Limitations of glycosylated haemoglobin as an index of glucose intolerance.

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.