Effects of Obesity and Diabetes on α- and β-Cell Mass in Surgically Resected Human Pancreas

Context: The ethnic difference in beta-cell regenerative capacity in response to obesity may be attributable to different phenotypes of type 2 diabetes among ethnicities. Objective: This study aimed to clarify the effects of diabetes and obesity on beta-(BCM) and alpha-cell mass (ACM) in the Japanese population. Design, Setting, and Participants: We obtained the pancreases of 99 individuals who underwent pancreatic surgery and whose resected pancreas sample contained adequate normal pancreas for histological analysis. Questionnaires on a family history of diabetes and history of obesity were conducted in 59 patients. Pancreatic sections were stained for insulin or glucagon, and fractional beta- and alpha-cell area were measured. Islet size and density as well as beta-cell turnover were also quantified. Results: In patients with diabetes, BCM was decreased by 46% compared with age- and body mass index-matched nondiabetic patients (1.48% +/- 1.08% vs 0.80% +/- 0.54%, P < .001), whereas there was no difference in ACM between the groups. There was no effect of obesity or history of obesity on BCM and ACM irrespective of the presence or absence of diabetes. There was a negative correlation between BCM, but not ACM, and glycated hemoglobin before and after pancreatic surgery. In addition, reduced BCM was observed in patients with pancreatic cancer compared with those with other pancreatic tumors. Conclusions: These findings suggest that the increase in BCM in the face of insulin resistance is extremely limited in the Japanese, and BCM rather than ACM has a major role in regulating blood glucose level in humans.