Identification of insulin resistance in Asian Indian adolescents: classification and regression tree (CART) and logistic regression based classification rules.

OBJECTIVE: Biochemical measures for assessment of insulin resistance are not cost-effective in resource-constrained developing countries. Using classification and regression tree (CART) and multivariate logistic regression, we aimed to develop simple predictive decision models based on routine clinical and biochemical parameters to predict insulin resistance in apparently healthy Asian Indian adolescents. DESIGN: Community based cross-sectional study. SUBJECTS AND PATIENTS: Data of apparently healthy 793 adolescents (aged 14-19 years) were used for analysis. WHO's multistage cluster sampling design was used for data collection. METHODS AND MEASUREMENTS: Homeostasis Model of Assessment value > 75th centile was used as cut-off for defining the main outcome variable insulin resistance. CART was used to develop the decision tree models and multivariate logistic regression used to develop the clinical prediction score. RESULTS: Three classification trees and an equation for prediction score were developed and internally validated. The three decision trees were termed as CART I, CART II and CART III, respectively. CART I based on anthropometric parameters alone has sensitivity 88.2%, specificity 50.1% and area under receiver operating characteristic curve (aROC) 77.8%. CART II based on anthropometric and routine biochemical parameters has sensitivity 94.5%, specificity 38.3% and aROC 73.6%. CART III based on all anthropometric, biochemical and clinical parameters together has sensitivity 70.7%, specificity 79.2% and aROC 77.4%. Prediction score for insulin resistance = 1 x (waist circumference) + 1.1 x (percentage body fat) + 1.6 x (triceps skin-fold thickness) - 1.9 x (gender). A score cut-off of > 0 (using values marked for each) was a marker of insulin resistance in the study population (sensitivity 82.4%, specificity 56.7%, and aROC 73.4%). CONCLUSION: These simple and cost-effective classification rules may be used to predict insulin resistance and implement population based preventive interventions in Asian Indian adolescents.

Heterogeneous phenotypes of insulin resistance and its implications for defining metabolic syndrome in Asian Indian adolescents.

OBJECTIVE: To assess the phenotypic correlations of insulin resistance with obesity and its relationship with the metabolic syndrome in Asian Indian adolescents. DESIGN AND SUBJECTS: We analyzed clinical, anthropometric (body mass index [BMI], waist circumference [WC]) and laboratory (fasting blood glucose [FBG], lipids and fasting serum insulin) data from 793 subjects (401 males and 392 females) aged 14-19 years randomly selected from Epidemiological Study of Adolescents and Young (ESAY) adults (n=1447). The percentile cut-offs for 14-19 years age from ESAY cohort were used for defining abnormal values of variables. We devised three sets of definitions of metabolic syndrome by including BMI and fasting insulin levels with other defining variables. RESULTS: Nearly 28.9% of adolescents had fasting hyperinsulinemia despite normal values of BMI, WC, FBG, lipids, and blood pressure. Remarkably, NCEP criteria with appropriate percentile cut-off points for Asian Indian adolescents identified metabolic syndrome in only six (0.8%) subjects. Inclusion of both BMI and WC in the definition resulted in increase in the prevalence of metabolic syndrome to 4.3%. With inclusion of hyperinsulinemia, the prevalence of metabolic syndrome increased to 4.2% (from 0.8%) in the modified NCEP definition, 5.2% (from 0.9%) when BMI was substituted for WC, and 10.2 (from 4.3%) when both BMI and WC were included. CONCLUSIONS: Our data show marked heterogeneity of phenotypes of insulin resistance and poor value of NCEP definition to identify metabolic syndrome. We propose that BMI and fasting insulin should be evaluated in candidate definitions of metabolic syndrome in Asian Indian adolescents.

Simple anthropometric measures identify fasting hyperinsulinemia and clustering of cardiovascular risk factors in Asian Indian adolescents.

Correlations of easily measurable parameters of obesity (body mass index [BMI], waist circumference [WC], and subscapular skinfold thickness) with fasting hyperinsulinemia and cardiovascular risk factors (CRFs) have not been investigated in adolescents. We evaluated the screening performance of 3 anthropometric measurements, BMI, WC, and subscapular skinfold thickness, in identifying fasting hyperinsulinemia and clustering of CRFs in 680 male and 521 female adolescents and young adults aged 14 to 18 years in a cross-sectional population survey. CRFs considered were hypercholesterolemia, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, impaired fasting blood glucose, hypertension, and fasting hyperinsulinemia. The ability of the anthropometric measurements to identify the clustering of CRFs without (cluster 1) and with fasting hyperinsulinemia (cluster 2), and fasting hyperinsulinemia alone was evaluated. BMI, WC, and subscapular skinfold thickness identified the clustering of CRFs and fasting hyperinsulinemia better in males than in females. Among individual risk factors, WC was better in identifying the presence of 3 or more risk factors in cluster 1 for both males and females, and in cluster 2 in females. Subscapular skinfold thickness was better than BMI and WC in identifying hyperinsulinemia in males, and the presence of 3 or more risk factors in cluster 2 in females. All 3 measurements were more accurate in identifying fasting hyperinsulinemia than presence of 3 or more CRFs in either cluster 1 or cluster 2 with higher odds ratio for males. This study shows gender differences in identification of insulin resistance and clustering of CRFs by using simple anthropometric parameters in Asian Indian adolescents. These simple measurements are useful for preventing and predicting cardiovascular risk and for generating a correct definition of the metabolic syndrome.

C-reactive protein and dietary nutrients in urban Asian Indian adolescents and young adults.

OBJECTIVE: The relationship between C-reactive protein (CRP), a surrogate marker of cardiovascular risk, and dietary nutrients is not known. We investigated the relationship between serum CRP levels and dietary nutrients in young Asian Indians residing in a major metropolitan city in north India. METHODS: Dietary nutrient intake values (24-h dietary recall and monthly consumption data) and serum CRP levels were studied in 359 healthy adolescents and young adults (312 male and 47 female) (mean age, 18.0 +/- 2.3 y; range, 14-25 y), after carefully excluding those with history of infections and smoking. Bivariate and multivariate logistic regression analysis was performed with CRP [raised (>3.0 mg/L)/normal] as the outcome variable and various dietary nutrients and anthropometric variables as covariates. RESULTS: Mean CRP level was 1.3 +/- 2.3 mg/L (range, 0.02-17.5 mg/L). Raised CRP levels (>3 mg/L) were noted in 9% study subjects (8.6% males and 12.8% females). After adjustment for other covariates, saturated fat emerged as the single most important nutrient contributing to increase in serum CRP levels. The odds of having a raised CRP level in subjects consuming more than 10% energy as saturated dietary fat were twice as compared to subjects having a normal saturated fat intake [Adjusted odds ratio (OR) (95% CI) = 2.0 (0.94-4.1)]. For every one percent decrease in energy intake by saturated fat, CRP level was calculated to decrease by 0.14 mg/L. For decreasing CRP levels to <1.0 mg/L (low risk for cardiovascular disease), Asian Indian adolescents and young adults should ensure saturated fat intake <7% of caloric intake. CONCLUSION: We suggest that daily saturated fat intake should be limited to <7% of caloric intake in urban adolescents and young adult Asian Indians to decrease their future cardiovascular risk.

Association between subclinical inflammation & fasting insulin in urban young adult north Indian males.

BACKGROUND & OBJECTIVES: Elevated levels of c-reactive protein (CRP) are known to be associated with insulin resistance and metabolic syndrome in adults. A substantial prevalence of hyperinsulinaemia and elevated CRP levels have been shown in Indian young adults. We therefore studied the association of serum high-sensitivity C-reactive protein (hs-CRP) with fasting insulin and insulin resistance in urban adolescent and young adult males in north India. METHODS: In this cross-sectional study 324 healthy males, 14-25 yr of age were selected randomly and their clinical and anthropometric profile [body mass index (BMI), waist and hip circumferences, waist-to-hip circumference ratio (W-HR), and skinfold thickness at four sites], percentage of body fat (%BF) and biochemical (fasting blood glucose, lipoprotein profile, fasting insulin and hs-CRP) parameters were recorded. Insulin resistance was assessed by the homeostasis model of assessment (HOMA-IR). RESULTS: Fasting insulin and hs-CRP levels correlated significantly with BMI, waist circumference, and triceps and subscapular skinfold thickness. Fasting insulin also correlated with %BF, and hs- CRP correlated with W-HR. No correlation was observed between hs-CRP and fasting insulin levels or insulin resistance. In multiple logistic regression analysis different independent risk factors for hyperinsulinaemia and elevated hs-CRP levels were observed; hypercholesterolaemia, overweight and high subscapular skinfold thickness for the former, and high triceps skinfold thickness for the latter. INTERPRETATION & CONCLUSION: Lack of correlation between hs-CRP and surrogate markers of insulin resistance and different risk factors for each, in young Indian males are unique observations of our study. Further studies on a larger sample of both genders need to be done to confirm these findings.

Centile values for serum lipids and blood pressure for Asian Indian adolescents.

BACKGROUND: Reference data for plasma lipids and blood pressure are not available for Asian Indian adolescents. This study aimed to develop representative age- and sex- specific percentile reference data for serum lipids [total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL cholesterol] and blood pressure for urban Asian Indian adolescents aged 14-18 years. The sample consisted of 680 boys and 521 girls aged 14-18 years from the cross-sectional population survey, Epidemiological Study of Adolescents and Young Adults (ESAY) for whom the data for serum lipid levels and blood pressure were recorded. Smoothed age- and sex- specific 5th, 10th, 25th, 50th, 75th, 85th, 90th and 95th percentiles where derived using LMS regression. RESULTS: Percentile-based reference data for serum lipids and blood pressure are presented for adolescent Asian Indian boys and girls for the first time. Asian Indian adolescents had lower levels of serum TC, LDL-C and HDL-C and higher TG than their counterparts in the USA. Interesting trends in TC and HDL-C levels where observed, which might reflect changes in dietary pattern and physical activity in this age group in India. CONCLUSION: These reference data could be used to identify adolescents with an elevated risk of developing dyslipidemia, hypertension and cardiovascular disorders, to plan and implement preventive policies, and to study temporal trends.

Correlations of C-reactive protein levels with anthropometric profile, percentage of body fat and lipids in healthy adolescents and young adults in urban North India.

OBJECTIVE: To investigate the relationships of sub-clinical inflammation and regional and generalized obesity and lipids in adolescent and young adult Asian Indians in north India. METHODS: We determined serum levels of C-reactive protein (CRP), a marker for sub-clinical inflammation, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (W-HR), four skinfolds (biceps, triceps, subscapular and suprailiac), percentage of body fat (% BF) and lipid profile in 377 healthy adolescents and young adults (331 males and 46 females, age range: 14-25 years). RESULTS: Overweight subjects (BMI>85th percentile), and subjects with high values (>85th percentile) of WC and triceps skinfold thickness had significantly higher median CRP levels (P=0.04, P=0.001 and P=0.007, respectively) as compared with subjects with lower values of the variables. Elevated levels of CRP (>2.1 mg/l) were observed in 21.8% of the overweight subjects and 24.5% of the subjects with high (>85th percentile) % BF. After adjusting for age and gender, the odds ratios (95% CI) for elevated levels of CRP were 2.3 (1.1-4.7, P=0.02) for overweight subjects, 2.6 (1.2-5.4, P=0.01) for subjects with high % BF, and 3.7 (1.7-7.9, P=0.001) for subjects with high triceps skinfold thickness. Levels of CRP correlated significantly with % BF (r=0.13, P=0.009), W-HR (r=0.11, P=0.02), biceps skinfolds (r=0.13, P=0.01) and triceps skinfolds (r=0.13, P=0.01) for males only. CONCLUSIONS: The observations of substantial prevalence of elevated CRP levels in adolescents and young adults having increased generalized and abdominal adiposity may be important for the development of metabolic syndrome and atherosclerosis in Asian Indian adults.

Vitamin D and insulin resistance in postmenopausal Indian women.

PURPOSE: The purpose of this study is to investigate the association of the serum 25-hydroxyvitamin D (25-OHD) level with markers of insulin resistance (IR) in postmenopausal Indian women. MATERIALS AND METHODS: This was a cross-sectional study, conducted at a Tertiary Care Hospital in New Delhi, India. Seventy one postmenopausal women (mean age 56.3 ± 7.6 years) were enrolled. Exclusion criteria were known or newly detected diabetics, subjects with chronic renal failure, chronic liver disease or any other chronic inflammatory condition, chronic smokers and chronic alcoholics. Serum calcium (and albumin for calculating corrected calcium), phosphorus, alkaline phosphatase and 25-OHD were measured as parameters of calcium homeostasis. Fasting blood glucose (FBG), systolic and diastolic blood pressures, body mass index (BMI), fasting serum insulin, calculated glucose insulin ratio (GIR), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as parameters of IR. Data was then analyzed for statistical significance. RESULTS: The mean serum 25-OHD level was 12.73 ± 7.63 ng/ml. The mean BMI was 27.78 ± 5.37 kg/m(2). The mean calculated GIR was 13.14 ± 9.39 and HOMA-IR was 2.31 ± 1.70. Serum 25-OHD was inversely correlated with BMI (correlation coefficient -0.234, P value 0.050) and with HOMA-IR (correlation coefficient -0.237, P value 0.047). However, when 25-OHD was adjusted for BMI the correlation between 25-OHD and HOMA-IR lost its significance. No correlation was found between serum 25-OHD and any other parameters of IR studied. CONCLUSIONS: There is a significant negative linear correlation between 25-OHD and BMI. The significant negative linear correlation between 25-OHD and HOMA-IR was confounded by BMI. There is no correlation between 25-OHD and parameters of IR.

Clinical experience with exenatide in obese North Indian patients with type 2 diabetes mellitus.

OBJECTIVE: To share our clinical experience with exenatide in obese North Indian subjects with type 2 diabetes. MATERIALS AND METHODS: We share our experience with use of exenatide in 74 patients treated at Indraprastha Apollo Hospital, a tertiary care centre in New Delhi, India Subjects included obese / overweight subjects (mean weight and BMI; 97.67 ± 5.6 kg and 34.56 kg/m(2)) with known history of type 2 DM (Mean: 9 ± 5.6 years) and maintaining suboptimal glycemic control (HbA1c >7%) on oral antidiabetic agents, with or without basal insulin. Metformin and sulphonylureas were continued (with dose adjustment if indicated), as was basal insulin (glargine / detemir). TZDs and DPP4 inhibitors were discontinued. The dose of exenatide was increased to 10 mcg twice a day after 4-12 weeks. 56 patients completed minimum 3 month therapy. 42 patients completed 6 months, 32, 9 months and 25 completed 12 months. Data of patients who had completed at-least 3 months of therapy was included for analysis. RESULTS AND DISCUSSION: 69.77, 67.44, and 13.95% of the patients were receiving metformin, secretagogues or thiazolidinediones alone or in combination; 17.76% of the patients were on basal insulin. The change in fasting and post-prandial blood glucose levels were significant at 3, 6, 9 and 12 months with p-value <0.05. The mean weight loss at one, three, and six months and one year was 1.7 ± 1.3, 3.8 ± 2.5, 6.3 ± 3.4, and 8.3 ± 4.3 kg, respectively (P <0.05). The mean HbA1c (baseline: 8.8 ± 1.3%) at 3, 6 months and at one year was 7.8 ± 0.9, 7.7 ± 0.8 and 7.2 ± 0.8 (P <0.05). Thirty-five percent of the patients had a 'good' A1c value (< 7%) at the end of 12 months. 13 patients discontinued exenatide (three due to lack of response, six due to cost of therapy and four due to severe nausea). Nausea was the most common side effect, occurring in 95% patients within 1 month, although the incidence declined with passage of time. CONCLUSIONS: Clinical use of Exenatide is associated with significant improvement in glycemic control and major weight loss (8.3±4.3 kg at 1 year) in obese subjects with type 2 diabetes. Nausea is the most common side effect. In conclusion, exenatide is a effective and useful option for treatment of type 2 diabetes in obese Indian subjects.

Effect of two different doses of oral cholecalciferol supplementation on serum 25-hydroxy-vitamin D levels in healthy Indian postmenopausal women: A randomized controlled trial.

AIM: To compare the effect of two different doses (500 and 1000 IU/day) of oral vitamin D3 (cholecalciferol) on serum 25-hydroxy vitamin D [25(OH)D] levels in apparently healthy postmenopausal Indian women. MATERIALS AND METHODS: Serum 25(OH)D, calcium with albumin, phosphorus, and alkaline phosphatase were measured in 92 apparently healthy postmenopausal women. The subjects were randomly assigned to one of the three groups and received supplementation for 3 months each. Each group received 1000 mg calcium carbonate daily while groups B and C received 500 and 1000 IU of cholecalciferol in addition, respectively. The tests were repeated after 3 months. RESULTS: At baseline, 83.7% subjects had vitamin D deficiency (≤20 ng/mL). The difference in the percentage change in mean serum 25(OH)D levels from baseline in group A (-30.5 ± 5.3%), group B (+8.9 ± 19.7%), and in group C (+97.8 ± 53.3%) was statistically significant (P < 0.001) between the three groups. Serum 25(OH)D level >20 ng/mL was achieved in 4.7% (1/21), 16% (4/25), and 66.67% (12/18) subjects in groups A, B, and C, respectively. No significant change was found in serum calcium, phosphorus, and alkaline phosphatase levels at 3 months in either of the groups from baseline. CONCLUSIONS: Standard dose of cholecalciferol available in "calcium tablets" (250 IU per 500 mg calcium carbonate) is not adequate for achieving optimum serum 25(OH)D levels in Indian postmenopausal women. Higher dose of vitamin D supplementation with 1000 IU/day (500 IU per 500 mg calcium carbonate) daily is superior to the standard dose therapy. For achievement of optimum serum 25(OH)D levels (>30 ng/mL) in Indian postmenopausal women, still higher doses of vitamin D are likely to be required.

Centiles of anthropometric measures of adiposity for 14- to 18-year-old urban Asian Indian adolescents.

AIM: This study aimed to develop age- and sex-specific reference values for body mass index (BMI), percentage body fat (%BF), waist circumference, waist-to-hip circumference ratio, and triceps and subscapular skinfold thicknesses for 14- to 18-year-old urban Asian Indians and to develop BMI cut-off points using specific centiles linked to the adult BMI cut-off points. METHODS: A cross-sectional population survey of adolescents and young adults (14-25 years of age) in North India included 684 boys and 541 girls. Smoothed 5(th), 10(th), 25(th), 50(th), 75(th), 85(th), 90(th), and 95(th) percentiles for the various anthropometric parameters were derived using the least mean squares (LMS) method for constructing normalized growth standards. Age-sex specific cut-off values for body mass index for 14-17 years were obtained corresponding to the centiles that pass through BMI (kg/m(2)) of 23, 25, 27.5, and 30 at 18 years of age. RESULTS: In most instances, the centiles of BMI and waist circumference were lower and those of %BF and triceps and subscapular skinfolds were higher than those recorded in the populations of United States and Canada. The age- and sex-specific BMI cut-off points in 14- to 18-year-old Asian Indian adolescents are also described for the first time. CONCLUSIONS: These reference data could be used to identify adolescents with an elevated risk of developing obesity-related disorders and provide a baseline for future studies of temporal trends.