Limitations of glycosylated haemoglobin as an index of glucose intolerance
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Published on: January 7, 2018
C Snehalatha1, A Ramachandran, K Satyavani
1Diabetes Research Centre, Royapuram, Chennai, India. diabetes.research@gems.vsnl.net.in
Insights
This study determined a normal glycosylated hemoglobin (HbA1c) cut-off for South Indians, finding it has limitations in diagnosing glucose intolerance due to unexplained variations. While HbA1c > or = 6.0% shows reasonable sensitivity and specificity, it
Area of Science:
- Endocrinology and Metabolism
- Clinical Chemistry
- Public Health
Background:
- Glycosylated hemoglobin (HbA1c) is a key marker for glucose control.
- Establishing population-specific normal cut-off values is crucial for accurate diagnosis.
- Previous studies have shown variability in HbA1c across different ethnic groups.
Purpose of the Study:
- To establish a normal cut-off value for HbA1c in South Indian subjects.
- To evaluate the diagnostic utility of HbA1c in identifying glucose intolerance using WHO and ADA criteria.
- To assess the correlation between HbA1c and plasma glucose levels in this population.
Main Methods:
- HbA1c levels were measured in 1261 subjects without a history of diabetes using an immunoturbidimetric assay.
- Oral glucose tolerance tests (OGTT) were performed to categorize glucose tolerance.
- Receiver Operating Characteristic (ROC) analysis was employed to determine sensitivity and specificity.
Main Results:
- A cut-off value of HbA1c > or = 6.0% demonstrated a sensitivity of 88.5% and specificity of 62.8% for WHO criteria (2-h plasma glucose > or = 200 mg/dl).
- Using ADA criteria (fasting plasma glucose > 125 mg/dl), the same cut-off yielded 85.2% sensitivity and 61.2% specificity.
- Over 35% of the variation in HbA1c was not explained by fasting or 2-hour post-glucose plasma levels, indicating significant inter-individual variability.
Conclusions:
- HbA1c > or = 6.0% offers reasonable sensitivity and specificity for diagnosing glucose intolerance in South Indians based on established criteria.
- Significant unexplained inter-individual variations in HbA1c, even within the normoglycemic range, limit its sole diagnostic utility.
- Further research is needed to understand the factors contributing to HbA1c variability and refine diagnostic approaches.
Abstract:
This study was conducted (a) to establish a normal cut-off value for glycosylated haemoglobin measured as HbA1c in South Indian subjects, and (b) to evaluate its usefulness in demarcating different categories of glucose intolerance. HbA1c measurement was carried out in 1261 cases with no known history of diabetes, while being tested by oral glucose tolerance test (M:F 850:411, mean age 40+/-12 years). An immunoturbidimetric procedure for HbA1c assay (Tina-Quant, Boehringer Mannheim, Germany) was used. The specificity and sensitivity of HbA1c in demarcating normal glucose tolerance (NGT) from abnormal tolerance were calculated using the ROC procedure. By the ROC analysis, a cut-off value of HbA1c > or = 6.0% gave a sensitivity of 88.5% and specificity of 62.8% using the WHO criteria (2-h plasma glucose > or = 200 mg/dl). Using the ADA criterion (fasting plasma glucose > 125 mg/dl) the sensitivity and specificity for the same cut-off value were 85.2 and 61.2%. In NGT, only a small percentage of the variance in HbA1c was explained by the fasting plasma glucose (FPG) values. The overall correlation coefficient between the fasting plasma glucose and HbA1c was r = 0.8, r2 = 0.64 and, in the case of 2-h post glucose, r = 0.82, r2 = 0.67. This showed that more than 35% of the variations in HbA1c were not explained by the plasma glucose values. The study showed that HbA1c values of > or = 6.0% gave a reasonably high sensitivity and specificity for diagnosis using the WHO or ADA criteria. However, nearly 35% of the variations in HbA1c were not explained by the variations in plasma glucose. Wide inter-individual variations even in the normoglycaemic range make the test unsuitable for diagnostic purpose.
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