RISK FACTORS OF TYPE 2 DIABETES MELLITUS IN THE RURAL POPULATION OF NORTH KERALA, INDIA: A CASE CONTROL STUDY

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1 1 Department of Internal Medicine, Academy of Medical Sciences, Pariayaram, Kannur, Kerala, India; 2 Research Division, Gulf Medical University, Ajman, United Arab Emirates Original Research Article RISK FACTORS OF TYPE 2 DIABETES MELLITUS IN THE RURAL POPULATION OF NORTH KERALA, INDIA: A CASE CONTROL STUDY Balakrishnan Valliyot 1, Jayadevan Sreedharan 2, Jayakumary Muttappallymyalil 2, Sudha Balakrishnan Valliyot 1 Key words: diabetes mellitus, risk factors, rural population, North Kerala, India SUMMARY The aim of the study was to assess the risk factors associated with type 2 diabetes mellitus (T2DM) in rural population of North Kerala, India. The study included 100 T2DM cases randomly selected among patients with diabetes admitted to medicine ward and 200 controls without DM recruited from visitors and patient attendants at a tertiary care centre in the northern part of Kerala, India. A questionnaire that contained sociodemographic characteristics and risk factors was used for data collection. ANOVA was performed to find the significance of more than two means. Simple binary logistic regression and multiple binary logistic regression were performed to find the crude and adjusted odds ratio (OR) and 95% confidence interval (CI) was calculated to find the significance of the observed OR. A p value <0.05 was considered statistically significant. Study results showed those above 50 years of age to have five times more chance to get diabetes when compared with Corresponding author: Dr. Jayadevan Sreedharan, Assistant Director & Professor, Research Division, Gulf Medical University, Ajman, United Arab Emirates drjayadevans@gmail.com those in the age group. Gender and religion did not show any statistically significant association with diabetes. Physical activity was observed as a protective factor for the development of DM. Hypertension, especially systolic hypertension, emerged as a strong risk factor for T2DM in this study. Subjects with systolic hypertension had 4.6-fold chance to develop T2DM, making it mandatory to screen all patients with hypertension above 25 years of age for T2DM irrespective of the presence of other risk factors. In conclusion, results of the present study will be of use in planning primordial, primary and secondary measures of prevention at the community level. INTRODUCTION Type 2 diabetes mellitus (T2DM) is the commonest form of diabetes affecting more than 90% of the diabetic population worldwide. There is a rapid upsurge in the number of diabetic patients and this explosive growth is noted in both urban and rural areas. Wild et al. estimated the number of T2DM patients in the year 2000 at 174 million and predicted it to increase to 366 million in 2030 (1). Diabetologia Croatica 42-1,

2 The majority of the patients with diabetes in developed countries are above age 64. It is predicted that by 2030, the number of people aged above 64 with diabetes will be around 82 million, of which about 48 million in developing countries. India has the largest diabetic population and it is expected to increase to 174 million in the year 2025 (2). In developing countries, the majority of people with diabetes are in the age group (3). Seventy percent of the Indian population live in rural areas. It is a well-known fact that urban and rural populations have different lifestyles, work patterns, and environmental and sociocultural factors. The presentation of T2DM is not uniform throughout the world and there are geographical and ethnic variations in the presentation of T2DM across the world. Most studies from western countries (4-6) and urban studies from India point to lifestyle changes (7), sedentary life (5), diet and related epidemiological transition (8) as the major factors in the development of DM. The risk factors hitherto specified in the development of T2DM in the western and urban population cannot fully apply to a rural setting. So, when there is a rapid upsurge of T2DM in both urban and rural areas, it is an imperative to identify the factors predisposing to the development of the disease, which affects one out of every five Indians. There are only limited studies on the subject from India; of them, the most acclaimed studies are from Chennai and other metropolitan cities in India. The majority of the studies from India are prevalence studies on DM and only very few studies have focused on the profile and risk factors of T2DM. The North Malabar areas of Kerala state include Kannur, Kasargod and Wayanad districts and most of the population in this area have a traditional rural lifestyle. Hence, this study was undertaken to determine the risk factors of T2DM among rural population of North Kerala, India. MATERIALS AND METHODS This study was conducted at the Academy of Medical Sciences, Pariyaram, which is a Research Centre and Postgraduate Institute situated in the Kannur District of North Malabar area in Kerala, India. One hundred cases with T2DM and 200 unmatched controls without DM were recruited for the study. Cases were randomly selected among patients with diabetes admitted to the medicine ward and 200 controls among visitors and patient attendants. A case control ratio of 1:2 was adopted in this study. A pretested structured interviewer administered questionnaire was used for data collection. The questionnaire contained data pertaining to sociodemographic characteristics and various risk factors associated with the occurrence of DM. Collected data were analyzed using SPSS 13 version (IBM, Illinois, Chicago). Frequency, percentage, mean and standard deviation were calculated and associations between variables were assessed using chi-square test. Also, t-test was used to find significant differences of two means and ANOVA was employed to find the significance of more than two means. In addition to the above statistical tools, simple binary logistic regression analysis and multiple binary logistic regression were performed to find crude and adjusted odds ratio (OR). The 95% confidence interval (CI) was calculated to find the significance of observed OR. In all cases, p value <0.05 was considered statistically significant. RESULTS Gender wise distribution of subjects showed that 71.0% of cases and 59.0% of control subjects were males. A statistically significant association was found between cases and controls with regard to gender (p<0.05). With regard to age, 83.0% of the case group subjects and more than 56.0% of control group subjects were above age 40. A highly significant association was observed between cases and controls with regard to age (p<0.001). The majority of study subjects from both case and control groups belonged to Hindu religious groups. There was no statistically significant association between diabetes status and religion. When the participants were compared according to occupation, it was found that 29% of control subjects and 25% of cases were homemakers, whereas 8% of control subjects and 7% of cases were manual laborers. Other occupational groups included 34

3 professionals, mechanics, etc. A highly significant statistical association was observed between diabetes status and occupation (p<0.001). Dietary pattern showed that among controls 93% were having mixed diet and 7% were vegetarians, whereas among cases 89% were mixed diet consumers and 11% were on vegetarian food. When further analyzed with chi-square test, dietary pattern did not show any significant association. It was observed that 38% of the cases and 18.5% of the controls were tobacco users. When tested with chi-square test, tobacco use showed a statistically significant association (p<0.001). Assessment of self-reported physical activity showed that 42% of cases and 14.5% of control group subjects were involved in heavy work. Among cases and controls, 39% and 18% were involved in moderate physical activity, respectively, whereas 19% of cases and 67.5% of controls were involved in sedentary activity. The association between physical activity with regard to diabetes status was found to be statistically significant (p<0.01). With regard to family history of DM, 55.0% of cases and 37.5% of controls had a family history of DM. The association observed was high (p <0.001). A detailed study of the family history of DM showed that in 24% of cases and 11.5% of controls mothers were diabetic, whereas fathers were diabetic in 10.5% of controls and 7% of cases. When compared according to body mass index (BMI) less than 18.5 kg/m 2, both cases and controls were equally distributed, whereas 67% of cases and 62% of controls had BMI in the range of kg/m 2.Overweight was recorded in 25% of cases and 29% of control subjects. BMI greater than 30 kg/m 2 was found in only 3% of cases and 4.5% of controls. There was no statistically significant association between BMI and diabetic status. Systolic blood pressure of less than 140 mm Hg was measured in 93.5% of control subjects and 61% of cases. When this observation was tested with Pearson chi-square test, systolic blood pressure was found to be a significant factor associated with diabetes status (p<0.001). With regard to diastolic blood pressure, 88.5% of control group subjects and 82% of case group subjects had a diastolic blood pressure of less than 90 mm Hg. There was no statistically significant association between diastolic blood pressure and diabetic status. Details are given in Table 1. Table 2 shows that the mean age was lower in the case group than in the control group. The mean height in both cases and controls was found to be equal. Difference in the mean weight was not statistically significant. Age, gender, occupation, physical activity, family history, diet, tobacco use, and systolic blood pressure showed statistically significant correlation with diabetic status level. The above parameters that revealed significance were included in the simple binary logistic regression model and then in the multiple logistic regression model. The OR and its confidence interval are shown in Table 3. Age was found to be a significant factor. In comparison with the age group, the age group had a 4.7-fold and age group 5.5-fold likelihood of developing DM. On adjustment for all other factors, gender was not found to yield statistically significance. Physical activity was measured according to their type of work and was divided into minimal, moderate and hard physical activity. For those involved in doing hard activity, the chance of getting diabetic was by 89% less when compared to those doing minimal activity, which was statistically significant. Family history was found to be an important risk factor with a p value of Multiple logistic regression analysis showed an adjusted OR of Those with a family history of DM had 3.09-fold greater chance of getting the disease as compared to those without a family history of DM. Tobacco use appeared as a significant risk factor for the occurrence of DM. The adjusted OR was 2.49, which was statistically significant. Systolic blood pressure was another risk factor for the development of DM. After adjusting for all other factors, the OR observed was 4.69 with a CI of So, age, family history, physical activity, tobacco use and systolic hypertension emerged as significant independent risk factors for the occurrence of DM. Diabetologia Croatica 42-1,

4 Table 1. Sociodemographic characteristics and other correlates between cases and controls Variable Gender Age group (yrs) Religion Occupation Physical activity Family history Body mass index Pattern of diet Tobacco use Group Cases Controls Total n % n % n % Male Female Hindu Christian Muslim Home maker Laborer Farmer Teacher Others Heavy Moderate Minimal Yes No < > Mixed Vegetarian Yes No p value p<0.05 p<0.001 p<0.05 p<0.001 p<0.01 p<0.001 p<0.05 p<0.05 p<0.001 Systolic blood pressure Normal p<0.001 Hypertension Diastolic blood pressure Normal p<0.05 Hypertension Table 2. Distribution of cases and controls according to age, height, weight, body mass index (BMI) and blood pressure (mean ± standard deviation, SD) Factor Cases Control Mean SD Mean SD p value Age (yrs) p<0.001 Height (cm) NS Weight (kg) NS BMI (kg/m 2 ) NS Systolic blood pressure p<0.001 Diastolic blood pressure NS 36

5 Table 3. Distribution of significant variables: binary logistic regression analysis Variable Group Crude OR CI Adjusted OR CI Age (yrs) Gender Male Female Minimal Physical activity Moderate Heavy Family history No Yes Tobacco use No Yes Hypertension No Yes DISCUSSION Type 2 diabetes mellitus is one of the most important public health problems in the developed and developing countries. Age, gender, occupation, physical activity, obesity, family history, diet, tobacco use and hypertension were investigated in this study. It was observed that those above 50 years of age had a fivefold chance to get diabetes when compared to those of the age group. In a study of T2DM risk factors in southeast Anatolia, Turkey, Acemoglu et al. (9) found OR of 3.99 for age group, 4.3 for age group and 6.16 for those above 60 years of age. In our study, OR was 4.7 for those in the age group, which is consistent with the findings reported by Acemoglu et al. (9). The findings of the present study were in conformity with King et al. (10), the NUDS (11) and CUPS (12) studies, and the significance of this finding is that it will help greatly in planning the screening and preventive measures in diabetes. The screening should preferably be undertaken before 35 years of age and early intervention should start at an earlier age in this region. In the present study, gender was not found to be a statistically significant risk factor. Our results showed that physical activity is a protective factor for the development of DM. Acemoglu et al. (9) report that physical activity alone is not a factor, but leisure time activity is also as important in the development of T2DM. Kokiwar et al. (13) found the prevalence of diabetes among hard working group to be lower as compared with sedentary workers. Gill and Cooper also support the fact that physical activity has a protective role in the development of T2DM (14). Karter et al. (15) report that in the North California study conducted in 1999, the majority of patients had a maternal history of DM. Shashank and Rakesh (16) suggest that pedigree analysis is an excellent tool to study the genetic factor in diabetes. The finding of this study is very important in planning preventive strategy and will help identify the potential candidates who have a high chance to develop diabetes (16). Earlier, Kawakami et al. (17) have reported a 3.27 times higher risk for development of T2DM in those smokers who use cigarette per day when compared to non-smokers. The present finding is also similar to this finding. In various studies conducted in the United States, where women were followed up for 8 years, 2333 cases of T2DM were confirmed, with a 1.42-fold risk reported (18,19). Rimm et al. (20) showed that tobacco use may increase the risk of developing diabetes and the relative risk for men was 1.94-fold. The findings of the present study were higher than those reported by Rimm et al. (20). Diabetologia Croatica 42-1,

6 Hypertension, especially systolic hypertension, emerged as a strong risk factor for T2DM in the present study. Subjects with systolic hypertension had a 4.6-fold chance to develop T2DM, making it mandatory to screen for T2DM all patients with hypertension above 25 years of age, irrespective of the presence of other risk factors. Anderson and Mark noticed in their study that 57.4% of diabetics had hypertension (21). According to the Health Survey, 51% of diabetics had hypertension and a 2.5-fold risk of diabetes in hypertension, less than that noticed in the present study. According to a recent JNC VII report, hypertension is twice as common among diabetics (22). Acemoglu et al. (9), who studied the risk factors of T2DM in a region of Turkey, found that hypertension increased the risk of diabetes and recorded a 2.05-fold risk. Subtle autonomic dysfunction, decreased baroreceptor sensitivity, associated nephropathy, endothelial dysfunction due to hyperglycemia, and many other factors contribute to the development of hypertension in diabetes. Age is associated with a progressive rise in systolic blood pressure and aging vessels become stiffer due to the loss of elasticity, increased collagen cross-linking, fibrosis of vessel wall, and reduced vascular compliance (9). Isolated systolic hypertension occurs earlier in people with diabetes when compared to nondiabetics. The exact mechanism that leads to the development of diabetes in hypertension is not known. T2DM was associated with insulin resistance and long standing T2DM leading to endothelial changes. CONCLUSION The risk factors of T2DM have regional and ethnic variations. The results of the present study suggested a positive relationship of age with the incidence of diabetes, however, with no gender difference in the development of DM. Manual laborers are less affected compared to other occupations. Those engaged in hard work have a less chance to develop diabetes than those with sedentary habits. This also proves the protective effect of physical activity in the prevention of T2DM. Those with a family history of diabetes have three times greater chance to get T2DM compared to those without it. Dietary factors were not found to be a statistically significant risk factor in the development of T2DM. Hypertension is a significant risk factor in the development of T2DM. Many factors like obesity, diet, stress, occupation, which are considered more important in the western and urban studies, were not found to be significant in this rural area, whereas strong genetic factors, tobacco use, less physical activity and systolic hypertension emerged as strong risk factors. 38

7 REFERENCES 1. Wild SH, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimate for year 2000 and projections for Diabetes Care 2004;27(5): Diabetes atlas, Executive summary, World Diabetes Foundation, second Edition, Sicree R, Shaw JE, Zimmet PZ. Global burden of diabetes. Diabetes atlas, 2 nd edn. Brussels: International Diabetes Federation, 2003: Ziv E, Shaffir E. Psammomys obesus: nutritionally induced NIDDM-like syndrome on thrifty gene background. In: Shafrir E, ed. Lessons from animal diabetes. London: Smith-Gordon, 1995; Heimlich SP, Ragland DR, Lecins RQW. Physical activity and reduced occurrence of non insulin dependent diabetes. N Engl J Med 1991;325: Mooy JM, DeVries H, Grootenhuis PA, Bouter LM, Hein Major RJ. Stressful life events in relation to prevalence and undetected type 2 diabetes. Diabetes Care 2002;15(3): Arunachalam S, Guneshekharan S. Diabetes research in India and China today. From literature based mapping to health care policy. Curr Sci 2002;82: Ramachandran A, Snehalatha C, Latha F. Rising prevalence of NIDDM in an urban population in India. Diabetologia 1997;40: Acemoglu H, Ceylan A, Saka G, Plalanci Y, Erten M, Turgut S, et al. Risk factors for diabetes in South Eastern Anatolia of Turkey. Int J Epidemiol 2001;3(1): King H, Aubert RE, Herman WH. Global burden of diabetes Prevalence, numerical estimate and projections. Diabetes Care 1998;21: Ramachandran C, Snehalatha, Kapur A, Vijay V, Mohan V, Das AK, et al. High prevalence of diabetes and impaired glucose tolerance in India: National Urban Diabetes Survey (NUDS). Diabetologia 2001;44(9): Mohan V, Santhirani CS, Deepa R. Prevalence of diabetes and IGT in selected south Indian population with special reference to family history, obesity and lifestyle factor Chennai Urban Population Study [CUPS-14]. J Assoc Physicians India 2003;51: Kokiwar PR, Gupta S, Durge PM. Prevalence of diabetes in a rural area of central India. Int J Diabetes Dev Countries 2007;27(1): Gill JMR, Cooper AR. Physical activity and prevention of type 2 diabetes mellitus. Curr Opin Sports Med 2008;38(10): Karter AJ, Rowell SE, Ackerson LM, Mitchell BD, Ferrara A, Selby JV, et al. Excess maternal transmission of type 2 diabetes. The Northern California Kaisser Permanent Diabetes Registry. Diabetes Care 1999;22: Shashank RJ, Rakesh MP. Family history and pedigree charting a simple genetic tool for Indian diabetes. JAPI 2006;54: Kawakami N, Takatwuka N, Shimizu H, Ishibarshi H. Effect of smoking on the incidence of NIDDM. Replication and extension in a Japanese cohort of male employee. Am J Epidemiol 1997;145: Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Rodgers H, et al. The incidence of diabetes mellitus in an English community a 20-year follow up of the Wickham survey. Diabetes Med 1996;13: Giannini C, Dyck PJ. Basement membrane reduplication and pericyte degeneration precede development of diabetic polyneuropathy and are associated with its severity. Ann Neurol 1995;37: Diabetologia Croatica 42-1,

8 20. Rimm EB, Chan J, Stampfer MJ. Prospective study of cigarette smoking, alcohol use and the risk of diabetes in men. Br Med J 1995;310: Anderson EA, Mark AL. The vasodilator actions of insulin. Implication for the insulin hypothesis of hypertension revisited. Cardiovasc Risk Factors 1993;3: National High Blood Pressure Education programme working group report on HTN in Diabetes. Hypertension 1994;23:

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