Association of Fasting Proinsulin Levels with Glycemic Profile in Indian Type 2 Diabetes Patients

Type 2 diabetes mellitus is a major cause of cardiovascular disease and mortality, with mortality rate 27% higher in the diabetes cohort. Hyperproinsulinemia is a sign of beta cell dysfunction that is augmented by the increased demands placed on beta cell by chronic hyperglycemia. Hyperproinsulinaemia is the result of secretion of immature proinsulin-rich granules from beta cells, as a response to an increased demand for insulin i.e. an insulin resistant state According to previous studies intact proinsulin was a stronger predictor for type 2 diabetes than specific insulin. We plan to confirm this finding in the Indian demographic.

Material: An observational cross-sectional study was carried out in LHMC with 150 subjects having type 2 diabetes aged between 35-80 years. The subjects taking insulin or any diabetogenic drugs; with history of chronic respiratory, cardiac or metabolic illness other than diabetes were excluded from the study. laboratory examination was conducted after drawing 10ml of venous blood and patients consent. 3 ml of the blood was stored after centrifugation at -20c for assay of fasting proinsulin level. Fasting blood glucose, HbA1c and lipid profile were analyzed. Co-relation between said parameters was established using spearman test of correlation and Wilcoxin-Mann-Whitney U test was used to make comparisons.

Observation: Assessment of glycemic profile of the study population revealed half the subjects having FBS >150mg/dl (n=78, p= 52.0%). Mean HbA1c was 8.40 ± 2.26% with 61 subjects having a well-controlled HbA1c of <7.5%, 35 with 7.5-9.0 % and 54 with HbA1c >9.0%. Association of pro insulin with FBS and HbA1c was positive and strongly significant (rho=0.26 & p value= 0.001, rho=0.23& p value= 0.005 respectively). The mean values of proinsulin in normoglycemic and hyperglycemic subjects were 12.1ug/ml and 17.4 ug/ml respectively. Association of proinsulin with triglyceride levels was found to be positive and significant (rho= 0.22, p value= 0.008). The mean value of pro insulin in subjects with hypertriglyceridemia was 17.9ug/ml as compared to 12.7ug/ml in normal subjects.

Conclusion: The results of the study demonstrated significant positive association between fasting proinsulin levels and glycemic indicators (p value FBS =0.001, HbA1c= 0.005, triglyceride =0.008). Proinsulin however has multiple associations with the diabetes pathophysiology which need to be studied further. Other studies have also demonstrated proinsulin to be an independent cardiovascular risk factor by stimulating plasminogen activator inhibitor-1 secretion and blocking fibrinolysis. Hence, proinsulin needs to be evaluated for use as a early marker for diabetes progression.