Effects of genetic predisposition on proinsulin responses in Asian Indians.

This study was done in adult offspring of two diabetic (NIDDM) parents (ODP) to look for changes in specific insulin (insulin) and proinsulin responses due to strong familial background and also in different states of glucose intolerance. Equal numbers (20 in each group) of ODP with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes (DM) were chosen. Twenty, age and BMI matched healthy controls, without family history of diabetes, were also studied for comparison. Plasma specific insulin and proinsulin were measured by radioimmunoassays in fasting and 120' plasma samples collected during the GTT. Proinsulin to insulin ratio were calculated. Insulin resistance (IR-HOMA) was calculated. In NGT, fasting proinsulin-insulin ratio was significantly higher than the control value (P = 0.023). Insulin values at 120' was higher than control values, though it did not reach statistical significance. Proinsulin at 120' was higher than controls (P = 0.016). In IGT, the fasting proinsulin to insulin ratio, the 120' proinsulin and insulin values were higher than controls (P = 0.048, 0.0013 and 0.0001, respectively). Fasting proinsulin-insulin ratio in IGT was similar to the value in NGT. In diabetic subjects proinsulin concentrations were significantly higher than controls at fasting (P = 0.0004), and 120' (P = 0.0007). The fasting values were higher compared to NGT also (P = 0.037). Proinsulin-insulin ratios were higher than the values in controls (P = 0.0008), IGT (P = 0.047) and NGT (P = 0.05). Diabetic subjects had higher fasting insulin values compared to the control values although between the groups no statistical significance was found (P = 0.22 by Kruscall Wallis test). At 120' both insulin and proinsulin values increased from NGT to IGT, but with development of diabetes a reduction was seen in the responses. Insulin resistance (IR-HOMA) increased steadily from NGT to diabetes. The difference between NGT and controls in IR was not statistically significant. This study of Asian Indian offspring of diabetic parents has shown that genetic predisposition to diabetes resulted in increased proinsulin to insulin ratio at the fasting state. Absolute hyperproinsulinaemia occurred only with development of diabetes.