Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. METHODS: Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. RESULTS: Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm(3), p < 0.01) and number (5.10 × 10(8) ± 2.35 × 10(8) vs 8.16 × 10(8) ± 4.27 × 10(8), p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA(1c) (r = −0.45, p < 0.01). CONCLUSIONS/INTERPRETATION: Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00125-021-05467-7) contains peer-reviewed but unedited supplementary material.