Effect of single-dose DPP-4 inhibitor sitagliptin on β-cell function and incretin hormone secretion after meal ingestion in healthy volunteers and drug-naïve, well-controlled type 2 diabetes subjects

2018 ◽  
Vol 20 (4) ◽  
pp. 1080-1085 ◽  
Author(s):  
Wathik Alsalim ◽  
Olga Göransson ◽  
Richard D. Carr ◽  
Roberto Bizzotto ◽  
Andrea Tura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Dose ◽  
Cell Function ◽  
Hormone Secretion ◽  
Β Cell ◽  
Incretin Hormone ◽  
Β Cell Function ◽  
Drug Naïve ◽  
Meal Ingestion

scholarly journals Therapeutic efficacy and safety of initial triple combination of metformin, sitagliptin, and lobeglitazone in drug-naïve patients with type 2 diabetes: initial triple study

2020 ◽  
Vol 8 (1) ◽  
pp. e000807
Author(s):  
Soo Lim ◽  
Eu Jeong Ku ◽  
Seo Young Lee ◽  
Ji Hyun Lee ◽  
Jie-Eun Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Therapy Group ◽  
Efficacy And Safety ◽  
Β Cell ◽  
Β Cell Function ◽  
Conventional Therapy Group ◽  
Drug Naïve ◽  
Hba1c Levels

ObjectiveTo compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes.Research design and methodsAmong drug-naïve patients with 9.0%–12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and β-cell function, and hypoglycemia.ResultsAfter 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to β-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group.ConclusionsInitial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of β-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.

Effects of carbohydrate restriction on postprandial glucose metabolism, β-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes

2021 ◽  
Vol 320 (1) ◽  
pp. E7-E18
Author(s):  
Mads J. Skytte ◽  
Amirsalar Samkani ◽  
Arne Astrup ◽  
Jan Frystyk ◽  
Jens F. Rehfeld ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Cell Function ◽  
Hormone Secretion ◽  
Postprandial Glucose ◽  
Carbohydrate Restriction ◽  
Β Cell ◽  
Gut Hormone ◽  
Β Cell Function

Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and β-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed-meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), β-cell sensitivity to glucose ( Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% ( P < 0.001), 24 h glucose by 13% ( P < 0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, P < 0.05), and postprandial ISR (24%, P = 0.015), while IGI and Bup improved by 31% and 45% (both P < 0.001). The CRHP diet increased postprandial glucagon net AUC by 235% ( P < 0.001), subjective satiety by 18% ( P = 0.03), delayed gastric emptying by 15 min ( P < 0.001), decreased gastric inhibitory polypeptide net AUC by 29% ( P < 0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY, and cholecystokinin responses. A CRHP diet reduced glucose excursions and improved β-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

scholarly journals Serum Amylase Levels in Relation to Islet β Cell Function in Patients with Early Type 2 Diabetes

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162204 ◽  
Author(s):  
Lei Zhuang ◽  
Jian-bin Su ◽  
Xiu-lin Zhang ◽  
Hai-yan Huang ◽  
Li-hua Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Serum Amylase ◽  
Cell Function ◽  
Early Type ◽  
Β Cell ◽  
Β Cell Function

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

2020 ◽  
Author(s):  
Hayat Aljaibeji ◽  
Noha Mousaad Elemam ◽  
Abdul Khader Mohammed ◽  
Hind Hasswan ◽  
Mahammad Al Thahyabat ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Cell Function ◽  
Serum Levels ◽  
Insulin Content ◽  
Β Cell ◽  
Control Subjects ◽  
Β Cell Function

Abstract Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

Impact of lack of suppression of glucagon on glucose tolerance in humans

1999 ◽  
Vol 277 (2) ◽  
pp. E283-E290 ◽  
Author(s):  
Pankaj Shah ◽  
Ananda Basu ◽  
Rita Basu ◽  
Robert Rizza
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Cell Function ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Suppression

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a “prandial” glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic ( n = 10) or diabetic ( n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng ⋅ kg−1 ⋅ min−1, beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the “diabetic” insulin profile, lack of glucagon suppression resulted in a marked increase ( P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol ⋅ l−1 ⋅ 6 h) because of impaired ( P < 0.001) suppression of glucose production. In contrast, during the “nondiabetic” insulin profile, lack of suppression of glucagon resulted in only a slight increase ( P< 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol ⋅ l−1 ⋅ 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

Sign in / Sign up

Export Citation Format

Share Document