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OBJECTIVE--Type 2 diabetes has become a global epidemic, and Asian Indians have a higher susceptibility to diabetes than Europeans. We investigated whether Indians had any metabolic differences compared with Northern European Americans that may render them more susceptible to diabetes. RESEARCH DESIGN AND METHODS--We studied 13 diabetic Indians, 13 nondiabetic Indians, and 13 nondiabetic Northern European Americans who were matched for age, BMI, and sex. The primary comparisons were insulin sensitivity by hyper-insulinemic-euglycemic clamp and skeletal muscle mitochondrial capacity for Oxidative phosphorylation (OXPHOS) by measuring mitochondrial DNA copy number (mtDNA), OXPHOS gene transcripts, citrate synthase activity, and maximal mitochondrial ATP production rate (MAPR). Other factors that may cause insulin resistance were also measured. RESULTS--The glucose infusion rates required to maintain identical glucose levels during the similar insulin infusion rates were substantially lower in diabetic Indians than in the nondiabetic participants (P < 0.001), and they were lower in nondiabetic Indians than in nondiabetic Northern European Americans (P < 0.002). mtDNA (P < 0.02), OXPHOS gene transcripts (P < 0.01), citrate synthase, and MAPR (P < 0.03) were higher in Indians irrespective of their diabetic status. Intramuscular triglyceride, C-reactive protein, interleukin-6, and tumor necrosis factor-α concentrations were higher, whereas adiponectin concentrations were lower in diabetic Indians. CONCLUSIONS--Despite being more insulin resistant, diabetic Indians had similar muscle OXPHOS capacity as nondiabetic Indians, demonstrating that diabetes per se does not cause mitochondrial dysfunction. Indians irrespective of their diabetic status had higher OXPHOS capacity than Northern European Americans, although Indians were substantially more insulin resistant, indicating a dissociation between mitochondrial dysfunction and insulin resistance. Diabetes 57:1166-1175, 2008 [ABSTRACT FROM AUTHOR]

Presents information on several regarding primary prevention of type 2 diabetes to be discussed at the 65th Scientific Sessions of the American Diabetes Association at the San Diego Convention Center in California from June 10 to 14, 2005. Contribution of psychological risk factors to glucose metabolism in children; Effectiveness of lifestyle modification in preventing diabetes in non-obese Asian Indian prediabetic subjects; Prediction rule for incident type 2 diabetes in Framingham Offspring.

Asian Indians are highly susceptible to Type 2 Diabetes (T2D) and constitute the largest diabetic population in the world. The underlying etiology for this increased susceptibility for T2D among Asian Indians remains to be defined. To determine whether Asian Indians are more insulin resistant and whether their insulin resistance is associated with any differences in muscle gene transcript levels, we studied 13 non-diabetic (fasting glucose < 100 mg/dl) Asian Indians (Age=47.2±2.4 y, BMI=23.8±0.5 kg/m²) and 13 gender-matched Americans of North European origin (European Americans; Age=46.6±2.2 y, BMI=24.5±0.8 kg/m2). Insulin sensitivity was measured by hyperinsulinemic (1.5 mU/kg FFM/min) euglycemic clamp. To maintain identical plasma glucose levels, Asian Indians required a substantially lower glucose infusion rate than European American controls (42.3 ± 4.0 vs. 68.3 ± 4.2 µmol/Kg FFM/min,p<0.001). Percutaneous needle biopsy samples were collected for gene array analysis. Total RNA was extracted from snap frozen muscle biopsy samples, amplified, labeled with fluorescent probe, fragmented and hybridized to the U133 Pins 2.0 Affymetrix genechip and GCRMA software was used to analyze microarray data. Out of about 47,000 transcripts surveyed, 58 genes transcript levels were altered (52 increased and 6 decreased) in Asian Indians compared to European Americans. Examples are as follows: Lipid metabolism: Fatty acid binding protein 7 (↑3.7); Glucose metabolism: GAPDH (↑1.03), Lactate dehydrogenase A (↑1.3); Chaperone: heat shock proteins 70 (↓0.65); and Energy metabolism: NADH1 (↑1.07), ATP synthase (↑1.1), Cytochrome C oxidase Va (↑1.20), Cytochrome C oxidase VLLc (↑1.1). In conclusion, nondiabetic Asian Indians are significantly more insulin resistant and have altered skeletal muscle gene transcript levels involving multiple metabolic pathways including mitochondrial bioenergetics. The results indicate potential mechanisms for higher susceptibility of Asian Indians to become diabetic. [ABSTRACT FROM AUTHOR]

Provides information on several studies about insulin action to be presented at the 65th Scientific Sessions of the American Diabetes Association at the San Diego Convention Center in California from June 10 to 14, 2005. Correlation of low birth weight with adult insulin resistance in Asian Indian children; Effect of high-fat feed to induced insulin resistance on male and female rats; Background on the mechanism of pancreatic islet cell insulin resistance in high-fat-diet obese rats.

Corrections to the articles "Intracellular Angiotensin II Production in Diabetic Rats is Correlated With Cardiomyocyte Apoptosis, Oxidative Stress and Cardiac Fibrosis," by V. P. Singh, B. Le and K. M. Baker and "Asian Indians Have Enhanced Skeletal Muscle Mitochondrial Capacity to Produce ATP in Association With Severe Insulin Resistance," by K. S. Nair, Y. W. Asmann and B. A. Irving is presented.

Asian Indians have high prevalence of diabetes and premature coronary artery disease (CAD). The aim of this study was to determine the association of CAD in Asian Indian type 2 diabetic subjects with normo, micro and macroalbuminuria. Type 2 diabetic subjects [n= 1736], inclusive of self reported diabetic subjects [1382/1529, response rate 90.4%] and randomly selected newly diagnosed diabetic subjects [n=354] were recruited from the Chennai Urban Rural Epidemiology Study [CURES], a population based study in Chennai in Southern India. Microalbuminuria, estimated by immunoturbidimetric assay, was diagnosed if albumin excretion was between 30 - 299 µg/mg of creatinine and macroalbuminuria, if ≥300 µg/mg of creatinine. Coronary artery disease [CAD] was diagnosed based on a past history of documented myocardial infarction and/or electrocardiographic [ECG] evidence of Q wave and/or ST segment changes. Analysis was restricted to 1596 individuals on whom data on albumin excretion and CAD were available [1596/1736, response rate 91.9%]. The overall prevalence of micoalbuminuria was 26.8% [427 / 1596], macroalbuminuria, 5.5% [87/1596] and CAD, 13.0% [208/1596]. Subjects with macroalbuminuria had the highest prevalence of CAD [34.5%], followed by microalbuminuric subjects [14.8%] and normoalbuminuria [10.6%, p for trend: <0.0001]. Univariate regression showed both microalbuminuria [Odds ratio [OR]: 1.46, 95% confidence interval [CI]: 1.05 - 2.02, p<0.001] and macroalbuminuria [OR: 4.46, 95% CI: 2.7 - 7.1, p<0.001] to be significantly associated with CAD. After adjusting for age, glycated hemoglobin, smoking, triglycerides and LDL cholesterol, the association remained significant only for macroalbuminuria [OR:3.73, 95% CI: 2.2 - 6.4, p< 0.001]. In conclusion, there is an association between albumin excretion and CAD in Asian Indian type 2 diabetic subjects and this is stronger in those with macroalbuminuria. [ABSTRACT FROM AUTHOR]

Asian Indians (AI) are insulin resistant and have a higher risk of diabetes compared to Caucasians (C). However, potential abnormalities in insulin secretion and their relationship to the severity of insulin resistance in AI have not been carefully studied. To address this question we examined l) first (0-10 min) and second (l0-120 min) phase insulin secretion during a 2-hr hyperglycemic clamp at +90 mg/dl, 2) insulin secretion in response to a non-glucose secretagogue (arginine, 5 gm IV) at euglycemia and at the end of the hyperglycemic clamp, and 3) insulin sensitivity (M) during a 1 mU/kg⋅min hyperinsulinemic euglycemic clamp. Four healthy AI and 6 C of similar age (29±2 vs 38±6 yrs) and BMI (25.3±2.3 vs 24.7±1.3 kg/msup2;) were studied. AI and C had similar FPG (94±2 vs 90±2. mg/dl), but AI had higher fasting insulin levels (9.1±2.2 vs 3.4±0.6 µU/ml, p<0.05) and were very insulin resistant during the euglycemic clamp (M = 4.0±0.5 vs 9.7±0.6 mg/kg/min, p<0.001). During the hyperglycemic clamp, first phase (321±106 vs 102±22 µU/ml⋅0 min, p<0.05) and second phase (4920±959 vs 1340±174 pU/ml. 110 min, p<0.01) insulin secretion were significantly increased in AI vs C. The insulin responses to arginine at euglycemia (314±43 vs 145±9 µU/ml. l0 min, p<0.01) and hyperglycemia (2399±415 vs 1203±235 #U/ml. 10 min, p<0.05) also were significantly higher in AI. All measures of insulin secretion were inversely correlated with M (r = -0.69 to -0.82, p<0.05 to 0.005). The glucose disposition index (M x first phase insulin secretion) was increased moderately (by 29%), but not significantly, in AI vs C. Conclusion: Non-diabetic AI are characterized by l) marked insulin resistance, 2) enhanced first- and second-phase insulin responses to hyperglycemia, 3) increased insulin response to arginine at euglycemia and hyperglycemia, and 4) a moderate increase in the glucose disposition index. These data suggest that beta cell function remains intact in non-diabetic AI despite the presence of significant insulin resistance. [ABSTRACT FROM AUTHOR]

Transcription factor 7-like2 (TCF7L2) gene has been associated with type 2 diabetes in different ethnic groups. As TCF7L2 gene is involved in regulation of insulin secretion, we hypothesized that TCF7L2 gene variants may be associated with MODY. We examined the role of rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene in MODY, early-onset type 2 diabetes (EO-T2DM), late-onset type 2 diabetes (LO-T2DM), type 1 diabetes (T1DM) and normal glucose tolerant (NGT) Asian Indians. Subjects were selected from the Chennai Urban Rural Epidemiology Study, a population based study in south India (EO-T2DM, LO-T2DM and NGT) and a tertiary diabetes centre (MODY and TIDM). 136 MODY subjects with autosomal dominant inheritance (age at onset(AAO) <25years), 397 EO-T2DM (AAO:25-40years), 738 LO-T2DM (AAO:>40years), 174 T1DM and 996 NGT subjects were studied. Genotyping of the two polymorphisms was carried out using PCR-RFLP and confirmed by direct sequencing. Frequency of the 'T' allele of rs12255372 and rs7903146 was significantly higher in MODY (30%,p=0.00001 and 45%,p<0.00001 respectively) and EO-T2DM (25%,p=0.0004; 37%,p<0.00001) compared to NGT (19%;28%). Odds ratios (OR) for GT and TT genotypes of the rs12255372 were higher in the MODY (OR:l.53,p=0.032 and 3.77,p=0.00002 respectively) and EO-T2DM (OR:1.48,p=0.002 and 1.75,p=0.034) compared to GG. The OR for CT and TT genotypes of rs7903146 were higher in MODY (OR:2.73,p<0.00001 and 4.10,p<0.00001 respectively) and EO-T2DM (OR: 1.71,p=0.00002 and 1.94,p=0.001) compared to CC. The CT genotype of rs7903146 showed association with LO-T2DM (OR: 1.26,p=0.022 compared to CC) but the TT genotype did not show any association. There was no association of rs12255372 with LO-T2DM and both polymorphisms were not associated with T1DM. Among Asian Indians, rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene are more strongly associated with MODY and EOT2DM and rs7903146 less strongly with LO-T2DM, while both polymorphisms are not associated with T1DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes [T2D] and the metabolic syndrome are far more common and presents at a younger age in people of South Asian origin. The aim of the study was to determine the heritability of common traits associated with diabetes in South Indian families and compare them to those obtained in British white Caucasians. 1094 subjects from 296 families were studied from a community-based cross-sectional study in Chennai, India. Clinical details, anthropometric measures and fasting bloods were taken from all available family members. Heritabilities [h²] were calculated for individual waits using SOLAR v4.0.3. corrected for age, sex and BMI. h² [SE] for waist was 0.50 [0.06], WHR 0.33 [0.06], body fat 0.39 [0.07], BMR 0.57 [0.06], systolic (s)BP 0.30 [0.06], triglycerides (tg) 0.53 [0.06] and fasting glucose (FBG) 0.37 [0.06]. All p values were <0.0001. The h² values using a similar model implemented in SOLAR were generally higher than for a healthy white population in the UK (Freeman et al 2002: WHR 0.15 [0.11], sBP 0.14 [0.07], Tg 0.20 [0.08] and FBG 0.20 [0.08]) whereas they were similar apart from FBG to non diabetic relatives of patients with T2D ascertained for the Diabetes UK Warren2 family collection (Mills et al 2004: WHR 0.22 [0.08], sBP 0.30 [0.1], Tg 0.51 [0.1] and FBG 0.81 [0.09]). These studies suggest that risk variables for diabetes which are strongly influenced by lifestyle have an increased genetic component in south Asians compared healthy white Europeans. [ABSTRACT FROM AUTHOR]

We and others in a variety of ethnic groups have previously described associations of various SNPs of the uncoupling protein genes UCP2 and UCP3 (located within 17 kb of each other on chromosome 11q13) with both central fat disposition and BMI. The aim of this study was to do a replication study in South Indian subjects using a family based approach and selecting SNP's by' a priori hypothesis' defined by a previous association with obesity/waits in other studies and/or functional data. Five SNPs were studied; 1 by Ampliflour (UCP2-866 rs659366), 1 by SNAPSHOT (UCP3Y210Y rs2075577), 2 by TaqMan (UCP3-55 rs1800849, UCP2 A55V rs660339) and one by PCR-RFLP (UCP2 exon 8 INDEL) in 882 South Indian participants from 236 families ascertained from community based study of healthy families living in Chennai, India. Statistical analysis was performed using SOLAR and anthropometric variables were corrected for age and sex. The QTLD analysis showed the BMI was associated to the UCP3 rs1800849 (AA 23.9±0.29, AB 23.5±0.32, BB 23.0±0.5, p=0.027) and UCP3 rs2075577 (AA 24.6±0.37, AB 24.0±0.30, BB 23.4±0.39, p=0.022). Waist circumference to the UCP2 rs660339 (AA 84.3±0A8, AB 85.1±0.41, BB 85.9±0.65, p=0.028). Body fat percentage to UCP2 rs660339 (AA 22.9±0.31, AB 23.2±0.27, BB 23.5±0.42, p=0.048) and UCP2 rs659366 (AA 22.7±0.31, AB 22.9±0.26, BB 23.27±0.41, p=0.076). This detailed analysis confirms associations between anthropometric traits and the UCP2/UCP3 locus but that separate SNPs are associated with either BMI or fat distribution. [ABSTRACT FROM AUTHOR]

Asian Indians particularly those with type 2 diabetes have accelerated atherosclerosis at younger age. The aim of the present study was to assess the association of hsCRP, TNF-α with carotid IMT in individuals with different grades of glucose intolerance among Asian Indians. Three groups were randomly recruited from the Chennai Urban Rural Epidemiology Study [CURES], a population based study in Chennai in South India, Group 1: normal glucose tolerance (NGT) (n=150); Group 2: impaired glucose tolerance (IGT) (n=150) and Group 3: type 2 diabetes (DM) (n = 150). hs-CRP [Nephelometry, DadeBehring], TNF-α [enzyme linked immunosorbent assay] and carotid IMT [high resolution B-mode ultrasonography] were assessed. Subjects with diabetes had higher IMT values [0.85 ± 0.30 mm] compared to IGT [0.79 ± 0.16 mm; p<0.05] and NGT subjects [0.71 ± 0.12 mm; p<0.001]. HsCRP levels were higher in those with DM and IGT [DM: 2.8 mg/L, IGT: 2.1 mg/L] compared to NGT [1.2 mg/L, p for trend 0.003]. TNF-α levels were also higher in IGT and DM groups compared to NGT subjects [NGT: 3.5 ± 2.2, IGT: 4.6 ± 2.1, DM: 6.1 ± 2.4 pg / ml, p for trend <0.001]. HsCRP [r = 0.104, p=0.02] and TNF-α [r = 0.265, p<0.001] showed a positive correlation with IMT in the total study population and in subjects with NGT [hsCRP: r = 0.253, p = 0.002, TNF-α: r = 0.265, p = 0.001]. In multiple linear regression analysis, hsCRP [β =0.006, p<0.034] and TNF-α [β =0.015, p<0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. We conclude that among Asian Indians (1) levels of hsCRP and TNF-α increase with increasing degrees of glucose intolerance (2) among NGT subjects, both hsCRP and TNF-α are associated with increase in carotid IMT and this is independent of age and gender. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence of, and risk factors for, diabetic neuropathy among Asian Indian type 2 diabetic subjects. Subjects were recruited from CURES, a population-based study conducted on a representative population of Chennai city in south India. Of the 1529 known diabetic [KD] subjects, 1382 participated in the study [response rate: 90.4%]; in addition, 354 newly detected diabetic [NDD] subjects were also randomly selected. Neuropathy was diagnosed if the vibratory perception threshold of the right great toe measured by biothesiometry (Biomedical Instrument Co., Newbury, Ohio, USA) was ≥25. Of the total of 1736 individuals, biothesiometry studies were performed in 1632 subjects (94.0% response rate). The overall prevalence of neuropathy was 11% [age-standardized-5.8%], while it was 12.2% [age-standardized-6.5%] and 10% [age-standardized-5.2%] in male and female subjects respectively. The prevalence of neuropathy was significantly higher among KD subjects compared to NDD subjects [12.1% vs 6.8%, p=0.006]. It was also higher among subjects with diabetic retinopathy [26.9% vs 16.9%, p=0.001] and proteinuria [9.6% vs 5.3%, p=0.019] compared to those without. There was a linear increase in the prevalence of neuropathy with increasing age among both genders [p<0.0001]. The odds ratio (OR) for neuropathy in subjects having duration of diabetes >15 years was 5.51 [95% confidence interval (CI): 3.04-10.01, p<0.0001]. Multivariate logistic regression analysis showed age [OR: 1.16, 95% CI: 1.13-1.19, p<0.001], height [OR: 1.04, 95% CI: 1.01 -1.07, p=0.016] and fasting plasma glucose [OR: 1.00, 95% CI: 1.00 -1.01, p=0.001] to be significantly associated with neuropathy. Duration of diabetes showed an association with neuropathy but significance was lost when age was introduced into the model. This is the first population-based data on prevalence of diabetic neuropathy from India, which has the largest number of diabetic patients in the world. [ABSTRACT FROM AUTHOR]