Nutrition and physical activity in Asian Indians with non-alcoholic fatty liver: A case control study.

AIM: We tested the hypothesis that Asian Indians with non-alcoholic fatty liver disease (NAFLD) would have imbalanced diets and lower intensity of physical activity than those without NAFLD. METHODS: We studied dietary intake, intensity of physical activity and anthropometric and metabolic profiles in subjects with NAFLD and in healthy controls. Complete clinical, biochemical, dietary and physical activity profiles were studied for 169 cases and 173 controls in a prospective manner. Bivariate and multivariate analyses were carried out to identify the predictors of NAFLD [odds ratio (OR) and 95% confidence intervals (95%CI)]. RESULTS: The mean dietary intakes of total energy, carbohydrate, protein, total fat, saturated fat and total cholesterol were significantly higher, while intake of monounsaturated fatty acids and polyunsaturated fatty acids was significantly lower in cases as compared to controls (p < 0.01 for all). Further, mean physical activity in a day (expressed as MET.Minutes) and total energy expenditure were significantly lower in cases than in controls (33.3 ±â€¯3.6 vs.36.2 ±â€¯0.5, p = 0.001 and 2707.6 ±â€¯505.6 vs. 2904.3 ±â€¯690.3, p = 0.02, respectively). On multivariate analysis, percentage dietary total fat intake (OR: 13.4; 95% CI: 4.6-39.3, p = 0.001), homeostatis model assessment for insulin resistance (OR: 6.9; 95% CI: 3.2-14.8, p = 0.001) abdominal obesity (OR: 2.7; 95% CI: 1.5-5.0, p = 0.001) and high serum triglycerides (OR: 2.1; 95%CI: 1.2-3.8, p = 0.007) were associated with an increased risk for development of NAFLD. CONCLUSION: Decrease in intake of total dietary fats and improvement of insulin resistance, abdominal obesity and blood triglycerides should be important measures for management of NAFLD in Asian Indians in north India.

Phenotype, Body Composition, and Prediction Equations (Indian Fatty Liver Index) for Non-Alcoholic Fatty Liver Disease in Non-Diabetic Asian Indians: A Case-Control Study.

OBJECTIVE: In this study, we have attempted comparison of detailed body composition phenotype of Asian Indians with non-alcoholic fatty liver disease (NAFLD) vs. those without, in a case controlled manner. We also aim to analyse prediction equations for NAFLD for non-diabetic Asian Indians, and compare performance of these with published prediction equations researched from other populations. METHODS: In this case-control study, 162 cases and 173 age-and sex-matched controls were recruited. Clinical, anthropometric, metabolic, and body composition profiles, and liver ultrasound were done. Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR), and serum high sensitive C-reactive protein (hs-CRP) levels were evaluated. Multivariate logistic and linear regression analyses were used to arrive at prediction equations for fatty liver [Indian fatty liver index (IFLI)]. RESULTS: As compared to those without fatty liver, those with fatty liver exhibited the following; Excess dorsocervical fat ('Buffalo hump'), skin tags, xanthelasma, 'double chin', arcus; excess total, abdominal and subcutaneous adiposity, and high blood pressure, blood glucose, measures of insulin resistance (fasting insulin and HOMA-IR values), lipids and hs-CRP levels. Two prediction equations were developed; Clinical [Indian Fatty Liver Index-Clinical; IFLI-C]: 1(double chin) +15.5 (systolic blood pressure) +13.8 (buffalo hump); and IFLI-Clinical and Biochemical (CB): serum triglycerides+12 (insulin)+1(systolic blood pressure) +18 (buffalo hump). On ROC Curve analysis, IFLI performed better than all published prediction equations, except one. CONCLUSION: Non-diabetic Asian Indians with NAFLD researched by us were overweight/obese, had excess abdominal and subcutaneous fat, multiple other phenotypic markers, had higher insulin resistance, glycemia, dyslipidemia and subclinical inflammation than those without. Prediction score developed by us for NAFLD; IFLI-C and IFLI-CB, should be useful for clinicians and researchers.

Isosorbide Mononitrate a Nitric Oxide Donor: A Study of Its Efficacy and Safety as an Agent for Cervical Ripening.

OBJECTIVE: To study the efficacy and safety profile of isosorbide mononitrate (IMN) as an agent for cervical ripening. METHODOLOGY: This study was conducted in the Department of Obstetrics and Gynecology, M Y Hospital & M G M Medical College Indore from September 2011 to February 2013. Pregnant women attending the antenatal clinics were screened for possible participation in the study after explaining the nature of the study. This study was conducted on 150 patients. An initial dose of 40 mg IMN was applied in the posterior vaginal fornix, and the same dose was repeated after 6 h. Cervical ripening was assessed by the change in Bishop Score 12 h after the initial application. RESULTS: In a study of 150 cases, mean maternal age was 22.2 ± 2.6 years (range 19-35 years) and mean gestational age was 40.5 ± 1.07 (range 40-42 weeks). 52 women were primigravidas, while 98 were multigravidas. The mean Bishop Score-before drug administration was 1.94 ± 1.3 (range 0-5), and mean fetal heart rate was 137 ± 6.2 bpm. The mean of Bishop scores before IMN administration was 1.94 ± 1.3, while mean of Bishop score after drug administration was 6.7 ± 2.2; mean difference was equal to 4.76. P value was equal to 0.0001. By conventional criteria, this difference is considered to be statistically significant. The mode of delivery 96 (64 %) delivered vaginally, while 54 (36 %) were delivered by Cesarean section. Mean Apgar score at 1 min was 8.2 ± 0.9 SD (range 7-10), while mean Apgar score at 5 min was 9.4 ± 0.6 (range 8-10). The only side effect noted was headache, and 30 cases (20 %) complained of headache. CONCLUSION: IMN seems to be effective, safe, inexpensive, and well-tolerated agent for cervical ripening. It is cost effective and safe with minimal side effects.

Effect of a 6-month intervention with cooking oils containing a high concentration of monounsaturated fatty acids (olive and canola oils) compared with control oil in male Asian Indians with nonalcoholic fatty liver disease.

OBJECTIVE: We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: This was a 6-month intervention study including 93 males with NAFLD, matched for age and body mass index (BMI). Subjects were randomized into three groups to receive olive oil (n=30), canola oil (n=33), and commonly used soyabean/safflower oil (control; n=30) as cooking medium (not exceeding 20 g/day) along with counseling for therapeutic lifestyle changes. The BMI, fasting blood glucose (FBG) and insulin levels, lipids, homeostasis model of assessment for insulin resistance (HOMA-IR), HOMA denoting ß-cell function (HOMA-ßCF), and disposition index (DI) were measured at pre- and post-intervention. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey's Honestly Significant Difference multiple comparison test procedures. RESULTS: Olive oil intervention led to a significant decrease in weight and BMI (ANOVA, P=0.01) compared with the control oil group. In a comparison of olive and canola oil, a significant decrease in fasting insulin level, HOMA-IR, HOMA-ßCF, and DI (P<0.001) was observed in the olive oil group. Pre- and post-intervention analysis revealed a significant increase in high-density lipoprotein level (P=0.004) in the olive oil group and a significant decrease in FBG (P=0.03) and triglyceride (P=0.02) levels in the canola oil group. The pre- and post-intervention difference in liver span was significant only in the olive (1.14 ± 2 cm; P<0.05) and canola (0.66 ± 0.33 cm; P<0.05) oil groups. In the olive and canola oil groups, post-intervention grading of fatty liver was reduced significantly (grade I, from 73.3% to 23.3% and from 60.5% to 20%, respectively [P<0.01]; grade II, from 20% to 10% and from 33.4% to 3.3%, respectively [P<0.01]; and grade III, from 6.7% to none and from 6.1% to none, respectively). In contrast, in the control oil group no significant change was observed. CONCLUSIONS: Results suggest significant improvements in grading of fatty liver, liver span, measures of insulin resistance, and lipids with use of canola and olive oil compared with control oils in Asian Indians with NAFLD.

Independent associations of low 25 hydroxy vitamin D and high parathyroid hormonal levels with nonalcoholic fatty liver disease in Asian Indians residing in north India.

OBJECTIVE: We analysed the associations of 25 hydroxy vitamin D [25(OH) D] and parathyroid hormone (PTH) levels with clinical, anthropometric, biochemical and body composition parameters in Asian Indians with nonalcoholic fatty liver disease (NAFLD). METHODS: In this case-control study, 162 cases and 173 age and sex matched controls were recruited. Clinical, anthropometric, biochemical parameters and liver ultrasound were done. Percentage body fat (%BF), lean body mass and bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DXA). Fasting insulin levels, value of homeostasis model assessment of insulin resistance (HOMA-IR), serum 25(OH) D, calcium and PTH levels were measured. RESULTS: Subjects with NAFLD had lower serum 25(OH) D (19.4 ± 8.5 vs. 27.8 ± 9.4 ng/ml, p = 0.0001) and higher serum PTH (54.9 ± 19.5 vs.41.5 ± 18.3 pg/ml, p = 0.0001) levels as compared to controls. We observed significantly high values of systolic blood pressure (p = 0.002), waist circumference (p = 0.05), serum triglycerides (p = 0.002), total cholesterol (p = 0.002), alanine transaminase (p = 0.05), fasting insulin (p = 0.02) and HOMA-IR (p = 0.03) in the lowest 25(OH) D quartile. Multivariable-logistic regression showed that low serum 25(OH) D [OR (95%CI): 4.46 (2.58-7.72), p = 0.0001] and high PTH [OR (95%CI): 2.21 (1.50-3.30), p = 0.0001] level were independently associated with NAFLD. CONCLUSION: Low serum 25(OH) D and high PTH levels were independently associated with the presence of NAFLD in Asian Indians residing in north India.

Genetic variation in the patatin-like phospholipase domain-containing protein-3 (PNPLA-3) gene in Asian Indians with nonalcoholic fatty liver disease.

BACKGROUND: The association of the rs738409 polymorphism of patatin-like phospholipase-3 (PNPLA3) with nonalcoholic fatty liver disease (NAFLD) has been suggested in other populations, but not in Asian Indians. We investigated the association of the rs738409 polymorphism of PNPLA3 with clinical, anthropometric, and biochemical profiles in Asian Indians with NAFLD. METHODS: In this case-control study, 162 cases and 173 controls were recruited. Abdominal ultrasound, clinical, anthropometry, and biochemical profiles were determined. Fasting insulin levels and values for homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Polymerase chain reaction and restriction fragment length polymorphism of the PNPLA3 gene were performed. The associations of this polymorphism with clinical, anthropometric, and biochemical profiles were investigated. RESULTS: A higher frequency of C/G and G/G genotypes of the rs738409 polymorphism was obtained in cases as compared to controls (P=0.04), and as a consequence the frequency of the minor allele G was significantly higher in cases (P=0.003). In this study, the G allele was associated with significantly higher fasting insulin (P=0.002), HOMA-IR (P=0.05), alanine transaminase (P=0.003), and aspartate transaminase (P=0.04) values only in cases, but not in the controls. The values of serum triglycerides and total cholesterol were slightly higher in cases with G/C+G/G genotypes but statistically not significant (P>0.05). Using a multivariate logistic regression model after adjusting for age, sex, body mass index, and fasting insulin, subjects with the G/G genotype showed higher risk of NAFLD [odds ratio (OR), 1.98, 95% confidence interval (CI) 1.43-2.73, P=0.04). The relationships of the rs738409 polymorphism with the metabolic parameters were not significant after adjustment for multiple comparisons. CONCLUSION: Asian Indians in north India carrying the allele rs738490 of PNPLA3 is predispose to develop NAFLD.

Comparison of DEXA-derived body fat measurement to two race-specific bioelectrical impedance equations in healthy Indians.

AIM: Prevalence of obesity is increasing in Asian Indians. Reliable, precise and convenient methods to estimate body composition are required. This study aimed to test the accuracy of bioelectrical impedance analysis (BIA) estimates of body composition among Asian Indians according to two BIA equations--one developed for Asians, the other for Caucasians. METHODS: Two hundred apparently healthy Asian Indians (100 males, 100 females; mean age 36.6 ± 7.6 years; mean BMI 16.6-46.7 kg/m(2)) underwent BIA assessment of fat mass (FM), fat free mass (FFM) and percentage body fat (%BF) using Tanita Multi-Frequency Body Composition Analyzer MC-180MA (Tanita Corporation, Tokyo, Japan). One set of BIA values was automatically calculated by the analyzer (Caucasian figures), the other set by Tanita (Japanese Asian figures). Results were compared to dual X-ray absorptiometry (DEXA) as the standard measure. RESULTS: A moderate level of relative agreement was found between the DEXA-derived measurement of %BF and the estimate from both the Caucasian (r(2)=0.75; p<0.001) and Asian equation (r(2)=0.7; p<0.001). Despite this, the level of absolute agreement was poor, with large bias and wide limits of agreement. According to the Caucasian equation the mean difference between methods was -8.3 ± 3.9 (95% limits of agreement -20.10 to 9.40), for the Asian equations mean difference was -5.4 ± 4.3 (95% limits of agreement -20.63 to 11.41). INTERPRETATION AND CONCLUSIONS: When compared to DEXA, the current Asian and Caucasian Tanita formulae significantly under-estimate the %BF of Asian Indians.

Non-alcoholic fatty liver disease is closely associated with sub-clinical inflammation: a case-control study on Asian Indians in North India.

OBJECTIVES: Association between sub-clinical inflammation and non-alcoholic fatty liver disease (NAFLD) has not been studied in Asian Indians. In this case-control study, we aimed to analyse association of NAFLD with the sub-clinical inflammation and metabolic profile in Asian Indians in north India. METHODS: Ultrasound diagnosed 120 cases of NAFLD were compared to 152 healthy controls without NAFLD. Anthropometric profile [body mass index (BMI), waist circumference (WC), hip circumference (HC)], high-sensitivity C-reactive protein (hs-CRP), metabolic profile [fasting blood glucose (FBG), lipid profile] and hepatic function tests [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] were recorded. RESULTS: Metabolic parameters [FBG, total cholesterol (TC), serum triglycerides (TG),low-density lipoprotein (LDL-c)], hs-CRP and prevalence of the metabolic syndrome were higher in cases as compared to controls (p-value<0.05 for all). The median (range) of hs-CRP (mg/L) for cases [2.6(0.2-13.4)] were significantly higher than in controls [1.4(0.03-11.4), p = 0.01]. Similarly, higher values of hs-CRP were obtained when subgroups of cases with obesity, abdominal obesity and the metabolic syndrome were compared to controls [2.75 (0.03-14.3) vs. 1.52 (0.04-14.3), p = 0.0010; 2.8 (0.03-14.3) vs. 1.5 (0.06-14.3), p = 0.0014 and 2.7 (0.5-14.3) vs. 1.6 (0.06-8.5), p = 0.0013, respectively. On multivariate logistic regression analysis BMI (p = 0.001), WC (p = 0.001), FBG (p = 0.002), TC (p = 0.008), TG (p = 0.002), blood pressure (p = 0.005), metabolic syndrome (p = 0.001) and hs-CRP (p = 0.003) were significantly and independently associated with NAFLD. After adjusting for significant variables, the association between high hs-CRP and NAFLD remained large and statistically significant [adjusted OR = 1.17, 95% confidence interval (CI) = 1.05-1.29]. An increase in 1 mg/dl of hs-CRP level calculated to increase the risk of developing NAFLD by 1.7 times as compared to controls after adjusting for significant variables associated with NAFLD. CONCLUSIONS: In this cohort of Asian Indians in North India, presence of NAFLD showed independent relationships with sub-clinical inflammation.

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India.

BACKGROUND: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD. METHODS: In this case-control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction-restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed. RESULTS: Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist-hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p=0.04), total cholesterol (p=0.01), ALK (p=0.04) and gamma-glutamyl transpeptidase (p=0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1=0.1; p=0.006) and controls (D1=0.07; p=0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09-2.45, p=0.05)]. CONCLUSION: Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.

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.

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.

SREBP-2 1784 G/C genotype is associated with non-alcoholic fatty liver disease in north Indians.

BACKGROUND: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G>C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India. METHODS: In this study, (n=335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed. RESULTS: The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency of C/C genotype was higher in NAFLD as compared to obese and non-obese subjects (p=0.003). In NAFLD subjects 57.4% were G/G homozygous, 31.5% G/C heterozygous and 11.1% were C/C homozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X² = 6.39, p = 0.0114). Mean values of TG (p = 0.002), TC (p =0.002), ALT (p =0.04) and AST (p =0.03) levels were significantly higher in NAFLD subjects with G/C genotype as compared to G/G genotypes in obese and non-obese groups. Fasting insulin (p =0.03), HOMA (p =0.009) and hs-CRP levels were significantly higher in NAFLD subjects with G/C genotype as compared to obese and non obese subjects with G/G genotypes. CONCLUSION: In this study, conducted for the first time in Asian Indians, SREBP-2 1784 G>C genotype was associated with NAFLD.

Diet & insulin resistance: a review & Asian Indian perspective.

Insulin resistance is associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). These abnormalities have been aggravated because of imbalanced and excess nutrition in developed countries, and rapid nutritional and lifestyle transition occurring in developing countries. This review presents evidence linking dietary nutrients with insulin resistance and its metabolic correlates, and also describes these issues from a Asian Indians and South Asian perspective. Despite possible influences from genetic and perinatal factors, diet and physical activity are likely to have greater and often overriding influence in pathogenesis of the insulin resistance, the metabolic syndrome, and T2DM. In animal studies, a link has been established between dietary nutrients and insulin resistance. However, in human studies evidence is not as strong as in animals. Data suggest that dietary omega-3 polyunsaturated fatty acids (PUFAs) improve lipid profile and may have beneficial effect on insulin resistance. Dietary saturated fatty acids intake is positively associated with insulin resistance. Also, low glycaemic index foods and whole grain intake decrease insulin resistance. Importantly, high carbohydrate diets increase plasma triglycerides, cause hyperinsulinaemia and decreases low-density lipoprotein cholesterol. Among micronutrients, high magnesium and calcium intake have been reported to decrease insulin resistance. High intake of dietary carbohydrate and omega-6 PUFAs, low intake of omega-3 PUFAs and fiber, and high omega -6/omega-3 PUFAs ratio have been reported in South Asians. Our recent investigations have shown that increased dietary omega-6 PUFAs and saturated fat intake are significantly associated with fasting hyperinsulinaemia and sub-clinical inflammation, respectively. Such imbalanced diets contribute to high prevalence of insulin resistance, the metabolic syndrome and T2DM in South Asians and Asian Indians.