KINETICS OF HUMAN HOMOCYSTEINE METABOLISM

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elevated plasma homocysteine (Hcy) levels are an independent risk factor for cardiovascular disease (CVD), particularly in patients with type 2 diabetes. Thus, studies addressing the cause(s) of the elevated Hcy levels in patients with type 2 diabetes have important implications for CVD risk management in this population. This research will address the hypothesis that newly diagnosed patients with type 2 diabetes, who have poor metabolic control, have higher levels of Hcy due to defects in Hcy metabolism. The intracellular rate of Hcy production and disposal will be measured in patients with a new diagnosis of type 2 diabetes and in healthy controls, using isotopically labeled forms of nutrients (methionine), and will be analyzed using mass spectrometry. Patients and controls will be matched for sex and race, while controlling for age, BMI, and physical activity level. All subjects will have normal levels of plasma folate and B vitamins. This study will also address the hypothesis that improved metabolic control, achieved over 6 months of oral medication usage, decreases Hcy concentrations by altering the rate of Hcy production and/or disposal in newly diagnosed type 2 diabetes patients with initially poor metabolic control.