DEPRESSION AND INSULIN RESISTANCE IN TYPE 2 DIABETES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的总体目的是确定抑郁对糖尿病患者胰岛素抵抗(IR)的影响。IR是2型糖尿病(T2 DM)的特征，是糖尿病并发症的预测指标，尤其是冠心病(CHD)。反过来，糖尿病患者中50%以上的死亡和75%的住院是由冠心病造成的。正因为如此，人们正在寻找影响IR的潜在可修改因素。有证据表明，在非糖尿病受试者中，胰岛素抵抗与抑郁有关，在这些受试者中，随着抑郁的治疗，胰岛素抵抗可能会得到改善。大约20%的2型糖尿病(T2 DM)患者存在抑郁，平均比糖尿病诊断早5年以上，可能是T2 DM及其CHD风险的部分IR的原因。在一项对患有和不患有抑郁症的糖尿病女性进行的为期10年的前瞻性研究中，我们发现抑郁加速了冠心病的发展(P&lt；0.01)，增加了患CHD的风险(OR 3.1，95%CI 1.1-8.9)，并在多因素分析中被保留为CHD的独立预测因素。在这项拟议的研究中，我们计划招募160名初步诊断为T2 DM的未经治疗的受试者，其中80人患有严重抑郁症，80人没有严重抑郁症(根据DSM-IV)，性别和BMI匹配。所有受试者的IR(口服葡萄糖耐量试验)以及情绪、血糖控制、HPA轴活动、中心性肥胖、饮食和体力活动的测量将在基线上确定。抑郁症受试者还将接受频繁采样的静脉葡萄糖耐量测试(FSIGTT)，并对活动、肥胖和心肌细胞内脂肪进行更详细的分析。抑郁症受试者将被随机分配到12周的认知行为治疗或通常的抑郁症护理中；非抑郁症受试者将被观察以进行比较。所有基线测量(包括FSIGTT和最初抑郁的附加测试)将在干预/观察后重复。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和抑郁症状严重程度的变化对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(控制基线差异)的影响以及抑郁-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治愈的T2 DM患者的胰岛素抵抗增加有关，并且成功的抑郁治疗可以改善胰岛素抵抗。这项研究的结果可能确定一个潜在的可修改因素，以改善T2 DM患者的病程和结局。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall purpose of this study is to determine the impact of depression on insulin resistance (IR) in diabetes. IR characterized 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 that 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 analysis 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 test the initially-depressed) will be repeated after intervention/observation. Univariate tests, analyses of covariance, and least squares regression techniques will be used to assess the independent effects of depression adn 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 untreted 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.