Journal of cachexia, sarcopenia and muscle · 2026
Underweight Versus Obesity and Gastrointestinal Cancer Mortality in Type 2 Diabetes: A Nationwide Cohort Study.
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Park Ji-Hong, Han Kyungdo, Choe Hun Jee, Park Se Eun, Lee Won-Young, Moon Sun-Joon, Rhee Eun-Jung
Аннотация
BACKGROUND: Underweight is a well-established risk factor for cancer mortality, yet its impact relative to obesity remains unclear in individuals with type 2 diabetes mellitus (T2DM), where current guidelines focus primarily on obesity management with limited guidance on underweight-related risks. We evaluated the association between body mass index (BMI) and gastrointestinal (GI) cancer mortality across the full BMI spectrum in individuals with T2DM.
METHODS: This nationwide population-based cohort study utilized the Korean National Health Insurance Service database. We included 2 507 976 adults with T2DM screened in 2015-2016 and followed through 2022, with a 1-year lag period applied to minimize reverse causality. BMI was categorized into eight groups: severe underweight (< 16.0 kg/m2), moderate underweight (16.0-16.9 kg/m2), mild underweight (17.0-18.4 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2), Class I obesity (25.0-29.9 kg/m2), Class II obesity (30.0-34.9 kg/m2) and Class III obesity (≥ 35.0 kg/m2). Multivariable-adjusted hazard ratios (aHRs) for GI cancer mortality were estimated using Cox proportional hazards models adjusting for clinical variables.
RESULTS: During 5.75-year mean follow-up, 10 978 GI cancer deaths occurred (975 oesophageal, 4391 gastric, 5317 colorectal and 295 other GI cancers including small intestine and anal cancer). A reverse J-shaped association was observed with mortality nadir at BMI 25.0-29.9 kg/m2, which served as the reference group. Underweight was consistently associated with increased mortality across all severity categories: mild underweight aHR 2.54 (95% CI 2.26-2.85), moderate underweight aHR 2.51 (95% CI 1.96-3.20) and severe underweight aHR 2.96 (95% CI 2.14-4.09), with the highest risk observed in severe underweight. Notably, all underweight categories were associated with substantially higher mortality risk than Class III obesity (aHR 1.35, 95% CI 1.05-1.73). Cancer-specific analyses revealed that underweight was associated with the highest mortality risk for oesophageal cancer (aHR 13.23 [95% CI 6.77-25.85] for severe underweight), followed by gastric and colorectal cancers, whereas obesity significantly increased mortality only for colorectal cancer (aHR 1.52 [95% CI 1.10-2.08] for Class III obesity). Underweight was not significantly associated with GI cancer incidence after adjustment, and associations remained largely robust in 2-, 3-, and 4-year lag and competing risk analyses, except for colorectal cancer.
CONCLUSIONS: In individuals with T2DM, underweight status is associated with substantially higher GI cancer mortality risk than obesity, with severe underweight showing nearly threefold higher risk compared to the reference group (BMI 25.0-29.9 kg/m2). These findings suggest that underweight, rather than obesity alone, warrants greater clinical attention as a determinant of GI cancer mortality in this population.
METHODS: This nationwide population-based cohort study utilized the Korean National Health Insurance Service database. We included 2 507 976 adults with T2DM screened in 2015-2016 and followed through 2022, with a 1-year lag period applied to minimize reverse causality. BMI was categorized into eight groups: severe underweight (< 16.0 kg/m2), moderate underweight (16.0-16.9 kg/m2), mild underweight (17.0-18.4 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2), Class I obesity (25.0-29.9 kg/m2), Class II obesity (30.0-34.9 kg/m2) and Class III obesity (≥ 35.0 kg/m2). Multivariable-adjusted hazard ratios (aHRs) for GI cancer mortality were estimated using Cox proportional hazards models adjusting for clinical variables.
RESULTS: During 5.75-year mean follow-up, 10 978 GI cancer deaths occurred (975 oesophageal, 4391 gastric, 5317 colorectal and 295 other GI cancers including small intestine and anal cancer). A reverse J-shaped association was observed with mortality nadir at BMI 25.0-29.9 kg/m2, which served as the reference group. Underweight was consistently associated with increased mortality across all severity categories: mild underweight aHR 2.54 (95% CI 2.26-2.85), moderate underweight aHR 2.51 (95% CI 1.96-3.20) and severe underweight aHR 2.96 (95% CI 2.14-4.09), with the highest risk observed in severe underweight. Notably, all underweight categories were associated with substantially higher mortality risk than Class III obesity (aHR 1.35, 95% CI 1.05-1.73). Cancer-specific analyses revealed that underweight was associated with the highest mortality risk for oesophageal cancer (aHR 13.23 [95% CI 6.77-25.85] for severe underweight), followed by gastric and colorectal cancers, whereas obesity significantly increased mortality only for colorectal cancer (aHR 1.52 [95% CI 1.10-2.08] for Class III obesity). Underweight was not significantly associated with GI cancer incidence after adjustment, and associations remained largely robust in 2-, 3-, and 4-year lag and competing risk analyses, except for colorectal cancer.
CONCLUSIONS: In individuals with T2DM, underweight status is associated with substantially higher GI cancer mortality risk than obesity, with severe underweight showing nearly threefold higher risk compared to the reference group (BMI 25.0-29.9 kg/m2). These findings suggest that underweight, rather than obesity alone, warrants greater clinical attention as a determinant of GI cancer mortality in this population.