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Pancreatic triacylglycerol reduction may improve type 2 diabetes insulin response
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In patients with type 2 diabetes, reductions in pancreatic triacylglycerol during weight loss are related to diabetes itself and not only decreased total body fat, according to study findings.
“Type 2 diabetes can now be seen to be a simple condition of fat excess specifically affecting the pancreas,” Roy Taylor, MD, FRCP, professor of medicine and metabolism at Newcastle University in the United Kingdom, told Endocrine Today. “Previously, the poor insulin secretion in [type 2 diabetes] was a bit of a mystery, with suggestions of separate disease processes, such as amyloid deposition, mitochondrial dysfunction, intracellular signaling problems or insulin resistance. But if a person has type 2 diabetes, they simply have more fat on board than their body can cope with.”
Roy Taylor
Taylor and colleagues evaluated 18 adults with type 2 diabetes and nine age- and weight-matched controls with normal glucose tolerance to determine whether decreases in pancreatic triacylglycerol during weight loss in type 2 diabetes is reflective of whole-body fat or specific to diabetes. Researchers also sought to determine whether the decrease was associated with recovery of insulin secretory function. Participants were evaluated before and 8 weeks after Roux-en-Y gastric bypass surgery.
Similar weight loss and change in total body fat content were found between the two groups 8 weeks after surgery.
The diabetes group had higher pancreatic triacylglycerol content compared with controls before surgery (P = .009), but that amount decreased to levels similar to those seen in controls 8 weeks after surgery (P = .007); no change in pancreatic triacylglycerol levels was found among controls 8 weeks after surgery.
The first-phase insulin response (baseline to 6-minute insulin secretion rate) was found to be severely impaired among the diabetes group before surgery but was markedly restored after surgery (P = .005); no change in the first-phase insulin response was found among controls after surgery.
“At diagnosis, [type 2 diabetes] should not be said to be an irreversible, inevitably progressive disease,” Taylor told Endocrine Today. “If a person is sufficiently motivated to get rid of it, they can, and such very well-motivated individuals do well. However, there is another step needed before this is taken into routine clinical practice for all comers — the DiRECT (Diabetes Remission Clinical Trial) [study] will tell us whether, when applied to all, the outcomes are better after 2 years. ... Also, detailed work on how the fat can be blocked from getting into the pancreas will be helpful, especially as this could lead to development of drugs which might specifically reverse [type 2 diabetes].” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Sangeeta Kashyap, MD
Type 2 diabetes is commonly associated with obesity. Excess fat accumulation in the abdomen is specifically related to type 2 diabetes development and has been linked to impaired insulin secretion by the pancreas. In rodents, excess triacylglycerol and fatty acyl CoAs in the pancreas has been linked to beta-cell apoptosis and reduced beta-cell function. Very low-calorie diets that result in modest weight loss in the short term have been associated with improved insulin secretion and reduction in pancreatic fat content. Gastric bypass leads to marked weight loss and substantial improvement of type 2 diabetes. These effects have been linked to weight-loss-related mechanisms and improvement in gastrointestinal hormones that improve postprandial insulin secretion and glucose metabolism.
The study by Steven and colleagues examined whether the decrease in pancreatic triacylglycerol levels are specific to gastric bypass-induced weight/body fat loss or specific to endocrine pancreatic function itself. They compared pancreatic triacylglycerol levels in type 2 diabetic and matched normal glycemic subjects before and after gastric bypass at 8 weeks and linked these measures to insulin secretion dynamics and hepatic function. They found that first-phase insulin secretion was restored in type 2 diabetes similar to non-diabetic subjects after gastric bypass and was related to decreased pancreatic triacylglycerol levels. They concluded that intrapancreatic triacylglycerol levels decreased after gastric bypass and that this was linked to diabetes itself and not to reduction in weight or body fat.
The implications of these findings suggest that intrapancreatic fat is linked to impaired pancreatic endocrine function and that gastric bypass restores diabetes pathophysiology by reducing intraorgan fat levels. Thus, type 2 diabetes is a disease of excess fat accumulation of the pancreas and not necessarily reflected by body weight or body fat. Reducing intrapancreatic steatosis is an important target for future therapeutic strategies.
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