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Introduction: Asian Indians (AIs), the second largest immigrant population in the United States, are disproportionately affected by type 2 diabetes mellitus (T2DM) at a lower age and body mass index (BMI). The purpose of this study was to examine the relationship between social determinants of health (SDOH) and the diagnosis of T2DM among AIs in New Jersey (NJ). Methodology: This was a secondary data analysis of the Behavioral Risk Factor Surveillance System (BRFSS) in NJ from 2013 to 2017. Statistical analyses included descriptive and inferential statistics. Results: Among 1,132 AIs, 16% had T2DM or prediabetes (PDM) and 69.2% were overweight or obese. The risk for T2DM was significantly associated with internet use, older age, having medical check-ups, and having a personal doctor (p ≤.05). Discussion: These findings inform culturally congruent care by underscoring the importance of weight management, earlier screening, and provider involvement in diabetes prevention strategies for AIs. [ABSTRACT FROM AUTHOR]

Background & objectives: Screening of individuals for early detection and identification of undiagnosed diabetes can help in reducing the burden of diabetic complications. This study aimed to evaluate the performance of Madras Diabetes Research Foundation (MDRF)-Indian Diabetes Risk Score (IDRS) to screen for undiagnosed type 2 diabetes in a large representative population in India. Methods: Data were acquired from the Indian Council of Medical Research–INdia DIABetes (ICMR–INDIAB) study, a large national survey that included both urban and rural populations from 30 states/union territories in India. Stratified multistage design was followed to obtain a sample of 113,043 individuals (94.2% response rate). MDRF-IDRS used four simple parameters, viz. age, waist circumference, family history of diabetes and physical activity to detect undiagnosed diabetes. Receiver operating characteristic (ROC) with area under the curve (AUC) was used to assess the performance of MDRF-IDRS. Results: We identified that 32.4, 52.7 and 14.9 per cent of the general population were under high-, moderate- and low-risk category of diabetes. Among the newly diagnosed individuals with diabetes [diagnosed by oral glucose tolerance test (OGTT)], 60.2, 35.9 and 3.9 per cent were identified under high-, moderate- and low-risk categories of IDRS. The ROC-AUC for the identification of diabetes was 0.697 (95% confidence interval: 0.684-0.709) for urban population and 0.694 (0.684-0.704) for rural, as well as 0.693 (0.682-0.705) for males and 0.707 (0.697-0.718) for females. MDRF-IDRS performed well when the population were sub-categorized by state or by regions. Interpretation & conclusions: Performance of MDRF-IDRS is evaluated across the nation and is found to be suitable for easy and effective screening of diabetes in Asian Indians. [ABSTRACT FROM AUTHOR]

To study the association and possible predictive role of visfatin, resistin, fetuin-A and chemerin with incident type 2 diabetes (T2DM) among Asian Indians with prediabetes. Their association with insulin resistance, β-cell function, glycaemia and anthropometry were also studied. This is a nested case–control study of a large 2-year prospective prevention trial in persons at high risk of developing T2DM. Baseline HbA1c values between 6.0% (42 mmol/mol) and 6.2% (44 mmol/mol) were chosen for this analysis (n = 144). At follow-up, persons with incident T2DM (HbA1c ≥ 6.5%, 48 mmol/mol) were grouped as cases (n = 72) and those reverted to normoglycaemia, (HbA1c < 5.7% (39 mmol/mol) as controls (n = 72). Insulin resistance showed the strongest association with incident T2DM ((Odds Ratio (OR): 23.22 [95%CI 6.36–84.77]; p < 0.0001). Baseline visfatin (OR: 6.56 [95%CI 2.21–19.5]; p < 0.001) and fetuin-A (OR: 1.01 [95%CI (1.01–1.04)]; p < 0.0001) independently contributed to the conversion of prediabetes to T2DM. The contribution was significantly higher when their elevated levels coexisted (OR: 12.63 [95%CI 3.57–44.63]; p < 0.0001). The area under the curve was 0.77 ± SE 0.4 (95%CI 0.69–0.85) and 0.80 ± SE 0.04 (95%CI 0.73–0.88) for visfatin (median 17.7 ng/ml, sensitivity and specificity: 75%, p < 0.0001) and fetuin-A (mean 236.2 µg/ml, sensitivity: 71%, specificity: 75%, p < 0.0001) respectively. Higher baseline visfatin and fetuin-A concentrations are strongly associated with incident T2DM and are predictive of future diabetes. [ABSTRACT FROM AUTHOR]

In recent years, numerous studies have explored the quality of life (QoL) in those with diabetes mellitus. The aim of this scoping review was to explore the current state of knowledge on QoL and its various associated factors among people with diabetes in India. Three databases were searched (PubMed, Scopus, and Medline) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A total of 41 articles were included in the review. The included studies were largely conducted in the Southern states and mainly investigated individuals with type 2 diabetes. The World Health Organization Quality of Life (WHOQOL-BREF) and Short Form Health Survey (SF-36) were the instruments used most often. In general, the studies showed that people with diabetes had poorer QoL than those without diabetes, and women with diabetes reported poorer QoL than men, consistent with findings across the world. However, the studies had significant methodological flaws which limit the validity and generalizability of the findings. Therefore, there is an urgent need to conduct high-quality QoL studies which are representative of all states of India as well as different types of diabetes in India in order to address this gap in the evidence. [ABSTRACT FROM AUTHOR]

Introduction: We present a new diabetes risk score developed and validated in a multi-ethnic population in Guyana, South America. Measurement of in-country diabetes prevalence is a vital epidemiologic tool to combat the pandemic. It is believed that for every person diagnosed with type 2 diabetes there is another undiagnosed. The International Diabetes Federation (IDF) recommends a two-step detection programme using a risk score questionnaire to identify high-risk individuals followed by glycaemic measure. Methods: Data on 798 persons from the 2016 STEPwise Approach to Chronic Disease Risk Factor Surveillance (STEPS) were used to correlate responses to 36 questions with glycated haemoglobin (HbA1C) and fasting plasma glucose (FPG) results. Bootstrapping was used to internally validate the derived seven-variable model. This model with the addition of family history questions was tested in a convenience sample of 659 Guyanese adults and externally validated in a cohort of another 528. Results: An 8-item Guyana Diabetes Risk Score (GDRS) was derived. The final model performed with an area under the curve (AUC) of 0.812 Conclusions: The validated eight-item Guyana Diabetes Risk Score will be extremely useful in identifying individuals at high risk of having diabetes in Caribbean, Black or East Indian populations. [ABSTRACT FROM AUTHOR]

• Telomere length changes in metabolic and vascular disorders. • Peripheral blood lymphocytic telomere shortening in diabetic mellitus and idiopathic dilated cardiomyopathy (IDCM). • No correlation between echocardiography parameters & telomere length in IDCM. • Neuropathic complication does not influence telomere shortening phenotype. Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46). In addition, we evaluated the relationship between echocardiographic left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters (LVEDd and LVESd) and telomere length in IDCM patients. Telomere length negatively correlated with age in the cohorts with diabetes and IDCM, and in controls. Average telomere length in diabetes and IDCM patients was significantly shorter than that of controls either before or after adjustments for age and sex. Duration of diabetes in patients with type 2 diabetes did not correlate with telomere length. No correlation was found between the length of telomeres and echocardiography parameters like LVEF, LVEDd and LVESd in IDCM patients. Though echocardiographic characteristics of IDCM did not correlate with telomere length, telomere shortening was found to be accelerated in diabetes (both DM and DN) and IDCM in a south Indian population. Neuropathic complication in diabetes had no effect on telomere shortening. While telomere shortening is a cause or a consequence of diabetic and cardiac pathology remains further investigation, the current study substantiates the usefulness of telomere length measurements as a marker in conjunction with other biochemical markers of age-related diseases. [ABSTRACT FROM AUTHOR]

Background: Almost 15% of India's urban adult populace now lives with type 2 diabetes. This study aimed to characterize the eating patterns, knowledge, beliefs, and determinants of food choice, and assess associations with the metabolic health among urban Asian Indians with type 2 diabetes. Materials and Methods: A cross-sectional study of 258 individuals (mean age 55.7 ± 10 years; body mass index 27.1 ± 4.8 kg/m2 ; diabetes duration 10.1 ± 6.5 years) attending two out-patient clinics in New Delhi, India. Food-related information was collected during a semi-structured interview. Clinical, anthropometric, and biochemical data were recorded. Results: Beliefs related to health and diabetes played a role determining food choice and dietary patterns; erroneous views were associated with the poor food choices and greater metabolic perturbations. Average consumption of fruits/vegetables was low. Intakes were positively associated with intentions to manage diabetes; inversely associated with the waist circumference and negatively correlated with one's degree of personal responsibility for food choice. Household saturated fat usage was common. High fat intakes were positively associated with the taste preference, ratings of perceived "health-value;" waist circumference, glycosylated haemoglobin percentage (HbA1c%) and lipids. Conclusions: Strategies to enhance diabetes control among Asian Indians are required and should encourage fruit/vegetable intake, personal accountability, and consider individual beliefs and preferences. Greater emphasis and resources directed to regular dietary and behavioral counseling may assist.' [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess the efficacy and safety of pioglitazone in combination with other oral antidiabetics (OADs) in Indian patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This was an openlabel, prospective, no-randomized, single-center observational study conducted at a single center in India. A total of 958 adult patients with T2DM on OADs, with uncontrolled fasting (FBG) or postprandial blood glucose (PPG), were enrolled. Pioglitazone (7.5/15/30 mg) was added to existing therapy as a combination treatment with other OAD. Body weight (BW), body mass index (BMI), FBG and postprandial plasma glucose (PPPG) and glycosylated hemoglobin (HbA1c) were measured at the beginning (week 0) and at every follow-up treatment visit, i.e., 6 months (week 24), 1 year (week 48) and 2 years (week 96). Changes from baseline to each visit were analyzed using the Wilcoxon test. All patients also went through a urinalysis at baseline, and after 6 months, 1 year and 2 years of treatment, to assess for any abnormalities in the urine (pH, pus or protein), suggestive of bladder abnormalities. Results: The combined analysis was carried out on 958 completed patients in this study who were treated with pioglitazone 7.5 mg, 15 mg and 30 mg tablet and other OADs. The difference in mean value of FBG showed a highly significant decrease (P<0.0001) from baseline to end of treatment, i.e., from 167.0, (59.16) 172.6 (58.51) and 171.0 (39.47) to 140.2, (26.46) 143.8 (22.04) and 138.5 (27.82) mg/dL. Similarly, PPG showed a significant (P<0.0001, 0.002 and 0.008) decrease from baseline to end of the treatment, i.e., from 256.0, (61.79) 222.9 (67.88) and 223.6 (69.11) to 195.9, (46.92) 204.0 (48.03) and 187.6 (53.36) mg/dL, and there was a highly significant (P<0.0001) decrease in HbA1c levels, i.e., from 8.46, 8.34 and 8.42% to 7.781, 7.78 and 7.73%, respectively. However, gain in mean BW was also observed from baseline to end of the treatment, i.e., from 69.90, (9.44) 68.29 (8.62) and 67.64 (7.75) kg to 71.69, (8.35) 70.08 (7.96) and 69.70 (7.99) kg, respectively, and BMI increased from 26.74 (14.18-53.04) kg/m² at baseline to 27.45 (12.87-53.73) kg/m² at the end of the treatment, respectively (P<0.0001). No significant changes were found in urine in patients even after 2 years of treatment with pioglitazone. There was little variation in pH or presence of pus and proteins in the urine, indicating no increased risk of bladder-related abnormalities across all treated age groups even after 2 years of treatment with pioglitazone. Conclusion: Pioglitazone in combination with other OADs in Indian patients was an effective treatment protocol in glycemic control, reduction in FBG, PPPG and HbA1c and also helps in controlling weight gain in patients with T2DM. In this patient population, there was no increased risk of bladder-related abnormalities. Pioglitazone was therefore found to be a safe and efficacious addition to treatment in patients with poorly controlled diabetes. [ABSTRACT FROM AUTHOR]

India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the "diabetes capital of the world". According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The so called "Asian Indian Phenotype" refers to certain unique clinical and biochemical abnormalities in Indians which include increased insulin resistance, greater abdominal adiposity i.e., higher waist circumference despite lower body mass index, lower adiponectin and higher high sensitive C-reactive protein levels. This phenotype makes Asian Indians more prone to diabetes and premature coronary artery disease. At least a part of this is due to genetic factors. However, the primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of diabetes in the urban population. Even though the prevalence of microvascular complications of diabetes like retinopathy and nephropathy are comparatively lower in Indians, the prevalence of premature coronary artery disease is much higher in Indians compared to other ethnic groups. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long lasting adverse effects on nation's health and economy. Early identification of at-risk individuals using simple screening tools like the Indian Diabetes Risk Score (IDRS) and appropriate lifestyle intervention would greatly help in preventing or postponing the onset of diabetes and thus reducing the burden on the community and the nation as a whole. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses several studies related to diabetes, including fasting glucose criteria to diagnose diabetes in U.S. adults, the definition of glucose intolerance among Asian Indians and the effect of coffee consumption on the development of type 2 diabetes. On fasting glucose criteria, the percentages of population diagnosed by using glycated hemoglobin (HbA) were provided. The HbA levels which can determine diabetes in Asian population are explained. It was reported that coffee and tea consumption provided protection against diabetes development.

Objective:To investigate the association of insulin receptor substrate-2 (IRS-2) G1057D polymorphism with type 2 diabetes and obesity in Asian Indians.Methods:The study comprised of 1193 normal glucose tolerant (NGT) subjects and 1018 subjects with type 2 diabetes, aged 20 years with an average body mass index of 23.7±4.6 and 25.3±4.2 kg/m2, respectively. The subjects were unrelated and randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study in Chennai in southern India. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.Results:The genotype frequency of the IRS-2 G1057D polymorphism was significantly different between the NGT and type 2 diabetic groups (P=0.0007) in the total study subjects and among the obese subjects (P=0.00007). Logistic regression analysis showed that the DD genotype showed an increased susceptibility to diabetes with an odds ratio (adjusted for age and sex) of 2.19 (95% CI: 1.34–3.57, P=0.002) when compared to the GG+GD genotype, among the obese subjects, but not in non obese subjects. In order to explore possible interaction with obesity, logistic regression analysis was performed and the coefficient corresponding to the interaction parameter (genotype × obesity) was significant (P=0.0001).Conclusion:In Asian Indians, the DD genotype increases susceptibility to type 2 diabetes by interacting with obesity.International Journal of Obesity (2007) 31, 97–102. doi:10.1038/sj.ijo.0803356; published online 25 April 2006 [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]

Abstract: Objective:: Simple risk scores for identifying people with undiagnosed diabetes have been developed, mostly in Caucasian groups. This may not be suitable for Asian Indians, therefore this study was undertaken to develop and validate a simple diabetes risk score in an urban Asian Indian population with a high prevalence of diabetes. We also tested whether this score was applicable to South Asian migrants living in a different cultural context. Research design and methods:: A population based Cohort of 10,003 participants aged ≥20 years was divided into two equal halves (Cohorts 1 and 2), after excluding people with known diabetes. Cohort 1 (n =4993) was used to derive the risk score. Validation of the score was performed in the other half of the survey population (Cohort 2) (n =5010). The validation was also done in a separate survey population in Chennai, India (Cohort 3) (n =2002) (diagnosis of diabetes was based on OGTT) and in the South Asian Cohort of the 1999 Health Survey for England (n =676) (fasting glucose value≥7mmol/l and HbA1c≥6.5% were used for diagnosis). A logistic regression model was used to compute the β coefficients for risk factors. The risk score value was derived from a receiver operating characteristic curve. Results:: The significant risk factors included in the risk score were age, BMI, waist circumference, family history of diabetes and sedentary physical activity. A risk score value of >21 gave a sensitivity, specificity, positive predictive value and negative predictive value of 76.6%, 59.9%, 9.4% and 97.9% in Cohort 1, 72.4%, 59%, 8.3% and 97.6% in Cohort 2 and 73.7%, 61.0%, 12.2% and 96.9% in Cohort 3, respectively. The higher distribution of risk factors in the UK Cohort means that at the same cut point the score was much more sensitive but also less specific. (sensitivity 92.2%, specificity 25.7%, positive predictive value of 21.6% and negative predictive value of 93.7%). Conclusions:: A diabetes risk score involving simple non-biochemical measurements was developed and validated in a native Asian Indian population. This easily applicable simple score could play an important role as the first step in the process of identifying individuals with an increased likelihood of having prevalent but undiagnosed diabetes. The different distribution of risk factors with the migrant Asian Indians living in England and the different relationship between sensitivity and specificity for the same score demonstrate that risk scores and cut-points developed and tested even within one ethnic group cannot be generalized to individuals of the same ethnic group living in a different cultural setting where the distribution of risk factors for diabetes is different. [Copyright &y& Elsevier]

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]

Aim of Study: Endothelial dysfunction is a feature of cardiovascular disease, hypertension, dyslipidaemia and smoking, all of which are associated with diabetes induced nephropathy. The Cytokines have also found to play an important role in development of Diabetic nephropathy. Cytokines like monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) and their receptors CCR2 and CCR5 mediate macrophage infiltration into kidney whose over-expression leads to glomerulosclerosis and interstitial fibrosis. We investigated the association of three single nucleotide polymorphisms (SNPs) and three insertion deletion polymorphisms from CCR5, MCP-1 and endothelial nitric oxide synthase (eNOS) genes among 400 type 2 diabetic individuals with (DNP) and without nephropathy (DMT2). Materials and Methods: Genotyping of the Insertion/Deletion polymorphisms was performed by PCR whereas the SNPs were genotyped by the PCR-RFLP assay, followed by agarose gel electrophoresis. The serum nitric oxide and hs-CRP levels were also assessed. Results: The prevalence of the MCP-1 I/I (AGCTCCTCCTTCTC/AGCTCCTCCTTCTC) homozygotes was significantly higher among DNP than among DMT2 group (P<0.0001, OR: 2.19, 95% CI: 1.4-3.2), however frequency of both the alleles of MCP-1-2518 A> G promoter polymorphism did not vary significantly between the two groups. The frequency of D allele (CCR5 delta I/D) and DD genotype was significantly higher in DNP than among DMT2 patients (D allele: P=0.001, OR: 2.59, 95% CI: 1.4-4.6; DD genotype: P<0.0001, OR: 3.1, 95% CI: 2.1-4.6). The variant genotype (CO, II, and TT) frequencies of all the three eNOS polymorphisms (-786 T>C, Intron 4 I/D, and 1917 G > T) differed significantly (P< 0.05) between the two groups. The hsCRP levels were higher in DNP (2.15±2.0 mg/L; P<0.05) as compared to DMT2 group (1.89±1.7 mg/L; P<0.05), but were statistically non-significant. The NO levels of DNP group (0.4±0.04 nmol/L) were significantly lower as compared to DMT2 group (0.75±0.18 nmol/L). Conclusion: Although hs-CRP levels were increased in diabetic patients, no direct association of the increased hs-CRP levels was observed with DNE Also, this study reveals an association of CCR5 delta (32 bp I/D), and MCP-1 gene I/D, eNOS -786 T> C promoter, Intron 4 I/D and 1917 G>T polymorphisms, but not MCP-1 gene promoter polymorphism (-2518 A>G) with the development of type 2 DNP among North Indians. [ABSTRACT FROM AUTHOR]