Naval K. Vikram

Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots

OBJECTIVES To highlight the clinical and metabolic correlates of abdominal obesity and various abdominal adipose tissue depots. METHODS We researched the topic using the search terms abdominal obesity, central obesity, visceral obesity, regional obesity, and subcutaneous adipose tissue from MEDLINE (National Library of Medicine, Bethesda, MD), PubMed (National Library of Medicine, Bethesda, MD), Current Contents (Institute for Scientific Information, Thomson Scientific, Philadelphia, PA), and using manual search for the cited references. RESULTS Abdominal obesity contributes significantly to the metabolic perturbations and cardiovascular risk in human beings. Abdominal adipose tissue depots (intraabdominal and subcutaneous [deep subcutaneous, posterior subcutaneous]) are metabolically active and appear to be important for the pathogenesis of insulin resistance, dyslipidemia, glucose intolerance, hypertension, hypercoagulable state, and cardiovascular risk. Adipocyte anatomy (size), physiology (growth, catecholamine sensitivity, lipolysis, insulin action), and biochemistry (leptin, plasminogen activator inhibitor-1, cytokines, renin-angiotensin system) are reported to be relatively site-specific, highlighting unique roles of regional adipose tissue depots. CONCLUSIONS Several physiological and metabolic parameters are site-specific in abdominal adipose tissue. The epidemiological, clinical, and prognostic significance and relative importance of the regional adipose tissue depots, however, remain to be ascertained.

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.

Younger age of escalation of cardiovascular risk factors in Asian Indian subjects

BackgroundCardiovascular risk factors start early, track through the young age and manifest in middle age in most societies. We conducted epidemiological studies to determine prevalence and age-specific trends in cardiovascular risk factors among adolescent and young urban Asian Indians.MethodsPopulation based epidemiological studies to identify cardiovascular risk factors were performed in North India in 1999–2002. We evaluated major risk factors-smoking or tobacco use, obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre-specified definitions in 2051 subjects (male 1009, female 1042) aged 15–39 years of age. Age-stratified analyses were performed and significance of trends determined using regression analyses for numerical variables and Χ2 test for trend for categorical variables. Logistic regression was used to identify univariate and multivariate odds ratios (OR) for correlation of age and risk factors.ResultsIn males and females respectively, smoking or tobacco use was observed in 200 (11.8%) and 18 (1.4%), overweight or obesity (body mass index, BMI ≥ 25 kg/m2) in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9, females > 0.8) in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL cholesterol (≥ 130 mg/dl) in 9.4% and 8.9%, low HDL cholesterol (<40 mg/dl males, <50 mg/dl females) in 16.2% and 49.7%, hypertriglyceridemia (≥ 150 mg/dl) in 9.7% and 6%, diabetes in 1.0% and 0.4% and the metabolic syndrome in 3.4% and 3.6%. Significantly increasing trends with age for indices of obesity (BMI, waist, WHR), glycemia (fasting glucose, metabolic syndrome) and lipids (cholesterol, LDL cholesterol, HDL cholesterol) were observed (p for trend < 0.01). At age 15–19 years the prevalence (%) of risk factors in males and females, respectively, was overweight/obesity in 7.6, 8.8; high WHR 4.9, 14.4; hypertension 2.3, 0.3; high LDL cholesterol 2.4, 3.2; high triglycerides 3.0, 3.2; low HDL cholesterol 8.0, 45.3; high total:HDL ratio 3.7, 4.7, diabetes 0.0 and metabolic syndrome in 0.0, 0.2 percent. At age groups 20–29 years in males and females, ORs were, for smoking 5.3, 1.0; obesity 1.6, 0.8; truncal obesity 4.5, 3.1; hypertension 2.6, 4.8; high LDL cholesterol 6.4, 1.8; high triglycerides 3.7, 0.9; low HDL cholesterol 2.4, 0.8; high total:HDL cholesterol 1.6, 1.0; diabetes 4.0, 1.0; and metabolic syndrome 37.7, 5.7 (p < 0.05 for some). At age 30–39, ORs were- smoking 16.0, 6.3; overweight 7.1, 11.3; truncal obesity 21.1, 17.2; hypertension 13.0, 64.0; high LDL cholesterol 27.4, 19.5; high triglycerides 24.2, 10.0; low HDL cholesterol 15.8, 14.1; high total:HDL cholesterol 37.9, 6.10; diabetes 50.7, 17.4; and metabolic syndrome 168.5, 146.2 (p < 0.01 for all parameters). Multivariate adjustment for BMI, waist size and WHR in men and women aged 30–39 years resulted in attenuation of ORs for hypertension and dyslipidemias.ConclusionLow prevalence of multiple cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and metabolic syndrome) in adolescents and rapid escalation of these risk factors by age of 30–39 years is noted in urban Asian Indians. Interventions should focus on these individuals.

High Prevalence of Abdominal, Intra-Abdominal and Subcutaneous Adiposity and Clustering of Risk Factors among Urban Asian Indians in North India

Objective To assess the prevalence of abdominal obesity including intra-abdominal and subcutaneous adiposity along with other cardiometabolic risk factors in urban Asian Indians living in New Delhi. Methods We conducted a cross-sectional epidemiological descriptive study with 459 subjects (217 males and 242 females), representing all socio-economic strata in New Delhi. The anthropometric profile [body mass index (BMI), waist circumference (WC) and skinfold thickness], fasting blood glucose (FBG) and lipid profile were recorded. Percent body fat (%BF), total abdominal fat (TAF), intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal adipose tissue (SCAT) were quantified using predictive equations for Asian Indians. Results The overall prevalence of obesity was high [by BMI (>25 kg/m2), 50.1%]. The prevalence of abdominal obesity (as assessed by WC) was 68.9%, while that assessed by TAF was 70.8%. Increased IAAT was significantly higher in females (80.6%) as compared to males (56.7%) (p = 0.00) with overall prevalence being 69.3%. The overall prevalence of high SCAT was 67.8%, more in males (69.1%) vs. females (66.5%, p = 0.5). The prevalence of type 2 diabetes, the metabolic syndrome and hypertension was 8.5%, 45.3% and 29.2%, respectively. Hypertriglyceridemia, hypercholesterolemia and low levels of HDL-c were prevalent in 42.7%, 26.6% and 37% of the subjects, respectively. The prevalence of hypertriglyceridemia was significantly higher in males (p = 0.007); however, low levels of HDL-c were more prevalent in females as compared to males (p = 0.00). Conclusion High prevalence of generalized obesity, abdominal obesity (by measurement of WC, TAF, IAAT and SCAT) and dysmetabolic state in urban Asian Indians in north India need immediate public health intervention.

Consensus physical activity guidelines for Asian Indians.

India is currently undergoing rapid economic, demographic, and lifestyle transformations. A key feature of the latter transformation has been inappropriate and inadequate diets and decreases in physical activity. Data from various parts of India have shown a steady increase in the prevalence of lifestyle-related diseases such as type 2 diabetes mellitus (T2DM), the metabolic syndrome, hypertension, coronary heart disease (CHD), etc., frequently in association with overweight or obesity. Comparative data show that Asian Indians are more sedentary than white Caucasians. In this review, the Consensus Group considered the available physical activity guidelines from international and Indian studies and formulated India-specific guidelines. A total of 60 min of physical activity is recommended every day for healthy Asian Indians in view of the high predisposition to develop T2DM and CHD. This should include at least 30 min of moderate-intensity aerobic activity, 15 min of work-related activity, and 15 min of muscle-strengthening exercises. For children, moderate-intensity physical activity for 60 min daily should be in the form of sport and physical activity. This consensus statement also includes physical activity guidelines for pregnant women, the elderly, and those suffering from obesity, T2DM, CHD, etc. Proper application of guidelines is likely to have a significant impact on the prevalence and management of obesity, the metabolic syndrome, T2DM, and CHD in Asian Indians.

Waist Circumference Measurement by Site, Posture, Respiratory Phase, and Meal Time: Implications for Methodology

Waist circumference (WC) has been advocated as a simple, reliable, and cost‐effective measure to understand an individuals cardio‐metabolic risk. Although several protocols exist for measuring WC, the variation induced by a few factors has not been investigated. We compared several established and experimental WC measurement protocols to identify factors that may cause variations in WC measurement. In this cross‐sectional study, we examined the variations in the measurement of waist circumference (WC) measures carried out in 11 ways differing by anatomical site, posture, respiratory phase, and time since last meal, using repeated measure analysis of variance (using mixed models) after Tukey‐Kramer adjustment. We estimated the proportion of variance in percentage of body fat (%BF) and fat‐free mass (FFM) explained by each of the WC measures. We studied 123 apparently healthy Asian Indians (75 females), with mean (s.d.) age of 34 (8.7) years and BMI of 23.9 (4.8) kg/m2. Overall, the mean of WCs measured using the 11 protocols were statistically different. Further, post hoc analysis showed statistically significant, yet mostly small, differences between most of the pairs. No single WC measure explained highest variance in %BF or FFM for both genders. Although, the National Institute of Health (NIH), USA, protocol was convenient and may be less prone to errors, at present it does not control for many variables tested in this study. Measures of WC measured using different protocols were statistically different. We suggest that the site of measurement, posture, phase of respiration, and time since last meal should be standardized for the development of a protocol for measurement of WC for worldwide use.

Imbalanced Dietary Profile, Anthropometry, and Lipids in Urban Asian Indian Adolescents and Young Adults

Objective: To analyze the macronutrient, micronutrient, food intake pattern, anthropometry, and lipid profile of urban Asian Indian adolescents and young adults and compare it with the nutrient profile of rural Asian Indian and American adolescents. Methods: This was a cross-sectional, epidemiologic descriptive study. Body mass index (BMI), percentage body fat, waist and hip circumferences, skinfold thickness, serum lipids, and dietary intake were assessed in 1236 subjects (607 males, 629 females) aged 13–25 years from schools and colleges of a metropolitan city of India. Results: The mean age and BMI of study subjects were 17.6 ± 2.4 years (range 13–25 years) and 19.8 ± 3.3 kg/m2 (range 11.9–35.9 kg/m2), respectively. The mean daily percentages of total energy contributed by carbohydrates, total fats, proteins, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), ω-3 PUFAs, ω-6 PUFAs, and trans-fatty acids for all subjects were 53%, 34%, 11%, 11%, 10%, 9%, 1%, 8%, and 0.3%, respectively. The absolute daily intake of total fat was 84 ± 29 g/d in males and 72 ± 21 g/d in females, which was approximately 4 times the recommended dietary allowance for Asian Indians (20–22 g/d). Among food groups, a high intake of milk, milk products, roots, and tubers was observed. In these young individuals, the prevalence of hypercholesterolemia (males ≥169 mg/dl; females ≥181 mg/dl) and overweight (BMI ≥23.1 kg/m2) was 14.4% and ∼16%, respectively. On comparison with rural Asian Indian adolescents, an inappropriately high intake of total fat was observed in our subjects. On the other hand, the percentage of energy intake of SFAs in Asian Indian and American adolescents was at par. Conclusions: High total fat and SFA intake and a low intake of MUFAs and ω-3 PUFAs showed imbalanced nutrition, which could be responsible for the increasing prevalence of obesity and insulin resistance in urban Asian Indian adolescents and young adults. Nutritional strategies for reducing SFA intake and balancing the ω-3/ω-6 PUFAs ratio should be urgently applied in Asian Indian adolescents and are also presented in this paper.

Predictive Equations for Body Fat and Abdominal Fat With DXA and MRI as Reference in Asian Indians

Objective: To develop accurate and reliable equations from simple anthropometric parameters that would predict percentage of total body fat (%BF), total abdominal fat (TAF), subcutaneous abdominal adipose tissue (SCAT), and intra‐abdominal adipose tissue (IAAT) with a fair degree of accuracy.

Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo (31P) phosphorus magnetic resonance spectroscopy

OBJECTIVE To study hepatic gluconeogenesis pathway in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo ((31)P) phosphorous magnetic resonance spectroscopy (MRS) and correlate these data with anthropometry and insulin resistance. RESEARCH DESIGN AND METHODS Forty non-diabetic patients with NAFLD and 20 healthy controls were divided into (i) obese with NAFLD (group I, n=20), (ii) non-obese with NAFLD (group II, n=20) and (iii) non-obese without NAFLD (group III, n=20). Anthropometric and biochemical profiles, short insulin tolerance test (SITT), liver ultrasound, and (31)P MRS (to determine hepatic gluconeogenesis metabolite; phosphomonoesters (PMEs), inorganic phosphate (Pi) and their ratios with respect to ATP) were done. RESULTS Insulin resistance (Kitt value) was highest in group I (p<0.05; compared to other two groups), but was also higher in group II as compared to group III (p=ns). The values of PME/Pi, PME/gammaATP, PME/betaATP, PME/tATP ratios were higher (p<0.05) in group I compared to other two groups. Interestingly, non-obese subjects with NAFLD also showed more derangements of hepatic gluconeogenesis metabolites than non-obese subjects without NAFLD. Positive correlation was observed between PME and other ratios in relation to body mass index, waist circumference, body fat percentage and fasting serum insulin levels in all the three groups. CONCLUSIONS Derangements in hepatic gluconeogenesis as assessed non-invasively using (31)P MRS, was observed in obese and non-obese, non-diabetic Asian Indians with NAFLD. Further research is warranted whether this investigation in NAFLD subjects could be developed as a non-invasive tool to assess those predisposed to develop hyperglycemia.

Dietary Nutrients and Insulin Resistance in Urban Asian Indian Adolescents and Young Adults

Background: Asian Indians have a high prevalence of insulin resistance that may underlie their higher tendency to develop type 2 diabetes mellitus and early-onset atherosclerosis. Objective: To investigate the relationship between dietary nutrients and insulin resistance in Asian Indian adolescents and young adults. Design: Dietary nutrient intake values (24-hour dietary recall and monthly consumption data) and fasting serum insulin levels were studied in 352 (311 males and 41 females) healthy adolescents and young adults (mean age 18.0 ± 2.3 years; range 14–25 years). Bivariate and multivariate logistic regression analyses were performed with hyperinsulinemia as the outcome variable and various dietary nutrients and anthropometric variables as covariates. Results: Mean fasting serum insulin levels were 107.4 ± 35.0 pmol/l (36.5–230.4 pmol/l). The intake of polyunsaturated fatty acids (PUFAs) was higher, saturated fat and the ω–6 to ω–3 PUFA ratio were in the upper limit, and ω–3 PUFAs (% caloric intake, En) were lower than the recommended dietary allowance for Asian Indians. The PUFAs (% En), BMI, percent body fat and waist circumference were significantly higher in the hyperinsulinemic group compared with the normoinsulinemic group (p = 0.021, 0.0021, 0.0006, and 0.0041, respectively). Multiple regression analysis showed that the lowest tertile of ω–6 (<3% En) PUFA intake [adjusted OR (95% CI) = 0.3 (0.1–0.7)] and BMI [adjusted OR (95% CI) = 2.9 (1.4–6.0)] were the significant independent predictors of fasting hyperinsulinemia. Conclusion: For prevention and amelioration of insulin resistance in Asian Indian adolescents and young adults, it is prudent to have normal BMI and low intake of ω–6 PUFAs.