Inconvenient relationship of haemoglobin A1c level with endothelial function in type 2 diabetes in a cross-sectional
Takayuki Yamaji1, Takahiro Harada1, Yu Hashimoto1
1Department of Cardiovascular Medicine, Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Insights
This study reveals an inverted U-shaped relationship between hemoglobin A1c (HbA1c) levels and flow-mediated dilation (FMD) in type 2 diabetes patients. Critically, low HbA1c levels (<6.5%) are linked to endothelial dysfunction.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Diabetes Research
Background:
- Endothelial dysfunction is a key factor in the progression of cardiovascular complications in type 2 diabetes.
- Hemoglobin A1c (HbA1c) is a standard measure of long-term glycemic control.
- The relationship between HbA1c levels and endothelial function, particularly at lower ranges, requires further elucidation.
Purpose of the Study:
- To investigate the association between hemoglobin A1c (HbA1c) levels and endothelial function, specifically flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID).
- To determine if varying levels of glycemic control, including lower HbA1c ranges, impact vascular function in patients with type 2 diabetes.
Main Methods:
- A cross-sectional study involving 1215 patients with type 2 diabetes across 22 university hospitals in Japan.
- Patients were categorized into four groups based on HbA1c levels: <6.5%, 6.5%-6.9%, 7.0%-7.9%, and ≥8.0%.
- Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were assessed, along with HbA1c levels.
Main Results:
- An inverted U-shaped association was observed between HbA1c levels and FMD, peaking around 7% HbA1c.
- FMD was significantly lower in patients with HbA1c <6.5% compared to those with HbA1c 6.5%-6.9% and 7.0%-7.9% (p<0.001 for both).
- No significant differences in NID were found across the HbA1c groups, suggesting a specific impact on endothelium-dependent vasodilation.
Conclusions:
- The study indicates an inverted U-shaped relationship between FMD and HbA1c levels in type 2 diabetes.
- A low HbA1c level (<6.5%) is associated with endothelial dysfunction, highlighting potential risks of overly aggressive glycemic control on vascular health.
- These findings underscore the importance of optimizing, rather than solely minimizing, glycemic control for cardiovascular health in diabetes management.
Objective:
The aim of this study was to determine the relationship of haemoglobin A1c (HbA1c) level with flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) in patients with type 2 diabetes.
Design:
Cross-sectional study.
Setting:
22 university hospitals and affiliated clinics in Japan.
Participants:
1215 patients with type 2 diabetes including 349 patients not taking antidiabetic drugs.
Measures:
We evaluated FMD and HbA1c level. All patients were divided into four groups based on HbA1c level: <6.5%, 6.5%-6.9%, 7.0%-7.9% and ≥8.0%.
Results:
An inverted U-shaped pattern of association between HbA1c level and FMD was observed at the peak of HbA1c of about 7%. FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%-6.9% group and HbA1c 7.0%-7.9% group (p<0.001 and p<0.001), and FMD values were similar in the HbA1c <6.5% group and HbA1c ≥8.0% group. There were no significant differences in NID values among the four groups. After adjustments for confounding factors, FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%-6.9% and HbA1c 7.0%-7.9% group (p=0.002 and p=0.04). In patients not taking antidiabetic drugs, FMD was also significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5%-6.9% group and HbA1c 7.0%-7.9% group (p<0.001 and p=0.02), and there were no significant differences in NID values among the four groups.
Conclusions:
These findings suggest that there is an inverted U-shaped pattern of association between FMD and HbA1c and that a low HbA1c level of <6.5% is associated with endothelial dysfunction.
Trial Registration Number:
UMIN000012950, UMIN000012951, UMIN000012952 and UMIN000003409.
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