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）： 新兴的证据表明，较高的维生素D血液水平与更好的健康结果有关，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状况。 VA Healthcare优先考虑的人口是一名非洲裔美国男性（AAM）退伍军人，其风险增加了T2DM。拟议的研究的目的是确定与具有T2DM风险的非裔美国人（AAM）退伍军人相比，与安慰剂相比，与安慰剂相比，改善T2DM，CVD和炎症的早期标记的功效维生素D治疗方法。我们将随机分配具有血浆葡萄糖（95-125 mg/dL）和低25-羟基维生素D（25OHD <20 ng/ml）的低血浆葡萄糖（95-125 mg/dl）的AAM退伍军人，每周接受每周维生素D ergocalciferol 50,000 IU（d2）或12个月的安慰剂（pla），以每组分析和90个分析率，并接受12个月的汇总（均为90个单位）。在研究结束时，我们将进行临床测量（拟人化和血液生物标志物，HBA1C和脂质谱）以及完整的口服葡萄糖耐受性测试（OGTT），并经常采样静脉内葡萄糖耐受性测试（FSIVGTT）。我们将使用Biorad Bioplex多体分析型探测仪同时测量心血管疾病（敏感的C-反应性蛋白质和纤溶酶原激活剂抑制剂1）以及脂肪因子（脂肪蛋白和脂肪蛋白和脂肪蛋白）的炎症（白介素-6和肿瘤坏死因子-Alpha）的生物标记。此外，我们将在6个月时测量禁食等离子体葡萄糖和HBA1C。我们将在3和6个月的时间调整D2剂量（同时保留研究的双盲设计），以将25OHD水平保持在40-100 ng/ml的足够范围内。主要结果将是根据OGTT（Mari的公式）计算出的口服葡萄糖胰岛素敏感性（OGIS）的变化（治疗后减去基线）。从FSIVGTT计算出的关键参数将是胰岛素灵敏度（SI，基于Bergman的最小模型提供了胰岛素介导的葡萄糖处置的估计值）。我们预计，在12个月时，D2将使OGIS增加约10％，而SI将增加20％，并且这些变化将比PLA中看到的变化明显好（P <0.05）。与PLA组相比，我们还期望D2的生物标志物在D2中的10-25％提高。我们希望D2可以很好地耐受性，而没有重大不良事件。如果该研究表现出阳性结果，则表明维生素D可能通过简单，重量独立和成本效益的干预措施改善胰岛素 - 葡萄糖相互作用来增强葡萄糖代谢。由于生活方式的改变很难实现和维护以防止T2DM，因此D2可能是一种选择，应考虑在较大人群中持续时间更长的试验以证明其在非糖尿病人群中的使用是合理的。