Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals: The Hisayama Study

Aims/Introduction: Changes in histologically quantified beta- and alpha-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in beta- and alpha-cell mass according to the glucose tolerance status. Materials and Methods: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75-g oral glucose tolerance test within 5 years before death were selected from 643 community-based autopsy samples collected from 2002 to 2016. Fractional beta-cell area (BCA) and alpha-cell area were quantified with Image Pro Plus software. Associations of BCA and alpha-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and beta-cell function were estimated. Results: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean +/- standard error 1.85 +/- 0.10% in normal glucose tolerance, 1.59 +/- 0.11% in prediabetes and 1.17 +/- 0.11% in type 2 diabetes mellitus,Pfor trend < 0.001), whereas there was no significant association between alpha-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (allP < 0.01). Conclusions: beta-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining beta-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus.