Primacy of β-cell dysfunction in the development of hyperglycemia: a study in the Japanese general population

Abstract

To elucidate the hierarchy in the evolution of glucose intolerance in the general population, the relationship between plasma glucose (PG), β-cell function (insulinogenic index [II] = ΔIRI 0–30/ΔPG 0–30 on 75 g oral glucose tolerance test [OGTT], where IRI is immunoreactive insulin), insulin sensitivity (Si; determined by quantitative insulin sensitivity check index [QUICKI]), age, and body mass index (BMI) were analyzed in 504 Japanese health examinees (men/women: 347/157). The mean (±SD) age was 53 (±11) years, BMI 23.6 (±3.2) kg/m 2, fasting PG (FPG) 5.61 (±0.97) mmol/L, 2-hour PG 7.42 (±3.1) mmol/L, II 74.2 (±169.3) [pmol/L] · [mmol/l] −1, and QUICKI 0.385 (±0.057) [log (μU/mL) + log (mg/100 mL)] −1. Higher FPG and 2-hour PG, respectively, were independently correlated with lower II, lower QUICKI, higher age, and higher BMI; the standardized correlation coefficient was largest for the correlation between PG and II. Based on the multiple linear regression, FPG = 8.565 − 1.201 · log [II] − 5.374 · QUICKI + 0.007 · age + 0.030 · BMI ( r 2 = 0.442), and 2-hour PG = 14.239 − 4.206 · log [II] − 0.141 · QUICKI + 0.034 − age + 0.141 · BMI ( r 2 = 0.493). Thus, elevation of PG correlated most prominently with β-cell dysfunction and less prominently with decreased Si, higher age, and BMI (especially so in the case of 2-hour PG). In conclusion, the primacy of β-cell dysfunction in the process of developing glucose intolerance was strongly suggested in the Japanese general population.