Postprandial glycemia and insulin secretion following glutamine administration: A randomized controlled trial

2020 ◽  
Vol 90 (5-6) ◽  
pp. 425-429
Author(s):  
Asieh Mansour ◽  
Mohammad Reza Mohajeri-Tehrani ◽  
Mostafa Qorbani ◽  
Mahsa Ghamari ◽  
Bagher Larijani ◽  
...  

Abstract. Objective: The objective of the present study is to investigate the effects of glutamine administration on postprandial glycemia, insulin, and C-peptide concentration in patients with type 2 diabetes. Methods: A randomized, double-blind, placebo-controlled trial was conducted on patients with type 2 diabetes so that 33 subjects were recruited in each group. The patients were randomly allocated to receive either 30 g/d glutamine or placebo (with instructions to take in half glass of ice-cold water 5 to 10 min before each main meal) for 6 weeks. Postprandial C-peptide, insulin, and glucose were measured at the baseline and at the end of the study at 30 and 90 min after consuming a meal comprising wheat-cake and reduced fat milk. Results: The repeated measures ANOVA revealed no significant difference between the groups for glucose and insulin after 6 weeks of intervention ( p > 0.05). However, C-peptide was reduced in both intervention groups at all measurement points. Between-group differences remained significant by the end of the study ( p = 0.02). Conclusions: Glutamine supplementation before each main meal does not represent an effective nutritional strategy to improve postprandial glycemic control or postprandial insulin secretion in type 2 diabetes patients.

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 486 ◽  
Author(s):  
Hana Kahleova ◽  
Andrea Tura ◽  
Marta Klementova ◽  
Lenka Thieme ◽  
Martin Haluzik ◽  
...  

Diminished postprandial secretion of incretins and insulin represents one of the key pathophysiological mechanisms behind type 2 diabetes (T2D). We tested the effects of two energy- and macronutrient-matched meals: A standard meat (M-meal) and a vegan (V-meal) on postprandial incretin and insulin secretion in participants with T2D. A randomized crossover design was used in 20 participants with T2D. Plasma concentrations of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), amylin, and gastric inhibitory peptide (GIP) were determined at 0, 30, 60, 120, and 180 min. Beta-cell function was assessed with a mathematical model, using C-peptide deconvolution. Repeated-measures ANOVA was used for statistical analysis. Postprandial plasma glucose responses were similar after both test meals (p = 0.64). An increase in the stimulated secretion of insulin (by 30.5%; 95% CI 21.2 to 40.7%; p < 0.001), C-peptide (by 7.1%; 95% CI 4.1 to 9.9%; p < 0.001), and amylin (by 15.7%; 95% CI 11.8 to 19.7%; p < 0.001) was observed following consumption of the V-meal. An increase in stimulated secretion of GLP-1 (by 19.2%; 95% CI 12.4 to 26.7%; p < 0.001) and a decrease in GIP (by −9.4%; 95% CI −17.3 to −0.7%; p = 0.02) were observed after the V-meal. Several parameters of beta-cell function increased after the V-meal, particularly insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. Our results showed an increase in postprandial incretin and insulin secretion, after consumption of a V-meal, suggesting a therapeutic potential of plant-based meals for improving beta-cell function in T2D.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502


2021 ◽  
Vol 12 ◽  
pp. 204062232110269
Author(s):  
Yipin Zhao ◽  
Huawei Wang ◽  
Dazhi Ke ◽  
Wei Deng ◽  
Yingying Ji ◽  
...  

Background and Aims: Studies have shown that dipeptidyl peptidase-4 (DDP-4) inhibitors have anti-atherosclerotic effects. However, in the PROLOGUE study, sitagliptin failed to slow the progression of carotid intima-media thickness (CIMT) relative to conventional therapy. We conducted a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in CIMT in subgroups with or without hyperuricemia. Methods: The PROLOGUE study was a randomized controlled trial of 442 patients with type 2 diabetes mellitus (T2DM). Patients were randomized to receive sitagliptin added therapy or conventional therapy. Based on the serum uric acid levels of all study populations in the PROLOGUE study, we divided them into hyperuricemia subgroup ( n = 104) and non-hyperuricemia subgroup ( n = 331). The primary outcome was changed in carotid intima-media thickness (CIMT) parameters compared with baseline during the 24 months treatment period. Results: In the hyperuricemia subgroup, compared with the conventional therapy group, the changes in the mean internal carotid artery (ICA)-IMT and max ICA-IMT at 24 months were significantly lower in the sitagliptin group [−0.233 mm, 95% confidence interval (CI) (−0.419 to 0.046), p = 0.015 and −0.325 mm, 95% CI (−0.583 to −0.068), p = 0.014], although there was no significant difference in the common carotid artery CIMT. Conclusion: The results of our analysis indicated that sitagliptin attenuated the progression of CIMT than conventional therapy in T2DM and hyperuricemia patients.


2007 ◽  
Vol 292 (6) ◽  
pp. E1775-E1781 ◽  
Author(s):  
Kenneth Cusi ◽  
Sangeeta Kashyap ◽  
Amalia Gastaldelli ◽  
Mandeep Bajaj ◽  
Eugenio Cersosimo

Elevated plasma FFA cause β-cell lipotoxicity and impair insulin secretion in nondiabetic subjects predisposed to type 2 diabetes mellitus [T2DM; i.e., with a strong family history of T2DM (FH+)] but not in nondiabetic subjects without a family history of T2DM. To determine whether lowering plasma FFA with acipimox, an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine FH+ volunteers were admitted twice and received in random order either acipimox or placebo (double-blind) for 48 h. Plasma glucose/insulin/C-peptide concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates (ISRs) were assessed during a +125 mg/dl hyperglycemic clamp. Acipimox reduced 48-h plasma FFA by 36% ( P < 0.001) and increased the plasma C-peptide relative to the plasma glucose concentration or ΔC-peptide/Δglucose AUC (+177%, P = 0.02), an index of improved β-cell function. Acipimox improved insulin sensitivity (M/I) 26.1 ± 5% ( P < 0.04). First- (+19 ± 6%, P = 0.1) and second-phase (+31 ± 6%, P = 0.05) ISRs during the hyperglycemic clamp also improved. This was particularly evident when examined relative to the prevailing insulin resistance [1/(M/I)], as both first- and second-phase ISR markedly increased by 29 ± 7 ( P < 0.05) and 41 ± 8% ( P = 0.02). There was an inverse correlation between fasting FFA and first-phase ISR ( r2 = 0.31, P < 0.02) and acute (2–4 min) glucose-induced insulin release after acipimox ( r2 =0.52, P < 0.04). In this proof-of-concept study in FH+ individuals predisposed to T2DM, a 48-h reduction of plasma FFA improves day-long meal and glucose-stimulated insulin secretion. These results provide additional evidence for the important role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed to T2DM.


2016 ◽  
Vol 101 (4) ◽  
pp. 1798-1806 ◽  
Author(s):  
Anna Vanderheiden ◽  
Lindsay B. Harrison ◽  
Jeremy T. Warshauer ◽  
Beverley Adams-Huet ◽  
Xilong Li ◽  
...  

Abstract Context: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. Objective: To evaluate changes in β-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. Design: A single-center, randomized, double-blind, placebo-controlled trial. Setting: University of Texas Southwestern and Parkland Memorial Hospital clinics. Patients: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (&gt;1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). Intervention: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. Main Outcome Measures: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. Results: Glycosylated hemoglobin improved significantly with liraglutide treatment, with an end-of-trial estimated treatment difference between groups of −0.9% (95% confidence interval, −1.5, −0.4%) (P = .002). Insulin secretion improved in the liraglutide group vs placebo, as measured by the area under the curve of C-peptide (P = .002) and the area under the curves ratio of C-peptide to glucose (P = .003). Insulin sensitivity (Matsuda index) and glucagon secretion did not change significantly between groups. Liver fat and sc fat decreased in the liraglutide group vs placebo (P = .0006 and P = .01, respectively), whereas neither visceral nor pancreatic fat changed significantly. Conclusions: Treatment with liraglutide significantly improved insulin secretion, even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and sc fat, but it did not alter glucagon secretion.


2020 ◽  
Vol 28 (3) ◽  
pp. 299-314
Author(s):  
Simona Cernea ◽  
Emőke Both ◽  
Adriana Fodor

AbstractAim: We evaluated the association between anthropometric parameters and markers of insulin and leptin secretion/resistance in patients with type 2 diabetes mellitus (T2DM).Material and methods: This post-hoc data analysis from a cross-sectional study included 176 T2DM patients. Laboratory tests (serum leptin, soluble form of leptin receptor (sObR), C peptide, glycemic and lipid parameters) and anthropometric parameters were obtained, adiposity indexes (including body adiposity index (BAI), visceral adiposity index (VAI)), indicators of insulin resistance, β-cell function, and leptin resistance (Free Leptin Index, FLI) were calculated.Results: The body mass index (BMI), diabetes duration, VAI and leptin correlated independently with HOMA-IR, while BMI, diabetes duration and HbA1c with HOMA-B. The total body fat mass (TBFM), C peptide, diabetes duration, BMI and BAI correlated with leptin concentrations, while the first three with FLI. VAI was an indicator of insulin resistance (β=0.166, p=0.003), while BAI of leptin secretion (β=0.260, p=0.010). TBFM strongly associated with leptin resistance and secretion (β=0.037, r=0.688, p<0.0001, and β=0.521, r=0.667, p<0.0001), and BMI correlated weakly with insulin secretion and resistance. While insulin and leptin secretion increased progressively with BMI, leptin and insulin resistance became significant only in case of obesity. The sObR was significantly associated with C peptide concentrations (β=-0.032; p=0.044), but not with HOMA-B or -IR. A strong positive correlation between the C peptide/leptin ratio and non-fat mass /TBFM ratio was noted (r=0.62 [0.52, 0.71], p<0.0001).Conclusions: Parameters of peripheral adiposity correlated better with markers of leptin system, and those of visceral adiposity with markers of insulin secretion/resistance. The sObR correlated independently and negatively with C peptide.


2006 ◽  
Vol 155 (4) ◽  
pp. 615-622 ◽  
Author(s):  
Wan Sub Shim ◽  
Soo Kyung Kim ◽  
Hae Jin Kim ◽  
Eun Seok Kang ◽  
Chul Woo Ahn ◽  
...  

Objective: Type-2 diabetes is a progressive disease. However, little is known about whether decreased fasting or postprandial pancreatic β-cell responsiveness is more prominent with increased duration of diabetes. The aim of this study was to evaluate the relationship between insulin secretion both during fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic patients. Design: Cross-sectional clinical investigation. Methods: We conducted a meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M0) and postprandial (M1) β-cell responsiveness. Results: The fasting C-peptide, postprandial C-peptide, M0, and M1 values were lower, but HbA1c values were higher, in patients with diabetes duration > 10 years than those in other groups. There was no difference in the HbA1c levels according to the tertiles of their fasting C-peptide level. However, in a group of patients with highest postprandial C-peptide tertile, the HbA1c values were significantly lower than those in other groups. After adjustment of age, sex, and body mass index (BMI), the duration of diabetes was found to be negatively correlated with fasting C-peptide (γ = −0.102), postprandial C-peptide (γ = −0.356), M0 (γ = −0.263), and M1 (γ = −0.315; P < 0.01 respectively). After adjustment of age, sex, and BMI, HbA1c was found to be negatively correlated with postprandial C-peptide (γ = −0.264), M0 (γ = −0.379), and M1 (γ = −0.522), however, positively correlated with fasting C-peptide (γ = 0.105; P < 0.01 respectively). In stepwise multiple regression analysis, M0, M1, and homeostasis model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbAlc after adjustment for age, sex, and BMI (R2 = 0.272, 0.080, and 0.056 respectively). Conclusions: With increasing duration of diabetes, the decrease of postprandial insulin secretion is becoming more prominent, and postprandial β-cell responsiveness may be a more important determinant for glycemic control than fasting β-cell responsiveness.


2017 ◽  
Vol 24 (9) ◽  
pp. 596-602 ◽  
Author(s):  
Leonard E Egede ◽  
Rebekah J Walker ◽  
Elizabeth H Payne ◽  
Rebecca G Knapp ◽  
Ronald Acierno ◽  
...  

Objective We evaluated the impact of telemedicine-delivered behaviour activation treatment (BAT) on glycemic control in a subgroup of older adults with diabetes who participated in a randomized controlled trial for depression. Research design and methods We randomized older adults with major depression to same-room or telemedicine BAT. Each group received eight weekly sessions. For the subgroup analysis, we identified individuals with type 2 diabetes and obtained hemoglobin A1c at baseline and 12 months’ follow-up. We used mixed-effects models (MEM) for repeated measures analysis to compare the longitudinal mean A1c. We estimated model-derived mean A1c values and considered an adjusted model to account for baseline health status. Results We included 90 individuals with type 2 diabetes of the original 241 in the subgroup analysis (43 in telemedicine and 47 in same room). Treatment groups were not significantly different at baseline for demographics, depression, anxiety or A1c levels (telemedicine 6.9 vs. same room 7.3, p = 0.19). Baseline mean A1c for the telemedicine group remained at 6.9 (55 mmol/mol) at 12 months, whereas baseline mean A1c for the same-room group increased to 7.7 (61 mmol/mol). Longitudinal trajectories of model-derived mean A1c indicated a significant main effect of treatment group on mean A1c value at study end (difference = −0.82, 95% CI −1.41, −0.24). Adjusted analyses gave comparable results. Conclusions Telemedicine-delivered BAT was superior to same room in achieving lower mean A1c values in participants with type 2 diabetes, suggesting BAT-delivered via telemedicine is a viable treatment option for adults with diabetes.


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