Adults with Type 1 Diabetes Have Higher All-Cause Mortality Risk

Patients with adult-onset type 1 diabetes (T1D) have a higher risk of all-cause mortality, mortality from both acute and chronic diseases, and cardiovascular disease risk (CVD) compared to diabetes-free individuals.1

Although T1D is well known to increase mortality, the majority of data regarding treatment recommendations are extrapolated from trials investigating type 2 diabetes (T2D). Little research exists as to whether this is appropriate for T1D, and clinicians have begun to find the control of CVD risk in T1D is suboptimal.2

“We aimed to study the prognosis of adult-onset T1D, especially for those diagnosed at age ≥40 years, and elucidate risk factors contributing to poor prognosis,” Yuxia Wei, MSc, Institute of Environmental Medicine, Karolinska Institute, and colleagues wrote. “To this aim, we investigated all-cause mortality, cause-specific mortality, and incident CVD in adult-onset T1D, T2D and population controls.”1

Wei and colleagues examined patients from the National Diabetes Register (NDR), a database specific to Sweden, collecting data on those diagnosed with adult onset (≥18 years) T1D and/or T2D between 2001 and 2020. Date of diagnosis was defined as the first record of diabetes in NDR or the National Patient Register (NPR), or first record of glucose-lowering drugs in the National Prescribed Drug Register (NPDR).1

Patients were then categorized by age at diagnosis into 3 categories – 18-29, 30-39, and ≥40 years. Within each subgroup, patients were matched by age, sex, and county to 50 population controls without diabetes. Patients with prevalent CVD at cohort entry were excluded from the analysis of CVD incidence.1

Mortality outcomes for the study included all-cause mortality, cardiovascular death, non-cardiovascular death, death from cancer, infection, and diabetic coma or ketoacidosis. Major adverse cardiovascular events (MACE) were used as CVD outcomes, defined as cardiovascular death or the first inpatient record of nonfatal myocardial infarction or nonfatal stroke in NPR.1

The team ultimately included 10,184 patients with T1D, 375,523 with T2D, and 509,172 controls. Among the T1D cohort, 40.4% (n = 4113) were diagnosed at age 18-29 years, 21.3% (n = 2172) at age 30-39, and 38.3% (n = 3899) at age ≥40 years (40-102). People aged ≥40 years were more often female, had high blood pressure, triglycerides, and HbA1c, had more severe insulin resistance, and were smokers. They also had a higher body mass index (BMI).1

During a median 10.2-year follow-up, 816 deaths and 361 MACE events occurred in the T1D cohort, versus 26,888 deaths and 14,034 MACEs in controls and 90,921 deaths and 48,374 MACEs in patients with T2D. All-cause mortality (hazard ratio [HR], 1.71; 95% CI, 1.6-1.84) and most cause-specific mortalities, including cardiovascular death, was higher in the T1D cohort than controls. The T1D cohort also saw higher MACE incidence (HR, 1.3; 95% CI, 1.17-1.45). The largest absolute risk difference was observed in the oldest group.1

Individual prognostic factors associated with mortality and MACE in T1D included smoking, being underweight or obese, physical inactivity, high HbA1c, high blood pressure, triglycerides, eGFR out of target, and albuminuria. These 8 risk factors exhibited a dose-response relationship; investigators cited the HR (95% CI) of all-cause mortality as 1.41 (1.17-1.71), 1.9 (1.55-2.32), and 2.86 (2.53-3.22) in those with 1, 2, and 3 risk factors, respectively.1

“The dose-response relationship between the number of risk factors and adverse outcomes highlights the importance of intervening on as many risk factors as possible,” Wei and colleagues wrote.1

References

1. Wei Y, Andersson T, Tuomi T, Nyström T, Carlsson S. Adult-onset type 1 diabetes: predictors of major cardiovascular events and mortality. Eur Heart J. 2025;46(38):3776-3786. doi:10.1093/eurheartj/ehaf304

2. de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014;130(13):1110-1130. doi:10.1161/CIR.0000000000000034