Central Adiposity Kills More Normoglycemic Adults Than Dysglycemia Kills Diabetics

Background. Cardiometabolic screening is organized around glycemic markers, which define who is flagged for risk and who is reassured. Central adiposity, a marker of visceral fat and its inflammatory consequences, is measured easily with a tape measure but is not part of routine glucose-based screening. We asked how much excess mortality central adiposity carries in adults with normal blood glucose, and how that burden compares with the burden carried by dysglycemia. Methods. We studied 426,275 participants of the UK Biobank with normal glycated hemoglobin (HbA1c < 42 mmol/mol) and a valid waist measurement, followed for all-cause mortality to July 8, 2024. Participants were classified by sex-specific World Health Organization waist thresholds (>102 cm in men, >88 cm in women) and into five waist strata per sex. We estimated stratum-specific mortality, the hazard ratio per SD of waist circumference (Cox regression, adjusted for age at recruitment), and excess deaths relative to the sex- specific lowest-waist stratum. For comparison, we computed excess deaths among the 21,287 participants with prediabetes and the 17,601 with diabetes, relative to the normoglycemic rate. Findings. Of 426,275 normoglycemic adults, 119,551 (28.0%) exceeded the sex-specific waist threshold. Mortality rose monotonically across waist strata, from 10.4% to 20.7% in men and from 6.1% to 12.3% in women, while HbA1c, glucose, LDL cholesterol, and the neutrophil-to-lymphocyte ratio were flat across strata and only high-sensitivity C-reactive protein (hsCRP) rose. Each SD of waist circumference carried a hazard ratio of 1.16 (95% CI 1.15-1.18) in men and 1.19 (1.17-1.20) in women; the association strengthened after adjustment for body-mass index (1.27 and 1.25). Central adiposity accounted for 4,411 excess deaths among normoglycemic adults, exceeding the 2,996 excess deaths attributable to diabetes (a 1.5-fold difference) and approaching the 5,270 excess deaths of the entire dysglycemic spectrum. The gradient persisted after excluding participants with prevalent major disease. Interpretation. A tape measure identifies a large mortality burden in adults whom glucose-based screening classifies as healthy. Waist circumference should be measured, and acted on, in normoglycemic adults.