Running title : Diabetes prevalence and management in Thailand

Objective To determine the prevalence of diabetes and impaired fasting glucose (IFG), their association with cardiovascular risk factors, and evaluate the management of blood glucose, blood pressure and cholesterol in individuals with diabetes by geographical regions of Thailand. Research design and methods Using a stratified, multistage sampling design, data from a nationally representative sample of 37,138 individuals aged ≥ 15 years was collected using questionnaires, physical examination and blood samples. Results Prevalence of diabetes and IFG weighted to the national 2004 population was 6.7% (6.0% in men and 7.4% in women) and 12.5% (14.7% in men and 10.4% in women), respectively. Diabetes was more common in urban compared to rural men but otherwise prevalence was relatively uniform across geographical regions. More than half of those with diabetes had not been previously diagnosed, although the majority of those diagnosed were treated with oral anti-glycemics or insulin. Prevalence of associated risk factors was high amongst individuals with diabetes as well as those with IFG. Two thirds of those with diabetes and concomitant high blood pressure (≥ 130/80mmHg) were not aware that they had high blood pressure, and more than 70% of those with diabetes and concomitant high cholesterol (total cholesterol ≥ 6.2 mmol/L) were not aware that they had high cholesterol. Conclusion Diabetes and IFG were uniformly high in all regions. Improvements in the prevention, diagnosis and treatment of diabetes and associated risk factors is required if the health burden of diabetes in Thailand is to be averted. Diabetes and its associated complications are a major health and economic burden worldwide (1,2), with this burden expected to continue to rise (3). This is particularly relevant to the Asia-Pacific region, where lifestyle changes associated with rapid economic development, improved survival from communicable diseases and genetic susceptibility have led to rising diabetes prevalence (4,5). Thailand provides a prime example of this trend (6). A survey in 1999 estimated that 9.6% of Thai adults aged ≥ 35 years had diabetes with 5.4% having impaired fasting glucose (fasting plasma glucose ≥ 6.1 mmol/L and < 7.0 mmol/L) (7). Half of those with diabetes had not been previously diagnosed, while of those diagnosed, 18% were not receiving oral anti-glycemics. Among those with diagnosed diabetes and concomitant hypertension, one third were not receiving blood-pressure lowering medication. These represent lost opportunities for reducing the risks of macroand microvascular diseases associated with diabetes. To monitor the effectiveness of the health system response, routine measurement of the prevalence and management of diabetes is crucial. In Thailand, subnational monitoring is also essential given health administration decentralization, as well as differences in economic development and life-style between geographical regions (8). In this paper, we describe the prevalence of diabetes and IFG as well as the diagnosis, treatment and control of blood glucose, blood pressure and cholesterol in those with diabetes by five geographic regions of Thailand. We use data from the 2004 Third National Health Examination Survey (NHESIII) of more than 37,000 fasting individuals aged ≥ 15 years, which to date, is the single largest survey of fasting plasma glucose in an adult population. Research design and methods NHESIII was conducted between January and May, 2004 by the Health Systems Research Institute (see acknowledgements). The study was approved by the Ethical Review Committee for Research in Human Subjects, Ministry of Public Health. All participants provided written informed consent. Sample design A multi-stage sampling frame based on government registers was used. For areas except for Bangkok, three provinces were chosen by probability proportional to size (PPS) for each of the twelve health administration areas. At the second stage, nine electoral units (EUs) or villages were selected by PPS from both urban and rural areas for each province. At the final stage, fifteen individuals were selected by simple random sampling with replacement from four broad age and sex-groups (Males/Females, 15-59 / 60+ years of age) for each EU/village. Replacements were randomly sampled within a 5-year age range, and of the same sex and EU/village. For Bangkok, nine EUs were selected PPS from six geographical zones. The final stage sampling was identical to the other provinces. The final collected sample, after selecting replacement individuals, was 39,290 individuals out of a target sample size of 42,120 (93.3%). The final collected sample as a percentage of the target sample size, after selecting replacement individuals, by geographic region was as follows: Central 99.1%; Northeast 96.5%; North 92.0%; South 89.2%; and Bangkok 72.2%. The proportion of the Thai population that is urban by geographic region is: Central 32.3%; Northeast 15.0%; North 20.1%; South 23.5%; and Bangkok 100.0%. Data collection and measurement Demographic characteristics, previous diagnosis of diabetes, high blood pressure, high cholesterol and corresponding medication use, and smoking habits were based on interview. Three serial measurements of blood pressure, one minute apart, were made using a mercury sphygmomanometer. Weight, height and waist circumference were directly measured using standard techniques (9). Participants were asked to fast for 8 hours overnight before the venous blood sample was obtained. Sera were frozen and transferred to a regional university laboratory for analysis of plasma glucose using a hexokinase enzyme method. Serum total cholesterol was measured using enzymatic methods. All regional laboratories were standardized by a central laboratory at the Ministry of Public Health. Definition Diabetes was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L, use of medication (oral anti-glycemics or insulin) for the treatment of diabetes during the previous 2 weeks, or a report of a previous diagnosis of diabetes by a medical doctor. Diagnosed diabetes was defined as meeting the criteria for diabetes and having previously been diagnosed by a medical doctor as having diabetes. As glycosylated hemoglobin (HbA1c) measurements were not obtained in the survey, control of plasma glucose was defined as FPG < 7.8 mmol/L (10). Impaired fasting glucose was defined as FPG ≥ 5.6 mmol/L and < 7.0 mmol/L. High blood pressure was defined as systolic blood pressure (SBP) ≥ 130 mm Hg or diastolic blood pressure (DBP) ≥ 80 mmHg (average of the two measurements with the lowest variability) or blood pressure lowering medication use during the previous 2 weeks (11). High cholesterol was defined as total serum cholesterol ≥ 6.2 mmol/l or cholesterol-lowering drug use during the previous 2 weeks. Central obesity was defined as a waist circumference of ≥ 90cm in males and ≥ 80cm in females (12). Overweight was defined as a body mass index (BMI) of ≥ 25kg/m (12,13) Statistical methods The analysis was restricted to respondents who had fasted over the previous eight hours before blood collection (94.5% of respondents) with the sample weighted against the registered 2004 population by public health administration area, area of residence (urban/rural; geographical zone for Bangkok), sex and 5-year age groups up to 80+ years. All comparisons by sex, area of residence, geographic region and fasting plasma glucose status were ageand sex-standardized to the national population. Adjusted Wald tests were used to determine statistical significance with p<0.05 considered statistically significant. Robust methods of variance estimation were used to take into account the complex survey design using Stata 9.2 (Stata corporation, Texas). Results Mean fasting plasma glucose (FPG) was 5.2 mmol/L (standard error [SE] 0.04), 5.3 mmol/L (SE 0.04) in men, and 5.2 mmol/L (SE 0.04) in women. Prevalence of diabetes and impaired fasting glucose (IFG) in Thais aged ≥ 15 years was 6.7% (95% confidence interval [95% CI] 5.9% to 7.6%) and 12.5% (95% CI 11.0% to 14.2%), respectively. Diabetes prevalence in men was lower than in women (6.0% vs 7.4%; p<0.05 for the age-standardized comparison), while prevalence of IFG was higher in men than in women (14.7% vs 10.4%; p<0.001 for the age standardized comparison) These figures equate to an estimated 3.0 million Thais with diabetes (1.3 million men and 1.7 million women), and 5.6 million with IFG (3.2 million men and 2.4 million women). Diabetes prevalence was notably higher amongst women aged 55 to 74 years compared to men of the same age (Table 1; p<0.001), whereas IFG prevalence was higher amongst men aged 25 to 54 years compared to women of the same age (Table 1; p<0.001). Diabetes was more common in urban males compared to rural males (Figure 1; p<0.01), but similar in urban and rural females (p>0.05). Male prevalence was higher in Bangkok compared to the urban North (Figure 1; p<0.01) and urban South (p<0.05). Bangkok and the urban and rural Northeast had the highest female prevalence of diabetes which was higher than the urban North and rural South (Figure 1; p<0.05 for all comparisons). Cardiovascular risk factors amongst those with impaired fasting glucose and diabetes Individuals with diabetes have high levels of concomitant cardiovascular risk factors (Table 2), except for smoking, with 72.7% (95% CI 68.7% to 76.4%) having high blood pressure (≥ 130/80 mmHg or on medication), 33.0% (95% CI 28.6% to 37.8%) having high total cholesterol (≥6.2 mmol/L or on medication), 48.8% (95% CI 43.6% to 54.1%) being overweight (BMI≥25kg/m) and 53.5% (95% CI 48.3% to 58.6%) having central obesity (waist circumference ≥ 90cm in males and ≥ 80cm in females). Those with diagnosed diabetes tended to have a higher prevalence of high blood pressure, high cholesterol and overweight but with lower smoking prevalence than those who had not been previously diagnosed (Table 2).