In people with a high genetic risk for diabetes, a pancreatic steatosis can lead to a decrease in insulin secretion. This is indicated by studies of the DZD, which have now been published in The Journal of Clinical Endocrinology & Metabolism.

So far, there are conflicting evidence on whether and how pancreatic steatosis affects insulin secretion. Accumulating evidence implicates that fat compartment as a modulator of islet function. Specifically, pancreatic steatosis was inversely associated with insulin secretion in subjects with prediabetes. However, subjects with normal glucose tolerance do not exhibit the negative association between pancreatic steatosis and insulin secretion. Researchers at the DZD in Tübingen therefore suspect that pancreatic steatosis only has a negative effect on the function of beta cells if there is a genetic predisposition for diabetes.

To test this hypothesis, they investigated the interaction between genotype and fat in the pancreas on insulin secretion. To this end, they evaluated the data of 360 nondiabetic individuals with elevated risk for T2D from the Tuebingen Family Study (TUEF), and 64 patients undergoing pancreatectomy. The fat content of the pancreas was measured by magnetic resonance imaging (MRI) and the genetic risk score for type 2 diabetes was determined.  Insulin secretion was determined by oral glucose tolerance testing and fasting blood sampling prior to surgery.

There was a negative association between pancreatic fat and insulin secretion in participants with high genetic risk. However, individuals with low genetic risk showed a positive correlation between pancreatic fat and insulin secretion. The researchers suspect that only genetic insulin resistance leads to pancreatic fat becoming harmful to insulin secretion.

Original publication:
Róbert Wagner et al: Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals. The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 11, November 2020, dgaa435, https://doi.org/10.1210/clinem/dgaa435