J Korean Med Sci.  2023 Jan;38(4):e24. 10.3346/jkms.2023.38.e24.

Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis

• Kim H
• Jung DY
• Lee SH
• Cho JH
• Yim HW
• Kim HS

• KMID: 2539190
• DOI: http://doi.org/10.3346/jkms.2023.38.e24

Abstract

Background
It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM).
Methods
In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1–4) was used to determine visit-to-visit HbA1c variability.
Results
Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients). The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0–6.9%]_Q1 (P = 0.006), HVS [6.0–6.9%]_Q2 (P = 0.013), HVS [6.0–6.9%]_Q3 (P = 0.018), and HVS [7.0–7.9%]_Q3 (P = 0.040).
Conclusion
To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

Keyword

Blood Glucose; Cardiovascular Disease; Diabetes Mellitus; Glycated Hemoglobin (HbA1c); HbA1c Variability Score

Figure

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  Fig. 1 The 9-year research design showing the observation, buffering and outcome windows (3 years each). The observation window indicates the first detection of type 2 diabetes, and the target outcome window indicates the detection of CVD after the 3-year buffering window.CVD = cardiovascular disease, HbA1c = glycated hemoglobin.

• 

  Fig. 2 Flowchart of patient selection for the study.HVS = glycated hemoglobin variability score.

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  Fig. 3 Comparison of the incidence of CVD according to baseline HbA1c and the HVS P values were calculated using the χ2 test or aFisher’s exact test for categorical variables.HbA1c = glycated hemoglobin, HVS = glycated hemoglobin variability score, NS = not significant, CVD = cardiovascular disease.

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  Fig. 4 Cumulative incidence of CVD (n = 4,817).HVS = glycated hemoglobin variability score, CVD = cardiovascular disease.

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