All-cause mortality risk of metabolically healthy obese individuals in NHANES III

Abstract

Mortality risk across metabolic health-by-BMI categories in NHANES-III was examined. Metabolic health was defined as: (1) homeostasis model assessment-insulin resistance (HOMA-IR) <2.5; (2) ≤2 Adult Treatment Panel (ATP) III metabolic syndrome criteria; (3) combined definition using ≤1 of the following: HOMA-IR ≥1.95 (or diabetes medications), triglycerides ≥1.7 mmol/L, HDL-C <1.04 mmol/L (males) or <1.30 mmol/L (females), LDL-C ≥2.6 mmol/L, and total cholesterol ≥5.2 mmol/L (or cholesterol-lowering medications). Hazard ratios (HR) for all-cause mortality were estimated with Cox regression models. Nonpregnant women and men were included (n = 4373, mean ± SD, age 37.1 ± 10.9 years, BMI 27.3 ± 5.8 kg/m², 49.4% female). Only 40 of 1160 obese individuals were identified as MHO by all definitions. MHO groups had superior levels of clinical risk factors compared to unhealthy individuals but inferior levels compared to healthy lean groups. There was increased risk of all-cause mortality in metabolically unhealthy obese participants regardless of definition (HOMA-IR HR 2.07 (CI 1.3-3.4), P < 0.01; ATP-III HR 1.98 (CI 1.4-2.9), P < 0.001; combined definition HR 2.19 (CI 1.3-3.8), P < 0.01). MHO participants were not significantly different from healthy lean individuals by any definition. While MHO individuals are not at significantly increased risk of all-cause mortality, their clinical risk profile is worse than that of metabolically healthy lean individuals.

Figure 1

Overlap and uniquely classified obese individuals by three different metabolic health definitions. For the description of definitions of metabolic health, see Table 1. HOMA-IR, homeostasis model assessment-insulin resistance; ATP-III, Adult Treatment Panel III; MHO, metabolically healthy obese; MUO, metabolically unhealthy obese. Obese participants, n = 1160.

Figure 2

Risk of Mortality Associated with Metabolic Health and Body Mass Index (BMI) by Three Definitions. Error bars represent 95% confidence intervals of hazard ratios. ***Significant difference from reference group (lean healthy) at P ≤ 0.001; **significant difference from reference group (lean healthy) at P ≤ 0.01; data analyzed using Cox Survival Analysis, adjusting for sex, age, income, education, race/ethnicity, smoking status, alcohol consumption, marital status, leisure time physical activity, and menopausal status. For description of definitions of metabolic health, see Table 1. HOMA-IR, homeostasis model assessment-insulin resistance; ATP-III, Adult Treatment Panel III.