Normal-weight obesity and adverse health outcomes in women: a systematic review and meta-analysis of observational studies

Abstract

Background Normal body mass index (BMI) can coexist with excess adiposity, a phenotype termed normal-weight obesity (NWO). Female-specific evidence remains fragmented; we synthesized associations between NWO and female adverse health outcomes. Methods This was a systematic review and meta-analysis of observational studies. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to May 28, 2026, for eligible female-specific studies comparing NWO with normal-weight lean/non-obese controls. Odds ratios (OR) and other effect ratios were synthesized separately; continuous outcomes were pooled as mean differences (MDs). Outcomes reported in ≥3 studies were pooled with random-effects models using Paule-Mandel between-study variance and Hartung-Knapp confidence intervals (CIs) with an ad hoc correction. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Exposures tool and the Joanna Briggs Institute cross-sectional checklist. Results Twenty studies (200,461 women with normal BMI) were included; 17 were cross-sectional. NWO was associated with metabolic syndrome (number of studies [k] = 4; OR 2.02, 95% CI 1.60 to 2.55), abdominal obesity (k = 3; OR 3.62, 95% CI 1.22 to 10.70), higher triglycerides (k = 7; MD 10.99 mg/dL, 95% CI 2.03 to 19.94), total cholesterol (k = 6; MD 6.86 mg/dL, 95% CI 2.60 to 11.11), and total cholesterol-to-high-density lipoprotein cholesterol (HDL-C) ratio (k = 3; MD 0.76, 95% CI 0.11 to 1.42). Associations with fasting glucose, diabetes, low-density lipoprotein cholesterol (LDL-C), HDL-C, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure were uncertain. Hard clinical outcomes were sparse, and two of three longitudinal studies had high risk of bias. Conclusion Among women with normal BMI, excess adiposity is associated with a less favorable cardiometabolic phenotype, most consistently metabolic syndrome and selected lipid measures. Evidence for diabetes, blood pressure, cardiovascular events, mortality, cancer, and reproductive or functional outcomes remains limited. Standardized NWO definitions and prospective female-specific studies are needed. (PROSPERO: CRD420261408853)