Life Expectancy Reduced With Early Type 1 Diabetes Diagnosis

Liam Davenport

August 09, 2018

Patients diagnosed at a young age with type 1 diabetes have a far greater risk of developing cardiovascular disease and dying early compared with the general population than has previously been appreciated, with such patients losing more than a decade of life, new registry data reveal.

Araz Rawshani, MD, PhD, department of molecular and clinical medicine, Institute of Medicine, University of Gothenburg, Sweden, studied more than 27,000 patients with type 1 diabetes and 135,000 matched controls. The research was published online in the Lancet on August 9.

They found that patients diagnosed with type 1 diabetes at 0 to 10 years of age had quadruple the risk of dying early from any cause compared with controls and were over seven times as likely to die from cardiovascular disease, leading to a loss in life expectancy of approximately 18 years in women and 14 years in men.

Moreover, patients with type 1 diabetes were 30 times more likely to develop coronary heart disease and myocardial infarction than controls. They were also 12 times more likely to end up with heart failure and 11 times more likely to have a stroke.

These estimates are far higher than those included in a recent statement by the American Heart Association (AHA) and American Diabetes Association (ADA), which did not include age as a risk stratifier.

The magnitude of loss of life expectancy in individuals diagnosed with type 1 diabetes at age up to 10 years in this new study "is something that we did not fully appreciate before," noted coauthor Naveed Sattar, MD, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK, in a Lancet press release.

Patients Diagnosed in Childhood Must Take Cardioprotective Drugs Earlier

One of the most important implications of these new findings, says Rawshani, is that people with type 1 diabetes mush start taking cardioprotective drugs, such as statins and blood pressure lowering agents, early.

While acknowledging absolute mortality and disease rates in the current study were low, he said that "age at disease onset appears to be an important determinant of survival as well as cardiovascular outcomes in early adulthood, warranting consideration of earlier treatment with cardioprotective drugs."

"Currently, only around 10% to 20% of individuals with type 1 diabetes are taking statins by the age of 40," Sattar stressed.

"Also, improving glycemic control and smoking cessation programs could meaningfully prolong the lives of these individuals," he added, noting, "the good news, however, is that recent technological advances are helping younger patients manage their glucose levels better."

In an accompanying editorial, Marina Basina, MD, and David M. Maahs, MD, PhD, division of endocrinology, Stanford University, California, describe the results as a "step forward" in understanding the impact of early type 1 diabetes diagnosis on mortality and cardiovascular disease risk.

But noting limitations of this study, more data are still needed to guide therapy decisions, they argue.

While Rawshani and colleagues call for earlier initiation of cardioprotective medications, they "specifically state that they do not advocate prescribing statins or angiotensin-converting enzyme inhibitors to children with type 1 diabetes," the editorialists point out.

They "instead argue for greater consideration of these treatments once individuals with type 1 diabetes reach 30 to 40 years of age, consistent with adult AHA and ADA guidelines."

Four Times Higher Risk of Early Death in Those With Type 1 Diabetes

To examine how age at diagnosis of type 1 diabetes is related to the risk of death and cardiovascular outcomes, the researchers gathered data on individuals included in the Swedish National Diabetes Register between 1998 and 2012.

They divided them into five groups by age at diagnosis: 0 to 10 years, 11 to 15 years, 16 to 20 years, 21 to 25 years, and 26 to 30 years. These patients were matched with five nondiabetic controls randomly selected from the Swedish population and matched for age, sex, and county, to account for geographical differences.

Socioeconomic information, coexisting conditions, and dates and causes of death were gathered from Statistics Sweden, Swedish Inpatient Registry, and Cause of Death Register for all individuals in Sweden, with follow-up to the end of 2014.

The team included 27,195 patients with type 1 diabetes and 135,178 matched controls who were a mean age of approximately 29 years and of whom 56% were men. Over a median follow-up of 10 years, 959 patients with type 1 diabetes and 1501 controls died.

The all-cause mortality rate was typically low, with a highest overall incidence of 1.90/100,000 person-years in patients with type 1 diabetes and 0.60/100,000 person-years among controls.

Researchers calculated that patients who developed type 1 diabetes up to the age of 10 years had a substantially higher risk of all-cause mortality than controls, at a hazard ratio (HR) of 4.11, rising to 7.38 for cardiovascular mortality. For noncardiovascular mortality, the HR was 3.96.

Patients with type 1 diabetes diagnosed in the first decade of life also had an increased risk of developing cardiovascular disease compared with controls, at an HR of 11.44, as well as coronary heart disease, at an HR of 30.50, acute myocardial infarction (HR, 30.95), heart failure (HR, 12.90), stroke (HR, 6.45), and atrial fibrillation (HR, 1.17).

Individuals who developed type 1 diabetes at 26 to 30 years also had an increased risk of mortality and cardiovascular disease, although the HRs were lower in each case, with a five fold difference across diagnostic age groups.

The team estimates that men diagnosed with type 1 diabetes at age 0 to 10 years lost 14.2 years of life, at an average life expectancy of 69.1 years versus 83.3 years in controls.

Women with type 1 diabetes diagnosed in childhood lost 17.7 years, at an average life expectancy of 70.9 years versus 88.6 years in controls.

Among patients with type 1 diabetes diagnosed at 26 to 30 years of age, men lost an average of 9.4 years of life compared with controls, while women lost 10.1 years.

Women with type 1 diabetes also had higher risks of developing cardiovascular disease than men.

"Sobering" Statistics Add to Data Needed to Improve Outcomes

The authors believe that the increased risk of cardiovascular-related death in patients with type 1 diabetes diagnosed at a younger age could be because loss of pancreatic beta-cells is more severe and rapid in these patients than those diagnosed later in life.

They point out, however, that their study has several limitations, such as a lack of data on how cardiovascular disease risk factors, such as HbA1c levels, blood pressure, and cholesterol, and their treatment affected outcomes.

In addition, the absolute mortality and cardiovascular disease rates were low as a result of the young average age of the participants and relatively short duration of type 1 diabetes, limiting their wider applicability.

In their editorial, Basina and Maahs say these new data "are sobering, have implications for therapy, and are a further impetus to delay, prevent, and cure type 1 diabetes."

However, they note that "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."

Therefore, any resulting recommendations in this article on the timing of treatment initiation in patients with type 1 diabetes "are more opinion based than evidence based," they comment.

Still, Basina and Maahs believe that the current results "will increase attention towards cardioprotection at younger ages and specifically for those with an earlier age of type 1 diabetes onset."

The study was funded by the Swedish Heart and Lung Foundation. Rawshani has received personal fees from Novo Nordisk. Sattar has consulted for Boehringer Ingelheim, Novo Nordisk, Janssen, Eli Lilly, AstraZeneca, Amgen, and Sanofi, and received grant support from Boehringer Ingelheim outside the submitted work. Disclosures for the other authors are listed in the article. Maahs has received research support from the NIH, JDRF, and National Science Foundation; research support and consulting fees from the Helmsley Charitable Trust; consulting fees from Abbott, Helmsley Charitable Trust, Sanofi, and Eli Lilly; and has served on an advisory board for Insulet. Basina has received research support to her institution from Novo Nordisk, research support from the Helmsley Charitable Trust, and has served on an advisory board for Allergan.

Lancet. 2018;392:477-486. Abstract

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