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BACKGROUND & OBJECTIVES: Diabetes is a metabolic pro-inflammatory disorder characterized by chronic hyperglycaemia and increased levels of circulating cytokines suggesting a causal role for inflammation in its aetiology. In order to decipher the role of interleukin-6 (IL-6) in type 2 diabetes mellitus (T2DM) we analyzed two promoter polymorphisms -597 A/G (rs1800797) and -174 G/C (rs1800795) in T2DM cases from north India, and in healthy controls. METHODS: DNA was isolated from venous blood samples of T2DM patients (n=213) and normal healthy controls (n=145). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed after biochemical analysis. The genotypic and allelic frequency distributions were analyzed. RESULTS: The clinical/biochemical parameters of T2DM cases when compared to controls showed a significant difference. No significant association was observed with -597A/G polymorphism while, -174 G/C showed a highly significant association (P<0.001). In haplotypic analysis, combination of -597GFNx01/-174CFNx01 showed significant association (P=0.010). INTERPRETATION & CONCLUSIONS: Our data suggest that IL-6 gene polymorphisms play a prominent role in T2DM disease susceptibility in population from north India.

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BACKGROUND & OBJECTIVES: The greater tendency to diabetes in Indians may be due to genetic factors in addition to environment and diet. CD36, a class B scavenger cell surface receptor mediates internalization of oxidized low density lipoprotein (Ox-LDL) leading to the formation of macrophage foam cells. CD36 deficiency is related to phenotypic expression of the metabolic syndrome, frequently associated with atherosclerotic cardiovascular diseases resulting in raised levels of glucose thereby contributing to type 2 diabetes (T2DM). Therefore, the association of human CD36 gene mutation to T2DM needs investigation. We undertook this study to investigate CD36 gene status in north Indian subjects by screening for the deletion of exons 3, 4 and 5 and certain polymorphisms. METHODS: Clinical characteristics were compared between 300 T2DM patients and 100 healthy controls. Deletion analysis was carried out for exons 3, 4 and 5 of CD36 gene in 300 T2DM patients using PCR and agarose gel electrophoresis. Genotype analysis for two polymorphisms 478C>T and delAC in exons 4 and 5 respectively was carried out using PCR-RFLP method. RESULTS: Biochemical parameters such as fasting and post-prandial glucose levels, total cholesterol, LDL-cholesterol and blood pressure were slightly raised in the T2DM patients when compared with controls with lowered HDL-cholesterol. No exonic deletion was observed in the 300 patients and 100 controls screened. All individuals were found to be homozygous (CC and -/-) for the two polymorphisms studied. INTERPRETATION & CONCLUSIONS: Although no exonic deletion was found in T2DM patients, our study suggests that all 15 exons need to be screened for mutations which lead to CD36 deficiency. Genotyping studies of the two SNPs in the CD36 gene confirmed the absence of exons 4 and 5 deletion. This is perhaps the first report from India suggesting that CD36 is one of the several important genes that need to be explored in relation to T2DM.

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The present investigations were aimed to identify the possible association between genetic polymorphism in interleukin-6 (IL-6) G-174C gene, which confers susceptibility to metabolic syndrome, and serum level of resistin in North Indian women. The study population comprised 370 unrelated Indian women (192 having abdominal obesity and 178 controls). Polymorphism in genotype (CC+GC) of IL-6 G-174C gene was determined using a combination of polymerase chain reaction (PCR) and sequence-specific primer with restriction fragment length polymorphism (RFLP) technology. Insulin resistance (IR) and serum resistin level were also analyzed along with metabolic risk factors. Of 192 abdominal obese women, 147 (76.56%) were found to have mutant CC+GC (p = 0.001) genotype and allele frequency (p = 0.001), which was significantly higher 45 (23.44%) than non-obese and their respective wild type. The mutant genotype (CC+GC) of IL-6 gene was found to be associated significantly with high triglyceride (p = 0.025) and resistin level (p < 0.001), when compared with respective wild genotype (GG) in obese women. Non-obese women with no signs of metabolic risk factors were found to have significantly low level of serum resistin and IR in comparison to obese women having genetic polymorphism for IL-6 G-174C gene. Study suggests that IL-6 G-174C gene is one among the susceptibility loci for metabolic syndrome in North Indian women. Genotype for this polymorphism may prove informative for prediction of genetic risk for metabolic syndrome. Further, high level of serum resistin molecules may be targeted to correlate with metabolic syndrome risk factors and could be used as early prediction marker.

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BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. AIMS: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. SETTINGS AND DESIGN: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. MATERIALS AND METHODS: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). STATISTICAL ANALYSIS: Fisher's exact test and chi2 statistics using SPSS software (Version-15.0). RESULTS: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325) and GSTP1 (I/V) (P=0.001, OR= 0.397, 95%CI=0.225-0.701) with T2DM and no significant association with GSTT1 (P=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496). CONCLUSIONS: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk.

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BACKGROUND: Inflammation is a key event closely associated with the pathophysiology of type 2 diabetes mellitus (T2DM). Association of genetic polymorphisms of inflammatory cytokines with T2DM is largely unknown. Our objective was to investigate the relationship of polymorphism of IL-1RN and IL-4, two important biomarkers of inflammation, with the risk of T2DM. SETTING AND DESIGN: We recruited 120 clinically diagnosed T2DM patients and 150 normal healthy controls for this study in order to evaluate the nature of polymorphisms of IL-1RN and IL-4. MATERIALS AND METHODS: Genomic DNA was isolated from the blood of all subjects, and the variable number of tandem repeat (VNTR) polymorphisms of IL-1RN and IL-4 genes was identified by polymerase chain reaction. STATISTICAL ANALYSIS USED: Genotype distribution and allelic frequencies were compared between patients and control group. Means, as well as odds ratios (ORs) with 95% confidence intervals (CI), were calculated using SPSS software (version 11.5). RESULTS: Our study revealed that distribution of both IL-4 and IL-1RN (VNTR) gene polymorphisms were significantly associated with T2DM subjects. We, however, failed to find any association of gene-gene (IL-4 and IL-1RN) interaction with T2DM. CONCLUSIONS: Both IL-4 and IL-1RN (VNTR) gene polymorphisms were significantly associated with T2DM subjects. This may suggest that the genetic polymorphisms of IL-4 and IL-1RN genes could serve as susceptibility indicators for T2DM in the Indian population, but the actual mechanism of these associations will require more elaborate investigations. Lack of association of gene-gene (IL-4 and IL-1RN) interaction with T2DM may indicate the independent nature of influence of both these genes on the risk of T2DM.

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OBJECTIVE: To study the prevalence of hypertension in our cases with psychiatric disorders and to study if the prevalence is higher in the cases with psychiatric disorders. METHODS: Four hundred twenty two cases with various psychiatric disorders attending the Outpatient Department of Psychiatry of our hospital were studied. Detailed clinical evaluation was done in all the cases. Blood pressure was recorded in the sitting position and mean of three readings was taken. Diagnosis and grading of hypertension was done according to the JNC V recommendations. Psychiatric disorders were diagnosed according to DSM IV criteria. RESULTS: Mean age of the cases was 36.3 years. Prevalence of hypertension in the cases was 7.1%. Prevalence in male and female cases were 7.2% and 7.0%, respectively. Prevalence of hypertension in various age groups was 20-39 years--1.48%, 40-60 years--24.4%, > 60 years--33.3%. CONCLUSION: The overall prevalence of hypertension in our cases with psychiatric disorders was 7.1% which was not higher than the reported prevalence of hypertension in our general population.

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The status of cytochrome P450-dependent oxidative biotransformation of aminopyrine and benzo(a)pyrene (Phase I reaction) and glutathione S-transferase (GST) catalyzed conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) (Phase II reaction) was evaluated in diabetic rats sacrificed 3 weeks after alloxan treatment (2 doses of 75 mg/kg at an interval of 48 h, i.p.). Alloxan treatment caused 3-4 fold increase in blood glucose level and 68% rise in glycosylated hemoglobin content. There were significant decreases in the activities of the hepatic aminopyrine N-demethylase and aromatic hydrocarbon hydroxylase (AHH) in diabetic rats as compared with the controls. The activity of GST was also significantly reduced in liver and kidney, whereas remained unchanged in the brain. These results suggest that a prolonged diabetic state depresses the metabolism of xenobiotics and probably of some endogenous compounds as well in liver and kidney.

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The aim of this study was to evaluate conjugated dienes in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and its metabolic control. To achieve good metabolic control in addition to dietary management oral hypoglycemic agents such as glibenclamide, gliclazide and metformin were given to patients. Human plasma low-density lipoproteins (LDL) were delipidised and triglycerides (LDL-TG) and cholesterol esters (LDL-CE) were separated. Conjugated dienes in LDL-TG and LDL-CE of subjects with NIDDM (n = 90) and normal glucose tolerance (NGT) (n = 30) were measured using second derivative of uv absorption spectrum. Hypoglycemic agents lowered substantially concentration of cis, trans (c, t) and trans, trans (t, t) conjugated dienes in LDL-CE and LDL-TG. The duration of NIDDM has shown significant correlation (p < 0.001) with conjugated dienes in LDL-TG. Concentration of c, t and t, t-conjugated dienes in LDL-CE and LDL-TG were found significantly higher in subjects with NIDDM than NGT (p < 0.001). In conclusion, NIDDM, status of metabolic control and duration of diabetes have strong positive relation with oxidative stress.

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Appearance of fluorescence emission between 380-550 nm (lambda exc 350-400 nm) in freshly prepared low-density lipoprotein from asymptomatic normolipemic human plasma revealed the presence of in vivo oxidative modification of its protein moiety. Low-density lipoprotein elicited seven fluorophores in three dimensional fluorescence spectrogram. Assignment of fluorescent chemical structures originating from oxidative modification of the protein moiety of low-density lipoprotein has been made with the help of second derivative fluorescence spectroscopy.

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The effect of the administration of 3.5 g of psyllium husk twice daily for 90 days was investigated in 24 patients of non insulin dependent diabetes mellitus (NIDDM) with hyperlipidaemia. After 90 days of treatment, psyllium was withdrawn and the patients were followed up for a further 90 days. Psyllium significantly decreased the levels of total cholesterol (TC; 19.7%), low-density lipoprotein cholesterol (LDL-C; 23.7%), triglycerides (TG; 27.2%) and the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C; 24.1%) and the lowering was sustained even up to 90 days after cessation of treatment. The level of HDL-C also showed a significant increase of 15.8 per cent but this effect was not sustained after cessation of treatment. The compliance was very good and no adverse effects were observed. This study indicated that psyllium husk is an effective and well tolerated adjunct to diet for the treatment of mild to moderate hyperlipidaemia in NIDDM patients.

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Conjugated dienes present in the fatty acyl chains of cholesterol esters and triglycerides associated with plasma apolipoprotein B containing lipoproteins of normal and Type 2 (non-insulin-dependent) diabetic patients (n = 17) have been analysed using second derivative electronic absorption spectroscopy. Characteristic spectral patterns for both normal subjects and Type 2 diabetic patients were observed. Cis, trans and trans, trans conjugated dienes in cholesterol esters of lipoprotein B of Type 2 patients and normal subjects were found to be 41.74 +/- 0.51 mg/litre, 8.20 +/- 0.20 mg/litre (p less than 0.01) and 24.70 +/- 0.33 mg/litre, 9.22 +/- 0.06 mg/litre (p less than 0.01), respectively. Levels of these dienes in triglyceride fraction were 21.21 +/- 0.52 mg/litre, 7.72 +/- 0.02 mg/litre (p greater than 0.05) and 15.49 +/- 0.36 mg/litre, 7.91 +/- 0.11 mg/litre (p greater than 0.05), respectively.

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85 patients with a variety of ischemic heart diseases were examined for the proportion of T cells and the presence of anticardiac antibodies. Patients with acute myocardial infarction during the 2nd and 3rd week of initial acute episode had a higher proportion of T lymphocytes and a higher proportion of patients developed anticardiac antibody. Similar was the case with patients with angina. The extent of infarction and accompanying complications did not change the immune parameters studied. The relationship of anticardiac antibodies and T lymphocytes in context of ischemic heart diseases is discussed.

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