scholarly journals Impact of Gastric Banding Versus Metformin on β-Cell Function in Adults With Impaired Glucose Tolerance or Mild Type 2 Diabetes

Diabetes Care ◽  
2018 ◽  
Vol 41 (12) ◽  
pp. 2544-2551 ◽  
Author(s):  
Anny H. Xiang ◽  
Enrique Trigo ◽  
Mayra Martinez ◽  
Namir Katkhouda ◽  
Elizabeth Beale ◽  
...  
2010 ◽  
Vol 298 (1) ◽  
pp. E38-E48 ◽  
Author(s):  
Viorica Ionut ◽  
Huiwen Liu ◽  
Vahe Mooradian ◽  
Ana Valeria B. Castro ◽  
Morvarid Kabir ◽  
...  

Human type 2 diabetes mellitus (T2DM) is often characterized by obesity-associated insulin resistance (IR) and β-cell function deficiency. Development of relevant large animal models to study T2DM is important and timely, because most existing models have dramatic reductions in pancreatic function and no associated obesity and IR, features that resemble more T1DM than T2DM. Our goal was to create a canine model of T2DM in which obesity-associated IR occurs first, followed by moderate reduction in β-cell function, leading to mild diabetes or impaired glucose tolerance. Lean dogs ( n = 12) received a high-fat diet that increased visceral (52%, P < 0.001) and subcutaneous (130%, P < 0.001) fat and resulted in a 31% reduction in insulin sensitivity (SI) (5.8 ± 0.7 × 10−4 to 4.1 ± 0.5 × 10−4 μU·ml−1·min−1, P < 0.05). Animals then received a single low dose of streptozotocin (STZ; range 30–15 mg/kg). The decrease in β-cell function was dose dependent and resulted in three diabetes models: 1) frank hyperglycemia (high STZ dose); 2) mild T2DM with normal or impaired fasting glucose (FG), 2-h glucose >200 mg/dl during OGTT and 77–93% AIRg reduction (intermediate dose); and 3) prediabetes with normal FG, normal 2-h glucose during OGTT and 17–74% AIRg reduction (low dose). Twelve weeks after STZ, animals without frank diabetes had 58% more body fat, decreased β-cell function (17–93%), and 40% lower SI. We conclude that high-fat feeding and variable-dose STZ in dog result in stable models of obesity, insulin resistance, and 1) overt diabetes, 2) mild T2DM, or 3) impaired glucose tolerance. These models open new avenues for studying the mechanism of compensatory changes that occur in T2DM and for evaluating new therapeutic strategies to prevent progression or to treat overt diabetes.


2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  

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.


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