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

J Diabetes Investig. 2020 Sep;11(5):1197-1206. doi: 10.1111/jdi.13232. Epub 2020 Mar 10.

Abstract

Aims/introduction: Changes in histologically quantified β- and α-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β- and α-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 β-cell area (BCA) and α-cell area were quantified with Image Pro Plus software. Associations of BCA and α-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and β-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, P for trend < 0.001), whereas there was no significant association between α-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 (all P < 0.01).

Conclusions: β-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus.

Keywords: Prediabetes; Type 2 diabetes mellitus; β-Cell mass.

MeSH terms

  • Aged
  • Autopsy
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Follow-Up Studies
  • Glucagon-Secreting Cells / pathology*
  • Glucose Intolerance / epidemiology*
  • Glucose Intolerance / pathology
  • Humans
  • Insulin-Secreting Cells / pathology*
  • Japan / epidemiology
  • Male
  • Prediabetic State / epidemiology*
  • Prediabetic State / pathology
  • Prognosis

Substances

  • Biomarkers
  • Blood Glucose

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