Elevated HbA1c levels in individuals not diagnosed with type 2 diabetes in Qatar: a pilot study

Background: The prevalence of type 2 diabetes (T2D) in Qatar and the Middle East is one of the highest in the world. It is estimated that about one quarter of the individuals with tbl2D are undiagnosed. Elevated HbA1c levels are an indicator of tbl2D or a pre-diabetic state. In this study we set out to examine which factors, such as anthropometric and socio-demographic risk factors, are associated with elevated HbA1c levels in a population without tbl2D. Methods: We examined 191 subjects with no record of tbl2D. Anthropometrics and HbA1c were measured. Socio-demographic (age, gender, ethnicity and educational level) and health information were assessed through questionnaires. Elevated HbA1c levels were defined as >6.0% (>42 mmol/mol). Individual risk factors were examined in relationship to having elevated HbA1c levels using logistic regression. Results: Thirty-eight (20%) study participants had elevated HbA1c levels. Participants from South Asian and Filipino descent were more likely to present with elevated HbA1c levels than Arab participants (adjusted odds ratios (OR): 13.30 (95% confidence interval (CI): 4.24, 41.79), p < 0.001 for South Asian and 4.54 (95% CI: 1.04, 19.83), p = 0.04 for Filipinos). A body mass index of above 30 kg/m2 was associated with elevated HbA1c levels (adjusted OR: 2.90 (95% CI: 1.29, 6.51), p = 0.01). Neither gender nor educational level was associated with elevated HbA1c levels. Conclusions: Elevated HbA1c levels in individuals not diagnosed with diabetes were most frequently found in the South Asian and Filipino immigrant population. Special attention should therefore be given to the early identification of tbl2D in these subjects.


INTRODUCTION
The prevalence of type 2 diabetes (T2D) in Qatar is estimated to be 23% and is one of the highest in the world. 1 In 1990, the prevalence was estimated at 6%, thus showing an exceptionally high rate of increase over the past decades. Furthermore, it is estimated that about a quarter of individuals with T2D in Qatar are still undiagnosed. 1 With this rate of increase, T2D has become an increasing burden on the Qatari society. It has become a growing public health challenge to identify those individuals that are at risk for developing T2D. Primary preventive strategies are focused on recognizing risk factors and when possible intervening, while screening strategies are aimed at identifying individuals with undiagnosed T2D. For example, elevated HbA1c levels are known to be predictive for the later development of T2D. Furthermore, an abundance of studies have shown that characteristics such as a high waist-hip ratio, lower socio-economic status, dark skin-color, fewer years of education and higher BMI are associated with elevated HbA1c levels. 2 -4 Qatar is a rapidly growing economy with a free nationalized healthcare program, which is accessible to all residents regardless of ethnic or social background. Many of the preventive strategies are based on research that was performed outside of Qatar, often in Western societies. 5 Also Qatar, like many other countries around the Gulf region, has a unique and dynamic socio-demographic structure with a stable native population and a rapidly growing expatriate population. Therefore, preventive strategies for T2D should be based on up-to-date studies from the region, and they also need to be stratified by population type. Thus, in this pilot study we set out to examine what anthropometric and

Population for analysis
In total, 191 subjects without T2D were enrolled, based on absence of self-reported T2D. Furthermore, we confirmed that the subjects were not taking oral glucose lowering drugs by questionnaire. Elevated HbA1c levels was based on the standard clinical cut-offs of . 6.0% (.42 mmol/mol). 7 This cut-off has also been approved by the American Diabetes Association (ADA) as a diagnostic cut-off for pre-diabetes. 7 Also, in several other populations, HbA1c has been shown to be a reliable alternative to fasting plasma glucose to detect diabetes. 8,9 In total, 38 participants (19.9%) had an elevated HbA1c level. Subject characteristics are shown in Table 1.

Statistical analyses
Individual risk factors were examined in relationship to having elevated HbA1c levels using logistic regression. Since the age distribution was different between the two groups, we used an unadjusted model (model 1), an age-and gender-adjusted model (model 2), and an age-, gender-and body mass index-adjusted model (model 3). Body mass index was calculated as weight divided by height squared (kg/m 2 ). Effect estimates for the risk of increased HbA1c levels for each individual risk factor are presented using odds ratios and their 95% confidence interval (95% CI). A p-value lower than 0.05 was considered statistically significant. All statistical analyses were performed using the IBM Statistical Package for the Social Sciences Version 20.0 (SPSS Inc., Chicago, IL, USA). There was no significant difference between males and females, nor was there an association between educational level and HbA1c levels.

DISCUSSION
In this study we set out to examine which factors are related to having elevated HbA1c levels in a population without T2D in Qatar. We found more than a 13-fold increased chance of having high HbA1c levels among South Asians in comparison to Arabs and a 4.5-fold increased chance among Filipinos compared to Arabs. Moreover, of all participants from South Asian descent who did not have T2D, 38% had HbA1c levels above 6.0% which is indicative of undiagnosed impaired glucose metabolism or T2D. Some methodological issues need to be considered. Most importantly, we consider this study to be a pilot due to the relatively low number of participants. Previous studies performed on undiagnosed diabetes in other populations are generally larger. 9,11 -13 For a number of the risk factors such as gender and education levels that we investigated, the absence of association may be due to lack of statistical power. Secondly, subjects were recruited through the Dermatology Department, which potentially may have led to selection bias. Some of the individuals may use topical steroids, which increases the risk of developing insulin resistance. Nonetheless, this risk would be increased in all ethnicities and therefore this is unlikely to have influenced our effect estimates. Finally, we used the known clinical cut-off of HbA1c levels above 6.0% (42 mmol/mol). This cut-off is generally accepted by the American Diabetes Association. 7 For impaired glucose metabolism and pre-diabetes, however, there has been some recent discussion whether the cut-off should be lowered to 5.7% (39 mmol/mol) instead of 6.0%. 14 Using a 5.7% cut-off also gave an increased risk for having high The concentration of HbA1c in plasma reflects glucose metabolism over the past two-three months. Positive associations have been found between the risk of T2D or hyperglycemia and total fat intake. 15 -18 Dietary fat intake may have an effect on glycaemia, and subsequently high HbA1c. High fat intake may also be related to obesity, which is in turn associated with insulin resistance. 19 -21 The racial and ethnic differences in HbA1c have been recognized for many years but have generally been attributed to differences in access to medical care or quality of care. 22 However, various studies have now shown that despite adjustment for socio-demographic characteristics, access to care, quality of care, and self-management behaviors, racial and ethnic differences in HbA1c remain. 23 -25 In this study, the BMI correction for HbA1c in the various ethnicities made the differences in HbA1c in Arabs compared to South Asian larger. The Arabs in our study had a markedly higher BMI and waist circumference than the South Asians and Filipinos. Therefore, one would expect a higher HbA1c level in the Arabs compared to the South Asians. However, the opposite is true, which emphasizes the important role of ethnicity in relation to HbA1c in Arabs and South Asians. Qatar has one of the fastest growing economies worldwide, with an equally rapidly increasing population. In our study almost 20% had an elevated HbA1c, which is similar to a screening pilot study that was recently performed in Saudi Arabia. 26 Like many other Gulf countries, the size of the local population has been relatively stable over the past decade, while the population growth has come from a huge surge of immigrants. Most of these immigrants are native to South Asia (India, Pakistan, Nepal, Sri Lanka and Bangladesh) and the Philippines. Our data suggests that these immigrant populations have a large increased risk of having undiagnosed T2D.

CONCLUSION
In this study we found large ethnic differences in the HbA1c levels amongst subjects without T2D in Qatar. Larger epidemiological studies are necessary to examine these differences and other risk factors in Qatar and the entire Gulf region. The ADA already recommends screening for T2D in all asymptomatic adults above 45 years old. 27 However, regarding this study, the screening and focus on the early detection of T2D should particularly be performed among the South Asian and Filipino populations in Qatar.