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Background: The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians. Methods: Mitochondrial substrate utilization was measured using high‐resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and nondiabetic subjects undergoing coronary artery bypass graft surgery. Western blotting and densitometric analysis were also done to compare the levels of proteins involved in fatty acid metabolism and regulation. Results: The mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased in diabetic subjects compared to nondiabetic subjects along with an unvaried mitochondrial DNA copy number and uniform levels of electron transport chain complex proteins and proteins involved in fatty acid metabolism and regulation. Decreased glutamate but unchanged pyruvate‐mediated state 3 respiration were also observed in diabetic subjects. Conclusion: The current study reports deranged cardiac mitochondrial fatty acid‐mediated complex I respiration in type 2 diabetic Asian Indians with comparable levels of regulators of fatty acid oxidation to that of nondiabetic myocardium. Altered glutamate‐mediated mitochondrial respiration also points toward possible alterations in mitochondrial complex I activity. When compared with previous reports on other ethnic populations, the current study suggests that Asian Indian population too have altered cardiac mitochondrial substrate utilization. [ABSTRACT FROM AUTHOR]

Aims The aim of the study was to investigate the association of serum adiponectin levels with the Pro12Ala polymorphism of the peroxisome proliferator activated receptor-γ ( PPARG) gene in Asian Indians. Methods We selected 400 diabetic subjects, 200 with the Pro12Pro genotype (100 male and 100 female) and 200 with the Pro12Ala genotype (100 male and 100 female) and 400 age- and sex-matched normal glucose tolerance subjects with similar genotype profiles from the Chennai Urban Rural Epidemiology Study. Fasting serum adiponection levels were measured using radioimmunoassay. The Pro12Ala polymorphism was genotyped by PCR–restriction fragment length polymorphism using BstUI. Results All clinical and biochemical parameters were similar in the subjects with the Pro12Pro and Pro12Ala genotypes. There was no significant difference in serum adiponectin values between subjects with the Pro12Pro and Pro12Ala genotypes (males 5.4 vs. 5.8 µg/ml, P = 0.546; females 6.9 vs. 7.2 µg/ml, P = 0.748). Adiponectin values did not differ among these two genotypes even when categorized based on their diabetes status (normal glucose tolerance Pro12Pro 7.9 vs. Pro12Ala 7.7 µg/ml, P = 0.994; diabetes Pro12Pro 4.7 vs. Pro12Ala 5.4 µg/ml, P = 0.622). Conclusion The Pro12Ala polymorphism of the PPARG gene is not associated with serum adiponectin levels in Asian Indians. [ABSTRACT FROM AUTHOR]

Aims The aim of the present study was to assess carotid intimal media thickness (IMT) in different grades of glucose intolerance and the metabolic syndrome (MS) in Asian Indians, a high-risk group for diabetes and coronary artery disease. Methods Subjects with normal glucose tolerance (NGT) ( n = 1600), impaired glucose tolerance (IGT) ( n = 330), newly diagnosed diabetes (NDD) ( n = 330) and known diabetes (KD) ( n = 1170) were recruited from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing study on a representative population of Chennai (formerly Madras), in southern India. Assessment of carotid IMT was performed using high-resolution B-mode ultrasonography. MS was defined using modified adult treatment parel (ATP) III guidelines. Subjects with self-reported diabetes, hypertension and dyslipidaemia were excluded from the analysis on MS. Results Subjects with glucose intolerance had significantly higher mean carotid IMT values compared with subjects with normal glucose tolerance (NGT 0.69 ± 0.12 mm, IGT 0.75 ± 0.16 mm, NDD 0.79 ± 0.19 mm and KD 0.87 ± 0.24 mm, P < 0.001). Regression analysis showed that there was a linear increase in mean IMT values with increasing severity of glucose intolerance, even after adjusting for age and gender. Mean IMT values were higher in those with MS and increased with increase in number of metabolic abnormalities (subjects without any metabolic abnormality 0.66 ± 0.12 mm, one abnormality 0.67 ± 0.13 mm, two 0.70 ± 0.12 mm, three 0.72 ± 0.12 mm, four 0.77 ± 0.15 mm, five 0.76 ± 0.13 mm). Regression models showed MS to be associated with IMT, even after adjusting for age, gender and presence of diabetes ( P = 0.021). Conclusio In Asian Indians, carotid IMT increases progressively with increasing severity of glucose intolerance and is also associated with the metabolic syndrome, independent of age, gender and presence of diabetes. [ABSTRACT FROM AUTHOR]

Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-γ co-activator-1 alpha (PGC-1α) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Haplotype frequencies were estimated using an expectation–maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) ( P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) ( P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264–2.241, P = 0.0004). Age adjusted glycated haemoglobin ( P = 0.003), serum cholesterol ( P = 0.001) and low-density lipoprotein (LDL) cholesterol ( P = 0.001) levels and systolic blood pressure ( P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G → A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [ABSTRACT FROM AUTHOR]

Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. Using Southern-blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes-related complications ( n = 40) and age- and sex-matched control non-diabetic subjects ( n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. Mean (± SE) TRF lengths of the Type 2 diabetic patients (6.01 ± 0.2 kb) were significantly shorter than those of the control subjects (9.11 ± 0.6 kb) ( P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects ( r = −0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA-IR) ( r = −0.4; P = 0.01) and age ( r = −0.3; P = 0.058) and positively correlated with HDL levels ( r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly ( P < 0.0001) associated with shortening of TRF lengths. Telomere shortening occurs in Asian Indian Type 2 diabetic patients. Diabet. Med. (2005) [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the association of high sensitivity C-reactive protein (hs-CRP) with body fat, diabetes and coronary artery disease (CAD) in an urban south Indian population. The study was conducted on 150 subjects selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing population-based study on a representative population of Chennai (formerly Madras). Group 1 comprised of non-diabetic subjects without CAD ( n = 50). Type 2 diabetic subjects without CAD formed Group 2 ( n = 50); Group 3 comprised of Type 2 diabetic subjects with CAD ( n = 50). CAD was diagnosed based on electrocardiographic (ECG) changes suggestive of ST segment depression and/or Q wave changes using appropriate Minnesota codes. All study subjects were non-smokers, and had no infectious or inflammatory diseases. The plasma levels of hs-CRP were measured using a highly sensitive nephelometric assay. Body fat was calculated using Siri's formula using skin fold measurements. Diabetic subjects with (2.89 mg/l) and without (2.25 mg/l) CAD had significantly higher hs-CRP levels compared with non-diabetic subjects without CAD (0.99 mg/l, P < 0.001). hs-CRP values increased with increases in tertiles of body fat ( anova P < 0.001) and HbA1c ( anova P < 0.001). Multiple logistic regression analysis revealed hs-CRP to be strongly associated with CAD (OR: 1.649, P = 0.040) and diabetes (OR: 2.264, P = 0.008) even after adjusting for age and gender. Regression analysis also revealed body fat to be strongly associated with diabetes and CAD even after adjusting for age and gender ( P < 0.001). hs-CRP influenced this association for diabetes but not for CAD. hs-CRP showed a strong association with CAD and diabetes, even after adjusting for age and gender. The association of body fat with diabetes seems to be mediated through hs-CRP. However, hs-CRP does not appear to mediate the relationship between body fat and CAD. Diabet. Med. 22, 863 –870 (2005) [ABSTRACT FROM AUTHOR]