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 proinsuli n responses due to strong familial background and also in different st ates of glucose intolerance. Equal numbers (20 in each group) of ODP w ith normal glucose tolerance (NGT), impaired glucose tolerance (IGT) a nd diabetes (DM) were chosen. Twenty, age and BMI matched healthy cont rols, without family history of diabetes, were also studied for compar ison. Plasma specific insulin and proinsulin were measured by radioimm unoassays in fasting and 120' plasma samples collected during the GTT. Proinsulin to insulin ratio were calculated. Insulin resistance (IR-H OMA) was calculated. In NGT, fasting proinsulin-insulin ratio was sign ificantly higher than the control value (P = 0.023). Insulin values at 120' was higher than control values, though it did not reach statisti cal significance. Proinsulin at 120' was higher than controls (P = 0.0 16). In IGT, the fasting proinsulin to insulin ratio, the 120' proinsu lin and insulin values were higher than controls (P = 0.048, 0.0013 an d 0.0001, respectively). Easting proinsulin-insulin ratio in IGT was s imilar to the value in NGT. In diabetic subjects proinsulin concentrat ions 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 value s in controls (P = 0.0008), IGT (P = 0.047) and NGT (P = 0.05). Diabet ic subjects had higher fasting insulin values compared to the control values although between the groups no statistical significance was fou nd (P = 0.22 by Kruscall Wallis test). At 120' both insulin and proins ulin values increased from NGT to IGT, but with development of diabete s a reduction was seen in the responses. Insulin resistance (IR-HOMA) increased steadily from NGT to diabetes. The difference between NGT an d controls in IR was not statistically significant. This study of Asia n Indian offspring of diabetic parents has shown that genetic predispo sition to diabetes resulted in increased proinsulin to insulin ratio a t the fasting state. Absolute hyperproinsulinaemia occurred only with development of diabetes. (C) 1998 Elsevier Science Ireland Limited. Al l rights reserved.