MD, c/o The Diabetes Prevention Program Coordinating Center, Biostatistics Center, George Washington University, 6110 Executive Boulevard, Suite 750, Rockville, Maryland 20852.
J Clin Endocrinol Metab. 2013 Oct;98(10):3989-98. doi: 10.1210/jc.2013-1452. Epub 2013 Aug 26.
Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied.
The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program.
This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT.
Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study.
Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity.
Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured.
ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance.
ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis.
尽管强化生活方式改变（ILS）和二甲双胍可降低葡萄糖耐量受损（IGT）患者的糖尿病发病率，但它们对脂蛋白亚组分的影响尚未得到研究。
本研究旨在描述 ILS 和二甲双胍与安慰剂干预对 IGT 患者脂蛋白亚组分的影响。
这是一项随机临床试验，旨在测试 ILS、二甲双胍和安慰剂对 IGT 患者糖尿病发展的影响。
选择参加糖尿病预防计划的 IGT 个体参加了该研究。
干预措施包括随机分配二甲双胍 850mg 或安慰剂，每日两次，或采用低脂饮食和增加体力活动的 ILS，目标是减轻 7%的体重。
基线和 1 年后通过磁共振和密度梯度超速离心测量脂蛋白亚组分的大小、密度和浓度。
ILS 降低了大而浮力的极低密度脂蛋白、小而致密的低密度脂蛋白（LDL）和小而高密度脂蛋白（HDL），并升高了大 HDL。二甲双胍适度降低小而致密的 LDL，并升高小而大的 HDL。胰岛素抵抗的变化在很大程度上解释了与干预相关的大 VLDL 的降低，而体重指数（BMI）和脂联素的变化与 LDL 的变化密切相关。基线和脂联素的变化与大 HDL 的变化有关，BMI 的变化与小 HDL 的变化有关。二甲双胍增加小 HDL 的作用独立于脂联素、BMI 和胰岛素抵抗。
ILS 和二甲双胍治疗对脂蛋白亚组分有有利影响，主要由干预相关的胰岛素抵抗、BMI 和脂联素变化介导。减缓糖尿病发展的干预措施也可能延缓动脉粥样硬化的进展。
