Depression and Insulin Resistance in Type 2 Diabetes

描述（由申请人提供）：本研究的总体目的是确定抑郁症对糖尿病患者胰岛素抵抗（IR）的影响。IR是2型糖尿病（T2DM）的特征，是糖尿病并发症，特别是冠心病（CHD）的预测因子。反过来，冠心病占糖尿病患者死亡人数的50%以上，占住院人数的75%。正因为如此，人们正在寻找可能导致IR的可改变因素。有证据表明，非糖尿病患者的IR与抑郁症有关，并且这些患者的IR可能随着抑郁症治疗而改善。大约20%的2型糖尿病（T2DM）患者存在抑郁，平均比糖尿病诊断早5年以上，并且可能是一些IR型T2DM及其冠心病风险的原因。在一项对伴有和不伴有抑郁症的糖尿病女性进行的10年前瞻性研究中，我们发现抑郁症加速了冠心病的发展（p <0.01）并增加了冠心病的风险（OR 3.1, 95%CI 1.1-8.9），并且在多变量分析中仍被保留为冠心病的独立预测因子。在拟议的研究中，我们计划招募160名未经治疗且临时诊断为T2DM的受试者，其中80名有重度抑郁症，80名无重度抑郁症（根据DSM-IV），性别和BMI相匹配。所有受试者的IR（来自口服葡萄糖耐量试验），以及情绪、血糖控制、hpa轴活性、中枢性肥胖、饮食和身体活动的测量将在基线时确定。抑郁症患者还将接受频繁取样的静脉葡萄糖耐量试验（FSIGTT）和更详细的活动、肥胖和细胞内脂肪分析。抑郁受试者将被随机分配接受为期12周的认知行为治疗或常规抑郁护理；观察非抑郁受试者进行比较。所有基线测量（包括FSIGTT和初始抑郁患者的附加测试）将在干预/观察后重复进行。将使用单变量检验、协方差分析和最小二乘回归技术来评估抑郁症和抑郁症症状严重程度对IR的独立影响以及IR随时间的变化。抑郁治疗和抑郁缓解对IR的影响（控制基线差异）以及抑郁-IR关系的潜在中介因素也将在最初抑郁的受试者中确定。我们假设抑郁症与未经治疗的T2DM患者IR增加有关，并且成功的抑郁症治疗可以改善IR。这项研究的发现可以确定一个潜在的可改变因素，以改善T2DM患者的病程和预后。

DESCRIPTION (provided by applicant): The overall purpose of this study is to determine the impact of depression on insulin resistance (IR) in diabetes. IR characterizes type 2 diabetes (T2DM) and is a predictor of diabetes complications, particularly coronary heart disease (CHD). CHD, in turn, accounts for more than 50% of deaths and 75% of hospitalizations among diabetic patients. Because of this, potentially modifiable factors contributing to IR are being sought. There is evidence linking IR to depression in nondiabetic subjects, and IR may improve with depression treatment in these subjects. Depression is present in approximately 20% of patients with type 2 diabetes (T2DM), precedes the onset of diabetes diagnosis by more than 5 years on average, and may be responsible for some of the IR typifying T2DM and its CHD risk. In a 10-year prospective study of diabetic women with and without depression, we found that depression accelerated the development of (p <0.01) and increased the risk for CHD (OR 3.1, 95%CI 1.1-8.9) and was retained as an independent predictor of CHD in multivariate analysis. In the proposed study, we plan to recruit 160 untreated subjects with a provisional diagnosis of T2DM, 80 with and 80 without major depression (per DSM-IV) matched for gender and BMI. IR (from oral glucose tolerance tests), as well as measures of mood, glycemic control, HPA-axis activity, central adiposity, diet, and physical activity, will be determined at baseline for all subjects. Depressed subjects also will undergo frequently sampled intravenous glucose tolerance tests (FSIGTT) and more detailed analyses of activity, adiposity, and intramyocellular fat. Depressed subjects will be randomly assigned to 12 weeks of cognitive behavior therapy or usual depression care; nondepressed subjects will be observed for comparison. All baseline measures (including FSIGTT and the additional tests in the initially-depressed) will be repeated alter intervention/observation. Univariate tests, analyses of covariance, and least squares regression techniques will be used to assess the independent effects of depression and change in the severity of depression symptoms on IR and change in IR over time. The effect of depression treatment and of depression remission on IR (controlling for baseline differences) and potential mediators of a depression-IR relationship also will be determined in the initially depressed subjects. We hypothesize that depression is associated with increased IR in untreated T2DM and that IR improves with successful depression treatment. The findings from this study could identify a potentially modifiable factor for improving the course and outcome of those living with T2DM.