APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome.

BACKGROUND: Despite the growing epidemic of the metabolic syndrome (MetS), few studies have evaluated genetic polymorphisms associated with the MetS phenotype. One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss of insulin downregulation. METHODS: One hundred twenty two consecutive MetS cases were matched by age, sex and race in a 1:1 case-control design to evaluate the prevalence of common polymorphisms in the following candidate genes: APOC3, APOE, B3AR, FABP2, GNB3, LPL, and PPARalpha and PPARgamma. RESULTS: Compared to controls, MetS subjects exhibited a greater prevalence of APOC3 promoter polymorphisms. Specifically, the frequency of the variant C-482T and T-455C alleles was 70.5 and 81.9% of cases compared to 43.4 and 54.1% in controls, respectively (p <0.0001). Overall, APOC3 promoter variants were associated with a greater likelihood of MetS compared to wild type [C-482T (OR: 4.3; 95% CI: 2.2, 8.6 [p <0.0001]), T-455C (OR: 3.6; 95% CI: 2.0, 6.7 [p <0.0001])]. No material differences were identified between the other genetic variants tested and prevalence of MetS. CONCLUSIONS: These data, therefore, suggest that the APOC3 promoter polymorphisms C-482T and T-455C are associated with the MetS.

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.

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.

Soluble inter-cellular adhesion molecule-1 in urban Asian north Indians: relationships with anthropometric and metabolic covariates.

BACKGROUND: High prevalence of diabetes, obesity, and dyslipidemias in people belonging to poor socio-economic strata in urban slums of northern India has been recorded recently. To assess whether this population has high levels of soluble intercellular adhesion molecule-1 (sICAM-1), a cytokine involved in the pathogenesis of atherosclerosis, we investigated subjects belonging to poor socio-economic strata in urban slums and compared them to healthy control subjects from non-slum urban areas of New Delhi. DESIGN: Cross-sectional study. METHODS: Subjects from a previously carried out cross-sectional study, Delhi Urban Slum Project (DUSP) were divided into two groups: Group-1 (n = 56) included subjects dwelling in slum area, having at least one risk factor (hypertension, hyperglycemia, hypertriglyceridemia and hypercholesterolemia), while group-2 (n = 60) consisted of subjects without any risk factor dwelling in the slum area. A third group (n = 29) of non-obese subjects without any risk factor living in non-slum urban area was included for comparison. Measurements included; body mass index (BMI), waist-hip ratio (W-HR), four skinfolds, percentage body fat, fasting plasma glucose (FPG), serum lipids, and serum levels of sICAM-1. RESULTS: Though statistically not significant, mean level of sICAM-1 was higher in group-1 (718.5 +/- 232.8 ng/ml) as compared to the other groups. Of note, 35% of subjects in group-1 (p < 0.05 as compared to other two groups), and 25.3% of all subjects had levels of sICAM-1 in uppermost quartile (> 850 ng/ml). Partial correlation coefficients (R) of sICAM-1 levels with various parameters adjusted for age were statistically significant for BMI (R = 0.27, p < 0.05) in group-1; W-HR (R = 0.26, p < 0.05) and BMI (R = 0.19, p < 0.05) for group-2; and FPG (R = 0.17, p < 0.05) for all the subjects considered together. For females, the levels of sICAM-1 were significantly higher in the following: BMI > OR = 25 kg/m2 (p = 0.04) and FPG > 7 mmol/l (p < 0.05). Multiple linear regression analysis suggests that an increment in BMI by one kg/m2 would correspond to an increase in the levels of sICAM-1 by 8.5 units controlling for the influence of age and W-HR in the pooled data of all subjects. CONCLUSIONS: High percentage of subjects had levels of sICAM-1 in the upper quartile in the study, particularly those dwelling in the slum area and having coronary risk factor (s). The levels of sICAM-1 strongly correlated to the anthropometric and metabolic parameters, particularly in females. These observations are of potential importance for the pathogenesis of atherosclerosis in this population, though further studies are needed to predict those prone to the complications of atherosclerosis, based on sICAM-1 levels, as has been observed in other ethnic groups.

Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian Indian adolescents.

High-sensitivity C-reactive protein (hs-CRP) levels are closely associated with adiposity and predict coronary heart disease and type 2 diabetes mellitus. However, relationships of CRP to adiponectin and other markers of insulin resistance have been inadequately researched in children. We measured fasting serum levels of adiponectin, insulin, hs-CRP, and lipoproteins, and recorded the anthropometric profile and percentage of body fat (%BF; bioimpedance method) in 62 (36 normal weight, 26 overweight) healthy, urban, postpubertal Asian Indian males (aged 14 to 18 years). Serum levels of adiponectin were lower (P = not significant [NS]), whereas those of fasting insulin (P = .01) and hs-CRP (P = .02) were higher in overweight subjects. Adiponectin levels inversely correlated with body mass index (BMI; r = -0.26, P < .05), %BF (r = -0.24, P < .05), fasting insulin (r = -0.32, P < .05) and insulin resistance measured by the homeostasis model of assessment (HOMA-IR; r = -0.31, P < .05), but not with hs-CRP levels. Fasting insulin and hs-CRP levels correlated significantly with BMI, %BF, waist circumference (WC), waist-to-hip circumference ratio (W-HR), and triceps and subscapular skinfold thickness. The correlation of adiponectin with insulin sensitivity was independent of abdominal obesity, but became nonsignificant after controlling for BMI and %BF. Further, BMI was an independent predictor of adiponectin levels and the ratio of adiponectin and %BF was an independent predictor of fasting insulin levels. Although adiponectin levels did not correlate with hs-CRP levels, we observed dichotomous relationships of adiponectin and hs-CRP levels with generalized and abdominal obesity, respectively. We conclude that generalized obesity affects the adiponectin-insulin relationship in postpubertal Asian Indian males; however, the relationship of adiponectin with hs-CRP needs further evaluation.

Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India.

OBJECTIVES: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of apolipoprotein E (apo E) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of apo E gene polymorphisms in premature MI patients and their relation to serum lipid levels. DESIGN AND METHODS: Apo E gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. RESULTS: Higher frequencies of the apo E4 allele (P<0.0001) and of genotypes E3/E4 (P<0.005) and E4/E4 (P<0.005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45.7 (4.9-421.3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8.7 (0.9-86.6)] and those with a high waist : hip ratio [OR (95% CI): 5.6 (1.4-21.2)]. CONCLUSION: Based on the robust association, the apo E4 allele should be considered as an independent risk factor for premature MI in Asian Indians.

Dhatrilauha: Right choice for iron deficiency anemia in pregnancy.

BACKGROUND: Anemia in pregnancy is multi-factorial. Iron deficiency anemia (IDA) is the most common one. Major cause is increased demand of iron during pregnancy. In Ayurveda, under Pandu-Roga the features of anemia are described. It is characterized by Vaivarnyata or Varnanasha (change/destruction in normal color of the body), a disorder of Pitta vitiation. Ayurvedic management is an effective way of curing anemia in general by a large number of Lauha preparations of which Dhatrilauha has been used widely for centuries. AIM: To evaluate the effect of Dhatrilauha in the management of IDA based on the scientific parameters among pregnant patients. MATERIALS AND METHODS: A total of 58 cases were selected by simple randomized sampling method as per inclusion criteria of pregnant women between 4(th) and 7(th) months of pregnancy with a clinical diagnosis and laboratory confirmation of IDA. Dhatrilauha 500 mg in two divided doses after food with normal potable water were given for 45 days with three follow-ups, each of 15 days intervals. Final assessment was done after completion of 45 days and results were statistically analyzed by using Cochran's Q-test and Student's t-test. RESULTS: Dhatrilauha showed statistically significant (P < 0.01) improvement in the majority of sign-symptoms and objective parameters such as weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn, pallor, constipation, hemoglobin, red blood cells (RBC), hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width, mean platelet volume, serum iron, and total iron binding capacity. CONCLUSION: Dhatrilauha possesses many fold effectiveness in anemia (IDA), which was evidenced with the significant results obtained in the majority of parameters in this study.

Pharmaceutical preparation of Saubhagya Shunthi Churna: A herbal remedy for puerperal women.

BACKGROUND: In the last few decades, there has been exponential growth in the field of herbal remedies. Pharmacopoeial preparations like avleha or paka (semi-solid), swarasa (expressed juice), kalka (mass), him (cold infusion) and phanta (hot infusion), kwatha (decoction) and churna (powder) form the backbone of Ayurvedic formulations. Newer guidelines for standardization, manufacture, and quality control, and scientifically rigorous research will be necessary for traditional treatments. This traditional knowledge can serve as powerful search engine that will greatly facilitate drug discovery. PURPOSE: The aim of the present study is to standardize Saubhagya Shunthi Paka in churna (powder) form. The powder form makes this traditional drug more stable for long-term storage and hence, easier to preserve. MATERIALS AND METHODS: Saubhagya Shunthi Paka is an ayurvedic formulation containing Shunthi (Zingiber officinalis) as one of its chief ingredients. The basic preparation of this drug is a semisolid. We checked the microbial load and nutrient values (using International Standard IS and Association of Official Analytical chemists AOAC methods) RESULTS: The powdered form of Saubhagya Shunthi Churna yielded a weight loss of approximately 17.64% of the total weight of ingredients. The total energy of Churna (calculated based on nutrient content) was found higher over Paka. CONCLUSION: Saubhagya Shunthi Churna may be a good therapeutic and dietary medicine for Indian women, which may be easily prepared at home.

Subclinical inflammation and soleus muscle intramyocellular lipids in healthy Asian Indian males.

OBJECTIVES: The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. METHOD AND DESIGN: We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy ((1)H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. RESULTS: Soleus muscle IMCL content was significantly correlated with age (rho=0.64, P<0.001), BMI (rho=0.41, P<0.05), %BF (rho=.53, P<= 0.01), waist circumference (rho=0.45, P<0.05) and waist-to-hip circumference ratio (rho=0.58, P<0.01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. CONCLUSIONS: Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data.

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 epsilon4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The epsilon3epsilon3 (p < 0.05) and epsilon2epsilon3 (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 epsilon4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE epsilon4 compared with the Caucasian population.

Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India.

BACKGROUND AND AIM: An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban nonslum area. METHODS: Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. RESULTS: Sex-adjusted serum levels of Hcy in micromol/L (Mean +/- SD) were high, though statistically comparable, in both the groups (group I: 20.8 +/- 5.9 and group II: 23.2 +/- 5.9). Overall, higher than normal serum levels of Hcy (> 15 micromol/L) were recorded in 84% of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4% in group I and 96.7% in group II, vitamin B12: 76.1 % in group I and 88.4% in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (1 = 4.6, p < 0.05) and males vs females (beta = 5.3, p < 0.01). CONCLUSIONS: Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent.