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.

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

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
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.

scholarly journals Rosiglitazone, But Not Glyburide, Reduces Circulating Proinsulin and the Proinsulin:Insulin Ratio in Type 2 Diabetes

2004 ◽  
Vol 89 (12) ◽  
pp. 6048-6053 ◽  
Author(s):  
Stephen A. Smith ◽  
Lisa E. Porter ◽  
Nandita Biswas ◽  
Martin I. Freed
Keyword(s):  
Type 2 Diabetes ◽  
Independent Risk Factor ◽  
Cell Function ◽  
Immunoreactive Insulin ◽  
Β Cell ◽  
Double Blind ◽  
Insulin Sensitizer ◽  
Β Cell Function ◽  
Dose Dependent

Abstract An elevation in the ratio of proinsulin (PI) to immunoreactive insulin (IRI) is inversely related to β-cell function in type 2 diabetes, and increased PI is an independent risk factor for coronary heart disease. An objective of the present studies was to assess the effects of the thiazolidinedione insulin sensitizer, rosiglitazone, on indirect markers of β-cell function and cardiovascular risk in people with type 2 diabetes by measuring plasma PI and the PI:IRI ratio. Parameters of insulin processing, including plasma PI and PI:IRI ratios, were determined in type 2 diabetes patients enrolled in two randomized double-blind studies comparing the effects of rosiglitazone (4 or 8 mg/d) with placebo (study 1, 26-wk treatment) or the sulfonylurea glyburide (study 2, 52-wk treatment). Treatment with rosiglitazone for 26 wk (study 1) produced significant dose-dependent decreases in both plasma PI concentrations (18–29%) and the PI:IRI ratio compared with baseline (7–14%) and placebo (19–29%) (P &lt; 0.001). A significant increase in the PI:IRI ratio in placebo-treated patients occurred (P &lt; 0.001). In study 2, rosiglitazone also significantly reduced both plasma PI and the PI:IRI ratio compared with baseline (P &lt; 0.001). In contrast, glyburide significantly increased both plasma PI (45%; P &lt; 0.001) and the PI:IRI ratio (10%) (P &lt; 0.05 vs. baseline). These results show that rosiglitazone and glyburide have differential effects on absolute PI levels and the PI:IRI ratio in people with type 2 diabetes.

scholarly journals Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes

2017 ◽  
Vol 313 (3) ◽  
pp. E314-E320 ◽  
Author(s):  
Stephan Nieuwoudt ◽  
Ciarán E. Fealy ◽  
Julie A. Foucher ◽  
Amanda R. Scelsi ◽  
Steven K. Malin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
High Intensity ◽  
Cell Function ◽  
Oral Glucose ◽  
Β Cell ◽  
High Intensity Training ◽  
Β Cell Function ◽  
Intensity Training

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying “exercise resistance.” Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R2= 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R2= 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: −1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D.

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

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

<p>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.</p>

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