Lipid droplet accumulation in beta cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and beta cell dysfunction involving decreased insulin granules

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in beta cells; however, the pathophysiological significance, especially for beta cell function, has not been elucidated. Our aim was to assess LD accumulation in beta cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in beta cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in beta cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in beta cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in beta cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in beta cells, which was associated with insulin resistance, hyperglycemia, aging and beta cell dysfunction involving decreased mature insulin granules.