— Elevated mortality largely driven by higher cardiovascular risk
An earlier diagnosis of type 1 diabetes was tied to a shorter overall lifespan, researchers reported.
According to a large nationwide cohort study, women who had been diagnosed with type 1 diabetes by the age of 10 lost an average of 17.7 years off their life (95% CI 14.5-20.4), while men lost around 14.2 life-years (95% CI 12.1-18.2), found Araz Rawshani, MD, PhD, of the University of Gothenburg in Sweden, and colleagues.
As shown in the study in The Lancet
, those who were diagnosed with type 1 diabetes between birth and the age of 10 had a more than four times higher risk for all-cause mortality compared with individuals without diabetes (HR 4.11, 95% CI 3.24-5.22), and a nearly four times higher risk specifically for non-cardiovascular mortality (HR 3.96, 95% CI 3.06-5.11).
However, the heart-related risks were most pronounced for those who developed type 1 diabetes at a younger age, with an up to nearly 31 times higher risk for also developing acute myocardial infarction (MI) -- specifically:
- Cardiovascular mortality: HR 7.38 (95% CI 3.65-14.94)
- Cardiovascular disease: HR 11.44 (95% CI 7.95-16.44)
- Coronary heart disease: HR 30.50 (95% CI 19.98-46.57)
- Acute MI: HR 30.95 (95% CI 17.59-54.45)
- Stroke: HR 6.45 (95% CI 4.04-10.31)
- Heart failure: HR 12.90 (95% CI 7.39-22.51)
- Atrial fibrillation: HR 1.17 (95% CI 0.62-2.20)
The majority of these heart-related risks tended to be higher amongs women than men. Alarmingly, women diagnosed with type 1 diabetes by the age of 10 saw a nearly 60 times higher risk for coronary heart disease (HR 58.73, 95% CI 28.86-119.55), as well as a more than 92 times higher risk for acute MI (HR 92.07, 95% CI 32.72-253.47) when compared with diabetes-free individuals.
Those who developed type 1 diabetes at a later age also had significantly elevated risks for mortality and heart-related conditions, although these risks generally lessened with older age of diagnosis. For example, those who developed type 1 diabetes between the ages of 26 and 30 had little less than three times higher risk for all-cause mortality (HR 2.83, 95% CI 2.38-3.37) and less than four times higher risk for cardiovascular mortality (HR 3.64, 95% CI 2.34-5.66).
Regardless of age at diagnosis, all individuals with type 1 diabetes had an elevated risk for all-cause mortality (incidence rate 1.9, 95% CI 1.71-2.11 per 100,000 person-years), the researchers reported.
"In light of the fact that around half of individuals with type 1 diabetes are diagnosed before 14 years of age, this study highlights a need to consider age at diagnosis in guidelines. The magnitude of these risk estimates -- with point estimates in double figures for several vascular outcomes in the early adult years -- appear at least as high as those conferred by familial hypercholesterolemia."
These elevated mortality and cardiovascular risks are likely attributed to diabetes duration, the team explained: "The longer the duration of diabetes, the greater the glycemic load and thus the damage. Another possible explanation for our findings is that patients with a younger age of onset have a more severe and rapid loss of β-cells, which contributes to increased glycemia."
Rawshani and colleagues used the Swedish National Diabetes Register to assess individuals diagnosed with type 1 diabetes. A total of 27,196 patients with diabetes were then matched to 135,178 diabetes-free controls. Over a median follow-up of 10 years, 959 of the cohort with diabetes died compared with 1,501 diabetes-free individuals.
Writing in an accompanying commentary, Marina Basina, MD, and David Maahs, MD, PhD, both of Stanford University in California, called the findings "sobering," with implications for therapy that should serve as "a further impetus to delay, prevent, and cure type 1 diabetes." Still, although these relative risks for mortality are "staggeringly high, the absolute risks are much lower, due to the relatively young age (mean 29) and relatively short duration of type 1 diabetes," the commentary stated.
Rawshani et al said that despite these risks, they are not advocating giving statins or ACE inhibitors to children with type 1 diabetes, although the researchers did suggest that greater consideration be given to statins when the patient is over age 30.
Basina and Maahs recommended an alternative approach of earlier initiation of non-insulin adjunctive antihyperglycemic medications for these patients, such as GLP-1 agonists and SGLT-2 inhibitors, which can improve glycemic control and reduce cardiovascular risk without weight gain: "Earlier initiation of these therapies requires further research, but is another potential strategy to reduce the risk of cardiovascular disease."
The study was funded by the Swedish Heart and Lung Foundation.
Rawshani reported a financial relationship with Novo Nordisk; other study authors also reported relationships with industry.
Maahs reported personal and institutional relationships with the U.S. National Institutes of Health, the Juvenile Diabetes Research Fund, the National Science Foundation, the Helmsley Charitable Trust, Abbott, Sanofi, Eli Lilly, Insuletand, Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche; Basina reported personal and institutional relationships with Novo-Nordisk, the Helmsley Charitable Trust, and Allergan.
Read the original article on Medpage Today: Younger Age of T1D Diagnosis Tied to Higher Mortality Risk