Diagnostic Testing for Diabetes Using HbA_1c in the Abu Dhabi Population: Weqaya: the Abu Dhabi Cardiovascular Screening Program

The Weqaya screening program commenced in April 2008 for UAE nationals (aged ≥18 years) residing in Abu Dhabi linked to the provision of free comprehensive health insurance (called Thiqa) (3). Individuals consented in line with the principles of the Abu Dhabi Medical Research Council (6). Further details about the screening program are described elsewhere (3), but in summary, it was conducted at a series of dedicated primary health care facilities with a systematic screening methodology (available at http://www.haad.ae/HAAD/LinkClick.aspx?fileticket=sj-gI8-BIv4%3d&tabid=820). Screening recorded demographics and self-reported indicators; anthropometric measures included waist-to-hip ratio, BMI, and a single-arterial blood pressure reading; and blood testing included nonfasting samples for glucose, LDL and HDL cholesterol, and HbA_1c.

Patients at higher risk of having diabetes (HbA_1c ≥6.1% or random glucose ≥11.1 mmol/L) or missing HbA_1c and glucose data from the first round of screening were invited back for further investigation. Fasting glucose levels (12 h fasting), oral glucose tolerance test (OGTT) using a 75-g glucose load in line with World Health Organization guidelines (7), and HbA_1c levels were recorded at follow-up. Only individuals attending public facilities were included to ensure standardized laboratory methods. HbA_1c was measured on whole blood using the Cobas Integra Instrument in line with the National Glycohemoglobin Standardization Program, standardized to the Diabetes Control and Complications Trial reference assay (8).

All statistical analyses were conducted using STATA version 10.0 (STATACorp LP, College Station, TX). Continuous variables were compared using t tests for comparison of means. The screening test was HbA_1c (ranging from 6.1 to 7%) and random glucose (≥11.1 mmol/L). The reference test was fasting and 2-h glucose after a 75-g glucose load. Diagnostic testing determined sensitivity, specificity, positive predictive value , and negative predictive value. The receiver operating characteristic (ROC) curve areas were determined to compare area under the curve (AUC) for sensitivity versus 1 − specificity.

A total of 1,028 subjects were included in this analysis. Mean (95% CI) for BMI and waist circumference were 30.4 kg/m² (29.9–30.9) and 97 cm (95.8–98.1). Means for systolic blood pressure and diastolic blood pressure, LDL and HDL cholesterol, triglyceride, and fasting and 2-h postload glucose levels were within normal ranges.

HbA_1c was diagnostic of diabetes using the American Diabetes Association criteria in 216 (21.0%) of the study sample.

Table 1 shows the sensitivity, specificity, positive predictive value, negative predictive value, and AUC for various thresholds of HbA_1c against OGTT as the reference test. The results show that the HbA_1c threshold of 6.4% had the highest AUC of 0.78 (95% CI 0.75–0.82) with sensitivity of 72% (65–78%) and specificity of 84% (82–87%). Using an HbA_1c threshold of 6.4% to diagnose diabetes would have resulted in 72% of patients with diabetes being correctly diagnosed and 16% being incorrectly diagnosed.

A comparison of the study cohort with the full Weqaya cohort found higher mean age in this study at 42 years compared with 35 years (P < 0.001). Nondiabetic patients in this cohort had higher mean age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, and LDL cholesterol than nondiabetic patients from the Weqaya cohort. For diabetic patients, mean age and systolic blood pressure were lower in this cohort than in diabetic patients in the Weqaya cohort.

This is one of the first studies to demonstrate the utility of HbA_1c for diagnosing diabetes and has shown that 6.4% is an optimum HbA_1c threshold for the Abu Dhabi national population.

Studies repeatedly demonstrate that within populations, over one-third of all patients with diabetes remain undiagnosed, with resulting complications due to late diagnosis (9). The availability of a single nonfasting blood test could facilitate successful population-level screening programs. The Weqaya study demonstrated this.

HbA_1c is an independent predictor of cardiovascular events in patients with diabetes and nondiabetic subjects (10), which makes HbA_1c data from screening programs a valuable resource for public health planning.

In this study, an HbA_1c threshold of 6.4% yielded the highest AUC (0.78). A recent study in China comparing HbA_1c screening with OGTT demonstrated sensitivity, specificity, and AUC of 63%, 96%, and 0.86, respectively (11). Sensitivities and specificities reported using fasting plasma glucose as the reference in the Chinese study were 56 and 97% for their optimum HbA_1c threshold of 6.4% (11) and in National Health and Nutrition Examination Survey data were 59 and 97% for their optimum HbA_1c threshold of 5.8% (12).

The higher sensitivity and lower specificity in the Weqaya study may be due to population factors affecting glycation of hemoglobin, such as hemoglobinopathies and other abnormal hemoglobin types, anemias (13), vitamins C and E, iron deficiency, and some medication use (14). Different ethnic groups have also been shown to have HbA_1c levels up to 0.4–0.7% higher than Caucasian populations despite similar glucose levels (15).

The choice of HbA_1c threshold for clinical practice will depend on whether the tool is being used for screening or diagnosis. Screening tests usually warrant the choice of high sensitivity over specificity. Because HbA_1c has now been recommended for use as a diagnostic test, specificity is increasingly important, and the threshold of 6.4% in this study provides a high specificity without too much compromise of sensitivity.

This study is the first in a Middle Eastern population to screen at population level using HbA_1c and has been shown to be representative (3); however, some differences were shown in nondiabetic subjects between this study sample and the overall Weqaya population.

HbA_1c has been validated as a suitable test for the definitive diagnosis of diabetes in the Weqaya population screening program in a high-risk Middle-Eastern population. This is a major step in the fight to tackle the increasing burden of diabetes in the UAE.

All authors were employees of the Health Authority, Abu Dhabi, for the duration of this study.

No potential conflicts of interest relevant to this article were reported.

C.H. designed the study, conducted data analysis and interpretation, and wrote the manuscript. O.H. and Z.A.S. contributed to the study design and review of the manuscript.