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胰岛素抵抗（IR）的影响。IR是2型糖尿病（T2 DM）的特征，是糖尿病并发症，特别是冠心病（CHD）的预测因子。CHD，反过来，占糖尿病患者死亡人数的50%以上和住院人数的75%。正因为如此，潜在的可修改的因素，有助于IR正在寻找。有证据表明，IR与非糖尿病受试者的抑郁症有关，IR可能会随着抑郁症治疗而改善。抑郁症存在于约20%的2型糖尿病（T2 DM）患者中，平均比糖尿病诊断早5年以上，并且可能导致一些IR典型的T2 DM及其CHD风险。在一项对糖尿病妇女伴抑郁和不伴抑郁的10年前瞻性研究中，我们发现抑郁加速了冠心病的发展（p <0.01），增加了冠心病的风险（OR 3.1，95%CI 1.1-8.9），并在多因素分析中被保留为冠心病的独立预测因素。在拟定的研究中，我们计划招募160例未经治疗的T2 DM临时诊断受试者，其中80例伴重度抑郁症，80例不伴重度抑郁症（根据DSM-IV），性别和BMI匹配。将在基线时测定所有受试者的IR（来自口服葡萄糖耐量试验）以及情绪、血糖控制、HPA轴活动、中枢性肥胖、饮食和体力活动指标。抑郁的受试者还将接受频繁的静脉葡萄糖耐量试验（FSIGTT）采样和更详细的活动，肥胖和肌内脂肪分析。抑郁症受试者将被随机分配接受12周的认知行为治疗或常规抑郁症护理;将观察非抑郁症受试者进行比较。所有基线测量（包括FSIGTT和初始抑郁患者的额外测试）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评估抑郁和抑郁症状严重程度变化对IR的独立影响以及IR随时间的变化。还将在初始抑郁受试者中确定抑郁治疗和抑郁缓解对IR（控制基线差异）和抑郁-IR关系的潜在介质的影响。我们推测，抑郁症与未经治疗的T2 DM患者的IR增加相关，并且成功的抑郁症治疗可改善IR。这项研究的结果可以确定一个潜在的可改变的因素，以改善T2 DM患者的病程和结局。

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.