Cause-specific risk of major adverse cardiovascular outcomes and hypoglycemic in patients with type 2 diabetes: a multicenter prospective cohort study
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Glycated hemoglobin A1c (HbA1c) 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 HbA1c and FPG levels. We described the risk of major adverse cardiovascular events (MACE) and hypoglycemic in type 2 diabetic patients according to both HbA1c and FPG levels.
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 HbA1c and FPG: Good glycemic control (HbA1c < 6.5%, FPG < 6.1 mmol/L); Insufficient glycemic control (HbA1c < 6.5%, FPG ≥ 6.1 mmol/L or HbA1c ≥ 6.5%, FPG < 6.1 mmol/L); Poor glycemic control (HbA1c ≥ 6.5%, FPG ≥ 6.1 mmol/L). Time-varying multivariable Cox proportional hazards models were employed.
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.
We observed a significant association of cause-specific risk of MACE and hypoglycemic with Insufficient glycemic control, particularly with insulin exposure.
KeywordsType 2 diabetes Major adverse cardiovascular events Good glycemic control Insufficient glycemic control Poor glycemic control
Glycated hemoglobin A1c
fasting plasma glucose
major adverse cardiovascular events
Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation
adjusted hazard ratio
body mass index
Action to Control Cardiovascular Risk in Diabetes
Veterans Affairs Diabetes Trail.
We acknowledge the contributions of ADVANCE group at 61 centers in China. We also thank all patients and participants who have contributed to the register.
This work was funded by grants from National Key Research and Development Program (No. 2016YFC0905000), National Natural Science Foundation of China (No 81522048, 81573511) and the Innovation Driven Project of Central South University (No 2016CX024).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
The study was approved by the local ethics committee and was in accordance with the 1964 Helsinki declaration and its later amendments.
All patients provide written informed consent.
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