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A Ramachandran

Publications and source records attributed to A Ramachandran.

At least 19 recordsLinked to original sources

Prevention of type 2 diabetes: a review.

One of the major public health challenges of the 21st century is type 2 diabetes. WHO estimates that by 2025 as many as 200-300 million people worldwide will have developed the disease. A distressing increase in children is perhaps the most alarming sign of something going wrong. Roughly half of the risk of type 2 diabetes can be attributed to environmental exposure and the other half to genetics. Central themes for prevention are the risk factors overweight, sedentary lifestyle, certain dietary components and perinatal factors. Overweight is the most critical risk factor, and should be targeted for prevention of type 2 diabetes especially among children and youths. Ethnicity and perinatal factors are also worth considering. Today we know that prevention helps. In the US Diabetes Prevention Programme for high risk individuals, there was a 58% relative reduction in the progression to diabetes in the lifestyle group compared with the controls. Within the lifestyle group, 50% achieved the goal of more than 7% weight reduction, and 74% maintained at least 150 min of moderately intense activity each week. This review discusses different forms of prevention, and proposes first of all to target people with Impaired Glucose Tolerance with increasing activity and altering dietary factors. And secondly, population-based measures to encourage increased physical activity and decreased consumption of energy-dense foods are important, and may target school children and young people, certain ethnic groups and women with gestational diabetes.

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Metabolic syndrome does not increase the risk of conversion of impaired glucose tolerance to diabetes in Asian Indians--Result of Indian diabetes prevention programme.

AIMS: In this study, we assessed for the prevalence of metabolic syndrome (MetS) in the cohort of subjects with impaired glucose tolerance (IGT) in the Indian Diabetes Prevention Programme and studied whether the syndrome enhanced the conversion to diabetes. METHODS: Effectiveness of lifestyle modification (LSM), metformin (Met) and LSM plus Met was tested in a randomised, controlled primary prevention study in subjects with IGT n=502 (M:W 397:105) at a median follow up of 30 months. Baseline prevalence of MetS was calculated using the WHO criteria. Insulin resistance (IR) was calculated using homeostasis model assessment (HOMA) method. RESULTS: MetS was present in 233 subjects (46.4%; 95% CI 41.9-50.9) in the total group, in men (n=168; 42.3%; 95% CI 37.4-47.3) and in women (n=65; 61.9%; 95% CI 51.9-71.2) (men versus women chi(2)=12.8, p=0.0005). Insulin resistance (HOMA-IR>or=4.1) was present in 69.1% with no gender difference. IR increased proportionately with increasing number of abnormalities, in IGT (39.8%), IGT plus one abnormality (56.5%) and IGT plus any two or more abnormalities (69.1%) (Mantel Haenszel chi(2)=22.8, p<0.0001). Incidence of diabetes was similar in subjects with (40.3%) (n=94/233) or without (40.1%) (n=108/269) MetS (p=0.97). Cox's regression analysis confirmed that MetS did not enhance the conversion rate of IGT to diabetes both in the control (HR=0.88, 95% CI 0.53-1.47, p=0.63) and in the total group (HR=1.02, 95% CI 0.78-1.35, p=0.88), after correcting for effects of intervention. CONCLUSION: Prevalence of MetS is high in Asian Indian IGT subjects, especially in women. However, it did not influence the rate of conversion of IGT to diabetes.

Adult↗

Persistent impaired glucose tolerance has similar rate of risk factors as for diabetes--results of Indian diabetes prevention programme (IDPP).

OBJECTIVE: To determine the occurrence of persistent impaired glucose tolerance (IGT) (two times OGTT positive) and to compare the physical and clinical characteristics with subjects having transient IGT or diabetes. RESEARCH DESIGN AND METHODS: Nondiabetic subjects aged 35-55 years were screened (n=10,839, M:W 8667:2172) using 2h capillary blood glucose. IGT was diagnosed in 1332 (12.3%). Among them, 1025 (77%) responded for a second OGTT and 531 subjects (51.8%) had persistent IGT. Biochemical, demographic and anthropometric characteristics were compared among the normal (NGT, 30.1%), IGT and diabetic subjects (DM, 18%) at second GTT. RESULTS: All had similar age. BMI, waist circumference and body fat percentage were lower in NGT than in IGT and diabetes. IGT and diabetes had similar characteristics. Family history of diabetes was the highest in persistent IGT. CONCLUSION: Among the screened subjects, 1 in 20 had persistent IGT. Subject with persistent IGT had higher rates of risk factors for diabetes, such as high BMI, waist circumference and body fat percentage.

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The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).

AIMS/HYPOTHESIS: Lifestyle modification helps in the primary prevention of diabetes in multiethnic American, Finnish and Chinese populations. In a prospective community-based study, we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger, leaner and more insulin resistant than the above populations. METHODS: We randomised 531 (421 men 110 women) subjects with IGT (mean age 45.9+/-5.7 years, BMI 25.8+/-3.5 kg/m(2)) into four groups. Group 1 was the control, Group 2 was given advice on lifestyle modification (LSM), Group 3 was treated with metformin (MET) and Group 4 was given LSM plus MET. The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria. RESULTS: The median follow-up period was 30 months, and the 3-year cumulative incidences of diabetes were 55.0%, 39.3%, 40.5% and 39.5% in Groups 1-4, respectively. The relative risk reduction was 28.5% with LSM (95% CI 20.5-37.3, p=0.018), 26.4% with MET (95% CI 19.1-35.1, p=0.029) and 28.2% with LSM + MET (95% CI 20.3-37.0, p=0.022), as compared with the control group. The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM, 6.9 for MET and 6.5 for LSM + MET. CONCLUSIONS/INTERPRETATION: Progression of IGT to diabetes is high in native Asian Indians. Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT; there was no added benefit from combining them.

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Stress and undetected hyperglycemia in southern Indian coastal population affected by tsunami.

AIM: Natural calamities are known to result in higher stress conditions and also result in adverse health outcomes including development of non-communicable diseases. The impact of tsunami on mental stress and prevalence of hyperglycemic conditions was assessed in a population affected by the calamity in coastal populations of southern India. METHODS: Two populations similar in demography and physical characteristics, but, one affected by tsunami were selected for a comparative study. Subjects aged 20 years or above were randomly selected (control population n = 1176; tsunami population n = 1184). Details of stress were assessed using Harvard trauma questionnaire and scores were assigned. Glucose tolerance was assessed using 2h capillary blood glucose (75gms glucose load) and diagnosis was made using WHO criteria. RESULTS: Stress score was significantly higher in tsunami population. Although the total prevalence of diabetes was similar (control - 10.0 %; tsunami population - 10.5 %) prevalence of undetected diabetes (5.7 % vs. 3.8 %; Z = 9.54, P < 0.001) and impaired glucose tolerance (9.8 % vs. 8.3 %; Z = 12.83, P < 0.001) higher in the tsunami area. Stress score was higher in women and in the young in the tsunami area. CONCLUSION: Population affected by tsunami was under high stress and also showed a high prevalence of undetected diabetes and impaired glucose tolerance.

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Bacterial cell microarrays for the detection and characterization of antibodies against surface antigens.

Bacterial cell surface antigens interact with the host immune system resulting in the production of antibodies. Detection of antibodies against surface antigens has applications in diagnosis of many bacterial infections, assessment of immune status and epidemiological studies. We developed a microarray platform, for antibody detection, by printing Gram-negative and Gram-positive whole bacterial cells on nitrocellulose coated glass substrates. Antibody binding was detected using fluorophore labeled secondary antibodies. The sensitivity of antibody detection was found to be 0.1 microg/ml. Using bacterial cell microarrays it was also possible to successfully detect antibodies against Francisella tularensis in canine serum samples declared positive for tularemia based on microagglutination antibody titer. Use of bacterial cells as the antigen source in immunoassays has the advantages of simulating in vivo presentation of surface antigens and also eliminating the need for antigen purification. The microarray format gives the added advantage of simultaneous detection of antibodies against multiple bacteria employing only small amounts of samples and reagents.

Animals↗

Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies.

Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

Activin Receptors, Type I↗

Derivation and validation of diabetes risk score for urban Asian Indians.

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 >or=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>or=7 mmol/l and HbA1c>or=6.5% were used for diagnosis). A logistic regression model was used to compute the beta 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.

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Lipopolysaccharide microarrays for the detection of antibodies.

Lipopolysaccharide (LPS) is the major component of Gram-negative bacterial outer membrane. LPS are immunogenic and show species/strain specificity. The demonstration of anti-LPS antibodies in clinical samples is of diagnostic value in certain Gram-negative bacterial infections. In the present study we explored the possibility of immobilizing LPS isolated from different bacteria in a microarray format for the detection of anti-LPS antibodies. LPS was successfully immobilized on nitrocellulose-coated glass slides, preserving the accessibility of epitopes for antibody binding. Specificity of the LPS arrays was established using four different monoclonal antibodies specific for Escherichia coli O111, E. coli O157, Francisella tularensis and Salmonella typhimurium O-antigens and a panel of LPS preparations. The detection limit of antibodies was found to be 10 ng/ml, which is about a 100-fold greater sensitivity compared to conventional immunofluorescence assays. Furthermore, using LPS arrays, tularemia positive canine serum samples could be differentiated from negative samples based on the presence of significantly higher levels of anti-F. tularensis LPS antibodies in positive samples. LPS arrays will facilitate simultaneous screening of samples against multiple antigens and are expected to find applications in diagnostics and seroepidemiology.

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Epidemiology of diabetes in India--three decades of research.

India has nearly 33 million diabetic subjects today, which is briefly contributed by the urban population. The scenario is changing rapidly due to socio-economic transition occurring in the rural areas also. Availability of improved modes of transport, and less strenuously as in the vicinity have resulted in decreased physical activities. Better economic conditions have produced changes in diet habits. The conditions are more favourable for expression of diabetes in the population, which already has a racial and genetic susceptibility of the disease. Recent epidemiological data show that the situations are similar throughout the country. Prediabetic conditions like impaired glucose tolerance and impaired fasting glucose are also on the rise, indicating the possibility of further rise in the prevalence of diabetes. Metabolic syndrome, which is a constellation of cardiovascular risk factors, of which hyperglycaemia and insulin resistance are components, is also widely prevalent. The conversion to diabetes is enhanced by the low thresholds for the risk factors, such as age, body mass index and upper body adiposity. Indians have a genetic phenotype characterized by low body mass index, but with high upper body adiposity, high body fat percentage and high level of insulin resistance. With a high genetic predisposition and the high susceptibility to the environmental insults, the Indian population faces a high risk for diabetes and its associated complications. Early diagnosis of high risk groups and appropriate intervention by lifestyle modification may solution for the disease burden.

Age Distribution↗

Development of a reliable and valid psychosocial measure of self-perception of health in type 2 diabetes.

OBJECTIVES: The aim was to develop a reliable and valid psychosocial measure of self-perception of health in type 2 diabetes. METHODS: Item analysis and factor analyses were done in order to stabilize and establish principal components of the questionnaire. Reliability (internal consistency aspect) was established using Chronbach's alpha method. Concurrent and discriminant validities were established using conventional methods. RESULTS: Factor analysis yielded 12 significant factors (eigen value > or =1), but first six components were retained based on Scree test. These six principal varimax factors explain 49.7% of variance of psychosocial measure of self-perception of health. CONCLUSIONS: The final version after all these psychometric procedures had 27 items with six principal components. They were appropriately named as follow: (I) Positive self-feeling; (II) Sociality; (III) Attention seeking; (IV) Feel healthy; (V) Worry about health; (VI) Dependence. Total variance explained is 49.7%.

Attitude to Health↗

Profile of diabetic foot complications and its associated complications--a multicentric study from India.

AIM: The aims of this study were to determine. The prevalence of foot complications such as neuropathy, peripheral vascular disease (PVD), amputations and infections and the associated diabetic complications and practice of foot care among these subjects. METHODS: A total of 1319 type 2 diabetic patients, were selected from four different centres across India. The centres were Diabetes Research Centre (DRC), Chennai, Government Rajaji Hospital (GRH), Madurai, Christian Medical College (CMC), Vellore and All India Institute of Medical Science (AIIMS), Delhi. Details were collected regarding foot problems and associated complications. RESULTS: The prevalence of neuropathy was 15% (n=193) and PVD was 5% (n=64). Infections were present in 7.6% (n=100) of patients. The infection rate varied from 6-11% in the different centres. Nearly 3% of subjects had undergone a minor or major amputation. DISCUSSION: This study found that the prevalence of infection was 6-11% and prevalence of amputation was 3% in type 2 diabetic patients. Neuropathy (15%) was found to be an important risk factor for diabetic foot infections. Effective foot care advice should be propagated to reduce the burden imposed by diabetic foot complication particularly in developing countries like India.

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Creating a pandemic of prediabetes: the proposed new diagnostic criteria for impaired fasting glycaemia.

AIMS/HYPOTHESIS: In November 2003 the American Diabetes Association expert committee on the diagnosis and classification of diabetes mellitus suggested a revision of the diagnostic criteria for IFG, lowering the diagnostic threshold from 6.1 to 5.6 mmol/l. The aim of the present study was to evaluate the consequences of this change with respect to: (i) the prevalence of IFG in five different countries; (ii) the concordance between IFG and IGT (classification of individuals); and (iii) the cardiovascular risk profile of these groups. Finally we discuss the likelihood that intervention for cardiovascular risk and prevention strategies developed for individuals with IGT are applicable to subjects with IFG. METHODS: The first part of the study is based on the population-based Danish Inter99 study, where 6265 individuals, aged 30 to 60 years and without previously diagnosed diabetes, underwent an oral glucose tolerance test. The second part is based on the DETECT-2 project, in which studies from China, India, France and USA were used to analyse the impact of the proposed revision of the diagnostic criteria in different ethnic groups. RESULTS: The proposed change in diagnostic criteria would increase the prevalence of IFG in Denmark from 11.8 to 37.6%. The proposed IFG category would identify 60.0% of all subjects with IGT compared to 29.2% with the old criteria, but among individuals with the new IFG category only 18.5% would also have IGT. Individuals with isolated IFG had lower insulin levels and a lower cardiovascular risk profile with the proposed criteria compared with the current WHO criteria. Data from the DETECT-2 study confirmed the marked increase in the prevalence of IFG, and the estimated number of individuals in the age range 40 to 64 years with IFG in urban India, urban China and the USA would increase by 78%, 135% and 193% respectively. CONCLUSIONS/INTERPRETATION: The proposed revised diagnostic criteria will lead to a dramatic increase in the prevalence of IFG, but the concordance rate between IFG and IGT remains low. This new IFG group will have a more favourable cardiovascular risk profile than the current IFG group as defined by the WHO. This seriously questions whether the existing intervention strategies are applicable to the new category of individuals with IFG.

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Temporal changes in prevalence of diabetes and impaired glucose tolerance associated with lifestyle transition occurring in the rural population in India.

AIMS/HYPOTHESIS: The rural Indian population is undergoing lifestyle transition due to socio-economic growth. This study was done to determine the temporal changes in prevalence of diabetes and IGT that could have occurred in a rural population in India as a result of the lifestyle transition. METHODS: A cross-sectional study of 1213 Asian-Indian subjects aged 20 years or over was done to look for the prevalence of diabetes and IGT using the 1999 WHO criteria. The temporal changes were assessed in comparison with a similar study conducted 14 years previously. The factors associated with the temporal changes were also analysed. RESULTS: Nearly a three-fold increase in age- and sex-adjusted prevalence of diabetes (from 2.20% to 6.36%) was seen in 2003 when compared with a similar study done 14 years before. Prevalence of IGT did not change significantly (7.44% in 1989 vs 7.18% in 2003). Improvement in living conditions had occurred during the period, occupational changes were seen, the number of manual labourers had decreased and economic conditions had improved. BMI and waist circumference had increased. After correcting for age, sex and differences in time periods, waist circumference and physical inactivity showed significant associations with the increased prevalence of diabetes. CONCLUSIONS/INTERPRETATION: Demographic transition due to improved living conditions in rural India was associated with a three-fold increase in the prevalence of diabetes. Increased upper body adiposity and physical inactivity showed significant association with this phenomenon.

Adipose Tissue↗

Flow mediated dilatation and carotid intimal media thickness in South Indian type 2 diabetic subjects.

OBJECTIVE: The aims of this study were to determine: (1). endothelial function in type 2 diabetic subjects with and without diabetic microvascular complications using flow mediated dilatation method (FMD); (2). influence of other variables on FMD; and (3). the correlation between FMD and carotid intimal media thickness (IMT). RESEARCH, DESIGN AND METHODS: In this cross-sectional study, flow mediated dilatation (FMD) and intimal media thickness (IMT) were determined using high resolution ultrasonography in 20 non-diabetic subjects, in 23 type 2 diabetic subjects without any complications and in 23 type 2 diabetic patients with nephropathy and retinopathy. RESULTS: Age-adjusted mean (S.D.) FMD value in diabetic subjects (8.9 +/- 5%) was lower (P < 0.0001) when compared with the group of control subjects (18.8 +/- 7.5 %. However, there was no difference in the age-adjusted FMD values between diabetic subjects with and without complications (7.3 +/- 3.3 % versus 10.5 +/- 5.9 %). FMD levels did not vary significantly between sexes in both non-diabetic and diabetic groups. FMD correlated negatively with carotid IMT (r = -0.23, P < 0.05). In multiple linear regression analysis, age adjusted FMD was associated only with type 2 diabetes with complications (P = 0.012). The variance explained was 21.9%. CONCLUSION: Abnormal FMD and increased carotid IMT were present in type 2 diabetes. Both these parameters negatively correlated with each other supporting an association between impaired FMD and atherogenesis. As these abnormalities existed even in diabetic subjects with no microvascular complications, it is likely that they preceded the development of these complications.

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Low risk threshold for acquired diabetogenic factors in Asian Indians.

India is facing an epidemic of type 2 diabetes, with high prevalence in urban areas. Urbanisation and associated life style changes adversely affect the risk factors for diabetes unmasking the high genetic tendency existing in the population. Various epidemiological studies in Indians have shown that the increasing prevalence of diabetes could be attributed to a high genetic risk and lower risk thresholds for acquired risk factors such as age, obesity, abdominal adiposity and a high percentage of body fat. Diabetes occurs at a younger age in Indians compared to Whites. The risk of diabetes increases with a body mass index (BMI) of >23 kg/m(2) and waist circumference of 85 cm for men and 80 cm for women in Asian Indians. For a given BMI, Asian Indians have higher central adiposity. There is also evidence of higher insulin resistance amongst Indians, and this is partly explained by higher body fat percentage. A large proportion of urban adults has the metabolic syndrome also which predisposes them to both diabetes and cardiovascular diseases. Recognition of these conditions and institution of early preventive measures are urgently needed.

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