Evaluation of Madras Diabetes Research Foundation-Indian Diabetes Risk Score in detecting undiagnosed diabetes in the Indian population: Results from the Indian Council of Medical Research-INdia DIABetes population-based study (INDIAB-15)

Background & objectives: Screening of individuals for early detection and identification of undiagnosed diabetes can help in reducing the burden of diabetic complications. This study aimed to evaluate the performance of Madras Diabetes Research Foundation (MDRF)-Indian Diabetes Risk Score (IDRS) to screen for undiagnosed type 2 diabetes in a large representative population in India. Methods: Data were acquired from the Indian Council of Medical Research–INdia DIABetes (ICMR–INDIAB) study, a large national survey that included both urban and rural populations from 30 states/union territories in India. Stratified multistage design was followed to obtain a sample of 113,043 individuals (94.2% response rate). MDRF-IDRS used four simple parameters, viz. age, waist circumference, family history of diabetes and physical activity to detect undiagnosed diabetes. Receiver operating characteristic (ROC) with area under the curve (AUC) was used to assess the performance of MDRF-IDRS. Results: We identified that 32.4, 52.7 and 14.9 per cent of the general population were under high-, moderate- and low-risk category of diabetes. Among the newly diagnosed individuals with diabetes [diagnosed by oral glucose tolerance test (OGTT)], 60.2, 35.9 and 3.9 per cent were identified under

Impact of coronary artery disease on augmentation index as measured by estimated central blood pressure: A case control study in Asian Indians

Aims We compared various components of blood pressure and arterial stiffness of healthy control with those of coronary artery disease (CAD) patients using BP+ machine™. Methods In this prospective, case-control study, total 585 individuals of both the genders were enrolled. The study population consisted of 277 controls (healthy siblings of diseased subjects not having CAD – group A) and 308 CAD patients (group B). Age and sex adjusted regression and receiver operative curve (ROC) analysis was performed to assess the strength of association of these parameters. Results We found that mean systolic blood pressure (SBP) (137.14 ± 22.49 vs. 129.26 ± 19.86), central systolic blood pressure (CSBP) (130.78 ± 21.89 vs. 117.53 ± 17.98), augmentation index (AI) (108.55 ± 44.98 vs. 49.38 ± 21.03) and pulse rate variability (98.82 ± 231.09 vs. 82.86 ± 208.77) were significantly (p < 0.05) higher in CAD population as compared to healthy counterparts. Left ventricular contractibility as measured by dP/dt was significantly lower in CAD patients. All these parameters were significantly abnormal in CAD as compared to healthy control population irrespective of the gender of the patient except for SBP in females. Both – odds ratio (1.108; 95% CI: 1.081–1.135; p < 0.0001) and ROC analysis (AUC: 0.937; 95% CI: 0.919–0.956; p < 0.0001) showed AI as the strongest predictor of CAD, closely followed by CSBP. Conclusion Central aortic blood pressure parameters such as AI and CSBP measured noninvasively with BP+ machine could be the effective predictors of CAD in Asian Indians.

Prevalence and significance of generalised and central body obesity among medical students

Background: Obesity is a major modifiable cardiovascular risk factor as studied by American Heart Association. Aim of present study was to determine the prevalence of generalised and central body obesity among Medical Students and association of obesity measured by body mass index (BMI) and waist circumference (WC) with health risk factors. Material and methods: The present study was conducted on 200 medical students including 102 males and 98 females in the age group of 18-23 years in the Department of Physiology, Govt. Medical College, Amritsar. For generalised obesity (BMI> 25 kg/m2 and abdominal or central obesity (WC 94>cm in males and 80 >cm in females) were used. Results: The prevalence of generalised obesity in males and females was 75.51% (males 50.0%, females 25.51%) and abdominal or central obesity 82% (males 14% and females 68%). Isolated generalised obesity (BMI increased and WC normal) in males and female was 62.96% and 37.04% and isolated abdominal obesity (WC increased and BMI normal) in males and females 17.28% and 82.72%. Combined obesity (BMI and WC both increased) in males and females 40.12% and 59.88%. Conclusion: Prevalence of combined obesity was found high among both sexes. While isolated generalised obesity was more common in males and isolated abdominal obesity more common in females. However, these prevalence rates vary markedly depending on cut points used. WC is a better marker of obesity related risk than BMI.

Explaining Overweight and Obesity in Children and Adolescents of Asian Indian Origin: The Calcutta Childhood Obesity Study.

The present study was aimed to find out the prevalence of overweight and obesity and its associated factors among Bengalee children and adolescents in the Kolkata, India. A total of 1061 Bengalee school children and adolescents (610 boys and 451 girls) participated and were divided into three age groups: Group I = 8-11 years; Group II = 12-15 years and Group III = 16-18 years. Overweight and obesity were defined as: Overweight (between ≥85th and <95th percentile) and obesity (≥95th percentile). Multivariate regression analyses (adjusted for age and sex) of body mass index (BMI) revealed that about 18% (R2 = 0.185) of total variance of BMI could be explained by monthly family income, participants think obese, consumption of too much junk foodstuffs, breakfast skip, extra consumption of salt, and computer hours. Sedentary lifestyles, including increasing fast food preferences may be responsible for increasing occurrence of pediatric and adolescent obesity in this population.

High prevalence of cardiovascular risk factors in Asian Indians: A community survey - Chandigarh Urban Diabetes Study (CUDS).

Background & objectives: Studies conducted to assess the prevalence of cardiovascular (CV) risk factors among different regions of the country show variation in risk factors in different age groups and urban and rural population. We undertook this study to determine the prevalence of cardiovascular risk factors among urban adults in a north Indian city. Methods: In a cross-sectional survey, 2227 subjects aged ≥ 20 yr were studied from April 2008 to June 2009 in Urban Chandigarh, a north Indian city. Demographic history, anthropometry and blood pressure were assessed. Fasting, and 2 h capillary plasma glucose after 75 g glucose load, HDL-C and triglycerides were estimated. Results: The most prevalent cardiovascular risk factors in the age group of 20-29 yr was sedentary lifestyle (63%), while from fourth decade and onwards, it was overweight/obesity (59-85%). The second most common prevalent cardiovascular risk factor in the age group of 20-29 yr was overweight/obesity, in 30-49 yr sedentary lifestyle, in 50-69 yr hypertension and in subjects ≥70 yr, it was hypertriglyceridaemia. The prevalence of overweight/obesity, hypertension, dysglycaemia and smoking was almost double in subjects in the fourth decade of life, as compared to those in the third decade of life. The prevalence of CV risk factors significantly increased with age irrespective of gender and prevalence of low HDL-C was significantly more common in women as compared to men. Interpretation & conclusions: Sedentary lifestyle, obesity and low HDL-C are the most prevalent CV risk factors in subjects in the third and fourth decade of life in this north Indian population and clustering of these cardiovascular risk factors increases with advancing age. Strategies need to be formulated to target this population to prevent the epidemic of cardiovascular disease.

Effect of Progressive Resistance Exercise Training on Hepatic Fat in Asian Indians with Non-Alcoholic Fatty Liver Disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance and lifestyle measures form the cornerstone of therapy. Objective: To study the effect of progressive resistance training (PRT) on hepatic fat content, body composition and insulin sensitivity in patients with NAFLD. Methods: This study included 24 adult patients with NAFLD diagnosed on ultrasonography. Subjects with alcohol intake >140 gm/week and any secondary cause of fatty liver were excluded. Patients underwent thrice weekly sessions (40 minutes each) of resistance exercises including flexion at biceps, triceps, and hip flexion, knee extension and heel rise for 12 weeks. Pre- and post-intervention evaluation included anthropometry, BIA analysis, short insulin tolerance test (SITT), lipid profile and hepatic fat quantification by MRI. Results: Twenty four patients (17 males, 7 females, mean age 39.8±10.5 yrs) completed the study protocol with 78.7% compliance to PRT protocol. There was significant decrease in waist, hip and mid-thigh circumferences and skinfold thicknesses at biceps, triceps, subscapular and suprailiac regions (p<0.05), with no significant change in BMI and WHR. Insulin sensitivity improved significantly at 12 weeks as indicated by increase in k-value (rate of change of glucose) on SITT (0.84 vs 1.3, p=0.002). A decrease in total cholesterol and LDL-c with increase in HDL-c was noted after 12 weeks (p<0.05). Hepatic fat content also decreased at 12 weeks (22.3±3.9 vs 21.4±4.0 %, p=0.01). Conclusion: Moderate intensity PRT is associated with significant improvement in hepatic fat, truncal subcutaneous fat and insulin sensitivity in patients with NAFLD.

Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes.

Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians.

Appropriate anthropometric indices to identify cardiometabolic risk in South Asians.

Background: South Asians show an elevated cardiometabolic risk compared to Caucasians. They are clinically metabolically obese but are considered normal weight based on current international cut-off levels of several anthropometric indices. This study has two main objectives: (i) to predict the most sensitive anthropometric measures for commonly studied cardiometabolic risk factors, and (ii) to determine optimal cut-off levels of each of the anthropometric indices in relation to these cardiometabolic risk factors in South Asians. Methods: The study was conducted on a random sample of 1178 adults of 20–80 years of age from an urban population of eastern India. Obesity, as evaluated by standard anthropometric indices of BMI (body mass index), WC (waist circumference), WHpR (waist-to-hip ratio) and WHtR (waist-to-height ratio), was individually correlated with cardiometabolic risk factors. Receiver operating characteristic (ROC) curve analyses were performed which includes: (i) the area under the receiver operating characteristic curve (AUROC) analysis to assess the predictive validity of each cardiometabolic risk factor; and (ii) Youden index to determine optimal cut-off levels of each of the anthropometric indices. Results: Overall, AUROC values for WHtR were the highest, but showed variations within the sexes for each of the cardiometabolic risk factors studied. Further, WHpR cut-offs were higher for men (0.93–0.95) than women (0.85–0.88). WC cut-offs were 84.5–89.5 cm in men and 77.5–82.0 cm in women. For both sexes the optimal WHtR cut-off value was 0.51–0.55. The optimal BMI cut-offs were 23.4–24.2 kg/m2 in men and 23.6–25.3 kg/m2 in women. Conclusion: WHtR may be a better anthropometric marker of cardiometabolic risks in South Asian adults than BMI, WC or WHpR.

Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians.

Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 ( 201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population.

Efficacy of Glycated Albumin (GA) in Comparison with Glycated Haemoglobin (HbA1c) in Type 2 Diabetic Subject in India.

The study was planned to determine the efficacy of GA in comparison with HbA1c among type2 diabetic subjects. A total of 94 type 2 diabetic (group2) subjects were selected for this prospective study and were compared with 50 non diabetic controls (group1). The subjects were reviewed for a period of 3months. Anthropometric, blood pressure, plasma glucose, GA and HbA1c measurements were done at baseline, 1st and final follow up visits for all the subjects.GA levels strongly correlated with HbA1c% both in control and study group. The mean GA and HbA1c values were significantly lower at the baseline and during follow up visits in controls than in study subjects (p<0.001). GA, HbA1c and the ratio decreased significantly within 4weeks, but GA showed a significantly larger decrease than HbA1c. There was no significant difference in the GA% after 3months. GA may be a useful marker for assessing short term glycemic changes in type2 diabetes.

Association of hypoadiponectinemia with non-alcoholic fatty liver disease in urban south Indians - (CURES - 81).

Background & objective: Association between adiponectin and non-alcoholic fatty liver disease (NAFLD) has been reported in west. Studies in Indian population are lacking. This study was undertaken to assess the association of hypoadiponectinemia with NAFLD in Asian Indians. Method: In this cross-sectional study, subjects were randomly selected from Phase 5 of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study based on a representative population of Chennai in south India. One hundred twenty one subjects without NAFLD and 72 subjects with NAFLD were selected. NAFLD was diagnosed by ultrasonography. Serum adiponectin levels were measured using radioimmunoassay. Insulin resistance was calculated using Homeostasis Assessment model (HOMA-IR). Results: Serum adiponectin values were significantly lower in subjects with NAFLD compared to those without [5.6 μg/ml (95% Confidence Interval (CI) 5.0 - 6.3 μg/ml] vs 7.4 μg/ml (95% CI: 6.7 - 8.1 μg/ml, P<0.01). Adiponectin levels decreased with increasing severity of NAFLD. Subjects with moderate to severe steatosis had significantly lower adiponectin levels (5.1μg/ml, 95% CI: 4.1- 6.4 μg/ml) compared to subjects with mild steatosis (5.9 μg/ml, 95% CI: 5.0 - 6.9 μg/ml; P<0.001) and subjects without NAFLD (7.3 μg/ml, 95% CI: 6.6 - 8.0 μg/ml; P<0.01). Multiple logistic regression analysis revealed adiponectin to be negatively associated with NAFLD [Odds Ratio (OR): 0.865, 95% Confidence Interval (CI): 0.792- 0.944, P=0.001]. This remained statistically significant even after adjusting for confounding factors age, gender, body mass index, insulin resistance, waist circumference, total cholesterol, triglycerides and glucose intolerance (OR: 0.873, 95% CI: 0.793 - 0.961; P=0.005). Interpretation & conclusion: NAFLD is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in Asian Indians known to have high prevalence of diabetes and coronary artery disease.

Heritability estimation of conventional cardiovascular disease risk factors in Asian Indian families: The Calcutta family study.

The genetic causes of the components of cardiovascular disease (CVD) risk factors and their intercorrelation are indeed complex and only partly understood. Keeping this view in mind, the present work was undertaken to estimate the heritability of conventional CVD risk factors using family study method. A total of twenty-four nuclear families inhabiting in Calcutta and adjacent areas was chosen randomly. Up to first degree relatives including father, mother and other sibs of the proband were considered as participants in the study. Anthropometric measures namely height, weight, waist circumference as well as skinfold thickness at biceps, triceps, subscapular and suprailiac were obtained using standard techniques. Body mass index (BMI), percentage of body fat (PBF), fat mass (FM), waist-hip ratio (WHR), sum of four skinfolds (SF4 ), arm muscle circumference (AMC), arm muscle area (AMA), arm fat area (AFA), systolic (SBP) and diastolic blood pressure (DBP) were also considered. To estimate’heritability’ in the study, the mid parent-offspring model was used where’heritability’ (h2 ) was equivalent to regression co-efficient (b). The regression sum of square (RSS) and total sum of square (TSS) ratio was also calculated both for mid parent-offspring and single parent-offspring. This ratio was considered as a measure of’heritability’ in the study with consideration that RSS is the variation due to genetic factor and the TSS is due to genetic and other additive factor. It was observed that the estimated heritability for BMI ranges from 0.69 to 0.31 using mid-parent off spring model while the range using single parent-offspring model was from 0.40 to 0.16. The range of heritability for SBP in mid parent-offspring model was 0.16 to 0.44 and 0.05 to 0.54 for single parent-offspring model. To conclude, it seems reasonable to argue that in the study a moderate to high h2 was evident for body fat level, body composition and blood pressure measures which indicate a moderate to high aggregation of gene(s) in the family.

A case-control study on insulin resistance, metabolic co-variates & prediction score in non-alcoholic fatty liver disease.

Background & objectives: Asian Indians have a high prevalence of insulin resistance and the metabolic syndrome. Currently, non-alcoholic fatty liver disease (NAFLD) is considered to be an integral part of the metabolic syndrome with insulin resistance as a central pathogenic factor. We studied anthropometric parameters, insulin resistance and metabolic co-variates in subjects with NAFLD as compared to those without NAFLD, and also developed a prediction score for NAFLD. Methods: Thirty nine subjects with NAFLD and 82 controls were selected for the study after ultrasonography of 121 consecutive apparently healthy subjects. Anthropometric profile [body mass index (BMI), waist circumference (WC) etc,], lipid profile, hepatic aminotransferases, fasting blood glucose (FBG), insulin were recorded and value of homeostasis model assessment of insulin resistance (HOMA-IR) was analysed. Step-wise logistic regression analysis and area under the receiver operator curve (aROC) were analysed to arrive at a prediction score. Results: Overall, prevalence of NAFLD was 32.2 per cent and prevalence of metabolic syndrome was seen in 41 per cent among cases and 19.5 per cent in controls (P<0.01). Subjects with NAFLD had significantly higher values of BMI, WC, hip circumference, FBG, fasting insulin, total cholesterol and serum triglycerides. Step-wise logistic regression analysis showed odds ratio (OR) and 95 per cent confidence interval (CI) for BMI [ 4.3 (1.6, 11.3)], FBG [5.5 (1.5, 19.8)] and fasting insulin [ 2.4 (1.0, 5.8)] as independent predictors of NAFLD. The prediction score for NAFLD was; 1 (fasting insulin) +1.6 (BMI) + 1.9 (FBG) (sensitivity of 84.6%, specificity of 51.2% and aROC 76%). Interpretation & conclusion: In this study, presence of NAFLD indicated close relationship with multiple features of metabolic syndrome. The prediction score developed could be used as a screening tool to predict NAFLD among Asian Indians in north India.

Apolipoprotein E gene polymorphism and dyslipidaemia in adult Asian Indians: A population based study from Calcutta, India.

AIM: The study was aimed to determine the association of Apolipoprotein E (apo E) gene polymorphisms on lipid levels in Asian Indian population. METHODS: A total of 350 (184 males and 166 females) adult (30 years and above) Asian Indians of Calcutta and suburb participated in the study. Anthropometric measures, lipids profiles, and blood glucose measures were collected. Out of 350 subjects, a sample of 70 individuals was selected randomly for genotyping after adjusting for age and sex. The apo E gene polymorphisms were determined by agarose gel electrophoresis. RESULTS: The apo E polymorphism showed significant association with dyslipidaemia (P=0.0135) with ε3/4 combination has had the highest occurrence of dyslipidaemia and metabolic syndrome (MS) followed by ε4/4 <ε3/3 <ε2/4 <ε2/3 in decreasing order. CONCLUSIONS: The ε4 allele of apo E gene independent of other risk factors is associated with dyslipidaemia in particular with low HDLc and high TC: HDLc ratio.