Pancreatic Fat Content and β-cell Function in Men With and Without Type 2 Diabetes

Abstract

Objective: Insulin resistance, associated with increased lipolysis, results in a high exposure of non-adipose tissues to lipids. Experimental data indicate that fatty infiltration of pancreatic islets may also contribute to β-cell dysfunction, but whether this occurs in humans in vivo is unknown.

Research Design and Methods: Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of β-cell function in 12 insulin-naïve type 2 diabetic and 24 age- and BMI-matched non-diabetic males.

Results: Patients versus controls had higher HbA1c, fasting plasma glucose, insulin and triglyceride levels, lower HDL-C, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients and controls was 20.4 (13.4-43.6) and 9.7 (7.0-20.2)%, respectively (P=0.032). Pancreatic fat correlated negatively with β-cell function parameters, including the insulinogenic index adjusted for insulin resistance, early glucose-stimulated insulin secretion, β-cell glucose sensitivity, rate sensitivity (all P<0.05), but not potentiation. However, these associations were significantly affected by the diabetic state, such that a significant association of pancreatic fat with β-cell dysfunction was only present in the non-diabetic group (all P<0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat account for further β-cell function decline. In controls, the association of pancreatic fat and β-cell function remained significant after correction for BMI, fasting plasma glucose and triglycerides (P=0.006).

Conclusions: These findings indicate that pancreatic lipid content may contribute to β-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans.