Effect of family history of type-2 diabetes on coronary flow reserve and it’s relationship with insulin resistance: an observational study

Abstract

Coronary microvascular function among offspring of patients with diabetes mellitus might be compromised when compared to persons with no first-degree relative with diabetes mellitus. The aim of the study was to evaluate effect of family history of type-2 diabetes on coronary flow reserve. In this observational study, we evaluated coronary flow reserve (CFR) via echocardiography of 95 subjects having a biological parent with type-2 diabetes and 34 healthy volunteers without any biological parent with type-2 diabetes. We have analyzed possible association with CFR and homeostasis model assessment - insulin resistance (HOMA-IR). Comparison analyses were made using independent samples t test, Chi-square test and one-way ANOVA. Association of independent variables with CFR was obtained by correlation analysis and stepwise linear regression model including potential confounders. CFR was significantly lower in the positive family history group than in the controls. Moreover, when compared with controls, the subgroup of insulin-sensitive subjects in the positive family history group also had significantly reduced CFR (2.67±0.28 vs. 2.83±0.19; p=0.01). Correlation analysis revealed that CFR was inversely correlated with HOMA-IR, (r=-0.433), fasting glucose (r=-0.331), fasting insulin (r=-0.396), and hemoglobin (Hb)A1c (r=-0.405). When the positive family history group was divided into tertiles of insulin resistance (HOMA-IR <1.3, 1.3-2.6, and >2.6; Groups 1-2, and 3), there was a significant difference in CFR between Groups 1 and 2 and between Groups 1 and 3 (p<0.05 for all). Though statistically not significant, there was also a difference in CFR between Groups 2 and 3. In a linear regression model, only fasting glucose level was independent predictor of CFR (β=-677; p value =0.001, 95% CI: -0.061 and -0.019). Nondiabetic first-degree relatives of patients with type-2 diabetes are at increased risk of developing coronary microvascular dysfunction.