Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians.

Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 ( 201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population.

Association of hypoadiponectinemia with non-alcoholic fatty liver disease in urban south Indians - (CURES - 81).

Background & objective: Association between adiponectin and non-alcoholic fatty liver disease (NAFLD) has been reported in west. Studies in Indian population are lacking. This study was undertaken to assess the association of hypoadiponectinemia with NAFLD in Asian Indians. Method: In this cross-sectional study, subjects were randomly selected from Phase 5 of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study based on a representative population of Chennai in south India. One hundred twenty one subjects without NAFLD and 72 subjects with NAFLD were selected. NAFLD was diagnosed by ultrasonography. Serum adiponectin levels were measured using radioimmunoassay. Insulin resistance was calculated using Homeostasis Assessment model (HOMA-IR). Results: Serum adiponectin values were significantly lower in subjects with NAFLD compared to those without [5.6 μg/ml (95% Confidence Interval (CI) 5.0 - 6.3 μg/ml] vs 7.4 μg/ml (95% CI: 6.7 - 8.1 μg/ml, P<0.01). Adiponectin levels decreased with increasing severity of NAFLD. Subjects with moderate to severe steatosis had significantly lower adiponectin levels (5.1μg/ml, 95% CI: 4.1- 6.4 μg/ml) compared to subjects with mild steatosis (5.9 μg/ml, 95% CI: 5.0 - 6.9 μg/ml; P<0.001) and subjects without NAFLD (7.3 μg/ml, 95% CI: 6.6 - 8.0 μg/ml; P<0.01). Multiple logistic regression analysis revealed adiponectin to be negatively associated with NAFLD [Odds Ratio (OR): 0.865, 95% Confidence Interval (CI): 0.792- 0.944, P=0.001]. This remained statistically significant even after adjusting for confounding factors age, gender, body mass index, insulin resistance, waist circumference, total cholesterol, triglycerides and glucose intolerance (OR: 0.873, 95% CI: 0.793 - 0.961; P=0.005). Interpretation & conclusion: NAFLD is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in Asian Indians known to have high prevalence of diabetes and coronary artery disease.

Visceral & subcutaneous abdominal fat in relation to insulin resistance & metabolic syndrome in non-diabetic south Indians.

Background & objectives: The objective of the study was to determine whether visceral or subcutaneous component of abdominal fat was associated with insulin resistance and metabolic syndrome in non-diabetic Asian Indians. Method: This cross-sectional study had on 120 individuals with normal glucose tolerance (49 males and 71 females). A single slice CT scan at L4- L5 was done for measurement of visceral and subcutaneous abdominal fat. Metabolic syndrome was defined according to the South Asian Modified National Cholesterol Education Program Adult Treatment Panel III criteria (SAM-NCEP) criteria. Insulin Sensitivity Index (ISI-Matsuda) was used to assess insulin sensitivity/resistance. Results: Linear regression analysis revealed that visceral, but not subcutaneous fat was associated with serum triglycerides (R2=0.457, β= 0.34; P=0.006), HDL cholesterol (R2=0.430, β= -0.051; P=0.018) and ISI-Matsuda (R2=0.437, β= -0.05; P=0.039) after adjusting for age, gender and BMI. Visceral fat showed significant association with metabolic syndrome (OR: 1.013, 95% CI: 1.001- 1.025; P=0.041) even after adjusting for age, gender, body mass index and glycated haemoglobin whereas subcutaneous fat did not show such an association. Interpretation & conclusions: These results indicate that in non-diabetic Asian Indians, visceral, but not subcutaneous component of abdominal fat is associated with insulin resistance, cardiovascular risk factors and metabolic syndrome.

Association of leukocyte count and hsCRP with metabolic abnormalities in subjects with normal glucose tolerance (CURES – 64).

Objective : The aim of the present study was to assess the association of leukocyte count and high sensitivity C-Reactive protein (hsCRP) with metabolic abnormalities in subjects with normal glucose tolerance. Methods : Subjects with Normal Glucose Tolerance (NGT) (n = 865) were recruited from the Chennai Urban Rural Epidemiology Study [CURES]. Standard methods were used for assessing hsCRP [Nephelometry, in a subset] and leukocytes [Flowcytometry, Sysmex SF-3000]. Insulin resistance was calculated using the Homeostasis Assessment model (HOMA-IR). Results : Body mass index, waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, HbA1c, serum cholesterol, LDL cholesterol, HOMA IR and hsCRP increased significantly with increasing tertiles of leukocyte count [p for trend < 0.001]. Both leukocyte count and hsCRP showed a positive correlation with cardiovascular risk factors. Leukocyte count showed a positive correlation with hsCRP [p=0.008]. Both mean leukocyte count [p<0.001] and hsCRP [p=0.04] were higher in subjects with Metabolic Syndrome (MS), which increased with increase in number of metabolic abnormalities [p for trend <0.001]. Regression models showed leukocyte count [p<0.001] and hsCRP [p=0.03] to be associated with MS, even after adjusting for age and gender. Conclusion : A significant association exists between systemic inflammation [leukocyte count and hsCRP] and MS/ cardiovascular risk factors in Asian Indians even among non-diabetic subjects. ©

Association of small dense LDL with coronary artery disease and diabetes in urban Asian Indians - the Chennai Urban Rural Epidemiology Study (CURES-8).

OBJECTIVE: Earlier studies in Europeans have identified small dense LDL to be associated with coronary artery disease and diabetes. In this study we assessed the association of small dense LDL with diabetes and CAD in Asian Indians. METHODS: Study subjects were selected from the Chennai Urban Rural Epidemiology Study (CURES), a population based study on representative sample of Chennai city in southern India. Group 1:non-diabetic subjects (n = 30); Group 2: diabetic subjects without CAD (n = 30); Group 3:diabetic subjects with CAD (n = 30). LDL subfractions were estimated using LipoPrint LDL system. LDL subfractions 3 and above, defined as small dense LDL was summed up to determine the overall small LDL. 75th percentile of the overall small dense LDL in non-diabetic subjects was used as a cut-off for defining elevated levels of small dense LDL. RESULTS: The mean age of the study subjects was not significantly different among groups. Overall small dense LDL was significantly higher in diabetic subjects with CAD (16.7 +/- 11.1 mg/dl, p < 0.05) and without CAD (11.1 +/- 8.0 mg/dl, p < 0.05) compared to non-diabetic subjects without CAD (7.2 +/- 6.8 mg/dl). Small dense LDL showed a positive correlation with fasting plasma glucose (r = 0.252, p = 0.023), HbA1c (r = 0.281, p = 0.012), total cholesterol (r = 0.443, p < 0.001), triglycerides(r = 0.685, p < 0.001), LDL(r = 0.342, p = 0.002), total cholesterol/HDL ratio (r = 0.660, p = < 0.001) and triglycerides/HDL ratio(r = 0.728, p < 0.001) and a negative correlation with HDL cholesterol (r = -0.341, p = 0.002) and QUICKI values (r = -0.260, p = 0.019). ROC curves constructed to predict elevated small dense LDL ((9.0 mg/dl) revealed that triglycerides/HDL ratio and total cholesterol/HDL ratio had higher AUC values compared to other parameters. A triglycerides/HDL ratio of 3.0 had the optimum sensitivity (80.0%) and specificity (78.0%) for detecting elevated small dense LDL. CONCLUSION: This data suggests that in Asian Indians, small dense LDL is associated with both diabetes and CAD and that a triglycerides/HDL ratio (3.0 could serve a surrogate marker of small dense LDL.