EPCs BEFORE AND AFTER TREATMENT WITH METFORMIN IN PATIENTS WITH FCHL AND INSULIN RESISTANCE

Background. Familial combined hyperlipidemia (FCHL) is a common disorder of metabolism, associated to increased cardiovascular (CV) risk; besides the overproduction of very low-density lipoprotein and altered remnants catabolism, a high prevalence of insulin resistance (IR) has been also described in FCHL subjects. IR is known to be associated with low-grade chronic systemic inflammation, and is a strong predictor of CV disease. Endothelial progenitor cells (EPCs) are a heterogeneous population of cells with the ability to differentiate into cell types of different organs and systems, and are vital for the maintenance and repair of the endothelium. We have already evaluated CD34+EPCs in several clinical conditions, characterized by both high-grade and low-grade inflammation, and we found inverse associations between disease severity and cell count. The antidiabetic drug metformin, which improves insulin sensitivity and reduces hepatic glucose production, was reported to increase EPC levels in diabetic patients. We sought to evaluate whether metformin could improve CD34+EPC count in non-diabetic, FCHL/IR patients. Methods and Results. We evaluated CD34+EPC count in newly diagnosed FCHL/IR patients at baseline (T0) and after six-months of metformin treatment (T1). We enrolled 29 patients (M:F 20:9; age 46±11 years) with no further CV or metabolic risk factor. After metformin treatment, there was a significant reduction in fasting plasma glucose (Δ=-4.45%; p<0.05), plasma insulin (Δ=-18%; p<0.05), HOMA-IR (Δ=-19.9%; p<0.05) and an increase in CD34+EPC count (Δ=69.1%; p<0.05). Moreover, we found an inverse correlation between CD34+EPC count and plasma insulin (r-0.571, p=0.01) and HOMA-IR (r-0.583, p=0.009). Dependence analysis showed an association between ΔHOMA and ΔCD34+ cells (t -2.961, p=0.009). Conclusion. Our study suggests that in FCHL/IR patients metformin, possibly by improving insulin-sensitivity, may increase CD34+EPC amount, which could positively impact CV risk in these patients.