Kalpana Luthra

High prevalence of insulin resistance in postpubertal Asian Indian children is associated with adverse truncal body fat patterning, abdominal adiposity and excess body fat.

OBJECTIVE: The objectives were to study the relationships of insulin resistance with generalized and abdominal obesity, and body fat patterning in urban postpubertal Asian Indian children.DESIGN: Cross-sectional, population-based epidemiological study.SUBJECTS: In all, 250 (155 males and 95 females) healthy urban postpubertal children.MEASUREMENTS: Anthropometric profile, percentage of body fat (%BF), fasting serum insulin, and lipoprotein profile.RESULTS: Fasting insulin correlated significantly with body mass index (BMI), %BF, waist circumference (WC), central and peripheral skinfold thicknesses and sum of four skinfold thicknesses (∑4SF) in both sexes, and with systolic blood pressure and waist–to hip circumference ratio (W–HR) in males only. Consistent increase in fasting insulin was noted with increasing values of central skinfold thickness at each tertile of peripheral skinfold thickness, WC, and %BF. Central skinfold thickness correlated with fasting insulin even after adjusting for WC, W–HR, and %BF. The odds ratios (OR) (95% CI) of hyperinsulinemia (fasting insulin concentrations in the highest quartile) were 4.7 (2.4–9.4) in overweight subjects, 8 (4.1–15.5) with high %BF, 6.4 (3.2–12.9) with high WC, 3.7 (1.9–7.3) with high W–HR, 6.8 (3.3–13.9) with high triceps skinfold thickness, 8 (4.1–15.7) with high subscapular skinfold thickness, and 10.1 (5–20.5) with high ∑4SF. In step-wise multiple logistic regression analysis, %BF [OR (95% CI): 3.2 (1.4–7.8)] and ?4SF [OR (95% CI): 4.5 (1.8–11.3)] were independent predictors of hyperinsulinemia, similar to insulin resistance assessed by HOMA (homeostatic model of assessment) in the study.CONCLUSION: A high prevalence of insulin resistance in postpubertal urban Asian Indian children was associated with excess body fat, abdominal adiposity, and excess truncal subcutaneous fat. Primary prevention strategies for coronary heart disease and diabetes mellitus in Asian Indians should focus on the abnormal body composition profile in childhood.

Effect of Supervised Progressive Resistance-Exercise Training Protocol on Insulin Sensitivity, Glycemia, Lipids, and Body Composition in Asian Indians With Type 2 Diabetes

OBJECTIVE—To evaluate the effect of supervised progressive resistance-exercise training (PRT) protocol on insulin sensitivity, glycemia (blood glucose and A1C levels), lipids, and body composition in Asian Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS—Thirty patients with type 2 diabetes underwent 12 weeks of PRT of six muscle groups (two sets, 10 repetitions each). The subjects were evaluated with detailed anthropometry and with measurements of the disappearance of glucose per unit time (K) during the short insulin tolerance test (KITT) for assessment of insulin sensitivity; of fasting blood glucose, A1C, lipids, and high-sensitivity C-reactive protein (hsCRP); of total body fat, regional fat, and lean body mass by dual-energy X-ray absorptiometry; and of cross-sectional skeletal muscle area of upper arm and thigh by computed tomography scan. RESULTS—Insulin sensitivity improved significantly from mean ± SD KITT 1.22 ± 0.73 to 2.13 ± 0.75 (P < 0.0001) after the intervention. Significant decline (mean difference ± SD) from baseline was recorded in levels of the following parameters: A1C (0.54 ± 0.4%, P < 0.001), fasting blood glucose (2.7 ± 2.2 mmol/l, P < 0.001), total cholesterol (0.39 ± 0.7 mmol/l, P = 0.003), serum triglycerides (0.39 ± 0.5 mmol/l, P < 0.001), and truncal and peripheral subcutaneous adipose tissue compartments (SCAT) (P < 0.001). However, no significant changes were noticed in BMI or levels of total body fat, truncal fat, lean body mass, cross-sectional skeletal muscle area of the extremities, or hsCRP levels. CONCLUSIONS—Moderate-intensity PRT for 3 months resulted in significant improvement in insulin sensitivity, glycemia, lipids, and truncal and peripheral SCAT in patients with type 2 diabetes. Resistance training should be an integral part of exercise regimen in Asian Indians with type 2 diabetes.

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.

CXCR7 mediated Giα independent activation of ERK and Akt promotes cell survival and chemotaxis in T cells

Chemokine receptors CXCR7 and CXCR4 bind to the same ligand stromal cell derived factor-1alpha (SDF-1α/CXCL12). We assessed the downstream signaling pathways mediated by CXCL12-CXCR7 interaction in Jurkat T cells. All experiments were carried out after functionally blocking the CXCR4 receptor. CXCL12, on binding CXCR7, induced phosphorylation of extra cellular regulated protein kinases (ERK 1/2) and Akt. Selective inhibition of each signal demonstrated that phosphorylated ERK 1/2 is essential for chemotaxis and survival of T cells whereas activation of Akt promotes only cell survival. Another interesting finding of this study is that CXCL12-CXCR7 interaction under normal physiological conditions does not activate the p38 pathway. Furthermore, we observed that the CXCL12 signaling via CXCR7 is Giα independent. Our findings suggest that CXCR7 promotes cell survival and does not induce cell death in T cells. The CXCL12 signaling via CXCR7 may be crucial in determining the fate of the activated T cells.

MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer's and vascular dementia and their epistatic interaction

Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795). CC genotype was associated with elevated levels of plasma homocysteine (p = 0.004) as compared with genotype AA of rs1801131. In AD, we observed a significant (p = 0.04) association with C alleles of rs1801131. Regression analysis revealed that the presence of both rs1801133 T and rs1800795 C alleles increased the odds of developing AD by 2.5 and VaD by 3.7-fold. While rs1800795 (CC or GC) genotypes alone increased the odds of developing VaD by 2.2-fold, the presence of CC genotype of rs1801131 nullified this effect. The findings support the hypothesis that multiple genes are involved to alter the odds of developing AD and VaD.

Association of the Myostatin Gene with Obesity, Abdominal Obesity and Low Lean Body Mass and in Non-Diabetic Asian Indians in North India

Background To determine the association of the A55T and K153R polymorphisms of the Myostatin gene with obesity, abdominal obesity and lean body mass (LBM) in Asian Indians in north India. Materials and Methods A total of 335 subjects (238 men and 97 women) were assessed for anthropometry, % body fat (BF), LBM and biochemical parameters. Associations of Myostatin gene polymorphisms were evaluated with anthropometric, body composition and biochemical parameters. In A55T polymorphism, BMI (p = 0.04), suprailiac skinfold (p = 0.05), total skinfold (p = 0.008), %BF (p = 0.002) and total fat mass (p = 0.003) were highest and % LBM (p = 0.03) and total LBM (Kg) were lowest (p = 0.04) in subjects with Thr/Thr genotype as compared to other genotypes. Association analysis of K153R polymorphism showed that subjects with R/R genotype had significantly higher BMI (p = 0.05), waist circumference (p = 0.04), %BF (p = 0.04) and total fat mass (p = 0.03), and lower %LBM (p = 0.02) and total LBM [(Kg), (p = 0.04)] as compared to other genotypes. Using a multivariate logistic regression model after adjusting for age and sex, subjects with Thr/Thr genotype of A55T showed high risk for high %BF (OR, 3.92, 95% Cl: 2.61–12.41), truncal subcutaneous adiposity (OR, 2.9, 95% Cl: 1.57–6.60)] and low LBM (OR, 0.64, 95% CI: 0.33–0.89) whereas R/R genotype of K153R showed high risk of obesity (BMI; OR, 3.2, 95% CI: 1.2–12.9; %BF, OR, 3.6, 95% CI: 1.04–12.4), abdominal obesity (OR, 2.12, 95% CI: 2.71–14.23) and low LBM (OR, 0.61, 95% CI: 0.29–0.79). Conclusions/Significance We report that variants of Myostatin gene predispose to obesity, abdominal obesity and low lean body mass in Asian Indians in north India.

Apolipoprotein E Gene Polymorphism in Indian Patients with Alzheimer’s Disease and Vascular Dementia

The association of apolipoprotein E (ApoE) gene polymorphism with Alzheimer’s disease (AD) has been reported in several populations including one from a rural community in North India. However, the association of ApoE polymorphism with vascular dementia (VaD) is yet to be established in this population. In a case-control study involving 54 cases of dementia (29 AD and 25 VaD) and 76 age-matched healthy controls, the frequency of Ε4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The Ε3Ε3 (p < 0.05) and Ε2Ε3 (p < 0.001) genotypes were found to be protective. The odds of developing AD or VaD were 4.4 and 3.7 times higher, respectively, in the presence of even a single Ε4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE Ε4 compared with the Caucasian population.

Diagnostic significance of nested polymerase chain reaction for sensitive detection of Pneumocystis jirovecii in respiratory clinical specimens

A total of 327 clinical specimens, including both invasive and noninvasive samples, obtained from 275 patients with various types of underlying immunocompromised conditions and a clinical suspicion of Pneumocystis pneumonia (PCP) were subjected to 2 different nested polymerase chain reaction (PCR) assays. The target genes used for nested PCR were mitochondrial large subunit ribosomal RNA (mtLSU rRNA) and internal transcribed spacer (ITS) region. The results were compared with a single-round PCR targeting major surface glycoprotein (MSG) gene. Amplification was successful in 16% of cases by mtLSU rRNA nested PCR, in 14.5% by ITS nested PCR, and in 10.9% by MSG PCR. The nested mtLSU rRNA PCR was found to be more sensitive (100% sensitive and 98.7% specific) and useful in detecting PCP for its use in routine diagnosis in our settings. Thus, this assay may be quite useful in the identification of patients who are in the early stage of Pneumocystis jirovecii infection with an organism load that could not be easily detected by the single-step PCR.

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.

Apolipoprotein E polymorphism in Northern Indian patients with coronary heart disease: phenotype distribution and relation to serum lipids and lipoproteins.

Apolipoprotein E (apo E), a genetic determinant of plasma lipid levels and coronary heart disease (CHD) needs to be investigated in Asian Indians since they have a propensity to develop dyslipidemia and accelerated atherosclerosis. We studied apo E phenotypes and plasma lipid levels in 52 Northern Indian male patients (aged 38–71 years) with angiographically proven CHD, and compared them to 50 healthy blood donors taken as the control group. High levels of Lp(a), (p < 0.05), and a definite trend towards lower levels of HDL-C (p < 0.05), was observed in the CHD patients as compared to the control subjects. The frequency of apo E allele ε3 was 0.86 and 0.862, and ε4 allele was 0.12 and 0.08 in the patients and controls, respectively. However, a lower frequency of the E2 allele was observed in the patient group (ε2 = 0.02) as compared to the controls (ε2 = 0.06) (p = ns). In individuals with apo E3/E3 phenotype, significantly lower HDL-C levels was observed in the CHD patients as compared to the control subjects (p < 0.05). A positive correlation was observed between apo E phenotypes and Lp(a) levels in the CHD subjects as compared to the controls (p < 0.05), the level being significantly high in CHD subjects with at least one E4 allele. To conclude, in this sample of Northern Indian subjects with CHD, there is a significant correlation between apo E3/E3 phenotype and low levels of HDL-C as compared to the control subjects. Further, apo E phenotype is positively correlated with high Lp(a) levels in the CHD subjects having at least one E4 allele. However, these relationships need to be explored in a larger sample of subjects.