Cause-specific risk of major adverse cardiovascular outcomes and hypoglycemic in patients with type 2 diabetes: a multicenter prospective cohort study

Abstract

Purpose: Glycated hemoglobin A1_c (HbA1_c) and fasting plasma glucose (FPG) was identified to account for the risk of cardiovascular diseases in type 2 diabetic patients, but no study evaluated the risk based on both HbA1_c and FPG levels. We described the risk of major adverse cardiovascular events (MACE) and hypoglycemic in type 2 diabetic patients according to both HbA1_c and FPG levels.

Methods: With the usage of databases of Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), 1815 patients from 61 centers in China was identified and grouped according to the criterion value of HbA1_c and FPG: Good glycemic control (HbA1_c < 6.5%, FPG < 6.1 mmol/L); Insufficient glycemic control (HbA1_c < 6.5%, FPG ≥ 6.1 mmol/L or HbA1_c ≥ 6.5%, FPG < 6.1 mmol/L); Poor glycemic control (HbA1_c ≥ 6.5%, FPG ≥ 6.1 mmol/L). Time-varying multivariable Cox proportional hazards models were employed.

Results: Average age was 64.8 ± 5.8 years, with a median of 4.8 years of follow-up. Overall, the incidence rates of MACE were 20.6 per 1000-person-years in Good glycemic control compared with 45.9 per 1000-person-years in Insufficient glycemic control (adjusted hazard ratio (aHR): 1.99; 95% CI 1.11-3.56; p = 0.02) and 54.7 per 1000-person-years in Poor glycemic control (aHR: 2.46; 95% CI 1.38-4.40; p = 0.002), respectively. The risk of hypoglycemic was highest in Insufficient glycemic control; 67.3 per 1000-person-years compared with 46.3 per 1000-person-years in Good glycemic control (aHR: 1.62; 95% CI 1.03-2.56; p = 0.04). Apart from this, we also observed that both MACE (aHR:1.41; 95% CI 1.13-1.77; p = 0.003) and hypoglycemic episodes (aHR: 1.82; 95% CI 1.48-2.24; p < 0.001) were sufficiently more frequent in the insulin-exposed group than the non-exposed group. In a post-hoc analysis, the risk of MACE (aHR:1.43; 95% CI 1.09-1.86; p = 0.01) and hypoglycemic (aHR: 1.99; 95% CI 1.46-2.69; p < 0.001) were more pronounced in Insufficient glycemic control with insulin exposure.

Conclusions: We observed a significant association of cause-specific risk of MACE and hypoglycemic with Insufficient glycemic control, particularly with insulin exposure.

Keywords: Good glycemic control; Insufficient glycemic control; Major adverse cardiovascular events; Poor glycemic control; Type 2 diabetes.