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Age at type 1 diabetes diagnosis associated with CV, mortality risk

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August 10, 2018

Adults diagnosed with type 1 diabetes before age 10 years have a 30 times increased risk for coronary heart disease and acute myocardial infarction in their early adult years, with that risk more than doubling for women vs. men with the disease, according to findings published in The Lancet.

“The younger one develops type 1 diabetes, the higher the risks for heart disease and the greater the average loss of life, up to 16 years on average (more for women) when type 2 diabetes develops under age 10 years,” Naveed Sattar, MD, professor of metabolic medicine at the BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, told Endocrine Today. “Whilst we know long duration of type 1 diabetes is relevant to higher risks, our work also suggests that something else about developing type 1 diabetes early in life — younger than age 10 years — may raise risks further.”

Sattar and colleagues analyzed data from 27,195 adults with type 1 diabetes identified from the Swedish National Diabetes Register, each matched by age, sex and county with five adults without diabetes (controls; n = 135,178) selected from the Swedish population (mean age, 29 years; 56% men). Researchers identified coexisting conditions and causes of death via linked data from Statistics Sweden, the Swedish Inpatient Registry and the Cause of Death Register. Researchers estimated the excess risk for all-cause mortality, cardiovascular mortality, non-CV mortality, acute MI, stroke, composite CVD, CHD, heart failure and atrial fibrillation. Adults with type 1 diabetes were stratified into five groups by age at diagnosis: aged 0 to 10 years; aged 11 to 15 years; aged 16 to 20 years; aged 21 to 25 years and aged 26 to 30 years. Follow-up started on the first date of the person’s registration in the registry and ended on date of an event, death or December 2014 (median follow-up, 10 years).

Researchers used Cox proportional hazard models to calculate the association between age at diabetes diagnosis and risk for outcomes vs. controls, with age as an underlying timescale, as well as survival analyses estimating life-years lost (the difference between predicted conditional median survival after age 18 years in the 0- to 10-year and 10- to 15-year age groups, and after the upper age interval for other age groups).

Life-years lost

During follow-up, 959 adults with type 1 diabetes and 1,501 controls died.

 

Overall, a diagnosis of type 1 diabetes before age 10 years resulted in 16 life-years lost (95% CI 14-18.1), according to researchers, with women experiencing more life-years lost vs. men (17.7 vs. 14.2).

Researchers observed an inverse association between age at diabetes diagnosis and excess risk for developing eight of the nine outcomes studied, the researchers wrote, with no excess risk observed only for atrial fibrillation.

HR for all-cause mortality was elevated for all groups, but highest for those diagnosed with type 1 diabetes at age 0 to 10 years (HR = 3.96; 95% CI, 3.06-5.11) vs. those diagnosed at age 26 to 30 years (HR = 2.78; 95% CI, 2.29-3.38). Similarly, HR for CV mortality was highest for those diagnosed at age 0 to 10 years (HR = 7.38; 95% CI, 3.65-14.94) vs. those diagnosed at age 26 to 30 years (HR = 3.64; 95% CI, 2.34-5.66).

Increased risk for women

Researchers observed marked differences for men and women with type 1 diabetes when analyzing excess risk for death and CVD.

“Among those who developed type 1 diabetes before 10 years of age, women had a six times increased risk of all-cause mortality, whereas men had a three times increased risk,” the researchers wrote. “Excess risks were particularly pronounced in women; women with type 1 diabetes had an approximately 60 times increased risk of coronary artery disease and an approximately 90 times increased risk of acute myocardial infarction.”

The HR for overall risk for CVD for those diagnosed with type 1 diabetes at age 0 to 10 years was 11.44 (95% CI, 7.95-16.44), with the risk rising further in women, according to researchers.

“Simply put, we need to help such individuals lower their risks of heart disease by several means,” Sattar said, including helping patients with glucose management and smoking cessation and discussing the use of statins and blood pressure medications with those who developed type 1 diabetes when very young when they reach age 30 to 40 years.

“This is especially important, as currently, fewer individuals with type 1 diabetes are prescribed statins than equivalently aged persons with type 2 diabetes, and yet the average risk for heart disease is much higher in those with type 1 diabetes,” Sattar said.

In commentary related to the study, Marina Basina, MD, clinical associate professor of endocrinology, gerontology and metabolism at Stanford University, and David M. Maahs, MD, PhD, professor of pediatrics and division chief of pediatric endocrinology at Stanford University, wrote that nonmodifiable CVD risk factors, such as age at the time of diagnosis, might help to direct timing of therapy for modifiable risk factors.

 

“These data will increase attention towards cardioprotection at younger ages and, specifically, for those with an earlier age of type 1 diabetes onset,” Basina and Maahs wrote. “Practitioners need a stronger evidence base, including confirmatory reports from other registries and clinical trials, to clarify proper therapy and translate research findings to care guidelines and clinical practice to improve mortality and cardiovascular disease outcomes for individuals with type 1 diabetes. These data are a step forward.” – by Regina Schaffer

For more information:

Naveed Sattar, MD, can be reached at the BHF Glasgow Cardiovascular Research Centre, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland; email: naveed.sattar@glasgow.ac.uk.

Disclosures: Basina reports she has received research support to her institution from Novo Nordisk and has served on an advisory board for Allergan. Maahs reports he has received consultant fees from Abbott, Eli Lilly, Sanofi and has served on an advisory board for Insulet. Sattar reports he has served as a consultant for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi. Please see the study for the other authors’ relevant financial disclosures.