Improved Pancreatic -Cell Function in Type 2 Diabetic Patients After Lifestyle-Induced Weight Loss Is Related to Glucose-Dependent Insulinotropic Polypeptide

Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA.
Diabetes care (Impact Factor: 8.42). 03/2010; 33(7):1561-6. DOI: 10.2337/dc09-2021
Source: PubMed


Restoration of insulin secretion is critical for the treatment of type 2 diabetes. Exercise and diet can alter glucose-induced insulin responses, but whether this is due to changes in beta-cell function per se is not clear. The mechanisms by which lifestyle intervention may modify insulin secretion in type 2 diabetes have also not been examined but may involve the incretin axis.
Twenty-nine older, obese (aged 65 +/- 1 years; BMI 33.6 +/- 1.0 kg/m(2)) subjects, including individuals with newly diagnosed type 2 diabetes (obese-type 2 diabetic) and individuals with normal glucose tolerance (obese-NGT), underwent 3 months of nutritional counseling and exercise training. beta-Cell function (oral glucose-induced insulin secretion corrected for insulin resistance assessed by hyperinsulinemic-euglycemic clamps) and the role of glucose-dependent insulinotropic polypeptide (GIP) were examined.
After exercise and diet-induced weight loss (-5.0 +/- 0.7 kg), oral glucose-induced insulin secretion was increased in the obese-type 2 diabetic group and decreased in the obese-NGT group (both P < 0.05). When corrected for alterations in insulin resistance, the change in insulin secretion remained significant only in the obese-type 2 diabetic group (1.23 +/- 0.26 vs. 2.04 +/- 0.46 arbitrary units; P < 0.01). Changes in insulin secretion were directly related to the GIP responses to oral glucose (r = 0.64, P = 0.005), which were augmented in the obese-type 2 diabetic group and only moderately suppressed in the obese-NGT group.
After lifestyle-induced weight loss, improvements in oral glucose-induced insulin secretion in older, obese, nondiabetic subjects seem to be largely dependent on improved insulin sensitivity. However, in older obese diabetic patients, improved insulin secretion is a consequence of elevated beta-cell function. We demonstrate for the first time that changes in insulin secretion after lifestyle intervention may be mediated via alterations in GIP secretion from intestinal K-cells.

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Available from: John P Kirwan, Sep 29, 2015
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    • " loss programs and intensive life - style interventions have a favorable short - term effect on body weight and glycemic control in obese patients with type 2 diabetes if compared to standard care ( Unick et al . , 2011 ) and also improve glucose - stimulated insulin secretion and beta - cell function associated with augmented incretin secretion ( Solomon et al . , 2010 ) . However , the long - term results of the Look AHEAD ( Action for Health in Diabetes ) trial turned out to be rather disappointing with only half of the patients obtaining a weight - loss over 5% of initial body weight , after 8 years of follow - up ( The Look AHEAD Research Group , 2014 ) ; impact on diabetes control and glycated he"
    02/2015, Degree: PhD, Supervisor: Francisco Castro e Sousa
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    • "Post hoc subgroup analysis dividing the trials in two groups according to mean age of participants showed a negative influence of age on GIP responses in patients with type 2 diabetes evaluated by tAUC, iAUC, and iAUC × min−1 (Table 1). Subgroup 1 included trials with participants with mean age younger than 60 years (11,13–15,18,19,21,23,24,27,29,30); subgroup two included trials with participants with mean age 60 years or older (6,10,17,19,20,25,26,28). "
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    ABSTRACT: OBJECTIVE To investigate glucose-dependent insulinotropic polypeptide (GIP) secretion in patients with type 2 diabetes and nondiabetic control subjects during oral glucose or meal tests.RESEARCH DESIGN AND METHODS Eligible trials were identified by The Cochrane Library, MEDLINE, Embase, and Web of Science. Data were retrieved and random-effects models for the primary meta-analysis, random-effects meta-regression, and subgroup and regression analyses were applied.RESULTSRandom-effects meta-analysis of GIP responses in 23 trials during 28 different stimulation tests showed that patients with type 2 diabetes (n = 363) exhibited no significant differences (P = not significant) in peak plasma GIP, total area under the curve (tAUC), time-corrected tAUC (tAUC x min(-1)), and time-corrected incremental area under the curve (iAUC x min(-1)) in comparison with nondiabetic control subjects (n = 325) but had lower GIP responses as evaluated from iAUC (weighted mean difference, -648 pmol/L x min; 95% CI, -1,276 to -21). Fixed-effects models meta-analyses confirmed most of the results of the primary meta-analysis but showed iAUC x min(-1) to be reduced and showed tAUC and tAUC x min(-1) to be higher in diabetic patients. Random-effects meta-regression of the primary meta-analysis showed that age (peak GIP, tAUC, iAUC, and iAUC x min(-1)), BMI (tAUC, iAUC, and iAUC x min(-1)), and HbA(1c) (iAUC and iAUC x min(-1)) predicted some of the GIP outcomes. Post hoc subgroup analysis showed a negative influence of age and of HbA(1c) on GIP responses and showed a positive influence of BMI on GIP responses.CONCLUSIONS Our results suggest that patients with type 2 diabetes are characterized by preserved GIP secretion in response to oral glucose and meal tests. They also suggest that high BMI is associated with increased GIP responses but increasing age and HbA(1c) are associated with reduced GIP secretion.
    Diabetes care 10/2013; 36(10):3346-52. DOI:10.2337/dc13-0465 · 8.42 Impact Factor
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    • "Regular exercise, although it may not necessarily reduce weight, enhances insulin sensitivity. Importantly, exercise concomitant with weight loss improves beta cell function (Dela et al., 2004; Solomon et al., 2010). Exercise maintained or enhanced beta cell function in older obese individuals, with improved beta cell function correlating with reduced glucose concentrations (Malin and Kirwan, 2012). "
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    ABSTRACT: Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis.
    Frontiers in Endocrinology 03/2013; 4:37. DOI:10.3389/fendo.2013.00037
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