A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17A1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome.

BACKGROUND & OBJECTIVES: Insulin resistance (IR) is a major confounding factor in polycystic ovarian syndrome (PCOS) irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. METHODS: Polymorphism study was performed by restriction fragment length polymorphism (RFLP) analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women. Serum testosterone, BMI and HOMA-IR (homeostatic model of assessment-insulin resistance) were analyzed by standard techniques. A realistic cut-off value for the HOMA-IR was obtained through receiver operating characteristic (ROC) curve for exploring any possible link between IR and T/C polymorphism in the case group. RESULTS: Significant increases in serum testosterone and HOMA-IR values were observed among the case group (P<0.001) without any significant elevation in BMI and FBG compared to controls. Cut-off value for IR in the PCOS patients was 1.40 against a maximum sensitivity of 0.83 and a minimum false positivity of 0.13. The analysis revealed an inconclusive link between the C/T polymorphic distribution and insulin resistant case subjects. INTERPRETATION & CONCLUSIONS: The results showed that CYP17A1 gene was not conclusively linked to either IR or its associated increased androgen secretion in non-obese women with PCOS. We propose that an increased sensitivity of insulin on the ovarian cells may be the predominant reason for the clinical effects and symptoms of androgen excess observed in non-obese PCOS patients in our region.

Protective Role of Bilirubin Against Increase in hsCRP in Different Stages of Hypothyroidism.

In conjunction with thyroxine, bilirubin may play an important role for regulation of hsCRP level and a consequent pro-inflammatory condition in hypothyroidism. In present study we evaluated the dependence of hsCRP changes on total bilirubin (BT) and fT4 level in thirty overt (OH) and thirty subclinical hypothyroidism (SH). Serum BT, hsCRP, thyroxine and TSH were measured in both groups and compared with forty control subjects. Serum values of TSH, hsCRP showed raised (P < 0.001 for both) values with lower levels for fT4 and BT (P < 0.001 and 0.03 respectively) in hypothyroid patients compared to the controls. ANOVA showed significant increments in TSH and hsCRP values with decreases in fT4 among the control, SH and OH groups respectively (P < 0.001). BT values showed decrease in OH group only in comparison to controls (P = 0.04). Regression analysis revealed that hsCRP was negatively dependent on fT4 (ß = -0.35, P = 0.002) and serum bilirubin (ß = -0.40 and P < 0.001 respectively). Univariate general linear model analysis showed this dependence persisted even when carried out distinctly in SH and OH groups separately (P < 0.001). TSH did not show any significant predictive value on the hsCRP level in either of these two tests. From these analyses we suggest that serum hsCRP is closely integrated to a lowered synthesis of bilirubin and fT4 in hypothyroid patients. Furthermore, this causal relationship is not only limited to overt but also extends to the SH.

Role of membrane cholesterol and lipid peroxidation in regulating the Na+/K+-ATPase activity in schizophrenia.

BACKGROUND: Na+/K+-ATPase (NKA) activity is compromised in several neuropsychiatric disorders. Oxidative stress and membrane lipid composition play important roles in regulating NKA activity. AIMS: The present study was undertaken to evaluate the effects of oxidative stress-induced membrane lipid damage and membrane cholesterol composition on NKA pump activity in schizophrenia. SETTINGS AND DESIGN: It was a hospital-based, cross-sectional, observational study in 49 cases and 51 controls for 1 year. MATERIALS AND METHODS: NKA pump activity in red blood cell membrane, serum levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) adducts, and cholesterol were measured by standard spectrophotometric techniques in newly diagnosed schizophrenia patients by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. Membrane cholesterol was analyzed by chloroform and isopropanol extraction followed by measuring the cholesterol concentration by spectrophotometric technique. STATISTICAL ANALYSIS AND RESULTS: Mean values for NKA pump activity, membrane cholesterol level, and serum cholesterol levels were significantly lower in the case group (P < 0.001). The activity of NKA pump was found to be directly correlated to membrane cholesterol level rather than with the serum cholesterol values. Although the NKA pump activity showed inverse relationship with the serum values of TBARS and PC products both, on multiple linear regression analysis, it was found to be significantly positively dependent on the membrane cholesterol (ß = 0.268, P = 0.01) and negatively dependent on the serum TBARS (ß = -0.63, P < 0.001) levels only. CONCLUSION: Reduced membrane cholesterol and oxidative stress-induced damage to membrane lipids play crucial roles in decreasing the NKA activity in schizophrenia. Hence, for a better prognosis and treatment, measures are required to maintain optimum levels of cholesterol in neuronal tissues along with a proper control on oxidative stress.

Association of single-nucleotide polymorphism of cholecystokinin receptor A gene with schizophrenia in an Eastern Indian population.

CONTEXT: Cholecystokinin A receptor (CCK-AR) gene polymorphism is being increasingly reported in schizophrenia. It varies among different population groups but is associated with several complications of schizophrenia. AIMS: The present study was undertaken to assess whether the CCK-AR polymorphism is stabilized and is more consistently associated with schizophrenia in an Eastern Indian sub-population. SETTINGS AND DESIGN: It was carried out as a cross-sectional, observational, hospital-based study on 95 schizophrenia patients and 138 control subjects selected by the method of convenience. MATERIALS AND METHODS: Single-nucleotide polymorphisms located in the regulatory region of the CCK-AR gene were assessed by restriction fragment length polymorphism (RFLP) in the polymerase chain reaction (PCR) amplified product of CCK-AR gene in study subjects. RFLP was done by the digestion of the PCR product by the restriction enzyme Pst-1 followed by gel electrophoresis. STATISTICAL ANALYSIS: Assessment of the stability of C/T polymorphism in the study population was done by applying Hardy-Weinberg equilibrium rule. The significance of difference in the allelic distribution between case and controls was analyzed by Chi-square (χ(2)) test and odds ratio (OR) analysis. RESULT: CCK-R polymorphism was in Hardy-Weinberg equilibrium in both groups. Distribution of the C allele of this gene was significantly higher in schizophrenia patients (χ(2) = 4.35, OR = 1.51; confidence interval at 95% =1.04-2.20). CONCLUSION: C/T polymorphism of the CCK-R gene is a stable polymorphism in our study population. Moreover, the C allele is significantly more abundant in schizophrenia patients imparting them a greater risk of development of complications like auditory hallucination.

Clinico-biochemical correlation between psoriasis and insulin resistance.

Psoriasis is a chronic inflammatory disease associated with an increased insulin resistance, obesity and cardiovascular risk. The present study was aimed to assess insulin resistance and pattern of body fat deposition in psoriasis. Body mass index (BMI) and waist circumference (WC) were measured in 40 psoriatic patients and 46 age- and sex-matched control subjects. Fasting blood glucose (FBG) and serum insulin level were measured by standard photometric method and ELISA respectively. HOMA-IR (homeostatic model of insulin resistance) was calculated by appropriate software. The results indicated that case and control groups were comparable in terms of age and sex (p = 0.934) with an increased prevalence of psoriasis among male subjects (60 %). FBG and mean WC between the two groups were statistically not significant (p value = 0.271 and 0.21 respectively). BMI was significantly higher in case group compared to the control group (p = 0.049). Serum insulin level and insulin resistance in the psoriatic patients were significantly higher (p value <0.001). Multiple regression analysis revealed that insulin resistance (measured by HOMA) was dependent on BMI and WC at a significance level of p < 0.001 and 0.043 respectively. Therefore, the psoriatic patients in this region have significantly high amount of fasting serum insulin level along with an increased IR though their FBG level remains normal. Furthermore, these abnormalities are significantly dependent on total body fat as well as abdominal fat deposits. We suggest that psoriatic patients need to be evaluated for metabolic syndrome and managed accordingly.

Predictors of insulin resistance and metabolic complications in polycystic ovarian syndrome in an eastern Indian population.

The purpose of this study was to assess the predictive values of central obesity and hyperandrogenemia in development of insulin resistance and dyslipidemia in the polycystic ovarian syndrome (PCOS) patients in our region. Differences of fasting blood glucose level, insulin resistance index HOMA-IR, lipid parameters, waist hip ratio (WHR), body mass index, LH/FSH ratio and testosterone levels between 45 PCOS cases and 35 age matched controls were obtained. Strength of association between different parameters in the case group was assayed by Pearson's correlation analysis. Dependence of insulin resistance and WHR on different predictors was assessed by multiple linear regression assay. Total cholesterol, LDL cholesterol, LH, FSH, LH/FSH ratio, WHR and insulin resistance were significantly higher in the case group (p < 0.05). Serum testosterone showed strong correlation with insulin resistance and LH/FSH ratio (r = 0.432 and 0.747, p = 0.01 and 0.001 respectively) in the PCOS patients while WHR and serum testosterone level stood out to be most significant predictors for the insulin resistance (ß = 0.361 and 0.498; p = 0.048 and 0.049 respectively). Hyperandrogenemia and central obesity were the major factors predicting development of insulin resistance and its related metabolic and cardiovascular complications in our PCOS patients. We suggest early monitoring for androgen level and WHR in these patients for predicting an ensuing insulin resistance and modulating the treatment procedure accordingly to minimise future cardiovascular risks.

Anthropometric parameters as indicators of metabolic derangements in schizophrenia patients stabilized on olanzapine in an Indian rural population.

CONTEXT: For any given body mass, Asian Indians have higher central obesity than Europeans. A periodic measurement of body mass index (BMI) and waist hip ratio (WHR) is practically more feasible than other parameters of metabolic syndrome by repeated blood collection. However, few studies are available on the relative importance of BMI and WHR as markers of dyslipidemia and insulin resistance in schizophrenia patients stabilized on second generation antipsychotics in Indian population. AIM: We conducted the present study on such patients to examine whether BMI or WHR can better predict dyslipidemia and insulin resistance in these patients in a rural area. SETTINGS AND DESIGN: The study was a hospital based case control study under rural settings on 38 schizophrenia patients stabilized on olanzapine and 30 matched controls. MATERIALS AND METHODS: Fasting concentrations of blood glucose, lipid parameters and serum insulin were assessed. Data for Homeostatic model for assessment of insulin resistance (HOMA-IR), BMI, and WHR were obtained to assess the insulin resistance, overall body fat distribution and abdominal fat dispensation respectively. STATISTICAL ANALYSIS USED: 't' test was performed to assay any difference in corresponding mean values between cases and controls. Dependence of HOMA-IR on key parameters was assessed by analysis of co-variance (ANCOVA) study. RESULTS: Cases exhibited significantly higher values for HOMA-IR, serum triglyceride and low density lipoprotein cholesterol (LDLc) with a significantly lower high density lipoprotein cholesterol (HDLc) level. ANCOVA study reflected that irrespective of age and sex, HOMA-IR was dependent on serum triglyceride level and WHR (F=8.3 and 5.7 respectively, P<0.05), but not on BMI (F<0.001, P=0.997). CONCLUSIONS: Central obesity could be more closely associated with the pathogenesis of prediabetic state in our case group. So, WHR is a better anthropometric parameter than BMI for an early assessment of insulin resistance and dyslipidemia in schizophrenia patients stabilized on olanzapine in our region.

Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder.

OBJECTIVES: Oxidative stress induced lipid peroxidation along with a reduced Na(+)-K(+)-ATPase activity has been implicated in the pathophysiology of bipolar disorders (BPD). Although, lithium therapy results in significant improvement in the symptoms of the disease, studies regarding its effect on the altered sodium pump activity and lipid peroxidation status have come out with conflicting results. The present study was undertaken to evaluate the status of lipid peroxidation and analyze the role of lithium and Na(+)-K(+)-ATPase activity in its regulation in BPD patients in our region. METHOD: We measured RBC membrane Na(+)-K(+)-ATPase activity and serum thiobarbituric acid reacting substances (TBARS) level in 73 BPD patients and serum lithium, in addition, in 48 patients receiving lithium therapy among them. RESULTS: Na(+)-K(+)-ATPase activity and serum TBARS level were significantly decreased and increased respectively in all BPD patients compared to age and sex matched healthy controls. Same trend was observed in the BPD patients stabilized on lithium therapy compared to the lithium naive ones. Although, the enzyme activity showed a reciprocal relationship with TBARS in all patients of BPD, a significant positive correlation and dependence of the enzyme activity was evident with serum lithium level only in the lithium stabilized BPD group. CONCLUSIONS: BPD patients showed significantly compromised Na(+)-K(+)-ATPase activity and increased lipid peroxidation. Lithium induced improvement in the enzyme activity was associated with significant reduction in lipid peroxidation. Enhancement of the Na(+)-K(+)-ATPase activity by optimum dosage of lithium may be a potential contributing factor for reducing oxidative stress in BPD patients.