Methodology in molecular genetics and its applications to diabetology

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Importance of controlling diabetes early - The concept of metabolic memory, legacy effect and the case for early insulinisation

Most of the microvascular complications of diabetes are related to the degree and the length of exposure to hyperglycaemia. New data from the follow-up studies of the Diabetes Control and Complications Trial- the Epidemiology of Diabetes Intervention and Complications Study (DCCT- EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) emphasize the role of glycemic control early in the course of the disorder and its value in prevention of later complications. The phenomenon of ongoing beneficial effects on diabetic complications after a period of improved glycemic control even if followed by a return to usual (often poorer) metabolic control has been described as representing "metabolic memory" by the DCCT/EDIC investigators and as a "legacy effect" by the UKPDS investigators. This article reviews these concepts and explores the role of early use of insulin as a tool to achieve good glycemic control in type 2 diabetes

New Exactly Solvable Isospectral Partners for PT Symmetric Potentials

We examine in detail the possibilty of applying Darboux transformation to non Hermitian hamiltonians. In particular we propose a simple method of constructing exactly solvable PT symmetric potentials by applying Darboux transformation to higher states of an exactly solvable PT symmetric potential. It is shown that the resulting hamiltonian and the original one are pseudo supersymmetric partners. We also discuss application of Darboux transformation to hamiltonians with spontaneously broken PT symmetry.Comment: 11 pages, 2 figures, To be published in Journal of Physics A (2004

Incidence of Diabetes and Pre-diabetes in a Selected Urban South Indian Population (Cups - 19)

Abstract Objectives: Several cross-sectional studies have reported on the prevalence of diabetes in India. However, there are virtually no longitudinal population-based studies on the incidence of diabetes from India. The aim of the study was to determine the incidence of diabetes and prediabetes in an urban south Indian population. Methods: The Chennai Urban Population Study [CUPS], an ongoing epidemiological study in two residential colonies in Chennai [the largest city in southern India, formerly called Madras] was launched in 1996; the baseline study was completed in 1997. Follow-up examination was performed after a mean period of 8 years. At follow-up, 501 [47.0%] subjects had moved out of this colonies and were lost to follow-up. Of the remaining 564 individuals, 513 [90.9%] provided blood samples for biochemical analysis. Regression analysis was done using incident diabetes as dependant variable to identify factors associated with development of diabetes or pre-diabetes. Results: Among subjects with normal glucose tolerance (NGT) at baseline [n=476], 64 (13.4%) developed diabetes and 48 (10.1%) developed pre-diabetes (IGT or IFG). The incidence rate of diabetes was 20.2 per 1000 person years and that of pre-diabetes was 13.1 per 1000 person years among subjects with NGT. Of the 37 individuals who were pre-diabetic at baseline, 15 (40.5%) developed diabetes [incidence rate: 64.8 per 1000 person years], 16 (43.2%) remained as pre-diabetic and 6 (16.2%) reverted to normal during the follow-up period. Regression analysis revealed obesity [Odds Ratio (OR): 2.1, p=0.001], abdominal obesity [OR: 2.23, p<0.001] and hypertension [OR: 2.57, p<0.001] to be significantly associated with incident diabetes. The Indian Diabetes Risk Score (IDRS) showed the strongest association with incident diabetes [OR: 5.14, p<0.001]. Conclusion: The study shows that the incidence of diabetes is very high among urban south Indians. While obesity, abdominal obesity and hypertension were associated with incident diabetes, IDRS was th

The Chennai Urban Rural Epidemiology Study (CURES) - study design and methodology (Urban Component) (CURES - 1)

The report of World Health Organization (WHO) shows that India tops the world with the largest number of diabetic subjects. This increase is attributed to the rapid epidemiological transition accompanied by urbanization, which is occurring in India. There is very little data regarding the influence of affluence on the prevalence of diabetes and its complications particularly retinopathy in the Indian population. Furthermore, there are very few studies comparing the urban / rural prevalence of diabetes and its complications. The Chennai Urban Rural Epidemiology Study (CURES) is designed to answer the above questions. CURES is initially planned as a cross-sectional study to evolve later into a longitudinal study. Subjects for the urban component of the CURES have been recruited from within the corporation limits of Chennai City. Chennai (formerly Madras), the largest city in Southern India and the fourth largest in India has been divided into 10 zones and 155 wards. 46 wards were selected by a systematic random sampling method to represent the whole of Chennai. Twenty thousand and one individuals were recruited for the study, this number being derived based on a sample size calculation. The study has three phases. Phase one is a door to door survey which includes a questionnaire, anthropometric, fasting capillary blood glucose and blood pressure measurements. Phase two focussed on the prevalence of diabetic complications particularly retinopathy using standardized techniques like retinal photography etc. Diabetic subjects identified in phase one and age and sex matched non-diabetic subjects will participate in these studies. Phase three will include more detailed studies like clinical, biochemical and vascular studies on a sub-sample of the study subjects selected on a stratified basis from phase one. CURES is perhaps one of the largest systematic population based studies to be done in India in the field of diabetes and its complications like retinopathy, nephropathy and neuropathy

Comparison of the world health organization and the International association of diabetes and pregnancy study groups criteria in diagnosing gestational diabetes mellitus in South Indians

We aimed to compare the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization (WHO) criteria to diagnose gestational diabetes mellitus (GDM) in Chennai, India. Materials and Methods: We reviewed the retrospective data of 1351 pregnant women who underwent screening for GDM at four selected diabetes centers at Chennai (three private and one government). All women underwent an oral glucose tolerance test using 75g glucose load and fasting, 1-h, and 2-h samples were collected. The IADPSG and WHO criteria were compared for diagnosis of GDM. Results: A total of 839 women had GDM by either the IADPSG or the WHO criteria, of whom the IADPSG criteria identifi ed 699 and the WHO criteria also identifi ed 699 women as having GDM. However, only 599/839 women (66.6%) were identifi ed by both criteria. Thus, 140/839 women (16.7%) were missed by both the IADPSG and the WHO criteria. 687/699 (98.2%) of the women with GDM were identifi ed by the WHO criteria. In contrast, each value of IADPSG criteria i.e., fasting, 1 h, and 2 h identifi ed only 12.5%, 14%, and 22%, respectively. Conclusions: A single WHO cut-point of 2 h140 mg/dl appears to be suitable for large-scale screening for GDM in India and other developing countries

A1C Cut Points to Define Various Glucose Intolerance Groups in Asian Indians

Objective: To determine A1C cut points for glucose intolerance in Asian Indians. Research Design and Methods: A total of 2,188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose (FPG) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose (IFG) (American Diabetes Association [ADA] criteria, FPG ≥5.5 and &lt;7 mmol/l, and World Health Organization [WHO] criteria, FPG ≥6.1 and &lt;7 mmol/l), impaired glucose tolerance (IGT) (2-h postload plasma glucose ≥7.8 and &lt;11.1 mmol/l), or diabetes (FPG ≥7 mmol/l and/or 2-h postload plasma glucose ≥11.1 mmol/l). A1C was measured using the Bio-Rad Variant machine. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1C cut points for diabetes, IGT, and IFG. Results: Mean ± SD values of A<SUB>1</SUB>C among subjects with normal glucose tolerance, IGT, and diabetes were 5.5 ± 0.4, 5.9 ± 0.6, and 8.3 ± 2.0%, respectively (P<SUB>trend</SUB> &gt; 0.001) with considerable overlap. To identify diabetes based on 2-h postload plasma glucose, the A1C cut point of 6.1% had an area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG ≥7.0 mmol/l, the A1C cut point was 6.4% (AUC = 0.966, sensitivity 93.3%, and specificity 92.3%). For IGT, AUC = 0.708; for IFG, AUC = 0.632 (WHO criteria) and 0.708 (ADA criteria), and the A1C cut point was 5.6%. Conclusions: In Asian Indians, A1C cut points of 6.1 and 6.4% defined diabetes by 2-h postload plasma glucose or FPG criteria, respectively. A value of 5.6% optimally identified IGT or IFG but was &lt;70% accurate