR1B). Research Design and Methods: In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant (n=845) underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime (“early dinner-timing”), and a late condition scheduled 1 hour prior to habitual bedtime (“late dinner-timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between early and late dinner-timing. Results: Melatonin serum levels were 3.5-fold higher in the late vs. early condition, with late dinner-timing resulting in 6.7% lower insulin area-under-the-curve (AUC) and 8.3% higher glucose AUC. In the late condition MTNR1B G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (Pint AUCgluc=0.009, Pint CIR=0.022, Pint DI=0.018). Conclusions: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in MTNR1B G-risk-allele carriers, attributable to insulin secretion defects.

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Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

10.2337/figshare.17122142.v1 ◽

2022 ◽

Author(s):

Marta Garaulet ◽

Jesus Lopez-Minguez ◽

Hassan S Dashti ◽

Céline Vetter ◽

Antonio Miguel Hernández-Martínez ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Area Under The Curve ◽

Serum Levels ◽

Postprandial Glucose ◽

Oral Glucose ◽

Elevated Concentration ◽

Endogenous Melatonin

Objective: We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (MTNR1B). Research Design and Methods: In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant (n=845) underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime (“early dinner-timing”), and a late condition scheduled 1 hour prior to habitual bedtime (“late dinner-timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between early and late dinner-timing. Results: Melatonin serum levels were 3.5-fold higher in the late vs. early condition, with late dinner-timing resulting in 6.7% lower insulin area-under-the-curve (AUC) and 8.3% higher glucose AUC. In the late condition MTNR1B G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (Pint AUCgluc=0.009, Pint CIR=0.022, Pint DI=0.018). Conclusions: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in MTNR1B G-risk-allele carriers, attributable to insulin secretion defects.

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1782-P: Impact of Treatment with Medication vs. Laparoscopic Gastric Banding (GB) on ß-Cell Function in Adults with Impaired Glucose Tolerance (IGT) or Type 2 Diabetes (T2D) in the Restoring Insulin Secretion (RISE) Study

Diabetes ◽

10.2337/db20-1782-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1782-P

Author(s):

DAVID A. EHRMANN ◽

SHARON EDELSTEIN ◽

ANNY XIANG ◽

THOMAS A. BUCHANAN ◽

SILVA A. ARSLANIAN ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Gastric Banding ◽

Impaired Glucose Tolerance ◽

Cell Function ◽

Laparoscopic Gastric Banding

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Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study

Diabetes Care ◽

10.2337/dc19-0538 ◽

2019 ◽

Vol 42 (8) ◽

pp. 1521-1529 ◽

Cited By ~ 1

Author(s):

Karla A. Temple ◽

Ashley H. Tjaden ◽

Karen M. Atkinson ◽

Elena Barengolts ◽

Tamara S. Hannon ◽

...

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cell Function ◽

Daily Physical Activity ◽

Β Cell ◽

Β Cell Function

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Dual Mechanism for Type-2 Diabetes Resolution after Roux-en-Y Gastric Bypass

The American Surgeon ◽

10.1177/000313480907500608 ◽

2009 ◽

Vol 75 (6) ◽

pp. 498-503 ◽

Cited By ~ 10

Author(s):

Edward Lin ◽

S. Scott Davis ◽

Jahnavi Srinivasan ◽

John F. Sweeney ◽

Thomas R. Ziegler ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Gastric Bypass ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Peripheral Insulin Resistance

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

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Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00339.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. E784-E792 ◽

Cited By ~ 5

Author(s):

Torsten P. ◽

Benedikt A. Aulinger ◽

Eric P. Smith ◽

Deborah L. Drazen ◽

Yve Ulrich-Lai ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Hormone Secretion ◽

Insulin Response ◽

Male Rats ◽

Oral Glucose ◽

Light Cycle ◽

Oral Glucose Tolerance ◽

Islet Hormone

Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2–4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l−1·min, P < 0.001), with left-shifted insulin secretion (AUC0–15: MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion.

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Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00506.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. E535-E544 ◽

Cited By ~ 37

Author(s):

Christoffer Martinussen ◽

Kirstine N. Bojsen-Møller ◽

Carsten Dirksen ◽

Siv H. Jacobsen ◽

Nils B. Jørgensen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Glucose Effectiveness ◽

Β Cell Function ◽

First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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Assessment of insulin secretion from the oral glucose tolerance test in white patients with type 2 diabetes

Diabetes Care ◽

10.2337/diacare.23.9.1440 ◽

2000 ◽

Vol 23 (9) ◽

pp. 1440-1441 ◽

Cited By ~ 22

Author(s):

M. Stumvoll ◽

A. Mitrakou ◽

W. Pimenta ◽

T. Jenssen ◽

H. Yki-Jarvinen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

White Patients

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Impaired Insulin Secretion in the Turner Metabolic Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-0122 ◽

2004 ◽

Vol 89 (7) ◽

pp. 3516-3520 ◽

Cited By ~ 84

Author(s):

Vladimir K. Bakalov ◽

Margaret M. Cooley ◽

Michael J. Quon ◽

Mei Lin Luo ◽

Jack A. Yanovski ◽

...

Keyword(s):

Diabetes Mellitus ◽

Body Mass Index ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Body Mass ◽

Cell Function ◽

Insulin Response ◽

Area Under The Curve ◽

Oral Glucose ◽

Glucose Challenge

Abstract An increased prevalence of impaired glucose homeostasis (IGH) and diabetes mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether IGH is an intrinsic feature of this syndrome, independent of obesity or hypogonadism, we compared results of a standard oral glucose challenge in age- and body mass index-matched women with TS and with karyotypically normal premature ovarian failure (POF). Fasting glucose levels were normal in both groups, but glucose values after oral glucose challenge were higher in TS [2-h glucose, 135 ± 36 mg/dl (7.5 ± 2.0 mmol/liter) in TS and 97 ± 18 mg/dl (5.4 ± 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was lower in TS; e.g. the initial insulin response (ΔI/ΔG30) was decreased by 60% compared with POF (P < 0.0001). We also compared responses to a standard iv glucose tolerance test in women with TS and in age- and body mass index-matched normal women and found that the insulin area under the curve was 50% lower in women with TS (P = 0.003). Insulin sensitivity measured by the quantitative insulin sensitivity check index was higher in women with TS compared with both control groups. Thus, IGH is not secondary to obesity or hypogonadism in TS, but it is a distinct entity characterized by decreased insulin secretion, suggesting that haploinsufficiency for X-chromosome gene(s) impairs β-cell function and predisposes to diabetes mellitus in TS.

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Circulating Retinol Binding Protein 4 is Inversely Associated with Pancreatic β Cell Function across the Spectrum of Glycemia

10.2337/dc20-1234/suppl.11985918.v1 ◽

2020 ◽

Author(s):

Rong Huang ◽

Songping Yin ◽

Yongxin Ye ◽

Nixuan Chen ◽

Shiyun Luo ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Retinol Binding Protein ◽

Β Cell ◽

Retinol Binding Protein 4 ◽

Β Cell Function ◽

Oral Minimal Model

OBJECTIVE: The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT) and type 2 diabetes were screened by standard 2-h oral glucose tolerance test (2-h OGTT) with the use of traditional measures to evaluate β cell function. 74 subjects from these participants were recruited in oral minimal model test and assessed β cell function with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. RESULTS: Circulating RBP4 levels were significantly and inversely correlated with β cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion (DI-PhiT). CONCLUSION: Circulating RBP4 levels are inversely and independently correlated with β cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.

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