Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin.

The pathophysiology is distinct in various state of glucose metabolism abnormalities. As the defect of individuals with normal oral glucose tolerance (NGT) but isolated high glycosylated hemoglobin (HbA1c), i.e. iHH, was ambiguous, we aimed to investigate the insulin sensitivity and β-cell function of iHH. According to the ADA criteria of HbA1c cut-off point (5.7%), 3,517 subjects with NGT screened from a total of 7,855 middle-aged and elderly Chinese without known diabetes were divided into two groups, 1,877 subjects with HbA1c < 5.7% and 1,640 with HbA1c ≥ 5.7% (i.e. iHH). A variety of indexes from blood glucose and insulin levels of oral glucose tolerance were calculated to evaluate insulin sensitivity and β-cell function. Compared with subjects with HbA1c < 5.7%, individuals with iHH had increased homeostasis model assessment of insulin resistance (HOMA-IR), early-phase and total insulin release indexes (insulin release index 30 min and 120 min, i.e. INRS30 and INSR120), and decreased Matsuda insulin sensitivity index (Matsuda ISI) and early-phase disposition index (DI30). After adjustment for confounding factors, the significant difference of HOMA-IR and INSR30 between the two groups vanished, however, Matsuda ISI and DI30 remained significantly lower and INSR120 was still higher in iHH group compared with HbA1c < 5.7%. In conculsion, subjects with NGT may not be perfectly healthy in glycometabolism, those with iHH have impaired early-phase β-cell function and decreased insulin sensitivity.