scholarly journals Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mildred Fátima de la Luz Alvarez-Canales ◽  
Sara Stephania Salazar-López ◽  
Diana Farfán-Vázquez ◽  
Yosceline Estrella Martínez-López ◽  
Jessica Noemí González-Mena ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Disposition Index ◽  
Oral Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Double Blind ◽  
Glucose Levels ◽  
Β Cell Function

AbstractThe goal of the study was to evaluate the effect of adding linagliptin to metformin and lifestyle on glucose levels and pancreatic β-cell function in patients with persistent impaired glucose tolerance (IGT) after 12 months of metformin and lifestyle. A single center parallel double-blind randomized clinical trial with 6 months of follow-up was performed in patients with persistent IGT after 12 months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850 mg twice daily (M group, n = 12) or linagliptin/metformin 2.5/850 mg twice daily (LM group, n = 19). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic β-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic β-cell function. Patients in the LM group had a reduction in weight (−1.7 ± 0.6, p < 0.05) and body mass index (BMI, −0.67 ± 0.2, p < 0.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc0_120min) as compared to the M group (−4425 ± 871 vs −1116 ± 1104 mg/dl/120 min, p < 0.001). Pancreatic β-cell function measured with the disposition index, improved only in LM group (2.3 ± 0.23 vs 1.7 ± 0.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic β-cell function persisted also after pairing groups for basal AUCGluc0_120min. The addition of linagliptin to patients with persistent IGT after 12 months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic β-cell function after 6 months of treatment.Trial registration: Clinicaltrials.gov with the ID number NCT04088461

scholarly journals Effect of chronic liraglutide therapy and its withdrawal on time to postchallenge peak glucose in type 2 diabetes

2018 ◽  
Vol 314 (3) ◽  
pp. E287-E295 ◽  
Author(s):  
Susan Tran ◽  
Caroline K. Kramer ◽  
Bernard Zinman ◽  
Haysook Choi ◽  
Ravi Retnakaran
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Controlled Trial ◽  
Oral Glucose ◽  
Β Cell ◽  
Double Blind ◽  
Time To Peak ◽  
Β Cell Function

Delayed timing of peak serum glucose following an oral glucose challenge can predict declining β-cell function and worsening glucose tolerance over time. Accordingly, postchallenge peak glucose is typically delayed in patients with type 2 diabetes (T2DM). However, little is known about the capacity of antidiabetic medications to reverse this delay. Thus, we sought to evaluate the effect of the glucagon-like peptide-1 agonist liraglutide on time to peak glucose in early T2DM. In this secondary analysis of a double-blind placebo-controlled trial, 51 patients with T2DM of 2.6 ± 1.9 yr duration were randomized to daily subcutaneous liraglutide or placebo injection for 48 wk, with oral glucose tolerance test (OGTT) performed every 12 wk while on therapy and after a 2-wk washout. On each OGTT, time to peak glucose was determined from venous glucose measurements at 0, 10, 20, 30, 60, 90, and 120 min. At randomization, most patients in both arms exhibited peak glucose at 90 min postchallenge. By 12 wk, 65.4% of the liraglutide arm had shifted to an earlier peak (vs. 36% on placebo; P = 0.19), with little change thereafter at 24, 36, and 48 wk. After the 2-wk washout, however, 57.7% of those who had been on liraglutide reverted to a later peak (vs. 4.5% on placebo; P < 0.001). This shift was associated with declining β-cell function ( P = 0.001), resulting in higher 2-h blood glucose at washout in the liraglutide arm compared with placebo ( P = 0.001). Thus, although liraglutide possibly might improve the delay in peak glucose, its cessation yielded a worsening thereof and higher glycemia. The mechanisms underlying these observations and their clinical implications warrant further investigation.

Identifying glucose thresholds for incident diabetes by physiological analysis: a mathematical solution

2015 ◽  
Vol 308 (7) ◽  
pp. R590-R596 ◽  
Author(s):  
Ele Ferrannini ◽  
Maria Laura Manca
Keyword(s):  
Insulin Sensitivity ◽  
Confidence Interval ◽  
Glucose Tolerance ◽  
Odds Ratio ◽  
Cell Function ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Glucose Levels ◽  
Β Cell Function

Plasma glucose thresholds for diagnosis of type 2 diabetes are currently based on outcome data (risk of retinopathy), an inherently ill-conditioned approach. A radically different approach is to consider the mechanisms that control plasma glucose, rather than its relation to an outcome. We developed a constraint optimization algorithm to find the minimal glucose levels associated with the maximized combination of insulin sensitivity and β-cell function, the two main mechanisms of glucose homeostasis. We used a training cohort of 1,474 subjects (22% prediabetic, 7.7% diabetic) in whom insulin sensitivity was measured by the clamp technique and β-cell function was determined by mathematical modeling of an oral glucose tolerance test. Optimized fasting glucose levels were ≤87 and ≤89 mg/dl in ≤45-yr-old women and men, respectively, and ≤92 and ≤95 mg/dl in >45-yr-old women and men, respectively; the corresponding optimized 2-h glucose levels were ≤96, ≤98, ≤103, and ≤105 mg/dl. These thresholds were validated in three prospective cohorts of nondiabetic subjects (Relationship Between Insulin Sensitivity and Cardiovascular Disease Study, Botnia Study, and Mexico City Diabetes Study) with baseline and follow-up oral glucose tolerance tests. Of 5,593 participants, 452 progressed to diabetes. Similarly, in the three cohorts, subjects with glucose levels above the estimated thresholds had an odds ratio of 3.74 (95% confidence interval = 2.64–5.48) of progressing, substantially higher than the risk carried by baseline conventionally defined prediabetes [odds ratio = 2.32 (95% confidence interval = 1.91–2.81)]. The concept that optimization of glucose concentrations by direct measures of insulin sensitivity and β-cell function identifies gender- and age-specific thresholds that bear on disease progression is proven in a physiologically sound, quantifiable manner.

scholarly journals Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 29 ◽  
Author(s):  
Alexander D. Nichol ◽  
Clara Salame ◽  
Kristina I. Rother ◽  
M. Yanina Pepino
Keyword(s):  
Glucose Tolerance ◽  
Cell Function ◽  
Normal Weight ◽  
Taste Perception ◽  
Metabolic Responses ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function ◽  
Weight Groups

Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20–40 min of the OGTT in normal-weight participants but increased within 90–120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.

Pancreatic β-cell function and fetal growth in gestational impaired glucose tolerance

2010 ◽  
Vol 89 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Kei Miyakoshi ◽  
Mamoru Tanaka ◽  
Yoshifumi Saisho ◽  
Akira Shimada ◽  
Kazuhiro Minegishi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Fetal Growth ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Detection of Glycemic Abnormalities in Young Adult Patients with Beta Thalassemia Major Using Continuous Glucose Monitoring System (CGMS) and Oral Glucose Tolerance Test (OGTT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2158-2158
Author(s):  
Mohamed A. Yassin ◽  
Ahmed M Elawa ◽  
Ashraf T Soliman
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Serum Insulin ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

Abstract Abstract 2158 Introduction: Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (BTM). The use of continuous blood glucose monitoring system (CGMS) among the different methods for early detection of glycaemic abnormalities has not been studied thoroughly in these patients. Aims: The aims of this study were: 1. to detect glycaemic abnormalities, if any, in young adults with BTM using fasting blood glucose (FBG), oral glucose tolerance test (OGTT), 72-h continuous glucose concentration by CGMS system, and serum insulin and C-peptide concentrations 2. To compare the results of these two methods in detecting glycaemic abnormalities in these patients and 3. To calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in these patients. In order to evaluate whether glycaemic abnormalities are due to insulin deficiency and/or resistance. Materials and methods: Randomly selected young adults (n = 14) with BTM were the subjects of this study. All patients were investigated using a standard oral glucose tolerance test (OGTT) (using 75 gram of glucose) and 72-h continuous glucose concentration by CGM system (Medtronic system). Fasting serum insulin and C-peptide concentrations were measured and HOMA-B, HOMA-IR were calculated accordingly. Results: Using OGTT, 5 patients had impaired fasting glucose (IFG) (Fasting BG from 5.6 to 6.9 mmol/L). Two of them had impaired glucose tolerance IGT (BG from 7.8 and < 11.1 mmol/L) and one had BG = 16.2 mmol/L after 2-hrs (diabetic). Using CGMS in addition to the glucose data measured by glucometer (3–5 times/ day), 6 patients had IFG. The maximum (postprandial) BG recorded exceeded 11.1 mmol/L in 4 patients (28.5%) (Diabetics) and was > 7.8 but < 11.1 mmol/L in 8 patients (57%) (IGT). The mean values of HOMA and QUICKI in patients with BTM were < 2.6 (1.6± 0.8) and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B %) on the one hand and the fasting and the 2-h BG (r= −0.6, and − 0.48, P< 0.01 respectively) on the other hand. Serum insulin concentrations were not correlated with fasting BG or ferritin levels. The average and maximum BG levels recorded by CGMS were significantly correlated with the fasting BG (r= 0.69 and 0.6 respectively with P < 0.01) and with the BG at 2-hour after oral glucose intake (r= 0.87and 0.86 respectively with P < 0.01). Ferritin concentrations were positively correlated with the fasting BG and the 2-h BG levels in the OGTT (r= 0.69, 0.43 respectively, P < 0.001) as well as with the average and the maximum BG recorded by CGM (r =0.75, and 0.64 respectively with P < 0.01). Ferritin concentrations were negatively correlated with the β-cell function (r= −0.41, P< 0.01). Conclusion: CGMS has proved to be superior to OGTT for the diagnosis of glycaemic abnormalities in young adult patients with BTM. In our patients, defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities. The significant correlations between serum ferritin concentrations and the beta cell functions suggested the importance of adequate chelation to prevent β-cell dysfunction Disclosures: No relevant conflicts of interest to declare.

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