Derivation & validation of glycosylated haemoglobin (HbA_1c) cut-off value as a diagnostic test for type 2 diabetes in south Indian population

Abstract

Background & Objectives:Glycosylated haemoglobin (HbA1c) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India.Methods:In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341).Results:On applying HbA1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8, 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant.Interpretation & conclusions:HbA1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India.

Authors' Response

“…In our study 2 the Youden's Index was 0.75; the HbA 1c cut-off that provided such index was >6.3; both (0,1) approach and the Youden's Index provided the same cut-off. As a note of caution we feel that any recommendations that arise from simulated data with various prevalence and cost assumptions should also be given consideration in addition to data (study) driven recommendations alone.…”

“…We read the correspondence by Habibzadeh et al 1 on our article 2 with great interest. They stated that Perkins and Schisterman 3 , in their article clearly recommended the use of the Youden's index (Se + Sp – 1) and warned about using the minimum distance criterion.…”

“…However, in order to do use glycosylated haemoglobin (HbA 1c ) as a diagnostic test for type 2 diabetes, the HbA 1c estimation must be carried out on an instrument functioning on high-performance liquid chromatography (HPLC)-based ion exchange chromatography that conforms to the National Glycohemoglobin Standardization Program (NGSP) standardized to the Diabetes Control and Complications Trial (DCCT) 9 as was used in our study 2 . In India, this facility is usually available in referral hospitals and large laboratories in big cities only.…”

“…Further, contrary to the argument raised by the Habibzadeh et al 1 of using HbA 1c as a screening test in general population in the studied region, we wish to state that we have derived and validated a HbA 1c cut-off for use as a confirmatory diagnostic test (rather than a screening test) in a hospital-based scenario (rather than in a general population). We have also stated in the last sentence in the Discussion section 2 that “…it would not be advisable to replace the oral glucose tolerance test (OGTT) by HbA1c as a diagnostic test for type 2 diabetes in the prevalence surveys in the general population.” We have also cautioned about the false-positive test results and stated that “However, the specificity was about 85 per cent which indicated that about 15-20 per cent of patients without type 2 diabetes would be wrongly labelled as having type 2 diabetes and would probably be started on unnecessary medication. While this may be resolved in a hospital-based situation on follow up of the patients, if HbA 1c is used as the diagnostic test in prevalence surveys of type 2 diabetes in the general population, the actual number of such misclassifications could be large 2 .”…”

Comparison of Hemoglobin A1c with fasting and 2-h plasma glucose tests for diagnosis of diabetes and prediabetes among high-risk South Indians

“…HbA1c >6.3% was found to be optimal cutoff value for the diagnosis of type 2 diabetes in a study from Andhra Pradesh state in South India. [ 27 ] A study from North India[ 6 ] found an optimal HbA1c cut-point of 6.1% for diabetes screening and HbA1c of 6.5% had optimal specificity for diabetes diagnosis. Optimal HbA1c cutoff for prediabetes diagnosis in the present study was 5.9%, with a much lower accuracy compared to diabetes diagnosis.…”