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Different Metabolic Phenotypes of Obesity and 2 Decades Risk of Cardio–Renal–Metabolic Multimorbidity: Tehran Lipid and Glucose Study

D. Molavizadeh,Soroush Masrouri,F. Esmaeili,F. Azizi,F. Hadaegh

Published 2025 in Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease

ABSTRACT

Background Less is known regarding the association between metabolic phenotypes of general and abdominal obesity and incident cardio–renal–metabolic (CRM) multimorbidity, defined as coexistence of at least 2 of the following: diabetes, chronic kidney disease, and cardiovascular diseases (hypertension or stroke or coronary heart disease). Methods Among 6343 participants (3555 women), with a mean age of 37.06 years, metabolically healthy status was defined as absence of any metabolic syndrome components. Participants were classified as metabolically healthy/unhealthy normal weight, overweight, and obese on the basis of body mass index; and metabolically healthy/unhealthy nonabdominal obese and abdominal obese according to waist circumference. Multivariable Cox hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, adjusted for age, sex, smoking status, education level, marital status, pulse rate, estimated glomerular filtration rate, family history of premature cardiovascular disease, and family history of diabetes. Results During a median follow‐up of 14.3 years, CRM multimorbidity occurred in 4.8, 13.4, 15.0, 10.8, 17.4, and 29.9% of participants with metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese phenotypes, respectively. In multivariable analyses, compared with the metabolically healthy normal weight, participants with metabolically healthy overweight (HR, 2.08 [95% CI, 1.35–3.20]), metabolically healthy obese (HR, 2.04 [95% CI, 1.11–3.75]), metabolically unhealthy normal weight (HR, 2.29 [95% CI, 1.61–3.27]), metabolically unhealthy overweight (HR, 2.83 [95% CI, 2.01–3.99]), and metabolically unhealthy obese (HR, 5.16 [95% CI, 3.64–7.32]) phenotypes had higher risk of developing CRM multimorbidity. Compared with the metabolically healthy abdominal obese phenotype, participants with metabolically healthy nonabdominal obese (HR, 1.77 [95% CI, 1.19–2.64)], metabolically unhealthy nonabdominal obese (HR, 1.95 [95% CI, 1.48–2.57]), and metabolically unhealthy abdominal obese (HR, 3.26 [95% CI, 2.49–4.28]) exhibited elevated risk. Generally, we found no statistically significant effect modification by sex and age; however, these associations were more pronounced among women and younger individuals. Conclusions Our results indicate that there is no benign phenotype of obesity beyond metabolically healthy normal weight regarding the incidence of CRM multimorbidity.

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