Department of Medicine, University of Alberta, Edmonton, AB, Canada.
School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
Int J Obes (Lond). 2022 Dec;46(12):2107-2113. doi: 10.1038/s41366-022-01211-2. Epub 2022 Aug 27.
BACKGROUND/OBJECTIVES: Obesity is often considered to increase the risk for premature mortality. Higher fasting insulin and c-reactive protein are associated with higher body mass index (BMI) and all-cause mortality, so may confound the association between obesity and mortality. Our objective was to determine the independent associations between BMI, fasting insulin, c-reactive protein, and all-cause mortality in a general population sample.
This prospective cohort study included non-institutionalized US adults (≥20 years) from the National Health and Nutrition Examination Surveys 1999-2000 to 2013-2014. The main exposures of interest were BMI, fasting insulin, c-reactive protein. Mortality data were obtained through linking participants to the National Death Index (ending December 31, 2015).
There were 12,563 participants with a median age of 45 years (range 20-85) and 47.9% were male. The median BMI was 27 kg/m (IQR 24-32), median fasting insulin was 54 pmol/L (IQR 35-87), and median c-reactive protein was 1.9 mg/L (IQR 0.8-4.4). In a Cox model adjusted for age, biological sex, cigarette smoking, and ten chronic conditions, higher BMI parameterized with quadratic and linear terms was not associated with mortality. When fasting insulin and the natural logarithm of c-reactive protein were included in the model, an inverse association between BMI and mortality was present (compared to the referent category of 5th percentile: 1st percentile, HR 1.10, 95% CI 1.06-1.13; 99th percentile, HR 0.48, 95% CI 0.34-0.69). In contrast, higher levels of fasting insulin and c-reactive protein were associated with an increased risk of mortality (for fasting insulin: 1st percentile, HR 0.98, 95% CI 0.97-0.99; 99th percentile, HR 1.83, 95% CI 1.48-2.26; for c-reactive protein, 1st percentile, HR 0.87, 95% CI 0.84-0.90; 99th percentile, HR 2.77, 95% CI 2.12-3.62).
Higher fasting insulin and higher c-reactive protein confound the association between BMI and the risk of all-cause mortality. The increase in mortality that has been attributed to higher BMI is more likely due to hyperinsulinemia and inflammation rather than obesity.
背景/目的：肥胖通常被认为会增加过早死亡的风险。较高的空腹胰岛素和 C 反应蛋白与较高的体重指数（BMI）和全因死亡率相关，因此可能会混淆肥胖与死亡率之间的关联。我们的目的是确定在一般人群样本中 BMI、空腹胰岛素、C 反应蛋白与全因死亡率之间的独立关联。
本前瞻性队列研究包括来自 1999-2000 年至 2013-2014 年全国健康与营养调查的非机构化美国成年人（≥20 岁）。主要感兴趣的暴露因素是 BMI、空腹胰岛素、C 反应蛋白。通过将参与者与国家死亡指数（截至 2015 年 12 月 31 日）联系起来获得死亡率数据。
共有 12563 名参与者，中位年龄为 45 岁（范围 20-85 岁），47.9%为男性。中位 BMI 为 27kg/m（IQR 24-32），中位空腹胰岛素为 54pmol/L（IQR 35-87），中位 C 反应蛋白为 1.9mg/L（IQR 0.8-4.4）。在调整年龄、生物性别、吸烟和十种慢性疾病的 Cox 模型中，用二次和线性项参数化的较高 BMI 与死亡率无关。当将空腹胰岛素和 C 反应蛋白的自然对数纳入模型时，BMI 与死亡率之间存在反比关联（与第 5 百分位的参考类别相比：第 1 百分位，HR 1.10，95%CI 1.06-1.13；第 99 百分位，HR 0.48，95%CI 0.34-0.69）。相比之下，较高的空腹胰岛素和 C 反应蛋白水平与死亡率风险增加相关（对于空腹胰岛素：第 1 百分位，HR 0.98，95%CI 0.97-0.99；第 99 百分位，HR 1.83，95%CI 1.48-2.26；对于 C 反应蛋白，第 1 百分位，HR 0.87，95%CI 0.84-0.90；第 99 百分位，HR 2.77，95%CI 2.12-3.62）。
较高的空腹胰岛素和较高的 C 反应蛋白混淆了 BMI 与全因死亡率风险之间的关联。归因于较高 BMI 的死亡率增加更可能是由于高胰岛素血症和炎症而不是肥胖。
