Metabolic syndrome is a constellation of

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1 A Study of Metabolic Syndrome and its Components in Type 2 Diabetes Mellitus Subjects and their Asymptomatic First-degree Relatives JL Patel*, AM Suthar*, VB Dalsaniya*, AP Parikh**, NN Suthar, KL Patel Abstract Objectives: To study clinical profile of metabolic syndrome and its individual components in type 2 diabetes mellitus subjects and their asymptomatic first-degree relatives. To identify risk factors of glucose intolerance. Material and methods: Randomly selected type 2 diabetes mellitus (T2DM) subjects age >40 years (n = 20, 10 males, 10 females) and their asymptomatic first-degree relatives age >30 years (excluding pregnant women) (n = 80; 46 males; 34 females) subjected to regression analysis with reference to components of metabolic syndrome (waist circumference, serum triglyceride, serum high-density lipoprotein (HDL), fasting plasma glucose, hypertension) and other variables. Student t-test was used for comparison of results. Results: Among T2DM subjects: Ninety percent were hypertensive, 85% had low HDL, 30% males and 80% females had central obesity, 85% had metabolic syndrome. Among asymptomatic first-degree relatives of T2DM subjects: 48.7% had metabolic syndrome; hypertension, low HDL, central obesity, impaired glucose tolerance, T2DM were present in 52.5%, 68.7%, 48.7%, 26.2%, 35%, respectively. In subjects with abnormal glucose level (n = 49) 59.18% subjects and in subjects with normal glucose level (n = 31) 32.25% met the criteria for metabolic syndrome (p = 0.023). Impaired fasting glucose, increased hip circumference and low HDL independently determined two hours glycemia value in OGTT. (R 2 = 0.7; p = 0.001). Conclusion: In T2DM and their asymptomatic first-degree relatives, hypertension and low HDL were commonest components of metabolic syndrome, females were more obese. Glucose intolerance was significantly associated with other components of metabolic syndrome. Impaired fasting glucose, increased hip circumference and low HDL levels were risk factors for glucose intolerance. Keywords: Metabolic syndrome, diabetes mellitus, first-degree relatives of type 2 diabetes mellitus subjects, impaired glucose tolerance Metabolic syndrome is a constellation of metabolic abnormalities that includes central obesity, hypertension, elevated fasting glucose, low high-density lipoprotein (HDL) cholesterol, high triglyceride (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III]). It is associated with increased risk of coronary artery disease and stroke. In 1988, Reaven proposed the concept of syndrome X. In 1988, WHO proposed a formal definition of metabolic syndrome. Three years later, the NCEP *Final Year Resident **Professor Associate Professor Assistant Professor Dept. of Medicine, Vadilal Sarabhai General Hospital, Ellisebridge Ahmedabad, Gujarat Address for correspondence Dr JL Patel Final Year Resident E-7, Doctor Quarters, VS Hospital Campus, Ellisebridge, Ahmedabad jigsp2008@gmail.com ATP III proposed metabolic syndrome based on clinical parameters. The European Group for the study of Insulin Resistance (EGIR) has also developed its own definition. Different terminologies used for metabolic syndrome: Beer-Belly syndrome Atherothrombogenic syndrome Deadly quarter Dysmetabolic syndrome Insulin resistance syndrome Syndrome X NCEP ATP III 2001 criteria for metabolic syndrome The purpose of ATP III was to identify people at higher long-term risk for cardiovascular diseases (CVDs) who deserved clinical lifestyle intervention to reduce risk. Presence of three of the following five factors is required for diagnosis of metabolic syndrome. 520 Indian Journal of Clinical Practice, Vol. 23, No. 9 February 2013

2 Central obesity: Abdominal waist circumference: Men >102 cm, women >88 cm Fasting plasma glucose >110 mg/dl or diagnosed type 2 diabetes mellitus (T2DM) Fasting plasma triglyceride >150 mg/dl or medication Fasting plasma HDL cholesterol: Men <40 mg/dl, women <50 mg/dl or medication Blood pressure 130/85 mmhg or medication. ATP III specifically noted that some individual having only two criteria of metabolic syndrome appear to be insulin resistance when the waist circumference is only marginally elevated. If so they should be benefited from clinical intervention similarly to others who have greater increases in waist circumference. Recent definitions In 2003, the American Association of Clinical Endocrinologist (AACE) modified ATP III criteria to refocus on insulin resistance as the primary cause of metabolic risk factors. No specified number of factors qualified for diagnosis, which was left to clinical judgment. Other factors used for clinical judgement were a family history of CVD or T2DM, polycystic ovary syndrome and hyperuricemia. In 2005, the International Diabetes Foundation (IDF) published new criteria that again modified the ATP III definition. They considered that abdominal obesity is so highly correlated with insulin resistance. The IDF clinical definition thus makes the presence of abdominal obesity necessary for diagnosis. Insulin resistance syndrome is associated with: T2DM CVD Essential hypertension Polycystic ovary syndrome (PCOS) Nonalcoholic fatty liver disease Certain forms of cancers Sleep apnea One of the most important reasons for introducing concept of metabolic syndrome is to heighten the awareness of the increased risk associated with metabolic abnormalities. Metabolic syndrome is associated with increased risk of diabetes, coronary artery disease, stroke and cardiovascular mortality more than individual components. Family history of noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased risk of diabetes. First-degree relatives of NIDDM patients have 40% lifetime risk of developing diabetes. Diabetes occurs a decade earlier in Asian population. India has a large and growing population of diabetic patients, its prevalence will reach 350 million by Diabetes is associated with increased risk for CVD, stroke and other risk factors of metabolic syndrome. So, early recognition of metabolic syndrome in such subjects and timely intervention along with lifestyle modification can delay emergence of diabetes mellitus (DM), CVD, stroke and subsequent mortality. AIMS AND OBJECTIVES To study clinical profile of metabolic syndrome and its individual components in T2DM subjects and their asymptomatic first degree relatives. To study clinical profile of metabolic syndrome and its individual components in asymptomatic first degree relatives of T2DM subjects. To identify risk factors of glucose intolerance. MATERIAL AND METHODS For this study, 20 T2DM patients and their family members were subjected to analysis at a large teaching general hospital. Inclusion Criteria Patient with T2DM with age >40 years All asymptomatic first-degree relative age >30 years (men and nonpregnant women). Excluding Criteria Patient with T2DM age <40 years All first-degree relative age <30 years Pregnant women Family selection was random. Study Design Retrospective and cross-sectional study. Study Size Randomly selected T2DM subjects age >40 years (n = 20, 10 males, 10 females) and their asymptomatic first-degree relatives age >30 years (excluding pregnant women) (n = 80; 46 males; 34 females). Indian Journal of Clinical Practice, Vol. 23, No. 9 February

3 Table 1. Physical, Clinical and Metabolic Characteristics of Diabetic Patients Mean ± Standard deviation Males (n = 10) Females (n = 10) Total (n = 20) Age (years) ± ± ± 8.45 Ht (cm) 1.63 ± ± ± 0.12 Wt (kg) ± ± ± Waist (cm) ± ± ± Hip (cm) ± ± ± BMI (kg/m 2 ) ± ± ± BP systolic (mmhg) ± ± ± BP diastolic (mmhg) ± ± ± FBS (mg/dl) ± ± ± hr (mg/dl) ± ± ± S. TG (mg/dl) ± ± ± S. HDL (mg/dl) ± ± ± 7.28 S. LDL (mg/dl) ± ± ± S. VLDL (mg/dl) ± ± ± Total (mg/dl) ± ± ± Ht: Height; Wt: Weight; s.: Serum. Table 2. Physical, Clinical and Metabolic Characteristics of First-degree Relatives of T2DM Patients Mean ± Standard deviation Males (n = 46) Females (n = 34) Total (n = 80) Age (years) ± ± ± Ht (cm) 1.68 ± ± ± 0.10 Wt (kg) ± ± ± Waist (cm) ± ± ± Hip (cm) ± ± ± BMI (kg/m 2 ) ± ± ± 4.93 BP systolic (mmhg) ± ± ± BP diastolic (mmhg) ± ± ± FBS (mg/dl) ± ± ± hr (mg/dl) ± ± ± hr (mg/dl) ± ± ± S. TG (mg/dl) ± ± ± S. HDL (mg/dl) ± ± ± S. LDL (mg/dl) ± ± ± S. VLDL (mg/dl) ± ± ± Total (mg/dl) ± ± ± Indian Journal of Clinical Practice, Vol. 23, No. 9 February 2013

4 Table 3. Physical, Clinical and Metabolic Characteristics of First-degree Relatives Age-wise Mean ± Standard deviation years years years 60 years Age (years) ± ± ± ± 4.23 Ht (cm) 1.63 ± ± ± ± 0.04 Wt (kg) ± ± ± ± Waist (cm) ± ± ± ± 9.71 Hip (cm) ± ± ± ± BMI (kg/m 2 ) ± ± ± ± 4.28 BP systolic (mmhg) ± ± ± ± BP diastolic (mmhg) ± ± ± ± 9.44 FBS (mg/dl) ± ± ± ± hr (mg/dl) ± ± ± ± hr (mg/dl) ± ± ± ± S. TG (mg/dl) ± ± ± ± S. HDL (mg/dl) ± ± ± ± 8.18 S. LDL (mg/dl) ± ± ± ± S. VLDL (mg/dl) ± ± ± ± Total (mg/dl) ± ± ± ± Tenure August 2010 to October Protocol Participant were interviewed at home and were invited to attend the OPD at VS General Hospital, where they were asked to complete additional questionnaires, undergo various examinations and provide blood samples for: Glucose tolerance test (GTT) if they were undetected asymptomatic relatives of the patients with diabetes, or fasting blood glucose (FBS) and postprandial blood glucose (PPBS) levels in diabetic patients and serum lipid profile. Blood pressure was measured with a mercury sphygmomanometer and the mean of three seated resting values recorded. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meter. Waist Circumference Measurement Technique Place measuring tape, holding it parallel to the floor, around abdomen at the level of the iliac crest. Hold tape snug but don t compress the skin and measure circumference at the end of normal expiration. Hip Circumference Measurement Technique Place measuring tape, holding it parallel to the floor, around the hip at the level of greater trochanter of femur. Hold tape snug but don t compress the skin and measure circumference. Oral Glucose Tolerance Test (OGTT) After a 12-hour overnight fast, the subject ingested a solution that contained 75 g dextrose and venous blood samples were obtained at 0, 60 and 120 minutes for determination of plasma glucose. Stages of plasma glucose were classified as per American Diabetic Association (ADA). Blood glucose was measured using glucose oxidase/ peroxidase method. Low-density lipoprotein (LDL) and HDL fractions were separated from fresh serum by ultracentrifugation, CHOD-PAP method. Lipoprotein fraction cholesterol and triglycerides were measured by standard enzymatic spectrophotometric technique. Definition and Diagnostic Criteria We counted participants who reported currently using antihypertensive or antidiabetic medication (insulin or oral agents). Or antihyperlipidemic as participant with high blood pressure or diabetes or dyslipidemic, respectively. According to NCEP/ATP III report, participant who had 3 of the following criteria were defined as having the metabolic syndrome: Central obesity: Abdominal waist circumference: Men >102 cm, women >88 cm Fasting plasma glucose >110 mg/dl or diagnosed T2DM Fasting plasma triglyceride >150 mg/dl or medication Indian Journal of Clinical Practice, Vol. 23, No. 9 February

5 Table 4. Clinical and Metabolic Characteristics of NGT, IGT and DM Subjects Among First-degree Relatives P (T < t) two-tail Mean ± Standard deviation T-test: two sample assuming equal variance NGT (n = 31) IGT (n = 21) DMl (n = 28) NGT vs IGT NGT vs DM IGT vs DM Age (years) ± ± ± Ht (cm) 1.62 ± ± ± Wt (kg) ± ± ± Waist (cm) ± ± ± Hip (cm) ± ± ± BMI (kg/m 2 ) ± ± ± BP systolic (mmhg) ± ± ± BP diastolic (mmhg) ± ± ± FBS (mmhg) ± ± ± hr (mmhg) ± ± ± S. TG (mmhg) ± ± ± S. HDL (mmhg) ± ± ± S. LDL (mmhg) ± ± ± Fasting plasma HDL cholesterol: Men <40 mg/dl, women <50 mg/dl or medication Blood pressure 130/85 mmhg or medication. First-degree degree relatives were classified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and NIDDM after an OGTT. Classification of OGTT as per ADA FBS z Normal <110 mg/dl z IGT >110 mg/dl and <126 mg/dl z DM >126 mg/dl First hour blood glucose z Normal <140 mg/dl z IGT >140 mg/dl and <200 mg/dl z DM >200 mg/dl Second hour blood glucose z Normal <140 mg/dl z IGT >140 mg/dl and <200 mg/dl z DM >200 mg/dl Statistical Analysis All the data were computed on Excel database and statistical analysis were done using SPSS PC Windows. Student s t-test was used for comparison of means of frequencies. We calculated prevalence of metabolic syndrome by age and sex. Subjects with diabetes and Prevalence Figure 1. Prevalence of metabolic syndrome and its individual components in diabetic patients. IGT were grouped together as glucose intolerance for regression analysis. Variables like age, sex, waist, BMI, waist-hip ratio, systolic and diastolic blood pressure, family history of diabetes were used as independent variables for the regression analysis. The step wise multiple linear regression applied to first-degree relatives to assess the independent contribution of IGT (glycemia at 120 mins) to separate components of metabolic syndrome. RESULTS HTN Low HDL High TG Central obesity Metabolic syndrome Male Female Total In diabetic population, there were 10 males and 10 females. Among first-degree relatives, 46 were males and 34 were females. Tables 3 shows anthropometric, clinical and metabolic characteristics of first-degree relatives of patients with NIDDM globally and age-wise. Blood pressure, FBS, 2nd hour glucose, and total lipid tend to rise with age Indian Journal of Clinical Practice, Vol. 23, No. 9 February 2013

6 No. of components MS5 MS4 MS Total Female Male 90 Table 5. No. of first-degree relatives of T2DM Metabolic syndrome Total patients Present Absent With IGT/T2DM With NGT Total Figure 2. Percentage of diabetic patients with 4, 5 components of metabolic syndrome. No. of components of MS Figure 3. Percentage of first-degree relatives of diabetic patients with 4, 5 components of metabolic syndrome. Prevalence HTN Low HDL High TG Central obesity Figure 4. Percentage of individual components of metabolic syndrome and T2DM in first-degree relatives of diabetic patients. Prevalence MS5 MS4 MS Percentage Percentage Figure 5. Age-wise prevalence of metabolic syndrome in first-degree relatives of T2DM patients IGT T2DM MS3 MS4 MS5 Total MS No MS 61 Total Female Male Male Female Total Age group Percentage IGT/T2DM Figure 6. Prevalence of metabolic syndrome in first-degree relatives with IGT/T2DM and NGT. Table 6. Regression Analysis of Impaired Glucose Tolerance with Reference to FBS, Hip Measure, S. HDL Dependent variable Model 1 FBS Model 2 FBS Hip measure R 2 Standardized p value coefficient NGT Metabolic syndrome absent Metabolic syndrome present p = Model FBS Hip measure S. HDL a. predictors: (constant), FBS b. predictors: (constant), FBS, HIP c. predictors: (constant), FBS, HIP, s. HDL d. dependent variable: 2 hour glycemia In the diabetic patients, 90% were hypertensive and 85% had low HDL, which forms the commonest criteria for metabolic syndrome. Central obesity was more common in females (55% average, 30% males and 80% females); 40% had high TG level. Eighty-five percent of diabetic patient had metabolic syndrome (90% males and 80% females); 40% of Indian Journal of Clinical Practice, Vol. 23, No. 9 February

7 diabetic patient had four components of metabolic syndrome (60% males and 20% females) and 25% had five criteria satisfying metabolic syndrome (10% males and 40% females). Among first-degree relatives of diabetic patients, 48.75% had metabolic syndrome (39.13% males and 61% females); 13.75% had four criteria and 6.25% had five criteria satisfying metabolic syndrome. There was no significant difference in prevalence of metabolic syndrome in males and females (p = 0.4). Among asymptomatic first-degree relatives of T2DM subjects, hypertension, low HDL, central obesity, IGT, T2DM were present in 52.5%, 68.7%, 48.7%, 26.2%, 35%, respectively. Among first-degree relatives of diabetic patients prevalence, the prevalence of metabolic syndrome was at age years: 10%, at years: 13.75%, at years: 18.75% and at >60 years: 6.25%. Thus, the prevalence of metabolic syndrome was highest in age group years (Table 3). According to ADA, first-degree relatives were classified as NGT, IGT or DM after OGTT (Table 4). Forty-nine out of 80 subjects displayed an abnormal glucose level either as IGT (26.2%) or as DM (35%) (Table 4). T2DM subjects were significantly older than IGT (IGT vs DM; p = 0.01) and NGT (NGT vs DM; p = 0.03) subjects. Thus age was a contributing factor for DM. BMI (p = 0.029) was significantly higher in both pathological groups. When blood pressure was considered, diastolic values were higher in abnormal OGTT compared to NGT. No difference in terms of sex distribution was found in any category. In subjects with abnormal glucose level (n = 49), 59.18% subjects and in subjects with normal glucose level (n = 31), 32.25% met the criteria for metabolic syndrome (Table 5). So, prevalence of metabolic syndrome was significantly increased if the subject had glucose intolerance (p = 0.023). FBS, hip measure and serum HDL independently determined two hours glycemia value in OGTT (R 2 = 0.707, p = 0.001). FBS, Hip measure and serum HDL together explains 70% of variation in data of two hours glycemia control (Table 6). Table 7. Comparisons between Botnia study with our Study Components Botnia Study Our Study Male (%) Female (%) Male (%) Female (%) Metabolic syndrome Obesity Dyslipidemia Hypertension DISCUSSION Until 1970, the prevalence of T2DM was considered to be low in India. The projection from the World Health Organization (WHO) in the year 1998 has highlighted that India would lead the world in the prevalence of diabetes. Studies done in Western countries have confirmed that the prevalence of diabetes among migrant Indians is significantly higher than the host populations. This might be explained by a higher genetic susceptibility to the development of diabetes among Asian Indians or stronger environmental factors (e.g., decreased physical activities, eating habits, etc). Studies on native Indian population during the last 30 years have shown rising trends in the prevalence of diabetes. The prevalence of metabolic syndrome has also increased in the world. Metabolic Syndrome in Diabetic Patients In our study, 85% of the diabetic patients (n = 20), aged >40 years (female: 80% and male: 90%) met the criteria for diagnosis of metabolic syndrome as per ATP III guidelines. In Botnia study 2001 (in Finland and Sweden), the prevalence of metabolic syndrome according to WHO criteria in T2DM among males and females was 84% and 78%, respectively. Cardiovascular mortality was markedly increased in subjects with metabolic syndrome (12%; p < 0.001). The percentage of T2DM patients with age >40 years with metabolic syndrome in both the studies are comparable. Obesity in Botnia study was classified using BMI or Waist-hip ratios. This may explain a higher prevalence of obesity in Botnia study as compared to our study, where we used the ATP III criteria for central obesity (i.e., waist circumference >88 cm in females and >102 cm in males). The 526 Indian Journal of Clinical Practice, Vol. 23, No. 9 February 2013

8 cut-off for hypertension in Botnia study was higher; 160 mmhg systolic or 90 mmhg diastolic blood pressure, whereas in our study, hypertension was considered as per ATP III guidelines (normal levels were taken as 130/85 mmhg). Difference in cut-off value may explain higher percentage of study population having hypertension in present study. However, other racial, environmental and personal factors cannot be ruled out in both instances. In our study, 40% diabetic patients had four components satisfying criteria for metabolic syndrome. Twenty percent had three criteria and 25% had five criteria. It has been suggested by Cruz et al that number of criteria for metabolic syndrome may be inversely proportional to insulin sensitivity. The NCEP ATP III has recently recognized the metabolic syndrome as an important risk factor for IHD among men and women. It has been estimated, on the bases of the results of Third National Health and Nutrition Examination Survey (NHANES) that >1 in five adults in USA have metabolic syndrome with almost a doubling prevalence (43%) among people >60 years of age. The prevalence of unstable angina and myocardial infarction were highest among patients with five insulin-resistant syndrome features as defined by NCEPIII. Hence, for individuals with established DM, risk factor management must be intensified to diminish their higher risk for CVD. Among first-degree relatives of patients with T2DM, 48.75% aged >30 years (males 39.1% and among females 61%) met the criteria for metabolic syndrome. One-third of the first-degree relatives with metabolic syndrome belonged to the age group years. Hypertension and low HDL have contributed maximum among the components of metabolic syndrome. These data shows high prevalence of metabolic syndrome among the Indian population. The Deepa study in Chennai 2002 used the EGIR criteria to compute the prevalence of metabolic syndrome in random population with age group of years and hence a lower occurrence of metabolic syndrome is seen in this study. Gupta et al held at Jaipur, 2003 was carried out on random population with age >20 years while the present study was carried out on first-degree relatives of age >30 years. This may explain a high percentage of subjects having metabolic syndrome. Ramachandra et al observed a prevalence of 41% and the Strong Heart Study on American Indians observed a prevalence of 55.2%. The above studies had been done on random population, whereas our study was carried out on first-degree relatives. This explains higher percentage of study population having metabolic syndrome in the present study. Because of the documented high relatives risk of AV, CVD events and T2DM, the metabolic syndrome undoubtedly carries a relatively high lifetime risk for these disorders even when shorter term (10 years) risk is in low moderate range. The prime emphasis in management of metabolic syndrome per se is to mitigate the modifiable, underlying risk factor (obesity, physical inactivity and atherogenic diet) through lifestyle changes. Its absolute risk is high enough, therapeutic interventions like metformin, statins, etc. may be incorporated to the regimes. More than 61.25% (49 out of 80) of first-degree relatives of diabetic patient with NIDDM displayed abnormal glucose tolerance either as IGT (26.25%) or NIDDM (35%). The Catalonia study and Aragon study were done on general population and hence showed a lesser prevalence of abnormal glucose tolerance than our study. However, the Catalonia study done on firstdegree relatives with age >20 years shows a much higher prevalence of 30% for abnormal glucose tolerance than in general population (20%). Racial difference would explain the higher prevalence of abnormal glucose tolerance in our study. Further Indian studies are required to support our data. Individuals with a parent with T2DM have increased risk of DM and if both parents have T2DM it approaches 40%. Insulin resistance as demonstrated by decreased glucose utilization in skeletal muscle is present in many nondiabetic first-degree relative of T2DM. Annually, IGT carries 1-10% rate of progression to frank T2DM. Thus, all patients in whom diabetes develops probably go through stage IGT and this condition confirms a non-negligible risk in terms of CVDs as well as its progression to NIDDM. Thus by identifying this cluster of individuals at high-risk for metabolic syndrome, we can delay the emergence of DM, CVD, dyslipidemia, stroke and obesity by pharmacological and nonpharmacology measure. The Diabetes Prevention Program (DPP) demonstrated that intense lifestyle changes (diet and exercise for 30 mins/d) in individuals with IGT prevented or delayed development of T2DM by 58%. By lifestyle intervention, IGT lost 5.7% of body weight in three years. The use of metformin in IGT prevented DM by 31%. Indian Journal of Clinical Practice, Vol. 23, No. 9 February

9 When subjects with abnormal glucose tolerance were analyzed, they displayed a higher BMI, blood pressure, triglyceride level, central obesity and lower HDL levels, than NGT groups, all well-recognized features of metabolic syndrome. NIDDM subjects were significantly older than IGT (IGT vs DM; p < 0.01) and NGT (NGT vs DM; p < 0.03) subjects. BMI was significantly higher in both pathological groups (p < ). When blood pressure was considered, diastolic values were higher in abnormal OGTT compared to NGT. No difference in terms of sex distribution was found in any category. Our study dealt with the identification of factors, which determine plasma glucose concentration after two hours in OGTT. A step-wise multiple linear regression was applied using SPSS to all first-degree relatives to assess the independent contribution of IGT to separate components of metabolic syndrome; which demonstrated that FBG, hip circumference and low HDL levels were independent determined two hours glycemia value in OGTT (R 2 = 0.70; p < 0.00%) of oral glucose tolerance. So IGT, increased hip circumference and low HDL levels can be considered as risk factors for glucose intolerance. This piece of information can be further used with support from a larger Indian study in setting up criteria for precocious screening for IGT and DM in first-degree relatives. This would minimize the number of OGTT and thereby reduce the cost of screening for the given family. Our study shows a high prevalence of metabolic syndrome and IGT in a selected native Indian population. The study also demonstrates that impaired fasting glucose, increased hip circumference and low HDL levels were associated with glucose intolerance. Furthermore, synergistic effect on increasing the risk for diabetes by lifestyle factors and family history of diabetes was observed in this study. These populations with family history of DM have increased risk for both cardiovascular disease and T2DM. Metabolic syndrome being a cardiovascular risk factor according to ATP III lifestyle modification, timely therapeutic intervention is crucial in the prevention of both T2DM and premature CVD in a risk population. With high degree of heritability and increased urbanization, diabetes could become a major health hazard in India and this underscores the fact that prevention of diabetes must be one of the important health targets for the nation in this century. CONCLUSION In T2DM and their asymptomatic first-degree relatives, hypertension and low HDL were commonest components of metabolic syndrome, females were more obese. Glucose intolerance was significantly associated with other components of metabolic syndrome. Impaired fasting glucose, increased hip circumference and low HDL levels were independently associated with, so were the risk factors for glucose intolerance. Acknowledgment We sincerely acknowledge our medical institute VS General Hospital, their staff, our teachers and also the all patients and their relatives without whom this study can t be possible. SUGGESTED READING 1. 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). Executive summary publication no Bethesda, National Institutes of Health, Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287(3): Granner DK, O Brien RM. Molecular physiology and genetics of NIDDM. Importance of metabolic staging. Diabetes Care 1992;15(3): Reaven GM. Banting lecture Role of insulin resistance in human disease. Diabetes 1988;37(12): Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15(7): Balkau B, Charles MA, Drivsholm T, Borch-Johnsen K, Wareham N, Yudkin JS, et al; European Group For The Study Of Insulin Resistance (EGIR). Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab 2002;28(5): Assmann G, Nofer JR, Schulte H. Cardiovascular risk assessment in metabolic syndrome: view from PROCAM. Endocrinol Metab Clin North Am 2004;33(2): Harrison s Principles of medicine 18th Edition, 1995:p Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003;9(3): Indian Journal of Clinical Practice, Vol. 23, No. 9 February 2013

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14 10. Shah T, Jonnalagadda SS, Kicklighter JR, Diwan S, Hopkins BL. Prevalence of metabolic syndrome risk factors among young adult Asian Indians. J Immigr Health 2005;7(2): International Diabetes Federation. Worldwide definition of the metabolic syndrome. Available at: org/webdata/docs/idf_meta_def_final.pdf. 12. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 2004;24(2):e 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): Nyholm B, Nielsen MF, Kristensen K, Nielsen S, Ostergard T, Pedersen SB, et al. Evidence of increased visceral obesity and reduced physical fitness in healthy insulin-resistant first-degree relatives of type 2 diabetic patients. Eur J Endocrinol 2004;150(2): Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24(4): Cruz ML, Weigensberg MJ, Huang TT, Ball G, Shaibi GQ, Goran MI. The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab 2004;89(1): Shen BJ, Todaro JF, Niaura R, McCaffery JM, Zhang J, Spiro A 3rd, et al. Are metabolic risk factors one unified syndrome? Modeling the structure of the metabolic syndrome X. Am J Epidemiol 2003;157(8): Diabetes & Obesity: Time to Act. International Diabetes Federation Klein S, Sheard NF, Pi-Sunyer X, Daly A, Wylie- Rosett J, Kulkarni K Clark NG. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care 2004;27(8): Black Race, Diabetes with Complications CRVO Risk Factors Black race and diabetes mellitus (DM) with complications are two previously unrecognized risk factors for central retinal vein occlusion (CRVO), according to a large study of healthcare claims. The data also confirm that hypertension (HTN), which accelerates stiffening of arteries, and vascular disease are significant risk factors for CRVO. (Source: Medscape) Sugar is Nobody s Sweetheart any More The intake of free sugars or sugar-sweetened beverages is a determinant of body weight according to a systematic review and meta-analysis conducted for the World Health Organization (WHO). The findings are intended to support new WHO guidelines on dietary intake of sugar, which currently urge that it be kept to less than 10% of total energy. Gestational Diabetes Screening Based on Risk Misses too Many Selective screening of pregnant women for gestational diabetes by risk factors misses about a third of women who have the condition and who are at increased risk for adverse pregnancy outcomes, a large retrospective analysis shows. (Source: Medscape) Little Help from Lucentis for Diabetic Eyes Patients with vitreous hemorrhage related to diabetic retinopathy derived no short-term benefits from treatment with the angiogenesis inhibitor ranibizumab (Lucentis), results of a randomized trial showed. (Source: Medpage Today) Indian Journal of Clinical Practice, Vol. 23, No. 9 February