Why patients with type 1 diabetes are faced with the highest mortality from cardiovascular disease (CVD) compared to the general population, and can benefit from intensive diabetes therapy for both glycemic & nonglycemic CVD risk.
Though the mechanism isn’t clear and with little evidence on how to properly treat or prevent mortality due to CVD, there are ongoing studies to determine the role of glycemic control in patients with type 1. Previous studies have recognized hyperglycemia more clearly as a risk factor for clinical cardiovascular outcomes in patients with type 1. Glycemic levels that are poorly controlled result in traditional CVD risk factors, classified as “systolic and diastolic blood pressure, pulse pressure and pulse rate, triglycerides, LDL cholesterol, and HDL cholesterol”.
The Diabetes Control and Complication Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study performed a randomized controlled trial and observational study with the goal to identify risk factors in the causal pathway linking hyperglycemia and the risk of CVD. The authors wanted to determine “the extent to which the effect of glycemia (HbA1c) on the risk of CVD is potentially mediated by their traditional CVD risk factors”.
The study participants with type 1 were randomized into two groups, one group (n = 711) receiving intensive diabetes therapy (IDT) and the other group (n = 730) conventional therapy (CON). The IDT group goal was to obtain close to nondiabetic glycemic levels (HbA1c) if able to be done safely, whereas the CON group had no prespecified glucose targets, the researchers wanted to only maintain their clinical well-being. Both groups underwent testing to determine their cardiovascular risk factors, such as physical examination, collection of blood and urine samples, HbA1c, and fasting lipids (LDL calculated via the Friedewald equation). HbA1c was measured quarterly during DCCT and annually during EDIC, and fasting lipids were measured annually during DCCT and every other year during EDIC. Researchers were to then document any CVD events experienced, as well as any major atherosclerotic cardiovascular events (MACE).
To assess the effect of covariates on the risk of developing CVD event, Cox proportional hazards models were used. All models were adjusted for age at baseline due to age being the strongest risk factor of CVD events.
HbA1c was determined the second strongest risk factor for CVD after age. An increase in HbA1c by 1 unit increased the risk of any-CVD by 50% (P < 0.0001). Likewise, a 68% increased risk of MACE was determined (P < 0.0001). The researchers then adjusted what they considered as potential mediating risk factors one by one for both any-CVD as well as MACE. With adjustment, data still resulted as a highly significant association (P < 0.0001). The researchers then examined the effect of the two treatments groups on the risk of any-CVD and MACE. The data indicated that the mean updated HbA1c completely mediated the effect of treatment group. Aggressive glycemic management long-term plays a role in CVD risk reduction but isn’t enough alone.
Knowing the effects of long-term hyperglycemia and its role on CVD risk is important in efforts to reduce CVD morbidity and mortality in patients with type 1. The researchers’ findings determine that the risk of any-CVD and MACE are strongly associated with the mean HbA1c. While it is important to control the HbA1c, it is also important to control the levels of the non glycemic risk factors, as it can help with a ~50% reduction on the effect of glycemia on the risk of CVD. The authors suggest that patients with type 1 should receive both aggressive management of their glycemic levels and the levels of the non glycemic CVD risk factors to receive the best outcome.
- Patients with type 1 have a higher rate of mortality due to cardiovascular disease.
- The study determined that not only controlling glycemic levels is important, but controlling mediating risk factors for CVD can also decrease the effect of glycemia on the risk of CVD.
- Patients with type 1 need aggressive management of both glycemic and nonglycemic CVD risk factor levels.
Bebu, Ionut, Braffett, Barbara H., et al. Mediation of the Effect of Glycemia on the Risk of CVD Outcomes in Type 1 Diabetes: The DCCT/EDIC Study. Diabetes Care. 2019 April 29.
For more information about Type 1 Diabetes, visit our Type 1 section.
Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate