Association of Cardiovascular Disease Risk with Long-Term Glycemic Control in Patients with Type 1 Diabetes

Differences in long-term patterns of glycemic control are linked to varying risks of developing cardiovascular disease (CVD) in people with type 1 diabetes (T1D), according to research published in Diabetes Care.

Investigators studied the relationship between glycated hemoglobin (HbA_1C) trajectories, risk of CVD development, and major adverse cardiovascular events (MACE) over a 30-year period (1986-1988 to 2016-2018) in 536 people with T1D who participated in the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort.

The study participants were CVD-free at baseline when diagnosed with T1D during childhood or adolescence. Measurements of HbA_1c  were taken at a minimum of 2 and a maximum of 8 times during the 30-year study period. Height, weight, waist and hip circumferences, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, serum creatinine, urinary albumin, and blood pressure were also analyzed. Smoking history, insulin regimen, hypoglycemia, medications used to control blood pressure and lipids, aspirin use, and family history of myocardial infarctions (MI) data were obtained by questionnaire.

Markers for kidney function were also measured at different points throughout the study, including estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), and estimated glucose disposal rate (eGDR).

Over the 30 year study period, 47.4% of participants with T1D developed CVD and 31% developed MACE. Following analysis of HbA_1C trajectory with CVD-free survival curves, the investigators divided the cohort into low and high HbA_1C groups. Those with high HbA_1C had a threefold increased risk of developing CVD (P = .0001) and a fivefold higher risk of MACE (P < .0001) compared with those with a low HbA_1C. over time.

Risk factors increasing CVD risk in the low HbA_1C group included higher baseline non-HDL-C, lower recent eGFR, and most recent smoking status.  In the high HbA_1C group, the risk factor most associated with increased risk of CVD was higher baseline AER.

While the low HbA_1C group had a sixfold increase in CVD risk, they did not have significantly increased risk of MACE. Most CVD incidents (80%) in the low HbA_1C group involved coronary revascularization procedures prior to MI. The high HbA_1C group experienced only MACE.

Investigators acknowledged several limitations of the study–including the long-term nature of the study itself–since treatment regimens during the early study period may not reflect current treatments for patients with T1D.  Another limitation was the potential for “survivor bias” since cases of pre-existing CVD were excluded at baseline. The lack of demographic and ethnic diversity may have also affected study results, the researchers acknowledged, as 83% of the study participants were White.

“These risk factor differences suggest that pathways to CVD may differ by glycemic control, potentially resulting in important implications for prognosis in type 1 diabetes,” the researchers concluded.

Reference

Miller RG, Orchard TJ, Costacou T. 30-year cardiovascular disease in type 1 diabetes: risk and risk factors differ by long-term patterns of glycemic control. Diabetes Care. 2022;45(1):142-150. doi:10.2337/dc21-1381