第49届欧洲糖尿病研究协会年会(EASD2013)于9月23-27日在西班牙巴塞罗那召开。当地时间9月26日下午，“Obesity and diabetes”壁报专场上，英国赫尔约克大学的Pierluigi Costanzo博士及其同事的研究报道，在老年2型糖尿病患者中BMI较高的患者拥有比BMI较低患者更低的死亡率，而在年轻患者中却并未发现这样的“肥胖悖论”关系。
肥胖是胰岛素抵抗和2型糖尿病发生发展的关键因素，但是近来有证据表明肥胖的2型糖尿病患者可能具有较低的死亡率，在本次会议上所报道的研究采用的是一项前瞻性队列研究，较以前的报道有更强的统计学说服力和避免了一些混杂因素。该研究利用1995年至2011年间英国赫尔&东约克郡医院国家健康服务(HNS)基金所提供的数据，将受试者按照BMI和年龄的四分位进行分组，总共登记12 025例糖尿病患者(54%为男性，平均年龄60±15岁，1761例1型糖尿病，其余为2型糖尿病)，平均随访10年。
正如预期，急性冠脉综合征、心衰以及脑卒中的风险随着BMI的增加而逐步增加。与之矛盾的是，全因死亡率却与BMI呈反比关系，即最高BMI组的全因死亡率较正常体重组降低25%。当按照年龄分组发现，各年龄组的心血管事件与全体人群呈现相似的模式。然而，对于全因死亡率，在≥67岁老年2型糖尿病患者中BMI 26~29kg/m2、29~30 kg/m2及>30 kg/m2各组的死亡风险均较BMI<26 kg/m2的正常体重降低(分别降低18%、25%及18%)。然而在最年轻的患者中，死亡率与BMI关系呈现U形曲线。排除1型糖尿病或体重过轻的患者对结果并没有显着影响。
研究者认为，由肥胖代谢应激诱导产生的糖尿病可能与那些不存在肥胖应激而罹患的糖尿病是两个根本不同的问题，另外肥胖可能会对老年糖尿病患者提供一个保护性代谢储备。下一步研究者将细分各种不同的死亡原因来展现肥胖型糖尿病的不同结局。
| Obesity paradox in diabetes mellitus: mortality and cardiovascular morbidity over 15 years of 12,025 patients |
| Background and aims: Obesity is a key factor for the development of insulin resistance and Type-2 diabetes mellitus (T2DM). However, recent evidence suggests that obese patients with T2DM may have lower morbidity and mortality compared to patients of normal weight. These reports are limited by statistical power and confounders. In this analysis, the relationship between Body Mass Index (BMI), mortality and cardiovascular (CV) morbidity is investigated in a prospective cohort, with a long-term follow up and a large number of events. Materials and methods: Between 1995 and 2011, the following data were collected in patients attending the diabetes service at Hull & East Yorkshire Hospitals NHS Trust; age, sex, height and weight (and therefore body mass index), blood pressure, biochemical and information on co-morbidities (cardiovascular (CV) disease, chronic renal failure (CRF), chronic obstructive lung disease (CPD) and cancer). Total mortality and hospital admissions for acute coronary syndrome (ACS), cerebrovascular accidents (CVA) and heart failure (HF) were gathered. Subjects were divided according to BMI quartiles and in age tertiles. ANOVA and Chi square were used to compare covariates among the BMI groups. Cox-Regression analysis was used to assess the prognostic impact of BMI and confounders on the above-defined events. Sensitivity analysis was performed accounting for T1DM and BMI<18.5. Results: In total, 12025 patients with diabetes (54% men, mean age 60±15 years, 1761 (15%) T1DM) were enrolled and followed for a mean of 10±4 years during which ACS occurred in 1098 (9%), a CVA in 893 (7%) and a HF hospitalization occurred in 731 (6%) subjects and 4125 (34%) died. The risk of ACS was lowest in the normal BMI group and increased progressively with increasing quartiles of BMI, being greatest in obese subjects (BMI >30 HR 1.49; 95%CI 1.24-1.79; p30 HR 1.53 95% CI 1.53; 95% CI 1.24-1.88; p30) (HR 0.75 95% CI 0.69-0.82). Adjusting the analysis for comorbidity did not significantly affect the results but adjusting for age did. Therefore, we divided the results according to age tertiles. CV events showed a similar pattern in each age tertile as in the overall population. However, for all-cause mortality higher BMI was associated with a survival benefit in the eldest age tertile, whilst in the youngest age tertile, the relationship assumed a U shape, with the highest and lowest quartiles being associated with and increased risk of death. Sensitivity analysis was applied by excluding T1DM or underweight patients. However, this did not significantly affect the results. Conclusion: In this study, in patients with T2DM, although being overweight was associated with an increased risk of CV events, higher BMIs were associated with a survival benefit, especially amongst older patients. DM induced by the metabolic stress of obesity may be a fundamentally different problem from DM that develops in the absence of the stress of obesity. Alternatively, obesity may provide a protective metabolic reserve in older diabetic patients. |
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