Vani Gupta

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women.

BACKGROUND Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. METHODS The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. RESULTS Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. CONCLUSIONS Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.

Resistin 420C/G gene polymorphism on circulating resistin, metabolic risk factors and insulin resistance in adult women

OBJECTIVE To investigate the frequency association between resistin gene polymorphism with its circulating levels, metabolic risk factor and insulin resistance in adult women. DESIGN Totally 615 subjects were enrolled for the study, 305 women were with metabolic syndrome and 310 women were without metabolic syndrome according to NCEP-ATP III criteria. Fasting circulatory level of resistin, insulin, plasma glucose and lipid profiles were estimated along with calculation of insulin resistance. Resistin 420C/G promoter region polymorphism was done by RFLP method. RESULTS Variant genotype (CC vs CG+GG) (p<0.001: OR=2.22: 95% CI=1.60-3.10) of 420C/G resistin gene polymorphism was less frequently observed in control population. Further dividing subjects into two groups according to absence (Resistin -1) or presence (Resistin-2) of the G allele, significantly high levels of triglyceride (p<0.001), plasma glucose (p=0.012), systolic blood pressure (p<0.001), diastolic blood pressure (p<0.001), waist hip ratio (p<0.001), body mass index (p<0.001) and resistin (p<0.001), were observed in resistin-2 group. CONCLUSION Present study shows that 420C/G polymorphism of resistin gene directly correlated to its high circulating level and metabolic risk factors, specifically markers of obesity and atherosclerosis, so it may have an important role in the development of metabolic syndrome and cardio metabolic diseases.

IL-6 gene expression in adipose tissue of postmenopausal women and its association with metabolic risk factors

Adipose tissue secretes various kinds of adipokines that controls the glucose and lipid metabolism in humans. The abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) both are associated with metabolic syndrome and insulin resistance. IL-6 is one of the adipokines, which promotes insulin resistance and dyslipidemia in humans. The association of adipokines with metabolic syndrome at protein levels are well documented. However, their association at gene expression level are lacking. The present study was design to investigate IL-6 mRNA expression in adipose tissues (VAT and SAT) and its correlation with metabolic risk factors and insulin resistance (HOMA) in post menopausal women. A total of 108 Asian North Indian post menopausal women, 54 without metabolic syndrome (controls) and 54 with metabolic syndrome (cases) were recruited and evaluated. Overnight fasting blood samples were collected at admission and abdominal visceral and subcutaneous adipose tissues were collected during open abdomen surgery. The results showed significantly (p < 0.05 or p < 0.01 or p < 0.001) higher mean SBP, glucose, insulin, HOMA, TG, VLDL and serum IL-6 while significantly (p < 0.001) lower HDL and estrogen in cases as compared to controls. In cases, the relative mean SAT IL-6 expression was also significantly (p < 0.05) higher as compared to VAT. Further, in cases, the VAT IL-6 expression showed significant (p < 0.05 or p < 0.001) and negative correlation with WC, WHR, glucose, HOMA, TC, LDL and estrogen while SAT IL-6 expression also showed significant (p < 0.05 or p < 0.01 or p < 0.001) and negative correlation with WC, WHR and estrogen. The Cox regression analysis found VAT IL-6 mRNA expression the significant (p < 0.05 or p < 0.01) an independent predictor of WC, HOMA, TC, LDL and estrogen while SAT IL-6 mRNA expression the significant (p < 0.01) an independent predictor of TG and VLDL. The study concluded that IL-6 expressions of both visceral and subcutaneous tissues may be associated with metabolic risk factors in postmenopausal Asian North Indian women.

Vascular endothelial growth factor gene polymorphisms and association with age related macular degeneration in Indian patients

Background Age-related macular degeneration (AMD) is an important cause of visual impairment in elderly people. AMD is a multifactorial disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD. Aim This study was aimed to investigate the association of polymorphisms in VEGF genes with age related macular degeneration (AMD) in Indian patients. Method Genotyping for the VEGF − 1154 (G > A), − 2578 (C > A), + 405 (G > C) and − 460 (C > T) SNPs was performed in 100 AMD patients and 100 controls by polymerase chain reaction (PCR), restriction fragment length polymorphism (PCR-RFLP) and sequencing method. Results Out of the four SNPs, heterozygous genotypes of VEGF − 1154 G > A (OR = 2.58, p = 0.0035), + 460 C > T (OR = 2.90, p = 0.0046), and + 405 G > C (OR = 2.02, p = 0.02) have shown susceptible association with AMD. However, VEGF − 2578 C > A did not show any statistical significance. Further A-A-G-T haplotype comprising of three mutant alleles revealed risk association (OR = 12.7, p = 0.0030) with AMD. Conclusion The present study suggests significant genetic associations for VEGF − 1154 G > A, + 460 C > T, and + 405 G > C polymorphisms with AMD. Early detection of individuals with risk to these SNPs could lead to strategies for prevention, early diagnosis, and management of AMD.

L:A ratio, Insulin resistance and metabolic risk in women with polycystic ovarian syndrome

BACKGROUND AND AIMS The plasma leptin-adiponectin ratio (L:A) has been suggested as a one of the potentially independent predictor of metabolic risk and Insulin resistance in women with polycystic ovarian syndrome (PCOS). METHODS This is a case-control study, total 439 female subjects, comprises in to two group 223 cases (PCOS) and 216 control (non-PCOS women) according to their clinical characteristics. Further both case and control group were sub-grouped in PCOS and non-PCOS with metabolic syndrome (wMetS) and without metabolic syndrome (woMetS) as per National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Anthropometrical measurements and biochemical analysis were done. Leptin and adiponectin level were estimated by enzyme-linked immunosorbent assay. RESULTS Results indicated that SAD, WHR, BMI, BP, lipid profile, FPG, fasting plasma insulin, IR (HOMA-IR), leptin and L:A ratio were significantly higher (p=<0.001) in PCOS women compare to non PCOS. Furthermore anthropometrical values and level of FPG, TC, TG, Insulin, IR (HOMA-IR) and L:A ratio were significantly high (p=<0.001) in PCOS wMetS compare woMetS, however HDL (p=<0.001) and adiponectin level (p=<0.001) were significantly low. The same trend was also found in comparison between with and without MetS among non-PCOS women. The correlation between L:A Ratio with different metabolic risk markers, L:A ratio was positively significant with SAD (r=0.97, p <0.001), FPG (r=0.96, p<0.001), TC (r=0.44, p<0.001), insulin (r=0.98, p<0.001), IR (r=0.97, p<0.001), Adiponectin (r=0.21, p<0.01) and negatively significant with HDL(r=-0.42, p<0.001) in PCOS wMetS whereas L:A ratio was also positively correlated with SAD, BMI, TG in PCOS woMetS. CONCLUSIONS Study concluded L:A ratio may be one of the potential biomarker for metabolic syndrome and insulin resistance which is independent for presence of PCOS disease.

Serum magnesium in relation with obesity

Background: Obesity is the leading public health crisis of our time. A chronic imbalance between energy intake and energy expenditure will eventually lead to obesity. Several micronutrients are found to be involved in the development of obesity. Magnesium is found to have some role in the development of obesity. Aims and Objective: Objective of this study was to evaluate the correlation of serum magnesium with different parameters of obesity such as body weight, basal metabolic rate, waist circumference (WC), and waist-hip ratio on the basis of the hypothesis that subjects with hypomagnesemia are more prone to develop obesity. Materials and Methods: This is a population-based cross-sectional study. A total of 130 apparently healthy adults of age between 25 and 65 years, were recruited with prior ethical approval and written informed consent. Results: Serum magnesium was found to have significant negative correlation with body weight (r = −0.30, P = 0.003) and WC (r = −0.21, P = 0.03). Correlation with rest of the parameters was not significant. Conclusion: On the basis of results it is concluded that hypomagnesemia can be proved to be one of the important predictors of obesity.

Association of Leptin: Adiponectin ratio and metabolic risk markers in postmenopausal women

Leptin and adiponectin play an important role in the regulation of body weight and energy homeostasis. The purpose of the present study was to ascertain the relationship between leptin to adiponectin ratio (L:A) and metabolic risk factors in postmenopausal women.This is a cross sectional case-control study. A total of 523 postmenopausal women were recruited for the study 270 postmenopausal women with metabolic syndrome and 253 apparently healthy control postmenopausal women without metabolic syndrome. Biochemical and Anthropometrical parameters were measured. Leptin and adiponectin levels were determined by sandwich enzyme-linked immunosorbent assay, insulin resistance was determined by homeostasis model assessment for insulin resistance (HOMA-IR). Results of this study indicate that leptin (15.92 ± 10.50 vs.9.43 ± 4.39 pg/ml, p < 0.001), L:A ratio (1.08 ± 1.06 vs.0.42 ± 0.38 pg/ml, p < 0.001), HOMA-IR, the lipid profile, and other metabolic risk factors (waist circumference (WC), waist-to-hip ratio(WHR), body mass index((BMI)), fasting plasma glucose (FPG) level and fasting plasma insulin(FPI)) were significantly higher but HDL, HDL/LDL and adiponectin level (20.55 ± 10.76 vs.30.08 ± 13.08 pg/ml, p < 0.001)were significantly lower in postmenopausal women with metabolic syndrome than in women without the syndrome (p < 0.001). Further, in postmenopausal women with metabolic syndrome, L: A ratio was significantly positive (p < 0.05 or p < 0.001) correlated with WC, BMI, WHR, TG, FPG, TC/HDL, LDL/HDL, FPI and HOMA-IR (p < 0.01), and negatively correlated with HDL and HDL/LDL (p < 0.001). Conclusively L: A ratio was found to be significantly associated with central obesity and other metabolic risk factors so that high L:A ratio may act as a diagnostic marker for metabolic syndrome in postmenopausal women.

Association of acylation stimulating protein and adiponectin with metabolic risk marker in North Indian obese women

BACKGROUND Plasma concentrations of Acylation stimulating protein (ASP) and adiponectin are associated with body weight and energy homeostasis. The purpose of this study is to describe the potential role of acylation stimulating protein and adiponectin with metabolic risk marker in North Indian obese women. METHODS This is a case control study. Total 520 women were recruited for the study n = 260 women with obesity (BMI>30) study group and n = 260 women without obesity (BMI<25) control group. Serum ASP and adiponectin level were determined by enzyme linked immunosorbent assay. RESULTS Result indicated that WC, BP, lipid profile, FPG, FPI, IR (HOMA-IR), ASP were significantly higher but adiponectin and HDL were significantly lower in women with obesity than in women without obesity. Furthermore ASP was significantly positive correlated with WC, FPG, TG, VLDL, FPI and IR, whereas the correlation of adiponectin was significantly negative correlated with WC, FPG, TG, IR, ASP and significantly positive correlated with HDL in women with obesity. CONCLUSION The study shows that high level of ASP and low level of Adiponectin could be a potential marker of women with obesity among metabolic syndrome.

Interleukin-10 as a novel biomarker of metabolic risk factors

BACKGROUND Interleukin-10 (IL-10) is an adipocytokine that is abundantly expressed in visceral fat tissue. We investigated the association of interleukin-10 with the number of metabolic risk factors. FINDING The study population comprised 220 children who underwent annual health checkups. Plasma Interleukin-10 levels were determined by enzyme-linked immunosorbent assay. We divided the subjects into 4 groups according to Interleukin-10 levels. A reduction of plasma interleukin-10 levels significantly correlated with an increase in the mean number of metabolic risk factors such as increased waist circumference, BMI, dyslipidaemia, high blood pressure and glucose intolerance. CONCLUSIONS Circulating Interleukin-10 levels negatively correlated with the multiplicity of metabolic risk factors, suggesting that IL-10 acts as a biomarker of metabolic disorders.

Correlation of serum magnesium with insulin resistance in North Indian adult population

BACKGROUND Globalization has lead to such lifestyle changes which have produced increase in incidence and prevalence of Type 2 Diabetes Mellitus (T2DM). Magnesium is found to have some role in glucose metabolism. The aim of this study was to investigate the relationship between serum magnesium levels with insulin resistance in apparently healthy adults. OBJECTIVE The objective of our study was to evaluate correlation of serum magnesium with fasting blood sugar, insulin level and Homeostasis model assessment-insulin resistance (HOMA-IR) index (indicator of insulin resistance) on the basis of the hypothesis that subjects with hypomagnesaemia are more prone to develop hyperglycemia and insulin resistance. MATERIAL AND METHODS The study was a cross-sectional study which was population based. Total 130 apparently healthy adults of age between 25-65 years, were recruited with prior ethical approval and written informed consent. RESULTS Serum magnesium was found to be negatively correlated with fasting blood sugar (FBS), insulin level and HOMA-IR. Co-relation of magnesium with FBS (r = -0.55, p<0.0001), insulin (r = -0.45, p< 0.0001) and HOMA-IR (r = -0.52, p<0.0001) was significant. CONCLUSION As per findings it was concluded that serum magnesium was found to have significant negative correlation with fasting blood sugar (FBS), insulin and HOMA-IR, thus hypomagnesaemia can be suggested to be one of the important predictor of type 2 diabetes mellitus.