Prevention of Cardiovascular Disease in Type 1 Diabetes 

N Engl J Med April 3 2024

https://www.nejm.org/doi/full/10.1056/NEJMra2311526

Camila Manrique-Acevedo, M.D., Irl B. Hirsch, M.D., and Robert H. Eckel, M.D.

From the text

Introduction
Type 1 diabetes mellitus is a chronic metabolic disease resulting from autoimmune destruction of pancreatic beta cells. More than half the cases of type 1 diabetes are diagnosed in adulthood; 62% of new cases in 2021 were diagnosed in patients over the age of 20 years.

There are key genetic, immune, and metabolic differences between childhood- and adult-onset type 1 diabetes.  As a result of both a later age at diagnosis and longer life span, the mean age of a person living with type 1 diabetes is now 40 years.

Scope of the Problem
Despite remarkable advances in diabetes care, patients with type 1 diabetes continue to have a life expectancy that is approximately 13 years shorter than that of the general population. Cardiovascular disease is the primary cause of this short- ened life expectancy, and throughout their lifetime, persons with type 1 diabetes are at greater risk for cardiovascular disease than the general population.

In the Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, cardiovascular disease was the leading cause of death, and participants randomly assigned to a glycated hemoglobin goal of 9% (75 mmol per mole), the conventional goal, had a higher risk of death from cardiovascular causes at 20 years than those randomly assigned to the more stringent goal of 7% (53 mmol per mole).

Similarly, an analysis of data from the Swedish National Diabetes Register revealed the close association between levels of glycated hemoglobin and the risk of death from cardiovascular causes. Notably, in a 2014 study using data from the Swedish National Diabetes Register, even patients with a glycated hemoglobin level of 6.9% (52 mmol per mole) or lower had a risk of death from cardiovascular causes that was greater by a factor of 2 than that of nondiabetic controls.

A systematic review and metaanalysis of data from more than 214,000 patients with type 1 diabetes showed that the relative risk of cardiovascular events was twice as high for women as it was for men.

Conclusions
There are many questions about approaches to mitigating the risk of cardiovascular disease among patients with type 1 diabetes, including the timing and dose of statins, specific bloodpressure targets, the use of aspirin for primary prevention, the comparative efficacy of incretin mimetic therapy and bariatric surgery, and the risks and benefits of SGLT2 inhibition.

Which of these potential interventions require more rigorous study through a randomized clinical trial? Currently, cardiovascular disease prevention in persons with type 1 diabetes must depend on data from observational studies and, in some circumstances, data obtained from the small number of patients with type 1 diabetes who have been included in trials primarily involving patients with type 2 diabetes.

Realworld data and artificial intelligence may help answer some questions. Cardiovascular disease is the leading cause of substantial illness and death in patients with type 1 diabetes, and observational data remain the basis for decisions about therapy, since evidence from randomized clinical trials is lacking. Until such evidence is available, current recommendations from the many nonprofit professional organizations are useful but need to be compared and consolidated.

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