Glycemic control and cardiovascular disease in 7,454 patients with type 1 diabetes: an observational study from the Swedish National Diabetes Register (NDR)

Abstract

Objective: We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years.

Research design and methods: A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007).

Results: Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002-0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8-11.9% (mean 9.0), fully adjusted also for albuminuria.

Conclusions: This observational study of patients in modern everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes.

Figure 1

Five-year rates (%) of fatal/nonfatal CHD and CVD in a Cox regression model, fully adjusted as in model 2 of Table 2. A and B: Splines for event rates in all 7,454 patients, as a cubic function of baseline A1C (solid line) or updated mean A1C (dashed line). C and D: Adjusted mean (SD) rates by deciles of updated mean A1C, with a solid line for the linear association by deciles. E–H: Splines for event rates in subgroups by median duration 20 years.