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

To elucidate the hierarchy in the evolution of glucose intolerance in the general population, the relationship between plasma glucose (PG), beta-cell function (insulinogenic index [II] = DeltaIRI(0-30)/DeltaPG(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/m2, 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 (microU/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 (r2 = 0.442), and 2-hour PG = 14.239 - 4.206. log [II] - 0.141. QUICKI + 0.034 - age + 0.141. BMI (r2 = 0.493). Thus, elevation of PG correlated most prominently with beta-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 beta-cell dysfunction in the process of developing glucose intolerance was strongly suggested in the Japanese general population.