“肥胖悖论”被推翻

《新英格兰医学杂志》(New England Journal of Medicine) 1月15日在线发表的一份研究报告显示，在确诊时超重或肥胖的糖尿病成年患者的死亡率，并不是像“肥胖悖论”支持者所说的那样低于体重正常患者。



美国哈佛大学公共卫生学院营养学系的Deirdre K. Tobias博士及其同事对护士健康研究(NHS)和医务人员随访研究(HPFS)中在基线(分别为1976年和1986年)至2010年1月之间患上糖尿病的11,427例受试者的数据进行了分析。在NHS研究的女性受试者中，确诊时的平均年龄为62岁(范围35~86岁)；在HPFS研究的男性受试者中确诊时的平均年龄为64岁(41~91岁)。

该研究的主要结局指标是2012年1月之前任何原因导致的死亡。在平均15.8年的随访期内，共出现了3,083例死亡。

从整个试验人群来看，体重指数(BMI)与全因死亡率之间呈J型相关。与糖尿病确诊时BMI正常(22.5~24.9 kg/m²)的受试者相比，BMI过低和BMI过高的受试者死亡率均显著增加。BMI最低组(18.5~22.4 kg/m²)的危险比为1.29，BMI最高组(35.0 kg/m²或以上)的危险比为1.33。

Tobias博士及其同事指出，吸烟状态对肥胖与死亡率之间的相关性有显著影响。在不吸烟者中，这一相关性呈现出强线性关系，BMI升高与死亡率升高直接相关。而在吸烟者中，这一相关性没有呈现出线性关系，提示在这类分析中充分控制吸烟状态非常必要(N. Engl. J. Med. 2014 Jan. 15 [doi:10.1056/NEJMoa1304501])。

敏感性分析的结果也支持了主体研究的结果，其中一项分析采用了不同的、更传统的BMI分类(正常体重、超重和肥胖)临界点。

如果根据死亡原因进行数据分析，在不吸烟者中BMI与心血管死亡率之间呈现出强线性关系，在吸烟者中也呈现出线性关系但强度稍弱；BMI与癌症死亡之间的相关性也与之类似。BMI与呼吸系统疾病、自杀和意外死亡之间则呈J型相关。

研究者总结道，针对这2项大规模长期前瞻性队列研究的数据分析表明，2型糖尿病确诊时的BMI与全因死亡率之间明显呈J型相关。脂肪过多并不能降低死亡率。他们指出，报告称肥胖能降低死亡率的既往研究样本量要小得多，而且没有充分控制受试者的吸烟状态。“在体重和死亡率分析中吸烟是一个很重要的因素，因其与体重下降相关，但也与死亡风险增加相关。”

Tobias博士及其同事说，从我们的研究结果以及肥胖与其他重大公共卫生问题(例如心血管疾病和癌症)相关的已知结果来看，都明确提示“无论吸烟状态如何，维持健康的体重都是糖尿病管理的基础。”

这项研究的局限性在于NHS和HPFS队列的同质性相对较高，几乎完全由接受过良好教育的白人组成，所以研究结果可能不适用于其他种族和其他经济状况的人群。

该研究由美国国立卫生研究院和美国糖尿病学会资助。Tobias博士声明无相关利益冲突；有一名作者声明与默克、诺和诺德公司之间存在利益关系。

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By: MARY ANN MOON, Cardiology News Digital Network

Mortality is not lower among adults with diabetes who were overweight or obese at diagnosis than among those who were of normal weight, as has been suggested by proponents of the "obesity paradox," according to a report published online Jan. 15 in the New England Journal of Medicine.

An analysis of data from two large, long-term, prospective cohort studies showed a clear J-shaped association between body mass index (BMI) at diagnosis of type 2 diabetes and all-cause mortality. Excess adiposity did not confer any mortality benefit, said Deirdre K. Tobias, Sc.D., of the department of nutrition, Harvard School of Public Health, Boston, and her associates.

Previous studies that reported such a benefit had much smaller sample sizes and did not adequately control for smoking status. "Smoking is a concern in analyses of body weight and mortality because it is associated with decreased body weight but an increased risk of death," they noted.
 
Their findings, added to the known association between obesity and other critical public health concerns such as cardiovascular disease and cancer, clearly show that "maintenance of a healthy body weight should remain the cornerstone of diabetes management, irrespective of smoking status," Dr. Tobias and her colleagues said.

For their study, the investigators analyzed data on 11,427 participants in the Nurses’ Health Study and the Health Professionals Follow-Up Study who developed diabetes between baseline (1976 and 1986, respectively) and January 2010. The mean age at diagnosis was 62 years (range, 35-86 years) among the women in the NHS and 64 years (range, 41-91 years) among the men in the HPFS.

The primary outcome measure of the study was death from any cause through January 2012. There were 3,083 such deaths during a mean follow-up of 15.8 years.

For the study population as a whole, there was a J-shaped association between BMI and all-cause mortality. Compared with participants who had a normal BMI of 22.5-24.9 kg/m2 at the time of diabetes diagnosis, those with lower BMIs and those with higher BMIs both had significantly elevated mortality. The hazard ratio was 1.29 for subjects in the lowest BMI category (18.5-22.4 kg/m2) and 1.33 for those in the highest BMI category (35.0 kg/m2 or higher).

Smoking status exerted a significant effect on the association between obesity and mortality. Among nonsmokers, this association showed strong linearity, with a direct correlation between increasing BMI and increasing mortality. This association was not linear among smokers, confirming that adequate control for smoking status is essential in such analyses, Dr. Tobias and her associates said (N. Engl. J. Med. 2014 Jan. 15 [doi:10.1056/NEJMoa1304501]).

The results of sensitivity analyses supported those of the main study, including one analysis that used different, more traditional cutoff points for the BMI categories of normal weight, overweight, and obesity.

When the data were analyzed by cause of death, the association between BMI and cardiovascular mortality was strongly linear among nonsmokers and less strong but still linear among smokers, as was the association between BMI and cancer death. The association between BMI and death from respiratory disease, suicide, and accidents was J-shaped.

This study was limited in that the NHS and HPFS cohorts were relatively homogenous, comprising well-educated white participants almost entirely, so the findings may not apply to other racial/ethnic and economic groups.

This study was supported by the National Institutes of Health and the American Diabetes Association. Dr. Tobias reported no potential conflicts of interest; one of her associates reported ties to Merck and Novo Nordisk.