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Aim To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 ( GLP-1) analogues on ectopic fat stores. Methods A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue ( EAT), myocardial triglyceride content ( MTGC), hepatic triglyceride content ( HTGC) and pancreatic triglyceride content ( PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. Results The study population had a mean glycated haemoglobin ( HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m2. Ninety five percent had hepatic steatosis at baseline ( HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (−0.7 ± 0.3% vs. −0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (−5.5 ± 1.2 kg vs. −0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (−8.8 ± 2.1%) and HTGC (−23.8 ± 9.5%), compared with the reference treatment ( EAT: −1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). Conclusion Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent. [ABSTRACT FROM AUTHOR]

Objectives:Recent literature suggests that ectopic fat deposition in the pancreas may contribute to endocrine and exocrine organ dysfunction, such as type 2 diabetes (T2D), pancreatitis or pancreatic cancer. The aim of this study was to determine factors associated with pancreatic triglyceride content (PTGC), and to investigate the impact of bariatric surgery on ectopic fat pads, pancreatic fat (PTGC) and hepatic fat (HTGC).Subjects:In all, 45 subjects (13 lean, 13 obese nondiabetics and 19 T2D, matched for age and gender) underwent 1H-magnetic resonance spectroscopy, computed tomography of the visceral abdominal fat, metabolic and lipidomic analysis, including insulin-resistance homeostasis model assessment (HOMA-IR), insulin-secretion homeostasis model assessment (HOMA-B) and plasma fatty-acid composition. Twenty obese subjects were reassessed 6 months after the bariatric surgery.Results:PTGC was significantly higher in type 2 diabetic subjects (23.8±3.2%) compared with obese (14.0±3.3; P=0.03) and lean subjects (7.5±0.9%; P=0.0002). PTGC remained significantly associated with T2D after adjusting for age and sex (β=0.47; P=0.004) or even after adjusting for waist circumference, triglycerides and HOMA-IR (β=0.32; P=0.04). T2D, C18:1n-9 (oleic acid), uric acid, triglycerides and plasminogen activator inhibitor-1 were the five more important parameters involved in PTGC prediction (explained 80% of PTGC variance). Bariatric surgery induced a huge reduction of both HTGC (−51.2±7.9%) and PTGC (−43.8±7.0%) reaching lean levels, whereas body mass index remained greatly elevated. An improvement of insulin resistance HOMA-IR and no change in HOMA-B were observed after bariatric surgery. The PTGC or HTGC losses were not correlated, suggesting tissue-specific mobilization of these ectopic fat stores.Conclusion:Pancreatic fat increased with T2D and drastically decreased after the bariatric surgery. This suggests that decreased PTGC may contribute to improved beta cell function seen after the bariatric surgery. Further, long-term interventional studies are warranted to examine this hypothesis and to determine the degree to which ectopic fat mobilization may mediate the improvement in endocrine and exocrine pancreatic functions. [ABSTRACT FROM AUTHOR]