Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes.

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 -597G*/-174C* 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.

Preliminary studies on CD36 gene in type 2 diabetic patients from north India.

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.

Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: A study in the north Indian population.

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.

Prevalence of hypertension in psychiatric disorders.

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.

Oxidative stress and metabolic control in non-insulin dependent diabetes mellitus.

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.

Lipid-lowering efficacy of psyllium hydrophilic mucilloid in non insulin dependent diabetes mellitus with hyperlipidaemia.

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.

Conjugated dienes in lipids of apolipoprotein B containing lipoproteins of normal and type 2 (non-insulin-dependent) diabetic patients.

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.