ALTERED CIRCULATING LEVELS OF RETINOL BINDING PROTEIN 4 AND TRANSTHYRETIN IN RELATION TO INSULIN RESISTANCE, OBESITY, AND GLUCOSE INTOLERANCE IN ASIAN INDIANS.

OBJECTIVE: Retinol binding protein 4 (RBP4) has been implicated in metabolic disorders including type 2 diabetes mellitus (T2DM), but few studies have looked at transthyretin (TTR) with which RBP4 is normally bound to in the circulation. We report on the systemic levels of RBP4 and TTR and their associations with insulin resistance, obesity, prediabetes, and T2DM in Asian Indians. METHODS: Age-matched individuals with normal glucose tolerance (NGT, n = 90), impaired glucose tolerance (IGT, n = 70) and T2DM (n = 90) were recruited from the Chennai Urban Rural Epidemiology Study (CURES). Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Circulatory RBP4 and TTR levels (in µg/mL) were highest in T2DM (RBP4: 13 ± 3.9, TTR: 832 ± 310) followed by IGT (RBP4: 10.5 ± 3.2; TTR: 720 ± 214) compared to NGT (RBP4: 8.7 ± 2.5; TTR: 551 ± 185; P<.001). Compared to nonobese NGT individuals, obese NGT, nonobese T2DM, and obese T2DM had higher RBP4 (8.1 vs. 10.6, 12.1, and 13.2 µg/mL, P<.01) and TTR levels (478 vs. 737, 777, and 900 µg/mL, P<.01). RBP4 but not TTR was significantly (P<.001) correlated with insulin resistance even among NGT subjects. In regression analysis, RBP4 and TTR showed significant associations with T2DM after adjusting for confounders (RBP4 odds ratio [OR]: 1.107, 95% confidence interval [CI]: 1.008-1.216; TTR OR: 1.342, 95% CI: 1.165-1.547). CONCLUSION: Circulatory levels of RBP4 and TTR showed a significant associations with glucose intolerance, obesity, T2DM and RBP4 additionally, with insulin resistance.

1,5 Anhydroglucitol in gestational diabetes mellitus.

OBJECTIVE: 1,5 Anhydroglucitol (1,5 AG) is reported to be a more sensitive marker of glucose variability and short-term glycemic control (1-2 weeks) in patients with type1 and type 2 diabetes. However, the role of 1,5 AG in gestational diabetes mellitus (GDM) is not clear. We estimated the serum levels of 1,5 AG in pregnant women with and without GDM. METHODS: We recruited 220 pregnant women, 145 without and 75 with GDM visiting antenatal clinics in Tamil Nadu in South India. Oral glucose tolerance tests (OGTTs) were carried out using 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) and GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Group criteria. Serum 1,5 AG levels were measured using an enzymatic, colorimetric assay kit (Glycomark®, New York, NY). Receiver operating characteristic (ROC) curves were used to identify 1,5 AG cut-off points to identify GDM. RESULTS: The mean levels of the 1,5 AG were significantly lower in women with GDM (11.8 ±â€¯5.7 µg/mL, p < 0.001) compared to women without GDM (16.2 ±â€¯6.2 µg/mL). In multiple logistic regression analysis, 1.5 AG showed a significant association with GDM (odds ratio [OR]: 0.876, 95% confidence interval [CI]: 0.812-0.944, p < 0.001) after adjusting for potential confounders. 1,5 AG had a C statistic of 0.693 compared to Fructosamine (0.671) and HbA1c (0.581) for identifying GDM. A 1,5 AG cut-off of 13.21 µg/mL had a C statistic of 0.6936 (95% CI: 0.6107-0.7583, p < 0.001), sensitivity of 67.6%, and specificity of 65.3% to identify GDM. CONCLUSION: 1,5AG levels are lower in pregnant women with GDM compared to individuals without GDM.

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.

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.

Relationship of glycemic control markers - 1,5 anhydroglucitol, fructosamine, and glycated hemoglobin among Asian Indians with different degrees of glucose intolerance.

OBJECTIVE: 1,5 anhydroglucitol (1,5 AG) is emerging as a marker of short-term glycemic control. We measured levels of 1,5 AG, fructosamine (FA), and glycated hemoglobin (HbA1c) in Asian Indians with different degrees of glucose intolerance. MATERIALS AND METHODS: We recruited 210 individuals with normal glucose tolerance (NGT; n = 60), impaired glucose tolerance (IGT; n = 50), and Type 2 diabetes mellitus (T2DM; n = 100) from a large tertiary diabetes center in Chennai in Southern India. Anthropometric measurements were obtained using standardized techniques. Serum 1,5 AG (enzymatic colorimetric assay), FA (NBT/kinetic), and HbA1c (high-performance liquid chromatography) estimations were performed. RESULTS: 1,5 AG levels were significantly lower in the T2DM followed by IGT compared with the NGT group (7.9 vs. 18.8 vs. 21.8 µg/ml, P < 0.05). FA and HbA1c were higher in T2DM and IGT compared with NGT individuals (313 vs. 237 vs. 200 µmol/L, P < 0.001) (8.3 vs. 5.8 vs. 5.3%, P < 0.001).1,5 AG showed a significant negative correlation with FA (r = -0.618, P < 0.001) and HbA1c (r = -0.700, P < 0.001). 1,5 AG decreased with increasing quartiles of postprandial glucose (P for trend <0.001). However, even among individuals with HbA1c ≤7%, 27% individuals had decreased 1,5 AG plasma level (<10 µg/ml). CONCLUSION: Circulatory levels of 1,5 AG correlate negatively with FA and HbA1c, and may provide an additional marker to assess glycemic control in patients with Type 2 diabetes.

Circulating levels of insulin-like growth factor binding protein-1 in relation to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai Urban Rural Epidemiology Study 118).

The objective was to assess the association of insulin-like growth factor binding protein-1 (IGFBP-1) with insulin resistance (IR), type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) in Asian Indians. Fifty subjects with normal glucose tolerance (NGT) and 50 with T2DM were randomly selected from the Chennai Urban Rural Epidemiology Study. Insulin-like growth factor binding protein-1 was measured by sandwich enzyme-linked immunosorbent assay. Serum insulin was estimated using Dako (Glostrup, Denmark) kits. Insulin resistance was calculated using the homeostasis model assessment. Subjects with T2DM had significantly decreased levels of IGFBP-1 (21.7 ± 3.5 ng/mL) compared with NGT subjects (34.4 ± 7.6 ng/mL, P < .001). The IGFBP-1 was significantly lower in NGT subjects with IR as measured by the homeostasis model assessment (25.5 ± 6.5 ng/mL) compared with NGT subjects without IR (40.7 ± 9.5 ng/mL, P < .001). On regression analysis, IR showed a significant association with IGFBP-1 even after adjusting for age, sex, body mass index, and glycated hemoglobin (ß = -3.714, P < .001). Type 2 diabetes mellitus was significantly associated with IGFBP-1 even after adjusting for age, sex, and body mass index (ß = -12.798, P < .001). The IGFBP-1 levels decreased with increasing number of metabolic abnormalities (P for trend < .001). Logistic regression analysis showed that IGFBP-1 had a strong negative association with MS even after adjusting for age and sex (odds ratio, 0.942; 95% confidence interval, 0.914-0.971; P < .001). Among Asian Indians, lower levels of circulating IGFBP-1 are seen in subjects with IR, T2DM, and MS.