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Nathan A.A.,Indian Institute of Technology Madras | Mohan V.,Madras Diabetes Research Foundation MDRF | Babu S.S.,SAIC | Babu S.S.,NCI Inc | And 2 more authors.
BMC Endocrine Disorders | Year: 2011

Background: Haematopoietic stem cells undergo mobilization from bone marrow to blood in response to physiological stimuli such as ischemia and tissue injury. The aim of study was to determine the kinetics of circulating CD34 +and CD133 +CD34 +progenitor cells in response to 75 g glucose load in subjects with normal and impaired glucose metabolism.Methods: Asian Indian male subjects (n = 50) with no prior history of glucose imbalance were subjected to 2 hour oral glucose tolerance test (OGTT). 24 subjects had normal glucose tolerance (NGT), 17 subjects had impaired glucose tolerance (IGT) and 9 had impaired fasting glucose (IFG). The IGT and IFG subjects were grouped together as pre-diabetes group (n = 26). Progenitor cell counts in peripheral circulation at fasting and 2 hour post glucose challenge were measured using direct two-color flow cytometry.Results: The pre-diabetes group was more insulin resistant (p < 0.0001) as measured by homeostasis assessment model (HOMA-IR) compared to NGT group. A 2.5-fold increase in CD34 +cells (p = 0.003) and CD133 +CD34 +(p = 0.019) cells was seen 2 hours post glucose challenge in the NGT group. This increase for both the cell types was attenuated in subjects with IGT. CD34 +cell counts in response to glucose challenge inversely correlated with neutrophil counts (ρ = -0.330, p = 0.019), while post load counts of CD133 +CD34 +cells inversely correlated with serum creatinine (ρ = -0.312, p = 0.023).Conclusion: There is a 2.5-fold increase in the circulating levels of haematopoietic stem cells in response to glucose challenge in healthy Asian Indian male subjects which is attenuated in subjects with pre-diabetes. © 2011 Nathan et al; licensee BioMed Central Ltd. Source

Nair M.,Public Health Foundation of India PHFI | Ali M.K.,Emory University | Ajay V.S.,CoE CARRS | Shivashankar R.,Center for Chronic Disease Control | And 10 more authors.
BMC Public Health | Year: 2012

Background: Cardio-metabolic diseases (CMDs) are a growing public health problem, but data on incidence, trends, and costs in developing countries is scarce. Comprehensive and standardised surveillance for non-communicable diseases was recommended at the United Nations High-level meeting in 2011. Aims: To develop a model surveillance system for CMDs and risk factors that could be adopted for continued assessment of burdens from multiple perspectives in South-Asian countries. Methods. Design: Hybrid model with two cross-sectional serial surveys three years apart to monitor trend, with a three-year prospective follow-up of the first cohort. Sites: Three urban settings (Chennai and New Delhi in India; Karachi in Pakistan), 4000 participants in each site stratified by gender and age. Sampling methodology: Multi-stage cluster random sampling; followed by within-household participant selection through a combination of Health Information National Trends Study (HINTS) and Kish methods. Culturally-appropriate and methodologically-relevant data collection instruments were developed to gather information on CMDs and their risk factors; quality of life, health-care utilisation and costs, along with objective measures of anthropometric, clinical and biochemical parameters. The cohort follow-up is designed as a pilot study to understand the feasibility of estimating incidence of risk factors, disease events, morbidity, and mortality. Results: The overall participant response rate in the first cross-sectional survey was 94.1% (Chennai 92.4%, n=4943; Delhi 95.7%, n=4425; Karachi 94.3%, n=4016). 51.8% of the participants were females, 61.6%<45years, 27.5% 45-60years and 10.9% >60years. Discussion. This surveillance model will generate data on prevalence and trends; help study the complex life-course patterns of CMDs, and provide a platform for developing and testing interventions and tools for prevention and control of CMDs in South-Asia. It will also help understanding the challenges and opportunities in establishing a surveillance system across countries. © 2012 Nair et al.; licensee BioMed Central Ltd. Source

Nathan A.A.,Indian Institute of Technology Madras | Charan Tej M.A.,Indian Institute of Technology Madras | Chitiprolu M.,Indian Institute of Technology Madras | Rangan S.,Indian Institute of Technology Madras | And 4 more authors.
Diabetes and Vascular Disease Research | Year: 2015

Aim: To compare the adhesion, migration and endothelial differentiation potential of peripheral blood-derived mononuclear cells (PBMCs) obtained from drug-naive normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) Asian Indian men.Methods: Based on the 75-g oral glucose tolerance test, 30 NGT and 31 IGT subjects were recruited into the study. PBMCs were isolated from fasting blood using histopaque density gradient centrifugation. Isolated PBMCs were analysed for their ability to adhere to extracellular matrices, incorporation into tubular structures formed by matured endothelial cells and differentiation into endothelial cells upon 7-day culture in endothelial-specific growth medium.Results: PBMCs obtained from IGT subjects exhibit poor adherence to fibronectin and reduced incorporation into tubular structures. Migration towards stromal cell-derived factor-1? (SDF-1?) in a trans-well filter assembly was also reduced for these cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis revealed decreased expression of CXCR4 and ?2 integrin and increased expression of arginase II in IGT subjects. No differences were observed with regard to endothelial differentiation; however, cultured PBMCs of IGT subjects had decreased intracellular nitric oxide (NO) production.Conclusion: In pre-diabetic, Asian Indian men, PBMCs exhibit defective migration and homing potential. © The Author(s) 2014. Source

Deepa M.,Madras Diabetes Research Foundation MDRF | Grace M.,Public Health Foundation of India and Center for Chronic Disease Control | Binukumar B.,National Institute of Mental Health and Neuro Sciences | Pradeepa R.,Madras Diabetes Research Foundation MDRF | And 12 more authors.
Diabetes Research and Clinical Practice | Year: 2015

Aim: To estimate the prevalence of, and assess factors associated with, diabetes and prediabetes in three South Asian cities. Methods: Using a multi-stage cluster random sample representative of each city, 16,288 subjects aged ≥20 years (Chennai: 6906, Delhi: 5365 and Karachi: 4017) were recruited to the Centre for cArdio-metabolic Risk Reduction in South-Asia (CARRS) Study. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were measured in 13720 subjects. Prediabetes was defined as FPG 100-125. mg/dl (5.6-6.9. mmol/l) and/or HbA1c 5.7-6.4% (39-46. mmol/mol) and diabetes as self-report and/or drug treatment for diabetes and/or FPG. ≥. 126. mg/dl (≥7.0. mmol/l) and/or HbA1c. ≥. 6.5% (48. mmol/mol). We assessed factors associated with diabetes and prediabetes using polytomous logistic regression models. Results: Overall 47.3-73.1% of the population had either diabetes or prediabetes: Chennai 60.7% [95%CI: 59.0-62.4%] (diabetes - 22.8% [21.5-24.1%], prediabetes - 37.9% [36.1-39.7%]); Delhi 72.7% [70.6-74.9%] (diabetes - 25.2% [23.6-26.8%], prediabetes - 47.6% [45.6-49.5%]); and Karachi 47.4% [45.7-49.1%]; (diabetes - 16.3% [15.2-17.3%], prediabetes - 31.1% [29.5-32.8%], respectively). Proportions of self-reported diabetes were 55.1%, 39.0%, and 48.0% in Chennai, Delhi, and Karachi, respectively. City, age, family history of diabetes, generalized obesity, abdominal obesity, body fat, high cholesterol, high triglyceride, and low HDL cholesterol levels were each independently associated with prediabetes, while the same factors plus waist-to-height ratio and hypertension were associated with diabetes. Conclusion: Six in ten adults in large South Asian cities have either diabetes or prediabetes. These data call for urgent action to prevent diabetes in South Asia. © 2015. Source

Balasubramanyam M.,Madras Diabetes Research Foundation MDRF | Lenin R.,Madras Diabetes Research Foundation MDRF | Monickaraj F.,Madras Diabetes Research Foundation MDRF
Indian Journal of Clinical Biochemistry | Year: 2010

The endoplasmic reticulum (ER) is a cellular compartment responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. A myriad of pathological and physiological factors perturb ER function and cause dysregulation of ER homeostasis, leading to ER stress. Accumulating evidence suggests that ER stress plays a role in the pathogenesis of diabetes, contributing to pancreatic β-cell loss and insulin resistance. ER stress may also link obesity, inflammation and insulin resistance in type 2 diabetes. In this review, we address the transition from physiology to pathology, namely how and why the physiological UPR evolves to a proapoptotic ER stress response in diabetes and its complications. Special attention was given to elucidate how ER stress could explain some of the 'clinical paradoxes' such as secondary sulfonylurea failure, initial worsening of retinopathy during tight glycemic control, insulin resistance induced by protease inhibitors and other clinically relevant observations. © 2010 Association of Clinical Biochemists of India. Source

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