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

描述（申请人提供）：阳光维生素能改善女性糖尿病患者的情绪和自我管理吗？在美国，每10个人中就有1人患有糖尿病，预计到2050年将增加到每4个人中就有1人患有糖尿病。女性2型糖尿病患者的预后比男性2型糖尿病患者差。这可能是由于超过25%的女性糖尿病患者患有抑郁症。抑郁干扰自我照顾行为，显著影响血糖控制。抗抑郁药对治疗抑郁症是有效的，但会破坏血糖控制，导致体重增加，使糖尿病的自我管理变得困难。研究表明，补充维生素D可以改善健康肥胖人群的抑郁症状，这表明在其他人群中，维生素D也可以改善这些症状。我们最近完成了一项为期六个月的概念验证研究，使用一组，前后测试设计来检查每周补充维生素D（每周50,000 iu）对有明显抑郁症状的2型糖尿病女性的影响(流行病学研究中心抑郁工具（CES-D） （NIH 5P60DK020595，试点项目）的得分为bbb16。我们发现抑郁症状显著减少，糖尿病自我管理改善，收缩压降低。几项小型研究表明，补充维生素D可能通过直接或间接的血管作用降低血压。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型糖尿病女性抑郁症状、自我管理和血压的疗效（n=150）。使用分层块随机化（基于抑郁症状严重程度的分层），女性将被分配到每周补充维生素D3 （50,000 iu）或匹配的每周安慰剂，为期六个月。由于指南建议在开始给药后三个月评估维生素D水平，因此研究将在基线、三个月和六个月收集测量数据。以下结果将被测量：抑郁症状、糖尿病自我管理（自我效能、糖尿病困扰、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补充剂的女性抑郁症状更少，抑郁改善介导的糖尿病自我管理增加，收缩压更低。我们还将探讨补充维生素D对抑郁症的可能机制作用。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。其中一些炎症性生物标志物通过刺激吲哚胺2,3 -双加氧酶（IDO）将色氨酸从血清素合成中分流，从而改变了色氨酸的代谢途径。几项研究（不是抑郁症研究）报告称，维生素D可以降低炎症生物标志物的水平。因此，我们将探索补充维生素D是否会降低炎症生物标志物（CRP，白细胞介素-6和肿瘤坏死因子-¿），为抗抑郁活性的合理机制提供证据。补充维生素D的副作用很小，成本也很低。因此，对于患有2型糖尿病的女性和其他慢性人群来说，使用这种疗法的潜力是非常重要的，这些人患有严重影响其健康自我管理的抑郁症症状。

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.