Vitamin K to Slow Progression of Dyslipidemia and Diabetes Risk

There has been a striking rise in dyslipidemia, type 2 diabetes, and prediabetes in the pediatric population in recent years, mirroring the surge in obesity. Given that dyslipidemia, insulin resistance, and type 2 diabetes predisposes children to atherosclerotic cardiovascular disease (CVD) in adulthood, it is critical to identify novel, safe, and inexpensive strategies for dyslipidemia and diabetes prevention. Our goal is to provide evidence for a new alternative mechanism and approach to dyslipidemia and diabetes prevention. Animal studies have revealed that the vitamin K-dependent proteins matrix Gla protein (MGP) and osteocalcin (OC) beneficially influence lipid and glucose metabolism, respectively. MGP and OC both undergo vitamin K'dependent modification in which carboxylation occurs to allow the proteins to bind calcium. The capacity to experimentally manipulate carboxylation of MGP and OC through the use of vitamin K supplementation has been established by our preliminary data and others. Therefore, vitamin K supplementation presents an opportunity to test the hypothesized link between the vitamin K dependent proteins with markers of lipid and glucose metabolism in children at risk for dyslipidemia and diabetes. Our objective is to conduct an 8-week vitamin K intervention (to manipulate carboxylation of MGP and OC) in order to determine its effects on markers of dyslipidemia (triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol) and diabetes risk (insulin sensitivity and beta-cell function). Sixty obese children will be randomly allocated to either the control group receiving placebo or the low-dose (45 mcg/d) or high-dose group (90 mcg/d) receiving vitamin K2 (menaquinone-7). The specific aims are to determine if vitamin K-induced changes in MGP and OC carboxylation improve markers of dyslipidemia and diabetes risk. The central hypothesis is that vitamin K-induced carboxylation of MGP and OC will influence markers of dyslipidemia and diabetes risk, respectively. The potential beneficial effects of vitamin K-dependent proteins on lipid and glucose metabolism is innovative and makes for a suitable area of investigation in a pediatric population at risk of developing atherosclerotic CVD in adulthood. Results will advance our understanding about vitamin K, which may propel therapeutic strategies to prevent and treat dyslipidemia and insulin resistance with vitamin K supplementation. (AHA Program: Grant-in-Aid)