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Long-term type 1 diabetes study reveals immune system links between blood glucose management and heart health

Two recent studies have found new connections between blood glucose (sugar) management and heart health, which may explain the increased risk of cardiovascular diseases (heart disease and stroke) in those with type 1 diabetes. Previous insights about type 1 diabetes and cardiovascular health have come from the landmark Diabetes Control and Complications Trial (DCCT) and its follow- up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. DCCT/EDIC demonstrated that early and intensive blood glucose control lowered the risk of cardiovascular diseases and cardiovascular-related deaths, though exactly how blood glucose levels affect cardiovascular health was not fully understood.

In new research, scientists further studied the health of DCCT/EDIC participants to examine how blood glucose management influenced these people’s risk of cardiovascular disease. In particular, researchers wondered if that risk was mediated through known cardiovascular factors or if there were unknown, diabetes-specific mechanisms at play, as well. The DCCT/EDIC research group investigated this question by analyzing whether or not an increased risk of heart problems could be accounted for by factors such as blood pressure, pulse rate, cholesterol levels, and/or measures of kidney function. Their analyses demonstrated that although having higher blood glucose levels over time was associated with many traditional risk factors for cardiovascular disease, these associations could not completely explain the increased risk seen in some DCCT-EDIC participants. This raised the question of what other factors were mediating the effect of high blood glucose levels on heart health.

Another research group hypothesized that the link between blood glucose levels and the heart is mediated by the immune system. By analyzing biological samples from a subset of DCCT participants, as well as samples from people with type 2 diabetes, scientists found signs of cardiac autoimmunity—i.e., the presence of at least two cardiac autoantibody types—in people who had type 1 diabetes and elevated blood glucose levels (measured as an HbA1c greater than 9 percent).

These autoantibodies were not found in people with type 2 diabetes who had similar blood glucose levels. People with type 1 diabetes and cardiac autoimmunity also had a higher risk of both accelerated atherosclerosis and cardiovascular events. Since cardiac autoantibodies developed decades before the cardiovascular complications, such autoantibodies might be useful as early biomarkers of cardiovascular disease risk specifically in people with type 1 diabetes. This study also suggested a new role for autoimmune mechanisms, possibly mediated by inflammation, in the development of cardiovascular complications of type 1 diabetes.

These results break new ground in the study of type 1 diabetes complications, identifying a novel cardiovascular disease pathway specific to type 1 diabetes and further emphasizing the importance of keeping blood glucose levels within a healthy range. More study is needed to clarify how exactly blood glucose levels affect heart health. Such studies could also lead to new insights into cardiovascular disease itself and to methods to detect, prevent, or treat cardiovascular complications in people with type 1 diabetes.

Sousa GR, Pober D, Galderisi A,…Lipes MA. Glycemic control, cardiac autoimmunity, and long-term risk of cardiovascular disease in type 1 diabetes mellitus. Circulation 139: 730-743, 2019.

Bebu I, Braffett BH, Orchard TJ, Lorenzi GM, and Lachin JM; DCCT/ EDIC Research Group. Mediation of the effect of glycemia on the risk type 1 diabetes: The DCCT/EDIC study. Diabetes Care 42: 1284-1289, 2019.

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