Relationship of serum proinsulin and glucagon levels in subjects with type 2 diabetes mellitus

Abstract

Interaction of insulin and glucagon in blood glucose homeostasis is a well known phenomenon, but the interaction between proinsulin and glucagon has not been adequately studied. Both hyperproinsulinemia and hyperglucagonemia have shown to have an independent association with T2 DM, but the determinants of the two hormonal abnormalities in T2 DM need to be clarified further. A proinsulin study has been previously done in a group of lean and young Bangladeshi patients, but it has not yet been done in normal to obese middle aged diabetic population who form the main bulk of patients in this country. Given the racial heterogenecity in nutritional habits and gastrointestinal functions, the effect of incretin hormones (GLP-1 and GIP-1) also vary from population to population and that, in turn, substantially modulate insulin (and proinsulin) as well as glucagon secretion. Thus the ethnicity specific studies are particularly required on these issues. Under this context the present study was undertaken to investigate the role of proinsulin and the association of proinsulin and glucagon in a group of Bangladeshi T2 DM patients. A group of forty four (44) T2 DM subjects along with a group of BMI-matched 44 Control subjects were included in the study. Serum triglycerides and cholesterol was significantly higher (p=0.021 and p=.030 respectively) in patients than that of controls. C-peptide level (median 2.6 ng/mL, range; 0.5-6.8) in the diabetic subjects did not show any significant difference compared to controls (median 1.9, range; 0.5-7.0); but the proinsulin level (28.3 pm/L, range; 2.1-268.0) was significantly higher (p=0.0001) in T2 DM patients than the controls (9.3 pm/L, range; 1.8-156.7). The diabetic subjects showed a highly significant P-cell dysfunction (p=0.0001) as evident from HOMA%B. T2 DM patients had a significantly lower HOMA%B than the healthy control subjects. On the other hand, the insulin sensitivity was marginally lower (p=0.024) in diabetic subjects than in control as evident from HOMA%S. The serum glucagon level was significantly lower (p=0.0001) in patients than in the controls. In the ratio analysis, Proinsulin/C-peptide ratio was significantly higher (p=0.005) in diabetics than the controls. There was marginally elevated Proinsulin/Glucose ratio in patients (2.85) than in controls (1.58). Proinsulin-glucagon ratio was also significantly higher (p=0.0001) in diabetics (3.0) than in controls (0.45). In muhiple regression analysis taking proinsulin as a dependable variable, proinsulin showed significantly negative association with glucagon (p=0.05) and HOMA%S (p=0.005). On the other hand glucagon had significantly negative association (p=0.001) Dhaka University Institutional Repository with group (Control/T2 DM), proinsulin (p=0.05) and HOMA%B (p=0.05) but it had no association with HOMA%S. The data suggests that T2 DM subjects of Bangladeshi population have pancreatic beta cell dysfunction with consequent defect in insulin secretion. Hyperproinsulinemia in T2 DM seem to result from a generalized failure of beta cells rather than from peripheral insulin resistance. On the other hand, Bangladeshi T2 DM subjects seem to show atypical feature in glucagon levels with normal to lower values which is probably related to relatively low insulin resistance in these subjects. There also seem to be a role of hyperproinsulinemia in regulating glucagon in these patients