Glucotoxicity is a critical determinant of insulin secretion over treatment types or disease duration in type 2 diabetes

초록

Background Progressive impairment of insulin secretion is a characteristic of type 2 diabetes (T2D). The relative contribution of age, duration of disease, types of treatment, glucotoxicity, and glycemic variability to insulin secretion is not well known. Aim This study aimed to identify the major factors affecting insulin secretion among patients with T2D. Method From an observational diabetes cohort in South Korea, 367 T2D patients with disease duration of 0 to 40 years were included. Insulin secretion was estimated by insulinogenic index (IGI) and HOMA-B based on 75 g oral glucose tolerance test (OGTT). Age, sex, disease duration, body mass index (BMI), HbA1c at the time of OGTT, area under the curve of HbA1c over time, coefficient of variation in HbA1c, and types and duration of anti-diabetic drug use were examined for the association with insulin secretion. The relative contribution of those factors to insulin secretion was compared by estimating beta coefficients per 1-standard deviation (β). Results The mean age of patients was 59.6 (±12.0) years and the median duration of disease was 8 (0–15) years. The annual decline of IGI was 2.7%. In the multivariate regression analysis, female sex (β = 0.135, p = 0.006) and BMI (β = 0.214, p < 0.001) were positively associated with IGI while the duration of disease (β = –0.227, p = 0.006) and HbA1c at the time of OGTT (β = –0.369, p < 0.001) were negatively associated. The association was similar in HOMA-B. Compared with patients with HbA1c ≥9% at the time of OGTT, IGI was 1.9, 2.6, 3.4, and 4.6-fold higher in those with HbA1c of 8–<9%, 7–<8%, 6–<7%, and <6%, respectively, after adjusting for other factors (p for trend <0.001). In contrast, insulin secretion was not affected by the types and duration of anti-diabetic drugs nor HbA1c variability. Conclusion Insulin secretion steadily declines over time in T2D patients, however, it is largely affected by the moment’s hyperglycemia itself. Specific drug use does not seem to be related to insulin secretion.