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作者：Nancy Fowler Larson  
出處：WebMD醫學新聞

　　December 8, 2009 — 根據一篇於11月23日線上發表在糖尿病照護（Diabetes Care）期刊的研究，罹患第二型糖尿病以及重鬱症的成人，不論他們自我照顧的習慣或疾病控制的程度，發生改變生活之微血管或大血管併發症的風險較高。
　　
　　華盛頓西雅圖團體健康研究中心的Elizabeth Lin醫師等人寫到，一項結合27項研究的綜合分析發現，憂鬱症與多項糖尿病併發症（包括神經病變、視網膜病變、腎臟病變、大血管併發症與性功能障礙）的關聯性。本研究結論的限制來自於個別小型的研究，以及同時收納第一型與第二型糖尿病的樣本數目太少。這些研究最大的限制在於橫斷面的設計，橫斷面設計的研究難以區分病患的憂鬱是否因為失能或擔心糖尿病引起的併發症，或是在發生嚴重及臨床上有意義的併發症前就已經憂鬱。
　　
　　研究者們收集縱向世代4,623位第二型糖尿病成人病患。在2000年到2002年之間，受試者以病患健康問卷第9版自評任何輕微或嚴重憂鬱的症狀，診斷標準根據美國精神疾病診斷與統計手冊第四版修訂版。本研究也記錄受試者先前的糖尿病併發症。
　　
　　5年過後，在2005到2007年間，研究員收集原本3,922位（85.1%）病患，不論他們是否有糖尿病後期併發症，例如小血管併發症（包括眼盲、截肢、末期腎臟疾病與腎臟衰竭死亡），還是大血管併發症（心肌梗塞、中風、心血管手術與死亡）。這些資訊是透過病歷取得；國際疾病分類第九版；診斷與術式編碼；以及死亡證明。
　　
　　研究者們發現，報告有重鬱症的，相較於那些僅有輕微或沒有憂鬱症的受試者，發生後期併發症的風險增加36%，而發生顯著大血管併發症的風險增加25%。校正血糖控制的差異（例如治療遵從性與飲食）、自我照護習慣（例如運動、吸菸以及HbA1c值，一種糖尿病控制的好不好的指標）降低了憂鬱與大血管併發症之間的關係，但是並未改變憂鬱症與小血管併發症之間的關係。
　　
　　作者們寫到，在校正過去併發症、流行病學、臨床與糖尿病自我照顧變項後，重鬱症與不良小血管併發症[危險比值（HR）為1.36；95%信賴區間（CI）為1.05~1.75]與不良大血管併發症[HR為1.24；95% CI為1.0~1.54]。
　　
　　試驗限制包括並未收集在他們參與研究之前是否有憂鬱症狀的資料，且這發生在單一地理區域。
　　
　　研究者們假設，生物與行為因子可能影響憂鬱與糖尿病併發症之間的關係。憂鬱症與持續存在的壓力誘發下視丘-腦垂體-腎上腺軸，喚起了交感神經系統，提升發炎與血小板凝集，且負向地影響病患的血糖控制與自我照護，這也會增加併發症風險。根據作者們表示，這項研究與未來相關研究們的重要性將會不斷增加。
　　
　　作者們寫到，這些發現的臨床與公共健康重要性隨著第二型糖尿病的發生率急速上升。需要未來的研究來釐清這些關係的機轉以及檢驗降低同時有憂鬱症病患們的糖尿病併發症風險。
　　
　　國家衛生研究院贊助這項研究。所有研究程序都由健康集團的倫理委員會核准，這是華盛頓大學的一項預付健康綜合計畫。研究作者們表示已無相關資金上的往來。


Patients With Type 2 Diabetes and Major Depression at Greater Risk for Significant Cardiovascular Complications

By Nancy Fowler Larson
Medscape Medical News

December 8, 2009 — Adults with type 2 diabetes who have major depression face a greater risk for life-altering microvascular and macrovascular complications regardless of their self-care habits or the degree to which their disease is controlled, according to a study published online November 23 in Diabetes Care.

"A meta-analysis of 27 studies found a significant association between depression and a wide variety of diabetes complications (neuropathy, retinopathy, nephropathy, macrovascular complications, and sexual dysfunction). The conclusions that can be drawn from individual studies are limited given their relatively small samples that included patients with both type 1 and type 2 diabetes," write Elizabeth H.B. Lin, MD, MPH, from the Group Health Research Institute in Seattle, Washington, and other study authors. "The greatest limitation of these studies was their cross-sectional design. Cross-sectional studies can not clarify whether patients are depressed because they have disabling and worrisome diabetic complications or whether having depression could actually precede occurrence of severe and clinically significant diabetic complications."

Researchers collected a longitudinal cohort of 4623 adults with type 2 diabetes. Between 2000 and 2002, participants self-assessed any minor and major depression symptoms using the Patient Health Questionnaire 9, based on criteria from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. The study also noted subjects' prior complications of diabetes.

Five years later, between 2005 and 2007, researchers collected data on 3922 of the original patients (85.1%) regarding the development of advanced complications of diabetes, both microvascular (eg, blindness, end-stage renal disease, amputations, and renal failure deaths) and macrovascular (eg, myocardial infarction, stroke, cardiovascular procedures, and deaths). This information was obtained through medical records; International Classification of Diseases, Ninth Revision; diagnostic and procedural codes; and death certificates.

Researchers found that participants who reported major depression had a 36% increased risk of developing advanced microvascular complications and a 25% greater risk of developing significant macrovascular issues compared with those with mild or no depression. Adjusting for disparities in glycemic control (eg, treatment adherence and diet) and self-care habits (eg, physical activity, smoking, and HbA1c results — a measure of how well diabetes is being controlled) lowered the association between depression and macrovascular issues, but not between depression and microvascular complications.

"After adjustment for prior complications, demographic, clinical and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes [hazard ratio (HR) 1.36, 95% confidence interval (CI): 1.05 to 1.75], and adverse macrovascular outcomes [HR: 1.24, 95% CI: 1.0 to 1.54]," the authors write.

Limitations include the fact that no depression data were collected on individuals before their participation in the study and that it took place in a single geographic area.

Researchers posit that both biologic and behavioral factors may affect the association between depression and diabetes complications. Depression and ongoing stress can trigger the hypothalamic-pituitary-adrenal axis, arouse the sympathetic nervous system, elevate inflammatory and platelet aggregation, and negatively affect the patient's glycemic control and self-care, which can also increase the risk for complications. According to the authors, the importance of this and related future studies will continue to escalate.

"Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars," the authors write. "Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with co-morbid depression."

The National Institutes of Health supported this study. All study procedures were approved by institutional review boards at Group Health, a mixed-model prepaid health plan, and the University of Washington. The study authors have disclosed no relevant financial relationships.

Diabetes Care. Published online November 23, 2009.