Vitamin D deficiency and treatment in male veterans at risk for diabetes

有糖尿病风险的男性退伍军人的维生素 D 缺乏症和治疗

• 批准号: 8392969
• 负责人: Elena Barengolts
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392969
• 关键词: 25-hydroxyvitamin D; Adverse event; African American; Aftercare; Blood; C-reactive protein; Cardiovascular Diseases; Clinical; Clinical Research; Clinical Sciences; Data; Diabetes Mellitus; Dose; Double-Blind Method; Drops; Ergocalciferols; Fasting; Generic Drugs; Glucose; Glycosylated hemoglobin A; Goals; Health; Health Benefit; Healthcare; High Density Lipoproteins; Illinois; Inflammation; Insulin; Interleukin-6; Lead; Leptin; Life Style; Lipids; Measurement; Measures; Mediating; Modeling; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oral; Outcome; Overweight; Patients; Pharmacy facility; Physicians; Placebos; Plasma; Plasminogen Activator Inhibitor 1; Population; Populations at Risk; Principal Investigator; Randomized; Randomized Controlled Trials; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Sampling; Supplementation; Symptoms; Testing; Translational Research; Tumor Necrosis Factor-alpha; Universities; Veterans; Vitamin D; Vitamin D Deficiency; Weight; Work; adipokines; adiponectin; base; cost effective; diabetes risk; effective intervention; experience; fasting plasma glucose; glucose disposal; glucose metabolism; improved; inflammatory marker; insulin sensitivity; interest; intravenous glucose tolerance test; low density lipoprotein triglyceride; male; non-diabetic; prevent; primary outcome; public health relevance; synthetic polymer Bioplex

DESCRIPTION (provided by applicant): Emerging evidence suggests that higher vitamin D blood levels are associated with better health outcomes including type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) but it remains unclear whether vitamin D supplementation could provide improvement of these health outcomes. A population of a priority interest to VA healthcare is a population of African American male (AAM) veterans at increased risk for T2DM. The goal of the proposed study is to determine the efficacy vitamin D treatment for improving early markers of T2DM, CVD and inflammation as compared to placebo in African American male (AAM) veterans at risk for T2DM. We will randomly assign AAM veterans with elevated plasma glucose (95-125 mg/dl) and low 25-hydroxyvitamin D (25OHD<20 ng/ml) to receive weekly vitamin D ergocalciferol 50,000 IU (D2) or placebo (PLA) for 12 months (90 subjects per group according to power analysis and assuming 15% drop out rate). At the baseline and at the end of the study we will perform clinical measurements (anthropometrics and blood bio-markers, HbA1c and lipid profile) and complete oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT). We will use Biorad BioPlex Multianalyte Profiler to simultaneously measure bio- markers of inflammation (interleukin-6 and tumor necrosis factor-alpha), of cardiovascular disease (sensitive C-reactive protein and plasminogen activator inhibitor-1), and adipokines (adiponectin and leptin). In addition we will measure fasting plasma glucose and HbA1c at 6 months. We will adjust D2 dose (while preserving double-blind design of the study) at 3 and 6 months to maintain 25OHD level in the sufficiency range of 40-100 ng/ml. The primary outcome will be change (post-treatment minus baseline) in oral glucose insulin sensitivity (OGIS) calculated from OGTT (Mari's formula). The key parameter calculated from FSIVGTT will be insulin sensitivity (SI, provides an estimate of insulin mediated glucose disposal based on Bergman's Minimal Model). We expect that at 12 months D2 will increase OGIS by about 10% and SI by 20%, and that these changes will be significantly better (p<0.05) than those seen in PLA. We also expect to see significant bio-markers' improvement of 10-25% in D2 compared to PLA group. We expect D2 to be well tolerated without significant adverse events. If the study shows positive outcomes it would suggest that vitamin D might be beneficial to enhance glucose metabolism by improving insulin-glucose interactions with a simple, weight- independent, and cost-effective intervention. Because lifestyle changes are difficult to achieve and maintain for preventing T2DM, D2 may be a possible option and should be considered for a trial of longer duration in a larger population to justify its use in the non-diabetic population.

描述（由申请人提供）： 新的证据表明，血液中较高的维生素 D 水平与更好的健康结果相关，包括 2 型糖尿病 (T2DM) 和心血管疾病 (CVD)，但尚不清楚补充维生素 D 是否可以改善这些健康结果。退伍军人管理局医疗保健优先关注的人群是患 T2DM 风险较高的非裔美国男性 (AAM) 退伍军人。拟议研究的目的是确定维生素 D 治疗与安慰剂相比，对有 T2DM 风险的非裔美国男性 (AAM) 退伍军人改善 T2DM、CVD 和炎症早期标志物的疗效。我们将随机分配血糖升高 (95-125 mg/dl) 和 25-羟基维生素 D 水平较低 (25OHD<20 ng/ml) 的 AAM 退伍军人，每周接受维生素 D 麦角钙化醇 50,000 IU (D2) 或安慰剂 (PLA)，为期 12 年个月（根据功效分析，每组 90 名受试者，并假设 15% 的退出率）。在基线和研究结束时，我们将进行临床测量（人体测量和血液生物标志物、HbA1c 和血脂谱）以及完整的口服葡萄糖耐量试验 (OGTT) 和频繁采样的静脉葡萄糖耐量试验 (FSIVGTT)。我们将使用 Biorad BioPlex Multianalyte Profiler 同时测量炎症（白细胞介素 6 和肿瘤坏死因子 α）、心血管疾病（敏感 C 反应蛋白和纤溶酶原激活剂抑制剂 1）和脂肪因子（脂联素和瘦素）的生物标志物）。此外，我们将在 6 个月时测量空腹血糖和 HbA1c。我们将在第 3 个月和第 6 个月调整 D2 剂量（同时保留研究的双盲设计），以将 25OHD 水平维持在 40-100 ng/ml 的充足范围内。主要结果是根据 OGTT（Mari 公式）计算的口服葡萄糖胰岛素敏感性 (OGIS) 的变化（治疗后减去基线）。 FSIVGTT 计算出的关键参数是胰岛素敏感性（SI，根据伯格曼最小模型提供胰岛素介导的葡萄糖处理的估计）。我们预计在 12 个月时，D2 将使 OGIS 增加约 10%，SI 增加 20%，并且这些变化将明显优于 PLA 中的变化（p<0.05）。我们还预计 D2 组的生物标志物比 PLA 组显着提高 10-25%。我们预计 D2 具有良好的耐受性，不会出现重大不良事件。如果研究显示出积极的结果，则表明维生素 D 可能通过简单、与体重无关且具有成本效益的干预措施改善胰岛素-葡萄糖相互作用，从而有益于增强葡萄糖代谢。由于生活方式的改变很难实现和维持以预防 T2DM，因此 D2 可能是一种可能的选择，并且应考虑在更大人群中进行更长时间的试验，以证明其在非糖尿病人群中使用的合理性。