Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study

OBJECTIVE

Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.

RESEARCH DESIGN AND METHODS

Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m²; obese: ≥30 kg/m²) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).

RESULTS

Obese insulin-sensitive subjects represented 11% (95% CI 8.1–14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08–1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46–2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.

CONCLUSIONS

In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.Metabolically healthy obese (MHO) individuals are considered as a subset of obese subjects without metabolic abnormalities (such as insulin resistance, proatherogenic lipoprotein profile, proinflammatory state, or hypertension) and a model for better understanding the pathogenesis of insulin resistance (1–3). The prevalence of the MHO phenotype in the general population, the reasons for not developing metabolic alterations, and the less aggressive therapeutic approach with respect to obese individuals with metabolic abnormalities are currently debated (4,5). In the Framingham Offspring Study, Meigs et al. (6) found that MHO individuals do not have increased risk of incident diabetes and cardiovascular disease (CVD). Conversely, in the Third National Health and Nutrition Examination Survey (NHANES III), Kuk et al. (7) reported increased all-cause mortality associated with the MHO phenotype. Finally, in a Scandinavian study (8), middle-aged overweight/obese subjects without metabolic syndrome also had an increased risk of CVD when compared with normal-weight individuals without metabolic syndrome. The present study shows the prevalence of the MHO phenotype, its metabolic features, and 15-year all-cause, CVD, and cancer mortality rates in the Caucasian population of the Cremona Study (9,10).