CHAPTER 3 DIABETES MELLITUS, OBESITY, HYPERTENSION AND DYSLIPIDEMIA IN ADULT CENTRAL KERALA POPULATION 3.1 BACKGROUND Diabetes mellitus (DM) and impaired glucose tolerance (IGT) have reached epidemic proportions globally [124] especially in developing countries like India [59]. The inevitable lifestyle changes brought about by rapid industrialization and urbanization of the Indian society is thought to be the prime cause for this epidemic and the solutions for tackling this problem still remain elusive and expensive. But recent studies have shown that lifestyle modifications can prevent or postpone the onset of diabetes in high-risk population [60-62]. During the last two decades, many population studies have been conducted in various parts of India looking at the prevalence of diabetes mellitus. In 1992, Ramachandran et al found that the prevalence of diabetes in south India was 8.2% & 2.4% in urban and rural population respectively [70]. This was much higher than their own earlier estimates done two decades ago, which showed prevalence rates of 2.3% and 1.5% in urban and rural population respectively. The same researchers found even higher prevalence rates of 11.6% in their follow-up study conducted 5 years later [71]. A recent large survey [72] has shown that the age and gender standardized prevalence rates for DM and impaired fasting glucose (IFG) in the total Indian population were 3.3 and 3.6% respectively (urban DM prevalence 4.6% versus rural DM prevalence 1.9%). This study also showed that the prevalence of 58
newly detected diabetes was 2.4% (urban 3% and rural 1.5%). As the Indian population is heterogeneous, the pattern of disease prevalence in one area may not be similar to that in another area, hence the necessity for obtaining data through regional studies. During the last five decades, Kerala state has achieved remarkable progress in reducing fertility and mortality [73] combating infectious diseases and poverty related illnesses [74]. Kerala has also achieved the lowest population growth rate and highest literacy rate in the country and shows similar demographic features of western countries. But over the last two decades, urbanization, westernization as well as general improvement in economic status and living standards have led to substantial changes in diet and lifestyle pattern of the population. This has been associated with a marked increase in the prevalence of non-communicable lifestyle related diseases such as diabetes, hypertension and coronary artery disease among the Kerala population. The National Urban Diabetes Survey conducted in 2001 was the only national study that had included a small sample population from Kerala. This reported a diabetes prevalence of 12.1%. There have been only two previous studies looking at the prevalence of diabetes in [76, 77] and both were conducted in South Kerala. These studies showed that 23.4% of diabetes cases are undetected in this population. 3.2 OBJECTIVES The aim of the present study was to evaluate the prevalence diabetes mellitus, obesity, hypertension and dyslipidemia and to identify the risk factors associated with type 2 diabetes in an urban population. 3.3 MATERIALS AND METHODS Sample Selection and Study Design is as described in Chapter 2. Houses were selected from four survey areas and obtained survey data from all adult residents above the age of 18 years from selected house clusters. A resident was 59
defined as a person who had resided in the surveyed house for at least fifteen days in the previous three months. The fieldworkers conducted a 15-minute survey collecting details of demographic and socio-economic status (SES), medical history, lifestyle details and dietary pattern. Economic status was assessed indirectly using a scoring system looking at the type of house, household possessions etc and classified as poor, middle or high-income group. Physical activity was assessed by questionnaire and graded into four categories of sedentary, mildly active, moderately active and highly active. The final study sample included 931 houses and 3069 adults. The surveyed population was invited to participate in the second phase of the study, which was conducted in their locality. About 32% (n= 986) underwent the second phase of the study, which included physical evaluation and biochemical investigations. Though, ideally a randomly selected sample would have been preferable, due to practical problems this could not be done. Informed consent was obtained from all those who participated in the second phase of the study. Fasting (10 hours overnight) venous blood samples and urine samples were collected from all phase 2 participants, which were stored in ice packs and transferred to the laboratory. A 75gm anhydrous glucose load was given orally in 250 ml of water to all subjects except those with known diabetes. Fasting and 2- hour post glucose load capillary blood glucose was assessed by a calibrated glucometer by the glucose oxidase method. Fasting serum sample was collected and transferred to laboratory for lipid profile and other blood tests. Fasting cholesterol was done using CHOD-PAP method and triglyceride was done GPO- PAP method using Elecsys Auto Analyzer. Participants underwent anthropometrical measurements such as height, weight, skin fold thickness, waist circumference and hip circumference. A medical doctor verified medical history and performed physical examinations including blood pressure (BP) and examination for acanthosis nigricans (AN). 60
3.3.1 MEASUREMENTS Blood pressure was recorded in the sitting position in the non-dominant arm to the nearest 2mm Hg using a standard adult mercury sphygmomanometer. Two readings were taken 5 minutes apart and the mean of the two readings was taken as the blood pressure. The first and the fifth Korotkoff s sounds were used to define systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively. Variations in BP measurements were minimized by ensuring a 10-minute rest period before the BP recorded. Fig. 3.1 Blood pressure check up Anthropometrical measurements included height and weight using a standard calibrated height and weight machine. The Body Mass Index (BMI) was calculated using the formula weight [kg / height (m) 2 ]. BMI for males and females were categorized according to Asian criteria for BMI: <20 (Underweight), 20-23 (Normal), 23.1-25 (Over weight), 25.1-30 (Obese), and >30 (Morbidly obese) [125]. 61
Fig. 3.2 Measuring waist circumference The triceps and subscapular skin fold thickness were measured to the nearest millimeter with the Lange skin fold caliper (Cambridge Scientific Industries Inc., Cambridge, MD). The subscapular skin fold thickness was measured immediately below the inferior angle of the scapula. Triceps skin fold thickness was measured at the midpoint between the lateral projection of the acromial process and the inferior border of the olecranon process of the ulna. Waist circumference (WC) was measured midway between the rib cage and the superior border of the iliac crest with a non-stretchable tape. Hip circumference was measured at the level of greater trochanters. These measurements were taken twice and the mean value for each anthropometric characteristic was used in all analyses. The subscapular-to-triceps skin fold-thickness ratio (STR) and the waist-to-hip ratio (WHR), two widely used indices of body fat distribution, were calculated. The participant s neck region was examined by the study physician for AN, [64] and was graded as present or absent. 62
3.3.2 DEFINITION AND DIAGNOSTIC CRITERIA Diabetes was defined by WHO criteria using capillary glucose measurements. Subjects with fasting capillary glucose >110 mg/dl and or 2- hr capillary glucose of >200 mg/dl were classified as having diabetes. Subjects were also considered to be diabetic if they reported history of diabetes diagnosed by a physician or if they were on anti-hyperglycemic agents irrespective of their present blood glucose values. A fasting capillary glucose of <110 and a 2-hr capillary glucose of >140 mg/dl and <200 mg/dl were diagnosed as having IGT. Impaired fasting glucose (IFG) was diagnosed when fasting capillary glucose was < 110 mg/dl and >100 mg/dl [126]. Those subjects with diabetes, IGT, IFG were grouped together (dysglycemic) whereas subjects without any form of glucose intolerance were considered normoglycemic. High cholesterol was defined as total cholesterol >230mg/dl and high triglyceride was defined as serum triglyceride value >150mg/dl [127]. Hypertension was defined as a systolic blood pressure (SBP) >140 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg or if taking antihypertensive medications. Hypertension was classified based on the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and treatment of High Blood Pressure [128]. 3.3.3 STATISTICAL ANALYSIS SPSS for Windows (Version 11) was used for data management and statistical analysis. The prevalence of diabetes and IGT were expressed as percent (number of cases per 100 population). Association between two categorical variables was tested using the X 2 test or Fisher s exact test wherever appropriate in case of contingency tables. Stepwise logistic regression analysis was performed to determine the relative risk of independent risk factors with type 2 DM. Age, gender, income, family history of diabetes, BMI, waist circumference, subscapularis-triceps skin fold ratio, and acanthosis nigricans were included as covariates for the analysis. Any p value <0.05 was considered as the level of statistical significance. 63
3.4 RESULTS The prevalence of known diabetes was 9.0% (276/3069) (Males- 8.7% (129/1479) and Females-9.2% (147/1590). The age and anthropometric variables of total of the 986 subjects (M 389, F 597) who participated in the second phase of the study are given in Table 3.1. 50.0 45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 Age and gender distribution Male Female 23.9 23.4 20.4 19.3 20.9 19.2 20.119.6 19.3 13.9 lessthan30 30-40 41-50 51-60 morethan60 Fig. 3.3: Age and gender distribution of study subject (986) 3.4.1 DIABETES MELLITUS There were 174 subjects with known DM. Based on OGTT, a further 85 new cases of DM (prevalence of newly diagnosed DM 10.5% i.e. 85/986-174) were identified. Newly detected diabetes was more common among males (11%) compared to females (8.4%) but this difference was not statistically significant. The prevalence of IGT was 4.1% (34/812) and IFG was 7.1 % (59/812). Prevalence of IGT was similar in both genders (Male 4.3%, Female 4.09%). Among the study subjects 38.8% were <40years old and 41.4% were between 40-60years and 19.85 were >60years old. Age and gender distribution is shown in Fig. 3.3. 64
Table 3.1: Distribution of Common Variables among screened population (986) Variables Male n 389 Female n 597 (Mean SD) (Mean SD) Age (Years) 45.3 15.4 44.4 14.7 Height (cm) 165.5 7.3 151.77 6.7 Weight (kg) 61.69 12.6 51.9 11 BMI (Kg/m 2 ) 22.4 3.8 23.4 4.3 Waist Circumference (cm) 81.6 11.6 76.8 10.7 Hip Circumference- (cm) 89.7 10.7 90.3 9.6 Waist Hip Ratio 0.9 0.06 0.85 0.07 Systolic BP (MmHg) 125.6 7.3 124.6 18.3 Diastolic BP (MmHg) 78.8 9.1 77.7 8.6 The prevalence of diabetes by age indicated a steady increase after age 50 (Table 3.2 and Fig. 3.5). The prevalence of IGT also showed similar age trend especially in females. The prevalence of DM according to BMI also suggested a progressive increase in DM prevalence with increasing BMI especially over 25 (Fig. 3.6). Acanthosis nigricans was present in 16.5% (152/963) of the population and was more common in females (20%) than males (11.2%). Subjects with diabetes 53.7% had positive family history of diabetes compared to 34% of non-diabetic subjects and this difference was statistically significant (p <0.001). Initially a univariate logistic regression analysis was carried out in order to find the risk factors for DM with respect to each of the variables. Univariate logistic regression analysis showed that factors such as increasing age (p<0.0001), gender (p= 0.001), family history of DM (p<0.0001), high income (p<0.0001), obesity (p<0.0001), presence of AN (p =0.01), increased WC (p<0.0001), sedentary lifestyle (p <0.0001) and increased STR (p <0.0001) were significantly associated 65
Percentage percent with DM. Level of education, type of diet and religion and other skin fold ratios are not significantly associated with DM. Those variables with a p value <0.2 in univariate regression were used in multivariate logistic regression analysis. Increasing age, positive family history of DM, increasing BMI, gender, high STR and presence of AN turned out to be the only significant variables. Age had the highest relative risk followed by positive family history of diabetes and BMI (Table 3.2). 100 90 80 70 60 50 40 30 20 10 Male Female 0 <30 31-40 41-50 51-60 >60 Fig. 3.4 The prevalence of DM and IGT by age category and gender BMI and Diabetes, IGT, IFG 30 25 20 15 10 5 0 7.90 7.4 4.25.1 5 2.2 28.40 23.90 16.90 8.1 5 3.4 <20 20.1-23 23.1-25 >25 BMI Category IFG IGT DM Fig. 3.5 Prevalence of DM, IGT and IFG among different BMI Categories 66
Table 3.2 Multivariate regression analysis SL Variables as Relative 95 % CI P VALUE NO Diabetes predictor Risk 1 INCREASING AGE < 30 1 31 40 2.89 1.42 5.8 0.003 41 50 5.1 2.58 10.1 <0.0001 51 60 9.62 4.84 19.16 <0.0001 > 60 17.23 8.91 36.07 <0.0001 2 GENDER FEMALE 1 MALE 1.92 1.38 2.68 <0.0001 3 POSITIVE FAMILY HISTORY NO 1 YES 2.49 1.79 3.48 <0.0001 4 ACANTHOSIS NIGRICANS NO 1 YES 1.79 1.6 2.78 0.009 5 BMI < 20 1 20 23 1.8 (1.07 3.0) 0.026 23 25 2.34 (1.37 4) 0.002 > 25 2.27 (1.37 3.76) 0.001 6 SUBSCAPULAR TRICEPS SKINFOLD RATIO Normal 1 Abnormal 1.42 1.02 1.96 0.036 67
3.4.2 HYPERTENSION In this study population 202 subjects (20.2%) had history of hypertension (M 22.4% F 19.2%). After evaluation 110 new subjects were found to have hypertension making a total prevalence of hypertension in this population as 32%. Prevalence of hypertension was similar in males and females (M 32.5% vs. F 31.8% p NS). Hypertension was significantly (p <0.001) higher among subjects with Diabetes (47.5%) than non-diabetic subjects (26%). Hypertension was similar among different income categories of subjects. Subjects with sedentary life style had more hypertension (44%) than people with mild activities (38.4%) or moderate activities (22.8%) and this was found to be significant (p <0.001). Linear correlation of systolic and diastolic BP with continuous variables was done using Pearson s correlation which showed significant positive correlations with age, BMI, and waist circumference but had mild positive correlations with blood sugars, total serum cholesterol, and LDL and triglyceride values. Neither systolic nor diastolic BP had any correlations with thyroid hormone levels and urine iodine levels (Table3.3). Table 3.3 Linear correlation of systolic and diastolic blood pressure Variables Systolic BP r value Diastolic BP r value Age in years 0.393 0.282 BMI Kg/M2 0.226 0.247 Waist circumference 0.253 0.275 FBS 0.171 0.144 PPBS 0.151 0.144 Total cholesterol 0.164 0.159 Triglycerides 0.172 0.200 Variables with P<0.001 are only shown here. 68
3.4.3 OBESITY Overweight and obesity (BMI >23) was seen in 50.5% of the total population (M 46.4% and F 53% p=0,008). Obesity (BMI >25) was present in 309 (31.7%) of the study subjects and was significantly higher in females (35.8%) than males (25.3%) (p<0.001). Prevalence of obesity in various age groups is shown in Fig. 3.7. Obesity was more common in 41-50yr age group and it showed a decreasing trend beyond this age group. Obesity was significantly higher in high income group (43.6%) than middle income (34.3%) and poor income group (20.4%) (p<0.001). 100 90 80 70 60 50 40 30 20 10 0 24.6 13.3 28.2 22 12.6 12 23 25.1 22.1 22.4 16.9 22.9 19 17.8 18.2 31.2 18.2 17.3 15.6 17.8 <30yrs 30-40yrs 40-50yrs 50-60yrs >60yrs >25 23-25 20-23 <20 Fig. 3.6 Prevalence of obesity in various age groups 3.4.4 DYSLIPIDEMIA In this population, 311 subjects 32% had total cholesterol >230mg/dl and 226 subjects had 23.2% had triglyceride >150mg/dl. Dyslipidemia was significantly more common in subjects with diabetes, hypertension, and obesity. Total cholesterol had significant (p<0.001) positive linear correlations with age, BMI and waist circumference. But Triglyceride level had stronger correlation with BMI and waist circumference than age (Table.3.4). 69
When the prevalence of all these metabolic problems is compared among the various age groups it showed some interesting trends. Prevalence of diabetes, hypertension, high cholesterol and high triglyceride increased with increasing age. But the prevalence of Acanthosis nigricans starts declining after the age of 40 whereas obesity start declining after the age of 50. Table 3.4: Linear correlations of serum total cholesterol and triglyceride with continuous variables Variables Total cholesterol r value Triglyceride r value Age in years 0.285 0.143 BMI Kg/M2 0.211 0.211 Waist circumference 0.195 0.291 FBS 0.124 0.174 PPBS 0.138 0.183 Systolic BP 0.164 0.172 Diastolic BP 0.159 0.200 All variables had p value <0.001 (r correlation coefficient). 3.5 DISCUSSION Over the last two decades, epidemiological studies conducted in different parts of India have shown that the prevalence of diabetes and impaired glucose tolerance is steadily increasing [129]. Regarding the population of Kerala, the first study conducted in an urban housing settlement of south Kerala [77] showed a diabetes prevalence of 16.2%, which was equally distributed between males and females. In another large population survey conducted in south Kerala [76], the ageadjusted prevalence of diabetes was 8.4% with a male preponderance (Male: 9.2% Female: 7.4%). However the prevalence varied within one geographic area. The 70
present study however is the first of its kind conducted in the Central part of Kerala state. 100 90 80 70 60 50 40 30 20 10 0 <30yrs 31-40yrs 41-50yrs 51-60yrs >60yrs Acanthosis nigricans Diabetes Obesity Hypertension High Cholesterol High triglycerides Fig. 3.7 Prevalence of various metabolic problems in different age groups in the study population (986) The results of this study have shown a much higher prevalence of DM compared to earlier studies. This may be due to two reasons. The previous two studies used old WHO criteria for diagnosing Diabetes (fasting plasma glucose of 140mg/dl), whereas this study used the new criteria (FPG 126mg/dl equivalent to capillary value of 110mg/dl). Moreover, our study population included only semi urban and urban populations who are likely to have higher prevalence rates of diabetes, as shown in previous south Indian studies. The prevalence of diabetes in Central Kerala has not been assessed to date; hence this high prevalence could reflect regional variations of diabetes prevalence in different parts of Kerala. 71
Prevalence of newly detected diabetes varies considerably in various parts of the world. This could be as low as 20% to as high as 56% in different communities [130]. Undiagnosed diabetes in our study population was much higher (10.3%) than in previous studies. The fact that more than 50% of diabetes remains undetected in this community despite better health standards, literacy and easy accessibility to primary health care centers highlights the need for designing wide spread screening program for early detection among high-risk populations in Kerala state. This also points to the need of a statewide large population survey of DM to assess the actual prevalence of glucose intolerance in the State. This would help to design appropriate prevention strategies based on public education and diabetes awareness program. Though males had higher prevalence rates of diabetes than females, this difference did not exist beyond the age of sixty. Previous studies from Kerala as well as other parts of India also have shown either male preponderance of DM or equal prevalence of DM between both genders similar to our study [76, 131]. IGT in this study population was much lower than in previous South India studies where IGT prevalence was reported as 8.1% [131]. IFG among this population was similar to the results of the previous studies of South India. Since IFG and IGT are considered to be strong risk factors for diabetes, these results demonstrate potential for ever increasing diabetes prevalence in Kerala. However identifying these high risk groups is important, as they could be the targets for primary prevention of diabetes. But as this study used capillary blood glucose these subjects need laboratory testing before confirming the diagnosis. A number of studies have associated AN with hyperinsulinemia and insulin resistance [132]. Many studies done in other countries however have shown variable prevalence of Acanthosis Nigricans from 18.1% to 34.2 % in different populations [133, 134]. To our knowledge this is the only study, which has assessed prevalence of Acanthosis nigricans among adults in India. The present study has also 72
demonstrated that AN, a simple cutaneous marker of insulin resistance is significantly associated with the risk of diabetes and IGT. Along with a positive family history and obesity, AN can be used as a reliable clinical marker to the presence of glucose intolerance. No previous studies have studied this association in India and hence comparison with other Indian studies was not possible. Results of other Indian studies have shown that DM was more common among subjects with high income and poor education. Results of the present study, however, did not reveal any such association. In our study, income was assessed indirectly using a scoring system which could be much more accurate than the reported income levels by the subjects in other studies as most people tend to understate their income. The socioeconomic features peculiar to Kerala and the high literacy of the population could also contribute to this. The results of this study failed to show any association of physical activity with risk of diabetes. This could be due to the fact that subjects with high physical activity were too few to form a group and were added to the moderately active category. Hence for analysis there were only sedentary and moderately active groups. This may be reflective of the low levels of physical activity prevalent in this population. The inadequate physical exertion was seen even among the younger age groups highlighting the necessity to raise public awareness about the value of regular physical activity in preventing DM. Prevalence of hypertension, another silent killer has been assessed in various population studies in different parts of the world. In the United States about 29% of adults have hypertension [135]. In a study conducted among subjects >60years in Trivandrum had shown prevalence of hypertension as 50% [136]. Blood pressure showed significant positive linear correlations with increasing age and body mass index and waist circumference. Hypertension was similar in males and females which is similar to other studies from Kerala [136]. 73
Obesity was seen in one third of the population and was significantly higher in females. This was similar to other studies from south India [137]. The overall prevalence of DM, obesity, hypertension, hypercholesterolemia, high triglycerides and AN in different age categories showed that prevalence of AN was highest among 31-40 year age group whereas obesity peaks a decade after. But despite this, DM prevalence is steadily increasing with advancing age. This may be explained by the natural history of insulin resistance and obesity, which is associated with hyperinsulinemia in the initial period and insulin deficiency and glucose intolerance in the later stages. Similarly high cholesterol and high triglyceride was also very common among this study population. These results were similar to the studies from Chennai and Trivandrum [138]. Total cholesterol levels showed significant positive correlation with age, and increasing BMI and weak positive association with other parameters, On the contrary triglyceride levels had strong positive association with BMI & waist circumference and diastolic BP. This may be due to the relation of triglyceride with visceral obesity and insulin resistance. The limitations of our study included the poor response rate in the second phase of the study. Only 32% of the surveyed population participated in phase 2 of the study despite repeated efforts to improve participant attendance. However as the basic socioeconomic and demographic features of the non-responders did not vary significantly from the responders we feel this limitation did not cause any serious bias in the sample population. Capillary blood glucose samples were used for the diagnosis of DM. Although this is an accepted method by WHO for epidemiological studies, fasting plasma glucose would have provided more accurate information. This data is the first of its kind from an adult Indian population from this region and has been added as a sample Kerala data in the Diabetes map of India (Fig. 3.8) and is widely quoted and referred to. 74
Fig. 3.8 Prevalence of Diabetes mellitus in different parts of India [139] 3.6 CONCLUSION This study showed that the prevalence of undetected diabetes and IGT among a sample of semi urban and urban populations in central Kerala was 10.5% and 4.1% respectively. Other than increasing age, obesity and a positive family history, presence of Acanthosis Nigricans should also be considered a strong indicator for glucose intolerance in this population. Obesity (BMI >25) was present in 31.7% of the study subjects and was significantly higher in females than males. In this study population 20.2% had history of hypertension another 12% had new hypertension. Prevalence of hypertension was similar in males and females. Among this population 32% had high cholesterol and 23.2% had high triglycerides. 75