It is currently estimated that diabetes prevalence by

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1 clinical Study The Prevalence and Pattern of Dyslipidemia among Type 2 Diabetic Patients at Rural Based Hospital in Gujarat, India Hetal Pandya*, JD Lakhani**, J Dadhania, A Trivedi Abstract Only proper control of diabetes has shown statistically significant difference (p < 0.001) on the prevalence and severity of dyslipidemia, consolidating the fact that the proper treatment and strict control of diabetes is the most important step in the prevention and treatment of complications of diabetes. Keywords: Dyslipidemia, atherogenic lipid profile, elevated triglycerides, HDL cholesterol, LDL cholesterol, obesity, metabolic syndrome, diabetes It is currently estimated that diabetes prevalence by 2030 will include 439 million adults worldwide. 1 South East Asian countries bear the highest burden of diabetes, including India which may have upto 33 million cases. 2 Coronary artery disease (CAD) accounts for the primary cause of death in almost all patients with diabetes. Despite major advances in primary and secondary prevention of CAD in the past 50 years, patients with diabetes still are relatively at an increased risk of CAD as compared to those without diabetes. 3 Even as the causes of increased cardiovascular risk in type 2 diabetes are multifactorial, an atherogenic lipid profile characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol are few major modifiable factors contributing progressively in cardiovascular risk. 4,5 Although three recent clinical trials of cholesterol lowering have shown that lowering low-density lipoprotein (LDL) cholesterol in diabetic persons does reduce the incidence of CAD. 6-8 The relative importance of LDL cholesterol, compared with the characteristic *Associate Professor **Professor and Head Junior Resident Dept. of Medicine, SBKS Medical Institute and Research Centre, Vadodara, Gujarat Address for correspondence Dr Hetal Pandya Associate Professor Dept. of Medicine, SBKS Medical Institute and Research Centre, Vadodara, Gujarat drhetalpandya@gmail.com dyslipidemia, in determining CAD risk in diabetic individuals is still a subject of debate. A question of particular importance is the relative role of various lipoprotein abnormalities in determining CAD risk in diabetic individuals in context to the ethnicity and region where they live. India has diverse lifestyle pattern and ethnic variations, thus epidemiological profile of diabetes mellitus may be different in different geographical areas. Gujarat is considered as one of the rich and developed States of India. A diet rich in oil and sugar content has pushed Gujarat to the forefront of contributors of diabetic patients in India. Ethnic Gujarati people are presumed to have high prevalence of CAD risk factors: Obesity, metabolic syndrome, diabetes, hypertension, dyslipidemia because of traditional Gujarati food and less physically active lifestyle. In our previous study on Diabesity in Gujarati population, even rural underdeveloped areas of Gujarat had shown an increasing trend of lifestyle disorders like diabetes and obesity. 9 Another study had also shown increasing prevalence of another lifestyle disorder - hypertension and obesity in Gujarati population. 10 Though the burden of diabetes and dyslipidemia in India is mainly contributed by urban population, the increasing trend of diabetes and even dyslipidemia is observed in rural population too, because of urbanization and changing lifestyle and food habits. There are very few data available for prevalence of dyslipidemia and diabetes from Indian continent, 36 Indian Journal of Clinical Practice, Vol. 22, No. 12, May 2012

2 which are mainly from South Indian urban population and few from North Indian urban population We were unable to find studies on prevalence and pattern of dyslipidemia in diabetic Gujarati population. The present study aims to bridge the gap by studying prevalence, pattern and severity of dyslipidemia in diabetic patients especially in rural areas of Gujarat. Material and Methods A prospective cross-sectional study was planned to analyze the pattern of dyslipidemia in diabetic patients attending the Diabetes Clinic and Outpatient Department of Dhiraj General Hospital attached with SBKS Medical Institute and Research Centre over a period of six months (July 2010 to December 2010). The study population included already diagnosed, on treatment diabetic patients and newly diagnosed diabetes mellitus (DM) patients. The patients who already had history of CAD or cerebrovascular accident (CVA) or were diagnosed as having CAD or CVA on enrolment and patients already taking lipid-lowering drugs were excluded from the study. Diabetic patients having other chronic systemic or metabolic disorder were not included in the study. Detailed history and clinical examination of all the enrolled patients was done. Anthropometric measurements (weight, height, waist circumference (WC) and hip circumference) were taken using standard methods. Fasting blood sample was collected for serum lipid profile investigation after 10 hours overnight fast. serum cholesterol, serum triglyceride, serum HDL, serum LDL, serum VLDL levels were measured using calibrated ERBACHEM 5 Plus, semi-automated machine. Cut-off normal values for individual lipid levels were taken as per the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 15 The term mixed dyslipidemia is used when two or more individual lipid levels were abnormal. The patients were categorized in different subgroups such as male/ female, urban/rural, controlled/uncontrolled, obese/ nonobese, hypertensive/nonhypertensive for subgroup analysis of diabetic dyslipidemia. All diabetic patients were categorized as urban if living in place with >1 lac population, obese or nonobese using body mass index (BMI) criteria of 23 proposed for South- Asian population (IDF-modified ATP III criteria) 15 and as hypertensive if their blood pressure is 130/85. ADA criteria for treatment of diabetes (HbA 1C <7% or fasting/preprandial plasma glucose <130 mg/dl and postprandial plasma glucose <180 mg/dl for two consecutive visits) were used to divide the patients in controlled and uncontrolled groups. 16 All the observations were tabulated and results were expressed as percentage and mean SD (standard deviation). Results Out of 171 diabetic patients enrolled in the study, 100 were male and 71 were female patients. The mean age of study population was 54.8 ± (male: 54.7 ± and female: 54.9 ± 9.42). The mean duration from the first diagnosis of diabetes for the study patients was 5.1 ± 4.64 years. Only 9.9% of patients had DM since >10 years and 23.4% were diagnosed as diabetics in last two years only. Around, 33.9% were diabetics since 2-5 years and 32.7% were diabetics since 5-10 years. Further, 43.9% (n = 75) of patients were from urban area and 56.1% (n = 96) were from the rural area. The mean BMI of study population was 25.6 ± 5.81 (male: 24.5 ± 4.71 and female: 27.2 ± 6.81). Also, 68.4% (n = 117) of all diabetic patients participated in study were found to be obese by modified ATP III criteria of BMI 23 for South-Asian population. Only 19.3% of study patients were well-controlled. Only 24% (n = 41) were hypertensive and 26.3% (n = 45) were smokers, all were males (Table 1). Individual serum lipid results were as follows. Mean serum cholesterol level was ± 43.70, mean serum triglyceride was ± 69.44, mean serum HDL was 46.2 ± 17.08, mean serum LDL was ± and mean serum VLDL level was 33.4 ± (Table 2). Out of 171 DM patients, 36.3% (n = 62) patients were having high serum cholesterol level, while almost similar no. of patients, 35.7% (n = 61) had low serum HDL levels. About 56.1% (n = 96) had high serum triglyceride level, while almost similar number of patients, 57.3% (n = 98) also had serum LDL levels above normal range. About 49.7% (n = 85) also showed high serum VLDL levels about (Table 2 and Fig. 1). Discussion Patients with DM have a 2- to 4-fold increased risk of cardiovascular, peripheral vascular and cerebrovascular disease, which are the leading causes of morbidity and mortality in this population. Many Western epidemiological studies have shown an association between diabetic dyslipidemia, which is characterized by hypertriglyceridemia; low levels of HDL cholesterol; postprandial lipemia and small, dense LDL cholesterol particles and the occurrence of cardiovascular disease Indian Journal of Clinical Practice, Vol. 22, No. 12, May

3 Table 1. Patient Characteristics and Prevalence of Dyslipidemia Characteristic No. of patients (n = 171, [%]) Dyslipidemia (n [%]) P value Age (years) <45 26 (15.2%) 22 (84.6%) < (52%) 72 (80.9%) >60 56 (32.8%) 47 (83.9%) Sex Male 100 (58.5%) 85 (85%) < 0.5 Female 71 (41.5%) 56 (78.9%) Locality Urban 75 (43.9%) 61 (81.3%) < 0.5 Rural 96 (56.1%) 80 (83.3%) Control of DM Controlled 33 (19.3%) 20 (60.6%) < Uncontrolled 138 (80.7%) 121 (87.7%) Obesity Obese (BMI 23) 117 (68.4%) 99 (84.6%) < 0.5 Nonobese (BMI <23) 54 (31.6%) 42 (77.8%) Hypertension Nonhypertensive (<130/85) 130 (76%) 106 (81.5%) < 0.5 Hypertensive ( 130/85) 41 (24%) 35 (85.4%) Smoking Smoker 45 (26.3%) 40 (88.9%) < 0.5 Nonsmoker 126 (73.7%) 101 (80.2%) Duration of DM <2 years 40 (23.4%) 33 (82.5%) < years 58 (33.9%) 45 (77.6%) 5-10 years 56 (32.7%) 48 (85.7%) >10 years 17 (9.9%) 15 (88.2%) Table 2. Serum Lipid Levels of Diabetic Patients Serum lipid Mean ± SD Abnormal value Deranged lipid level n (%) Cholesterol ± >200 mg/dl 62 (36.3%) Triglyceride ± >150 mg/dl 96 (56.1%) HDL 46.2 ± <40 mg/dl 61 (35.7%) LDL ± >100 mg/dl 98 (57.3%) VLDL 33.4 ± >32 mg/dl 85 (49.7%) The analysis of data from our study provides an opportunity to examine dyslipidemia a major CAD risk factor, in population-based sample of well-characterized type 2 diabetic individuals. The present study shows very high prevalence of dyslipidemia (82.5%) in ethnic Gujarati diabetic population, which recommends the use of terminology - diabetes lipidus for them (Fig. 2). Diabetic dyslipidemia is not only prevalent in urban Gujarat (81.3%) as assumed by lavish lifestyle of fat and sugar rich food and lesser physical work but it is also increasingly witnessed in rural remote areas in similar proportion (83.3%), which is a 38 Indian Journal of Clinical Practice, Vol. 22, No. 12, May 2012

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6 VLDL 49.70% 82.5% (141) Serum lipid LDL HDL Triglyceride Cholesterol 35.70% 36.31% 57.30% 56.10% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% Deranged lipid level % 17.55% (30) Patients without dyslipidemia Patients with dyslipidemia Figure 1. Prevalence of individual serum lipid abnormalities in diabetics. Figure 2. Percentage distribution of dyslipidemia in diabetic patients. Table 3. Age, Obesity, HT, Urban/Rural-Specific Prevalence of Dyslipidemia among Diabetic Males and Females Abnormal serum lipid level Cholesterol (>150 mg/l) Triglyceride (>150 mg/dl) HDL (<40 mg/dl) LDL (>100 mg/dl) VLDL (>32 mg/dl) M/F <45 (n = 26) Age group (years) (n = 56) >60 (n = 56) Control of DM Obesity HT Controlled (n = 33) Uncontrolled (n = 138) BMI <23 (n = 54) BMI 23 (n = 117) <130/85 (n = 126) Male Female /85 (n = 41) Total 11 (42.3%) 29 (32.6%) 22 (39.3%) 9 (27.3%) 55 (39.9%) 20 (37.1%) 42 (35.9%) 50 (39.7%) 12 (29.3%) Male Female Total 19 (50%) 51 (57.3%) 26 (46.4%) 17 (51.5%) 84 (61.6%) 23 (42.6%) 73 (62.4%) 76 (60.3%) 20 (48.8%) Male Female Total 12 (46.2%) 28 (32.5%) 21 (37.5)% 10 (30.3%) 49 (35.5%) 18 (33.3%) 43 (36.8%) 40 (31.7%) 21 (51.2%) Male Female Total 14 (53.8%) 53 (59.6%) 31 (55.4%) 15 (45.5%) 77 (55.8%) 29 (53.7%) 69 (59%) 74 (58.7%) 24 (58.5%) Male Female Total 18 (69.2%) 44 (49.4%) 23 (41.1%) 14 (42.4%) 70 (50.7%) 21 (38.9%) 64 (54.7%) 67 (53.2%) 18 (43.9%) worrisome scenario. More so, both males and females had deranged lipid levels in almost similar numbers (M: 85% and F: 78.9%). So diabetic dyslipidemia / diabetes lipidus might become a synonym for diabetes in Gujarati population as a whole with its serious impact on rapidly rising prevalence of CAD in Gujaratis. Another interesting finding observed was that diabetic patients having well-controlled blood sugar level had less prevalence of dyslipidemia. On enrolment most of the diabetic patients had uncontrolled status (80.7%). About 87.7% of these patients also had dyslipidemia, while only 60.6% of controlled or well-treated diabetes group had dyslipidemia (p < 0.001). This finding consolidates the theory that strict control of diabetes itself is very necessary for favorable lipid profile. The analysis of individual lipid levels shows that the mean levels of all lipids were in abnormal range except serum HDL level (Table 2), which is surprising as it is quite low in many studies on diabetic patients. There has been a recent focus on the characteristic dyslipidemia of type 2 diabetes, which includes elevated triglycerides, low HDL cholesterol and a preponderance of small dense LDL particles. These characteristics were highly prevalent in diabetic Indian Journal of Clinical Practice, Vol. 22, No. 12, May

7 < >60 0 Controlled (n = 33) Uncontrolled (n = 138) Figure 3a. Age-specific prevalence of different lipid levels. Figure 3b. Control of DM <23 >23 0 non-ht HT Figure 3c. Obesity-specific prevalence of different lipid levels. participants in this cohort. Hypertriglyceridemia (56.1%) and high serum LDL level (57.3%) were noted in large number of patients in our study has been observed in almost all studies done in diabetic patients but the prevalence of these abnormalities is quite high in Gujarati diabetic population in comparison to low serum HDL levels (35.7%) which is considered as one of the major component of diabetes dyslipidemia. Hypercholesterolemia (36.3%) and high level of serum VLDL (49.7%), were also found in large number of patients (Table 2). In our study, most of the diabetic patients had mixed dyslipidemia i.e. more than one lipid abnormality. The most common mixed abnormality detected was hypertriglyceridemia and high LDL level (39.1%), which is different from our western counterparts showing hypertriglyceridemia and low serum HDL Figure 3d. Hypertension specific prevalence of different lipid levels. as major abnormality. The serum LDL levels were not found to be very high in most of these studies as they had used a more relaxed cut-off point of 130 for serum LDL. 4,5 Individually also these two abnormalities (hypertriglyceridemia and high LDL level) are considered as major CAD risk factors, so both together can be considered as very critical CAD risk factors in diabetic patients and need very prompt management for the prevention of CAD. The other types of mixed dyslipidemia observed in our study were: 1) Hypercholesterolemia with high LDL level and 2) hypertriglyceridemia with hypercholesterolemia. All lipid levels were found to be deranged in 10.5% of the diabetic patients, suggesting very high rate of severe form of dyslipidemia in diabetic patients. 42 Indian Journal of Clinical Practice, Vol. 22, No. 12, May 2012

8 So, we suggest not to concentrate on any specific lipid level in Indian diabetic patients but to analyze the complete lipid profile as a whole and to start intensive therapy for the same as early as possible. We had also done subgroup analysis for dyslipidemia in these patients according to nonmodifiable and modifiable confounding factors that might affect dyslipidemia. Young diabetic patients (<45 years of age) had similar prevalence of dyslipidemia (84.6%) as older group (83.9%), which is a very dangerous trend correlating with higher rate of CAD in younger Indian population with statistically insignificant difference (p < 0.5) (Table 1). Hypertriglyceridemia and high LDL levels were observed in all age groups. Obesity (BMI 23 as per IDF, modified ATP III criteria for South- Asian population) better termed as Diabesity is seen in 68.4% of diabetic patients, which is similar to our previous study on prevalence of diabesity in Gujarati population. 9 A very high rate of dyslipidemia (84.6%) was observed in patients with diabesity which suggests that obesity, diabetes and dyslipidemia, all major CAD risk factors go hand in hand in Gujarati population. As observed in all other subgroups, hypertriglyceridemia and high LDL levels were also noted in diabesity group. But, more surprisingly even nonobese diabetic patients also had high prevalence of dyslipidemia (75.9%) with similar pattern as obese patients without any statistically significant difference (p < 0.5). In diabetic hypertensive subgroup of patients, 82.9% of patients had deranged lipid levels, while nonhypertensive DM group also showed similar trend (81.5%) with similar type of dyslipidemia. Similarly, urbanized lifestyle was found to have little impact on prevalence and pattern of dyslipidemia in diabetic patients. Both urban and rural diabetic population showed almost 82% prevalence of dyslipidemia. Other confounding factors like smoking and duration of diabetes also failed to show any statistically significant difference (p < 0.5) on prevalence and type of dyslipidemia in diabetic patients. So from the subgroup analysis, it can be interpreted that diabetes itself is responsible for very high rate dyslipidemia as well as for particular pattern of dyslipidemia by mechanism of insulin resistance. Age, duration of diabetes, obesity, hypertension like confounding factors were not able to influence the prevalence and pattern of diabetic dyslipidemia in our study. Only proper control of diabetes has shown statistically significant difference (p < 0.001) on prevalence and severity of dyslipidemia, consolidating the fact that the proper treatment and strict control of diabetes is the most important step in prevention and treatment of complications of diabetes. As shown in our study, dyslipidemia in diabetes, very critical CAD risk factor has a high prevalence in Gujarati population, but surprisingly only very few diabetic patients (14.3%) were investigated for their lipid profile in past. For this reason, we strongly recommend detailed lipid profile to be done for each and every diabetic patient at the time of diagnosis and regularly on follow-up. Conclusion Our study highlighted the very high prevalence of dyslipidemia associated with diabetes as one of the highest ranked risk factor for CAD in Indians, especially Gujarati population. One or another lipid level is found to be abnormal in most of the diabetic patients, suggesting that whole lipid profile must be done and evaluated at regular intervals in these patients. The present study also highlights the importance of strict control of diabetes in prevention and treatment of dyslipidemia associated with diabetes as dyslipidemia is more frequent in uncontrolled diabetic patients than controlled ones. It is of paramount importance to aim for the stricter goals and specific thresholds for dyslipidemia in Indian diabetic patients to start early and prompt preventive measures to reverse the tide of the rising CAD epidemic in Asian Indians. References Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and Diabetes Res Clin Pract 2010;87(1):4-14. Health situation in the South East Asia Region WHO Regional office for South East Asia, New Delhi American Heart Association. Heart Disease and Stroke Statistics Update. 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9 Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335(14): Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279(20): Pandya H, Lakhani JD, Patel N. Obesity is becoming synonym for diabetes in rural areas of India also - an alarming situation. Int J Biol Med Res 2011;2(2): Joshi A, Bhugra P, Lakhani J, Desai S. Body mass index and central obesity in Hypertensive patients. Guj Med Jr 2004;61(3):33-6. Misra A, Pandey RM, Devi JR, Sharma R, Vikram NK, Khanna N. High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India. Int J Obes Relat Metab Disord 2001;25: Mishra A. Khurana L. Obesity and metabolic syndrome in developing countries. J Clin Endocrinol Metab 2008;93: Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome in urban Asian Indian adults - a population study using modified ATP III criteria. Diabetes Res Clin Pract 2003;60(3): Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R; Chennai Urban Population Study (CUPS No. 4). Intra-urban differences in the prevalence of the metabolic syndrome in southern India - the Chennai Urban Population Study (CUPS No. 4). Diabet Med 2001;18(4): Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285(19): American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2007;30 Suppl 1: S4-S41. Campos H, Moye LA, Glasser SP, Stampfer MJ, Sacks FM. Low-density lipoprotein size, pravastatin treatment, and coronary events. JAMA 2001;286(12): Sacks FM, Campos H. Clinical review 163: Cardiovascular endocrinology: Low-density lipoprotein size and cardiovascular disease: a reappraisal. J Clin Endocrinol Metab 2003;88(10): Jungner I, Sniderman AD, Furberg C, Aastveit AH, Holme I, Walldius G. Does low-density lipoprotein size add to atherogenic particle number in predicting the risk of fatal myocardial infarction? Am J Cardiol 2006;97(7): Indian Journal of Clinical Practice, Vol. 22, No. 12, May 2012