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

描述（由申请人提供）：阳光维生素能改善糖尿病女性的情绪和自我管理吗？糖尿病影响美国十分之一的人，预计到2050年将增加到四分之一。2型糖尿病患者的饮食习惯和饮食习惯都有不同。这可能是由于抑郁症影响了超过25%的糖尿病女性。抑郁症会干扰自我护理行为，并显著影响血糖控制。抗抑郁药对抑郁症的治疗有效，但会破坏血糖控制并导致体重增加，使糖尿病自我管理具有挑战性。研究表明，维生素D补充剂可以改善健康肥胖个体的抑郁症状，这表明它可以改善其他群体的这些症状。我们最近完成了一项为期六个月的概念验证研究，采用一组前后测试设计，以检查每周补充维生素D（每周50，000 IU）对患有2型糖尿病的女性的影响，这些女性有显著的抑郁症状（流行病学研究中心抑郁工具（CES-D）评分> 16（NIH 5 P60 DK 020595，试点项目）。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。一些小型研究表明，维生素D补充剂可以通过直接和间接的血管效应降低血压。我们现在提出了一项随机试验，以确定维生素D3补充剂对抑郁症状，自我管理和血压的有效性2型糖尿病女性有显着的抑郁症状（n=150）。使用分层区组随机化（基于抑郁症状严重程度的分层），女性将被分配每周补充维生素D3（50，000 IU）或每周匹配安慰剂，为期6个月。由于指南建议在开始该剂量后三个月评估维生素D水平，因此将在基线、三个月和六个月收集研究测量值。将测量以下结局：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，与服用安慰剂的妇女相比，服用维生素D3补充剂的妇女将报告更少的抑郁症状，增加由抑郁改善介导的糖尿病自我管理，并且具有更低的收缩压。我们还将探讨维生素D补充剂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。这些炎性生物标志物中的一些通过刺激吲哚胺2，3-双加氧酶（IDO）将色氨酸从5-羟色胺合成中分流而改变色氨酸的代谢途径。一些研究（不是抑郁症研究）报告说，维生素D可以降低炎症生物标志物的水平。因此，我们将探讨维生素D补充剂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-β），为抗抑郁活性的合理机制提供证据。维生素D补充剂副作用小，成本低。因此，对于患有2型糖尿病的女性和患有抑郁症状的其他慢性人群，使用这种疗法的潜力是非常显著的，这会显著影响其健康的自我管理。

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.