School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
Pure North S'Energy Foundation, Calgary, Alberta, Canada.
Clin Nutr. 2019 Apr;38(2):820-828. doi: 10.1016/j.clnu.2018.02.025. Epub 2018 Mar 2.
BACKGROUND & AIMS: Previous studies assessing the prognosis of metabolically healthy obesity (MHO) have been limited by a lack of a harmonized definition of MHO phenotype. Furthermore, obesity is a risk factor for vitamin D deficiency and low vitamin D status has been associated with a higher risk of mortality; however, few studies have evaluated the joint association between vitamin D, metabolic health phenotype, and mortality risk. Using a harmonized definition, we investigated whether MHO is associated with subsequent all-cause and cardiometabolic mortality, and whether serum 25-hydroxyvitamin D [25(OH)D] modifies these associations.
This study included participants aged ≥20 years from the Third National Health and Nutrition Examination Survey (NHANES III). MHO phenotype was defined as a combination of obesity (≥30 kg/m) and zero component of metabolic syndrome. Multivariable Cox regression was used to assess the risk of mortality across metabolic phenotypes, and the joint association between metabolic phenotype and 25(OH)D. Fine and Gray regression was performed to account for competing risk events.
Among 11,333 participants, a total of 2980 deaths (937 cardiometabolic death outcomes) occurred during a median follow-up of 19.1 years. In the absence of any metabolic abnormality, obesity (MHO) was not associated with a higher risk of all-cause (hazard ratio [HR], 0.89 [95% CI, 0.52-1.51]) or cardiometabolic mortality (cause-specific HR, 1.21 [95% CI 0.33-4.46]). Similar results were obtained from competing risk analysis. No significant differences in average 25(OH)D levels were observed between MHO and non-MHO participants; however, there was a significant interaction between metabolic health phenotype and serum 25(OH)D in relation to cardiometabolic mortality such that levels of serum 25(OH)D < 50 nmol/L were associated with increased risk of cardiometabolic mortality, particularly in participants within the normal-weight and obese BMI ranges.
Our results support the hypothesis that MHO phenotype is a benign health condition. Vitamin D deficiency may exacerbate the risk of cardiometabolic death outcomes associated with metabolic dysfunction in normal weight and obese individuals. Further research is warranted to validate our findings.
先前评估代谢健康型肥胖（MHO）预后的研究受到 MHO 表型缺乏统一定义的限制。此外，肥胖是维生素 D 缺乏的一个危险因素，而维生素 D 状态较低与更高的死亡率风险相关；然而，很少有研究评估维生素 D、代谢健康表型和死亡率风险之间的联合关联。使用统一的定义，我们研究了 MHO 是否与随后的全因和心血管代谢性死亡相关，以及血清 25-羟维生素 D [25(OH)D] 是否会改变这些关联。
本研究纳入了来自第三次全国健康和营养调查（NHANES III）的年龄≥20 岁的参与者。MHO 表型定义为肥胖（≥30kg/m2）和代谢综合征零成分的组合。多变量 Cox 回归用于评估代谢表型的死亡风险，以及代谢表型和 25(OH)D 之间的联合关联。Fine 和 Gray 回归用于考虑竞争风险事件。
在 11333 名参与者中，中位随访 19.1 年后共发生 2980 例死亡（937 例心血管代谢性死亡）。在没有任何代谢异常的情况下，肥胖（MHO）与全因（危险比 [HR]，0.89 [95%CI，0.52-1.51]）或心血管代谢性死亡风险无关（特异性 HR，1.21 [95%CI 0.33-4.46]）。竞争风险分析也得到了类似的结果。MHO 组和非 MHO 组之间平均 25(OH)D 水平无显著差异；然而，代谢健康表型和血清 25(OH)D 之间存在显著的交互作用，与心血管代谢性死亡有关，即血清 25(OH)D<50nmol/L 与心血管代谢性死亡风险增加相关，尤其是在正常体重和肥胖 BMI 范围内的参与者。
我们的结果支持 MHO 表型是良性健康状况的假设。维生素 D 缺乏可能会加剧正常体重和肥胖个体中与代谢功能障碍相关的心血管代谢性死亡结局的风险。需要进一步的研究来验证我们的发现。
