Can the Sunshine Vitamin Improve Mood and Self-Management in Women with Diabetes?

描述(申请人提供)：阳光维生素能改善糖尿病女性患者的情绪和自我管理能力吗？在美国，每10人中就有1人患有糖尿病，预计到2050年将增加到每4人中就有1人患有糖尿病。患有2型糖尿病的女性比患有2型糖尿病的男性预后更差。这可能是由于抑郁症影响了超过25%的糖尿病女性。抑郁会干扰自我护理行为，并显著影响血糖控制。抗抑郁药对治疗抑郁症有效，但会扰乱血糖控制并导致体重增加，使糖尿病的自我管理具有挑战性。研究表明，补充维生素D可以改善健康的肥胖者的抑郁症状，这表明它在其他群体中用于改善这些症状。我们最近完成了一项为期六个月的概念验证研究，采用一组事前测试设计，以检查每周补充维生素D(每周50,000国际单位)对有明显抑郁症状的2型糖尿病女性的影响(在流行病学研究抑郁工具(CES-D)(NIH 5P60DK020595，试点项目)上得16分)。我们发现抑郁症状显著减少，糖尿病自我管理改善，收缩压下降。一些小规模的研究表明，补充维生素D可能通过直接和间接的血管效应来降低血压。我们现在建议进行一项随机试验，以确定补充维生素D3对有明显抑郁症状的2型糖尿病女性的抑郁症状、自我管理和血压的疗效(n=150)。使用分层随机分组(根据抑郁症状严重程度分层)，妇女将被分配到每周维生素D3补充剂(50000国际单位)或匹配的每周安慰剂，为期六个月。由于指南建议在开始服用该剂量后三个月评估维生素D水平，研究测量将在基线、三个月和六个月收集。将测量以下结果：抑郁症状、糖尿病自我管理(自我效能、糖尿病痛苦、糖尿病自我护理行为)和收缩压。我们假设，与服用安慰剂的女性相比，服用维生素D3补充剂的女性将报告较少的抑郁症状，通过改善抑郁而增强的糖尿病自我管理能力，以及较低的收缩血压。我们还将探索补充维生素D对抑郁症的可能机制效应。有证据表明，在抑郁症中，促炎生物标志物，特别是细胞因子和C反应蛋白(CRP)升高。其中一些炎性生物标志物通过刺激吲哚胺2，3-双加氧酶(IDO)使色氨酸从5-羟色胺合成中分流，从而改变了色氨酸的代谢途径。一些研究(不是抑郁症研究)已经报道，维生素D可以降低炎症生物标记物的水平。因此，我们将探讨补充维生素D是否降低炎症生物标志物(CRP、IL-6和肿瘤坏死因子-β)，为抗抑郁活性的合理机制提供证据。补充维生素D的副作用最小，而且成本较低。因此，对于患有2型糖尿病的妇女和其他患有严重影响健康自我管理的抑郁症症状的慢性人群来说，使用这种疗法的潜力非常大。

DESCRIPTION (provided by applicant): Can the Sunshine Vitamin Improve Mood and Self-Management in Women with Diabetes? Diabetes affects 1 in 10 persons in the United States and is projected to increase to 1 in 4 persons by 2050. Women with type 2 diabetes have worse outcomes than men with type 2 diabetes. This may be due to depression which affects over 25% of women with diabetes. Depression interferes with self-care behaviors and significantly impacts glycemic control. Antidepressants are effective for the treatment of depression but can disrupt glycemic control and cause weight gain, making diabetes self-management challenging. Research has shown that vitamin D supplementation can improve depressive symptoms in healthy, obese individuals suggesting its use for amelioration of these symptoms in other groups. We recently completed a six month proof of concept study using a one group, pre-post test design to examine the effects of weekly vitamin D supplementation (50,000 IUs weekly) in women with type 2 diabetes who had significant depressive symptoms (a score > 16 on the Center for Epidemiologic Studies Depression Tool (CES-D) (NIH 5P60DK020595, pilot project). We found a significant decrease in depression symptoms, improvements in diabetes self- management, and a decrease in systolic blood pressure. Several small studies have shown that vitamin D supplementation may lower blood pressure by direct and indirect vascular effects. We now propose a randomized trial to determine the efficacy of vitamin D3 supplementation on depressive symptoms, self- management, and blood pressure in women with type 2 diabetes who have significant depressive symptoms (n=150). Using a stratified block randomization (strata based on depression symptom severity) women will be assigned to either weekly vitamin D3 supplementation (50,000 IUs) or a matching weekly placebo for a period of six months. Since guidelines recommend assessing vitamin D levels at three months upon initiating this dose, study measurements will be collected at baseline, three, and six months. The following outcomes will be measured: depressive symptoms, diabetes self-management (self-efficacy, diabetes distress, diabetes self- care behaviors), and systolic blood pressure. We hypothesize that women receiving vitamin D3 supplementation will report fewer depressive symptoms, increased diabetes self- management mediated by depression improvement, and have a lower systolic BP compared to those taking placebo. We will also explore a possible mechanistic effect of vitamin D supplementation on depression. Evidence indicates that in depression, pro-inflammatory biomarkers, notably cytokines and C-reactive protein (CRP), are elevated. Some of these inflammatory biomarkers alter the metabolic pathway of tryptophan by shunting it away from serotonin synthesis via stimulation of the enzyme indoleamine 2, 3-dioxygenase (IDO). Several studies (not depression studies) have reported that Vitamin D can decrease levels of inflammatory biomarkers. Thus we will explore whether vitamin D supplementation decreases inflammatory biomarkers (CRP, interleukin-6, and tumor necrosis factor- ¿) providing evidence for a plausible mechanism of antidepressant activity. Vitamin D supplementation has minimal side effects and is low in cost. Thus, the potential for using this therapy is highly significant fr women with type 2 diabetes and other chronic populations who suffer from symptoms of depression which significantly impacts the self-management of their health.