Comparison of relative waist circumference between Asian Indian and US adults.

BACKGROUND: Relative to Europeans, Asian Indians have higher rates of type 2 diabetes and cardiovascular disease. Whether differences in body composition may underlie these population differences remains unclear. METHODS: We compared directly measured anthropometric data from the Chennai Urban Rural Epidemiology Study (CURES) survey of southern Indians (I) with those from three US ethnic groups (C: Caucasians, A: African Americans, and M: Mexican Americans) from NHANES III (Third National Health and Nutrition Examination Survey). A total of 15,733 subjects from CURES and 5,975 from NHANES III met inclusion criteria (age 20-39, no known diabetes). RESULTS: Asian Indian men and women had substantially lower body mass index, waist circumference, hip circumference, waist-to-hip ratio, and body surface area relative to US groups (P values <0.0001). In contrast, the mean (±se) waist-weight ratio was significantly higher (P < 0.001) in I (men 1.35 ± 0.002 and women 1.45 ± 0.002) than in all the US groups (1.09, 1.21, and 1.14 in A, M, and C men; 1.23, 1.33, and 1.26 in A, M, and C women (se ranged from 0.005 to 0.006)). CONCLUSIONS: Compared to the US, the waist-weight ratio is significantly higher in men and women from Chennai, India. These results support the hypothesis that Southeast Asian Indians are particularly predisposed toward central adiposity.

Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India.

India is a major contributor to the global public health burden of diabetes. We have undertaken a family study of large multiplex families from Chennai, South India, and report on the familial aggregation of quantitative traits associated with type 2 diabetes mellitus in these pedigrees. Five hundred twenty-four individuals older than 19 years from 26 large multiplex pedigrees were ascertained. Detailed questionnaires and phenotype data were obtained on all participating individuals including fasting blood glucose, fasting insulin, lipid profiles, height, weight, and other anthropometric and clinical measures. Heritability estimates were calculated for all quantitative traits at the univariate level, and bivariate analyses were done to determine the correlation in genetic and environmental control across these quantitative traits. Heritability estimates ranged from 0.21 to 0.72. The heritability estimates for traits most directly related to type 2 diabetes mellitus were 0.24 +/- 0.08 for fasting blood glucose and 0.41 +/- 0.09 for fasting insulin. In addition, there was evidence for common genetic control for many pairs of these traits. These bivariate analyses suggested common genes for fasting insulin and central obesity measures (body mass index, waist, and hip), with complete genetic correlation between fasting insulin and waist. Quantitative traits associated with type 2 diabetes mellitus have heritabilities suggestive of some familial or genetic effect. The evidence for pleiotropic control of insulin and central obesity-related traits supports the presence of an insulin resistance syndrome in South Asians with a tendency for central obesity.

Association of leukocyte count with varying degrees of glucose intolerance in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-26).

OBJECTIVE: This study assessed the association of leukocyte count with different grades of glucose intolerance in Asian Indian subjects. METHODS: Three groups of subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study, representative of Chennai (formerly Madras), a city in southern India. Group 1 represented normal glucose tolerance (NGT) (n = 840), group 2 included impaired glucose tolerance (IGT) (n = 180), and group 3 included type 2 diabetes (n = 1170). Anthropometric measurements including weight, height, and waist measurements were obtained using standardized techniques. Leukocyte count was measured by an automated flow cytometry instrument (Sysmex SF-3000, Japan). Fasting insulin was measured by enzyme-linked immunosorbent assay and insulin resistance was calculated using the homeostasis model assessment (HOMA-IR). RESULTS: Subjects with diabetes (8.0 +/- 1.5 x 10(3)/microL) and IGT (7.9 +/- 1.3 x 10(3)/microL) had a significantly higher mean leukocyte count compared to the NGT group (7.4 +/- 1.5 x 10(3)/microL) (P < 0.001). Leukocyte count was significantly increased in NGT subjects with insulin resistance (IR) as measured by HOMA-IR (7.5 +/- 1.5 x 10(3)/microL; P < 0.001) compared to NGT subjects without IR (7.0 +/- 1.4 x 10(3)/microL). Regression analysis showed that there was a linear increase in mean leukocyte count with increasing severity of glucose intolerance, even after adjusting for age, waist circumference, and HOMA-IR. CONCLUSIONS: Among Asian Indians who are known to have high risk of premature coronary artery disease and diabetes, a significant association exists between leukocyte count and glucose intolerance.

A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians.

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (-11377C-->G and -11282T-->C), one intronic SNP (+10211T-->G) and one exonic SNP (+45T-->G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T-->G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T-->G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07-1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3-1.8; P < 10(-7)) and that for GG genotype, 2.10 (95% CI 1.3-3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T-->G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.

Ethnic difference in sex gap in high-density lipoprotein cholesterol between Asian Indians and Whites.

OBJECTIVE: To study whether low plasma high-density lipoprotein cholesterol (HDL-C) reported in Asian Indians is common in both men and women when compared with whites and whether it is related to increased body mass index (BMI) and plasma triglyceride concentration. DESIGN: We evaluated the lipid profile and prevalence of low HDL-C (<40 mg/dL in men and <50 mg/dL in women) in the following cohorts of normoglycemic 1404 men and 1817 women: Asian Indians living in rural India; urban Chennai, India; and Dallas, TX; and whites living in Dallas, TX. RESULTS: After adjustment for age, BMI, and smoking, HDL-C was not significantly different in Asian Indian men compared with whites. However, Asian Indian women had lower HDL-C compared with white women, and rural Asian Indian women had the lowest HDL-C even in the absence of high triglycerides. Lean Asian Indian women with BMI of less than 23 kg/m had higher frequency of low HDL-C compared with lean white women with BMI of less than 25 kg/m (72%, 56%, 48%, and 25% in rural, urban, and Dallas Asian Indian and white women, respectively) and lean men (52%, 42%, 28%, and 35% in rural, urban, and Dallas Asian Indian and white men, respectively). Sex differences in HDL-C was estimated as 6.6+/-0.5 mg/dL for Asian Indians and 15.3+/-1.1 mg/dL for whites (P<0.0001 for sex difference in the 2 ethnic groups). CONCLUSIONS: Increased prevalence of low HDL-C independently of obesity or hypertriglyceridemia is observed in women but not in men of Asian Indian origin. The sex gap in HDL-C is significantly smaller in Asian Indians compared with whites independent of geographical location.

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31).

OBJECTIVE: To assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-alpha [TNF-alpha] with IMT in Asian Indians with different grades of glucose intolerance. DESIGN AND METHODS: Subjects with normal glucose tolerance [NGT](n=150), impaired glucose tolerance [IGT] (n=150) and type 2 diabetes (DM) (n=150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-alpha by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography. RESULTS: hsCRP and TNF-alpha levels were higher in those with DM [p<0.001] and IGT [p<0.001] compared to NGT. In linear regression analysis, both hsCRP [p=0.003] and TNF-alpha [p=0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-alpha was associated with IMT [p<0.001], while no association was observed either with hsCRP or TNF-alpha in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-alpha and hsCRP [0.83+/-0.1 mm; p<0.001] followed by those with high TNF-alpha+low hsCRP [0.74+/-0.09 mm; p<0.001], high hsCRPlow TNF-alpha [0.67+/-0.09 mm; p<0.001], and lowest in those with both low TNF-alpha and hsCRP [I tertile] [0.63+/-0.05 mm. CONCLUSION: We conclude that in Asian Indians 1. Levels of hsCRP and TNF-alpha increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-alpha are associated with IMT in NGT subjects while TNF-alpha alone is associated with IMT in IGT subjects 3. hsCRP and TNF-alpha have a cumulative effect on mean IMT values in NGT subjects.

Urban rural differences in prevalence of self-reported diabetes in India--the WHO-ICMR Indian NCD risk factor surveillance.

Recent reports show strikingly high prevalence of diabetes among urban Asian Indians; however, there are very few studies comparing urban, peri-urban and rural prevalence rates of diabetes and their risk factors at the national level. This study is a part of the national non-communicable diseases (NCD) risk factor surveillance conducted in different geographical locations (North, South, East, West/Central) in India between April 2003 and March 2005. A total of 44,523 individuals (age: 15-64 years) inclusive of 15,239 from urban, 15,760 from peri-urban/slum and 13,524 from rural areas were recruited. Major risk factors were studied using modified WHO STEPS approach. Diabetes was diagnosed based on self-reported diabetes diagnosed by a physician. The lowest prevalence of self-reported diabetes was recorded in rural (3.1%) followed by peri-urban/slum (3.2%) and the highest in urban areas (7.3%, odds ratio (OR) for urban areas: 2.48, 95% confidence interval (CI): 2.21-2.79, p<0.001). Urban residents with abdominal obesity and sedentary activity had the highest prevalence of self-reported diabetes (11.3%) while rural residents without abdominal obesity performing vigorous activity had the lowest prevalence (0.7%). In conclusion, this nation-wide NCD risk factor surveillance study shows that the prevalence of self-reported diabetes is higher in urban, intermediate in peri-urban and lowest in rural areas. Urban residence, abdominal obesity and physical inactivity are the risk factors associated with diabetes in this study.

Anthropometric cut points for identification of cardiometabolic risk factors in an urban Asian Indian population.

The aim of this study was to determine the anthropometric cut points for risk of cardiometabolic risk factors in an urban Asian Indian population. The Chennai Urban Rural Epidemiology Study representatively sampled 26001 individuals aged 20 years or older and detailed measures were obtained in every 10th subject: 90.4% (2350/2600). An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements such as body mass index (BMI) and waist circumference (WC) were obtained and serum lipid estimations were done in all subjects. Sensitivity, specificity, and distance on receiver operating characteristic curve were used to determine the optimal cut points for BMI and WC with cardiometabolic risk factors. Maximum sensitivity and specificity of BMI for all cardiometabolic risk factors such as diabetes mellitus, prediabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol ranged from 22.7 to 23.2 kg/m(2) for men and 22.7 to 23.8 kg/m(2) for women, and that of WC ranged from 86 to 88.2 cm for men and 81 to 83.8 cm for women. The optimal BMI cut point for identifying any 2 cardiometabolic risk factors was 23 kg/m(2) in both sexes, whereas that of WC was 87 cm for men and 82 cm for women. The study validates the World Health Organization Asia Pacific guidelines of BMI of 23 kg/m(2) for the designation of overweight; WC of 87 cm for men and 82 cm for women appear to be appropriate cut points to identify cardiometabolic risk factors including prediabetes in urban Asian Indians.

Prevalence and risk factors of diabetic nephropathy in an urban South Indian population: the Chennai Urban Rural Epidemiology Study (CURES 45).

OBJECTIVE: The aim of this study was to determine the prevalence of diabetic nephropathy among urban Asian-Indian type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Type 2 diabetic subjects (n = 1,716), inclusive of known diabetic subjects (KD subjects) (1,363 of 1,529; response rate 89.1%) and randomly selected newly diagnosed diabetic subjects (NDD subjects) (n = 353) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Microalbuminuria was estimated by immunoturbidometric assay and diagnosed if albumin excretion was between 30 and 299 microg/mg of creatinine, and overt nephropathy was diagnosed if albumin excretion was > or = 300 microg/mg of creatinine in the presence of diabetic retinopathy, which was assessed by stereoscopic retinal color photography. RESULTS: The prevalence of overt nephropathy was 2.2% (95% CI 1.51-2.91). Microalbuminuria was present in 26.9% (24.8-28.9). Compared with the NDD subjects, KD subjects had greater prevalence rates of both microalbuminuria with retinopathy and overt nephropathy (8.4 vs. 1.4%, P < 0.001; and 2.6 vs. 0.8%, P = 0.043, respectively). Logistic regression analysis showed that A1C (odds ratio 1.325 [95% CI 1.256-1.399], P < 0.001), smoking (odds ratio 1.464, P = 0.011), duration of diabetes (1.023, P = 0.046), systolic blood pressure (1.020, P < 0.001), and diastolic blood pressure (1.016, P = 0.022) were associated with microalbuminuria. A1C (1.483, P < 0.0001), duration of diabetes (1.073, P = 0.003), and systolic blood pressure (1.031, P = 0.004) were associated with overt nephropathy. CONCLUSIONS: The results of the study suggest that in urban Asian Indians, the prevalence of overt nephropathy and microalbuminuria was 2.2 and 26.9%, respectively. Duration of diabetes, A1C, and systolic blood pressure were the common risk factors for overt nephropathy and microalbuminuria.

Association of A1C with cardiovascular disease and metabolic syndrome in Asian Indians with normal glucose tolerance.

OBJECTIVE: This study examines the association of A1C with cardiovascular disease (CVD) risk factors, coronary artery disease (CAD), and metabolic syndrome in Asian Indians with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS: This cross-sectional study recruited subjects from phase III of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study in a representative population of Chennai (formerly Madras) in South India, conducted between January 2003 and June 2004. Included were 1,644 subjects with NGT, i.e., fasting plasma glucose <100 mg/dl (5.6 mmol/l) and 2-h postload plasma glucose <140 mg/dl (7.8 mmol/l). A1C was measured using the Biorad Variant machine. Metabolic syndrome was defined based on modified Adult Treatment Panel III guidelines. RESULTS: The mean +/- SD A1C value in the study cohort was 5.5 +/- 0.4%. A1C showed a significant association with BMI (beta = 0.017, P < 0.001), systolic (beta = 0.002, P = 0.028) and diastolic (beta = 0.202, P = 0.017) blood pressure, waist circumference (beta = 0.007, P < 0.001), serum cholesterol (beta = 0.002, P < 0.001), triglycerides (beta = 0.001, P < 0.001), LDL cholesterol (beta = 0.002, P < 0.001), fasting insulin (beta = 0.009, P < 0.001), and homeostasis model assessment of insulin resistance (beta = 0.047, P < 0.001) after adjusting for age and sex. Regression analysis showed that A1C had a strong association with metabolic syndrome that persisted after adjusting for age and sex (odds ratio [OR] 2.9 [95% CI 2.08-4.00]; P < 0.001). A1C also had a strong association with CAD (2.6 [1.23-5.63]; P = 0.01), but the significance was lost when adjusted for age and sex. CONCLUSIONS: There is a strong association of A1C with prevalent CVD risk factors in Asian-Indian subjects with NGT.

Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians.

To investigate the role of the novel adipokine visfatin in type 2 diabetes mellitus and obesity and to examine its association with visceral and subcutaneous fat in Asian Indians, who have increased susceptibility to type 2 diabetes mellitus and coronary artery disease, 150 subjects with type 2 diabetes mellitus (75 men, 75 women) and 150 age- and sex-matched subjects with normal glucose tolerance were recruited from the Chennai Urban Rural Epidemiology Study, a population-based study done in Chennai, southern India. Anthropometric and biochemical measurements were done by using standardized techniques. Fasting serum visfatin levels were measured by enzyme-linked immunosorbent assay. Visceral and subcutaneous fat were measured by computerized tomography in a subset of 130 individuals. Serum visfatin levels were significantly higher in diabetic subjects compared with nondiabetic subjects (11.4+/-5.9 vs 9.8+/-4.3 ng/mL, P=.008). However, this association was lost when adjusted for body mass index (odds ratio [OR], 1.048; 95% confidence interval [CI], 0.997-1.101; P=.067) or waist circumference (OR, 1.050; 95% CI, 0.999-1.104; P=.057). Serum visfatin showed a significant association with obesity even after adjusting for age, sex, and type 2 diabetes mellitus (OR, 1.060; 95% CI, 1.005-1.119; P=.033). Visceral fat, but not subcutaneous fat, was significantly associated with serum visfatin levels even after adjusting for age, sex, type 2 diabetes mellitus, and body mass index (P=.002). In Asian Indians, serum visfatin levels are associated with obesity and visceral fat but not with subcutaneous fat. Although visfatin levels are increased in type 2 diabetes mellitus, the association seems to be primarily through obesity.

Oxidized low-density lipoprotein and intimal medial thickness in subjects with glucose intolerance: the Chennai Urban Rural Epidemiology Study-25.

The aim of the present study was to assess the association of oxidized low-density lipoprotein (OX-LDL) with carotid intimal medial thickness (IMT) in different grades of glucose intolerance in Asian Indians. Three groups were recruited from the Chennai Urban Rural Epidemiology Study, a population-based study: group 1, normal glucose tolerance (NGT) (n = 175); group 2, impaired glucose tolerance (IGT) (n = 175); and group 3, type 2 diabetes mellitus (n = 175). Oxidized LDL (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 with those who have IGT (0.79 +/- 0.16 mm, P < .05) and NGT (0.71 +/- 0.12 mm, P < .001). Subjects with diabetes (40.1 +/- 13.1 U/L) and IGT (34.3 +/- 12.8 U/L) had significantly higher mean OX-LDL values compared with the NGT group (26.2 +/- 16.6 U/L, P < .001). Oxidized LDL showed a correlation with IMT (total population: r = 0.294, P < .001; subjects with NGT: r = 0.444, P < .001; and subjects with IGT: r = 0.481, P < .001). In multiple linear regression analysis, OX-LDL showed a strong association with IMT (beta = .005, P < .001), even after adjusting for age, sex (beta = .003, P < .001), and glucose intolerance (beta = .002, P < .001). In conclusion, OX-LDL levels increase with increasing glucose intolerance. Oxidized LDL is associated with carotid IMT and this is independent of age, sex, and glucose intolerance status.

Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy.

OBJECTIVE: Shortening of telomere length has been reported in several conditions including Type 2 diabetes and atherosclerosis. The aims of this study were (1) to assess whether telomere shortening occurs at the stage of pre-diabetes, i.e., impaired glucose tolerance (IGT) and (2) whether telomere shortening was greater in Type 2 diabetic subjects with atherosclerotic plaques. METHODS: Subjects with impaired glucose tolerance (IGT) (n=30), non-diabetic control subjects (n=30), Type 2 diabetic patients without (n=30) and with atherosclerotic plaques (n=30) were selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing epidemiological population-based study. Southern-blot analysis was used to determine mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leukocyte DNA. Levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and high sensitive C-reactive protein (hs-CRP) were measured by standard methodologies. Carotid intima-media thickness (IMT) was assessed by high resolution B-mode ultrasonography. RESULTS: The mean (+/-S.E.) TRF lengths were significantly lower in IGT subjects (6.97+/-0.3 kb; p=0.002) and lower still in Type 2 diabetic subjects without plaques (6.21+/-0.2; p=0.0001) and lowest in Type 2 diabetic subjects with atherosclerotic plaques (5.39+/-0.2; p=0.0001) when compared to control subjects (8.7+/-0.5). In IGT subjects, TRF length was positively correlated to HDL cholesterol and negatively correlated to glycated hemoglobin (HbA1c), TBARS, PCO, HOMA-IR and IMT. In multiple linear regression analysis, presence of diabetes, HDL cholesterol and increased TBARS levels appear as significant determinants of telomere shortening. CONCLUSION: Telomere shortening is seen even at the stage of IGT. Among subjects with Type 2 diabetes, those with atherosclerotic plaques had greater shortening of telomere length compared to those without plaques.

Type 2 diabetes in Asian Indian youth.

The prevalence of youth-onset type 2 diabetes is increasing worldwide in parallel with the obesity epidemic. In India, the age at onset of type 2 diabetes had traditionally been a decade or two earlier compared with the western population. Hence, it is not surprising that the prevalence of youth-onset type 2 diabetes is rapidly escalating in India not only among the more affluent sections of society but also in the middle and lower socioeconomic groups as well. In India, type 2 diabetes in youth overlaps with monogenic forms of diabetes such as maturity-onset diabetes of the young, fibrocalculous pancreatic diabetes, and malnutrition-modulated diabetes, all of which are ketosis-resistant forms of youth-onset diabetes. Screening of high-risk groups may help in the early detection of youth-onset type 2 diabetes and prevention of its complications. Primary prevention would require a multisectoral approach involving the government and non-governmental agencies with a focus on healthier lifestyles among children.

Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES).

The aim of this cross-sectional study was to assess the association of insulin resistance (IR) with inflammatory molecules C-reactive protein (CRP), interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic protein 1 (MCP-1) in urban South Indian subjects. The following groups were selected from the population-based Chennai Urban Rural Epidemiology Study: group 1 composed of 50 healthy subjects with normal glucose tolerance without IR; group 2 consisted of 50 normal glucose-tolerant subjects with IR as defined by homeostasis model assessment of IR (HOMA-IR); group 3 consisted of 50 subjects with impaired glucose tolerance (IGT); and groups 4 and 5 each comprised 50 newly diagnosed and known type 2 diabetic subjects, respectively. The inclusion criteria included nonsmokers; normal resting 12-lead electrocardiogram; and absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases, and not on statins or aspirin. Normal glucose tolerance without IR had the lowest values of CRP, IL-6, and VCAM-1 (CRP, 1.32 mg/L; IL-6, 12.56 pg/mL; VCAM-1, 277 pg/mL) followed by normal glucose tolerance with IR (CRP, 2.25 mg/L; IL-6, 20.97 pg/mL; VCAM-1, 289 pg/mL), impaired glucose tolerance (CRP, 2.37 mg/L; IL-6, 22.11 pg/mL; VCAM-1, 335 pg/mL), newly diagnosed diabetic subjects (CRP, 3.24 mg/L; IL-6, 23.21 pg/mL; VCAM-1, 568 pg/mL), and the highest levels were in the known diabetic subjects (CRP, 4.08 mg/L; IL-6, 29.44 pg/mL; VCAM-1, 577 pg/mL). This trend was statistically significant (P < .001). However, monocyte chemotactic protein 1 did not show such a trend and did not differ significantly between groups. In nondiabetic subjects, Pearson correlation analysis revealed that CRP (r = 0.299; P < .001) and IL-6 (r = 0.180, P = .025) had a significant correlation with HOMA-IR. Monocyte chemotactic protein 1 did not show any correlation with HOMA-IR. Multiple linear regression analysis revealed CRP to be significantly associated with HOMA-IR (beta = .229; P < .001) and this was unaltered by the addition of waist and IL-6 into the model (beta = .158; P = .028). In conclusion, this study shows that in Asian Indians, inflammatory markers (CRP, IL-6, and VCAM-1) increase with increasing degrees of glucose intolerance.

Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.

OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Association of lipoprotein lipase Hind III and Ser 447 Ter polymorphisms with dyslipidemia in Asian Indians.

Studies have shown an association between the lipoprotein lipase gene and dyslipidemia and atherosclerosis in some populations. The aim of this study was to investigate the association between the common lipoprotein lipase HindIII (T-G) and Ser447Ter (C-G) polymorphisms with dyslipidemia in Asian Indians, who are known to have very high rates of premature coronary artery disease. A total of 1,015 subjects, comprising 550 normal glucose-tolerant subjects and 465 patients with type 2 diabetes, were randomly selected from the Chennai Urban Rural Epidemiology Study. The total serum cholesterol, high-density lipoprotein (HDL) cholesterol, and serum triglyceride levels were assayed using enzymatic methods. Low-density lipoprotein cholesterol was calculated using the Friedewald formula. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism method. A significant association was found between the H+ allele of HindIII with low HDL cholesterol and elevated triglyceride levels. The Ser allele of Ser447Ter was also strongly associated with low HDL cholesterol levels. No association was found between the H+ allele and Ser Allele with the total or low-density lipoprotein cholesterol levels. Group-wise haplotype frequencies were generated using the expectation-maximization algorithm to detect differences in overall haplotype frequency profiles between the case-control groups. The haplotype analysis showed that the H+ Ser and H- Ter were the "high-risk" and "low-risk" haplotypes for low HDL cholesterol and elevated triglyceride levels, respectively. In conclusion, the H+ Ser haplotype of the lipoprotein lipase gene was associated with low HDL cholesterol levels and hypertriglyceridemia in Asian Indians.

Soluble P-selectin and CD40L levels in subjects with prediabetes, diabetes mellitus, and metabolic syndrome--the Chennai Urban Rural Epidemiology Study.

The aim of the study was to determine whether the levels of soluble P-selectin (sP-selectin) and soluble CD40L (sCD40L) are elevated in Asian Indian subjects with impaired glucose tolerance (IGT), diabetes, and metabolic syndrome (MS). Study subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing population-based study on a representative population of Chennai city in southern India, and were grouped as follows: group 1, normal glucose tolerance (NGT) (n = 60); group 2, IGT (n = 60); and group 3, type 2 diabetes mellitus (n = 60). Normal glucose tolerance, IGT, and diabetes were defined using World Health Organization consulting group criteria. The inclusion criteria were nonsmokers; normal resting 12-lead electrocardiogram; absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases; and subjects not on statins or aspirin. Insulin resistance was calculated using the homeostasis assessment model using the formula: fasting insulin (microIU/mL) x fasting glucose (mmol/L)/22.5. Soluble P-selectin and sCD40L were estimated by enzyme-linked immunosorbent assay. Metabolic syndrome was defined using Adult Treatment Panel III guidelines. Subjects with diabetes and IGT were older (diabetes: 53 +/- 9 years, P < .01; IGT: 51 +/- 10 years, P < .05) compared with the NGT group (48 +/- 10 years). Subjects with diabetes and IGT had higher levels of sP-selectin (diabetes: 162 +/- 79 ng/mL, P < .001; IGT: 102 +/- 37 ng/mL, P < .001) compared with the NGT group (55 +/- 48 ng/mL). Soluble CD40L levels were also higher in those with diabetes and IGT (diabetes: 3.2 +/- 2.0 ng/mL, P < .001; IGT: 2.0 +/- 1.3 ng/mL, P < .001) compared with the NGT group (1.1 +/- 0.9 ng/mL). Subjects with MS had significantly higher levels of sP-selectin (with MS, 118 +/- 76 ng/mL; without MS, 95 +/- 66 ng/mL; P = .028) and sCD40L (with MS, 2.4 +/- 1.8 ng/mL; without MS, 1.9 +/- 1.5 ng/mL; P = .036) compared with subjects without MS. Among subjects with NGT and IGT, the mean levels of sP-selectin (tertile I, 65.0 ng/mL; tertile II, 80.0 ng/mL; tertile III, 91.0 ng/mL) and sCD40L levels (tertile I, 1.2 ng/mL; tertile II, 1.7 ng/mL; tertile III, 1.8 ng/mL) increased with increase in tertiles of homeostasis assessment model-insulin resistance, and the difference reached statistical significance in the last tertile compared with the first tertile (P < .05). This study demonstrates that increased levels of sP-selectin and sCD40L are seen in Asian Indian subjects with IGT, type 2 diabetes mellitus, MS, and insulin resistance.

Natural history of endocrine failure in tropical chronic pancreatitis: a longitudinal follow-up study.

BACKGROUND AND AIMS: Diabetes in tropical chronic pancreatitis (TCP), also known as fibrocalculous pancreatic diabetes (FCPD), is frequently seen at diagnosis. The aim of the present study was to determine the natural history of endocrine failure in TCP subjects without diabetes at baseline. METHODS: Of 73 TCP subjects without diabetes according to World Health Organization (WHO) criteria at baseline who were seen at an out-patient center, 54 (74.0%) underwent periodic oral glucose tolerance tests on follow up. Another 54 sex-matched, non-diabetic subjects without chronic pancreatitis served as controls. Baseline demographic and clinical characteristics were noted. RESULTS: After a median follow up of 5.0 years in TCP subjects and 7.0 years in controls, 27 of 54 TCP subjects (50%) developed diabetes compared with 14 of 54 controls (25.9%). Of the TCP subjects, those who developed diabetes on follow up were older (31 +/- 12 vs 23 +/- 11 years; P = 0.013), had a higher body mass index (21.7 +/- 4.4 vs 18.2 +/- 3.5 kg/m2; P = 0.004), higher 2 h post-load plasma glucose (8.8 +/- 1.9 vs 6.7 +/- 1.4 mmol/L; P < 0.001) and lower fecal chymotrypsin (2.1 +/- 1.2 vs 4.3 +/- 2.5 U/g; P < 0.001) at baseline compared with those who did not develop diabetes. The median time for the development of diabetes after diagnosis of TCP was 9.6 years (compared with 14.4 years among controls). Only 2 of 13 TCP subjects (15.4%) who had undergone surgical interventions during the normal glucose tolerance phase developed diabetes during follow up. CONCLUSIONS: In TCP, there is progressive deterioration of endocrine pancreatic function, with development of diabetes in 50% of patients upon follow up, suggesting that FCPD is merely a later stage in the course of TCP. Early surgery may prevent the development of diabetes in TCP subjects.

A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians.

OBJECTIVE: Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians. RESEARCH DESIGN AND METHODS: Genotyping of Ala98Val was done by the PCR-restriction fragment-length polymorphism method in the following groups: 1) MODY, defined as non-insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups. RESULTS: The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2-like diabetes (groups 1-4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002). CONCLUSIONS: Among Asian Indians, the Ala98Val polymorphism of HNF1alpha gene is associated with MODY and with earlier age at onset of type 2 diabetes.