KINETICS OF HUMAN HOMOCYSTEINE METABOLISM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。血浆同型半胱氨酸（Hcy）水平升高是心血管疾病（CVD）的独立危险因素，特别是在2型糖尿病患者中。因此，研究2型糖尿病患者Hcy水平升高的原因对该人群的心血管疾病风险管理具有重要意义。本研究将解决新诊断的2型糖尿病患者代谢控制较差，由于Hcy代谢缺陷导致Hcy水平较高的假设。将使用同位素标记形式的营养物质（蛋氨酸）测量新诊断为2型糖尿病的患者和健康对照者的细胞内Hcy产生和处置率，并将使用质谱法进行分析。患者和对照组将根据性别和种族进行匹配，同时控制年龄、体重指数和身体活动水平。所有受试者血浆中叶酸和维生素B的含量都将达到正常水平。本研究还将探讨一种假设，即在最初代谢控制较差的新诊断的2型糖尿病患者中，通过改变Hcy产生和/或处置的速率，在6个月的口服药物使用中改善了代谢控制，从而降低了Hcy浓度。

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.