Background: We aimed to examine age-specific association and population attributable fraction (PAF) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes.

Methods: We used data from 360,202 people with type 2 diabetes who underwent metabolic assessment in 2000-20in Hong Kong. We included eight risk factors, including three baseline comorbidities: cardiovascular disease (CVD) , chronic kidney disease (CKD) and cancer; and five modifiable risk factors: suboptimal HbA1c (≥7.0%) , suboptimal blood pressure (SBP/DBP ≥140/90 mmHg) , suboptimal LDL-C (≥2.6 mmol/L) , smoking and suboptimal weight (BMI <24.0 or ≥28.0 kg/m2) . We used Cox regression models to compare the hazard ratios and PAFs of the risk factors for mortality risk across age groups (18-54, 55-64, 65-74, and ≥75 years) .

Findings: During a median 6.0 years of follow-up, 44,396 deaths were documented, with cancer, pneumonia, and CVD being the most common causes of death. When stratified by age group, the strength of the associations between most risk factors and all-cause and cause-specific mortality was strongest in the youngest age group and diminished with increasing age. The eight risk factors explained more population burden of mortality in the youngest (PAF: 51.6%) than the oldest (PAF: 35.3%) age group. In the youngest age group, the strongest population attributable risk factor for all-cause mortality was suboptimal control of blood pressure, followed by CKD. In the oldest age group, CKD and CVD were the largest contributors. CKD contributed most to mortality from CVD and pneumonia in the overall population, while cancer had the greatest PAF for cancer mortality across all age groups.

Conclusions: The contribution of each risk factor to mortality in people with type 2 diabetes showed a different pattern across age groups. Age-stratified prevention strategies targeting the major risk factors may have the potential to reduce premature mortality.


H.Wu: None. A.Luk: None. E.S.H.Lau: None. A.Yang: None. X.Zhang: None. B.Fan: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd.

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