Utility of glycosylated haemoglobin in diagnosing diabetes in an urban Sri Lankan community

Introduction: American Diabetes Association (ADA) has officially endorsed glycosylated haemoglobin (HbA1c) as a diagnostic tool. The recommended cut-off for diagnosing diabetes is  6.5%. Objectives: To compare use of HbA1c and fasting plasma glucose (FPG) to diagnose diabetes in an urban Sri Lankan community. Methods: This cross-sectional study is based on baseline data from a prospective study on non-communicable diseases in randomly selected individuals aged 35-64 years in a selected community. HbA1c was measured by National Glycohaemoglobin Standardization Program certified Bio Rad Variant HbA1c HPLC method. Diagnostic performance of HbA1c was evaluated in those without previous diabetes. Receiver Operating Characteristic Curve was used to identify optimum HbA1c threshold. Results: We studied 2516 individuals with no previous history of diabetes. Of these 53.8% were women. Mean age was 52 ± 7.9 years. FPG was 7mmol/l in 245 (9.7%). HbA1c was  6.5% in 173 (6.9%). Concordance between FPG and HbA1c was 95% (both criteria positive: 5.8%; both criteria negative: 89.2%). Compared to FPG, HbA1c cut-off of 6.5% had specificity of 98.9% (95% CI 98.3-99.3) and sensitivity of 60% (95% CI 53.6-66.2). Positive and negative predictive values were 85% (95% CI 78.8-89.9) and 95.8% (95% CI 94.9-96.6), respectively. Compared to FPG, optimum HbA1c threshold for diagnosing diabetes was 5.9% (sensitivity: 84%; specificity: 88.8%; area under the curve: 0.91). Conclusions: In the study population, detection of diabetes with ADA recommended HbA1ccriterion was 29% less than with FPG criterion. Compared to FPG, HbA1c had high specificity but sensitivity was low. Further research is needed to refine the optimum HbA1c threshold in Sri Lankans.

Risk estimates of cardiovascular diseases in a Sri Lankan community.

OBJECTIVES: Quantifying the risk of cardiovascular disease (CVD) in a community is important in planning preventive strategies, but such data are limited from developing countries, especially South Asia. We aimed to estimate the risks of coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan community. METHODS: A community survey was conducted in an urban health administrative area among individuals aged 35-64 years, selected by stratified random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were estimated using three risk prediction tools: National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk Evaluation (SCORE), and World Health Organisation/ International Society of Hypertension (WHO/ISH) charts. RESULTS: Among study participants (n=2985), 54.5% were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk) criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5-13.1) respectively were classified as at 'high risk'. The proportion of high risk participants increased with age. 'High risk' was commoner among males (30.3% vs 20.6%, p<0.001) according to NCEPATP III criteria, but among females (9.7% vs. 6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference was noted in SCORE risk categories. CONCLUSIONS: A large proportion of individuals in this community are at risk of developing cardiovascular diseases, especially in older age groups. Risk estimates varied with the different prediction tools, and were comparatively higher with NCEP-ATP III charts.

A Comparison between Revised NCEP ATP III and IDF Definitions in Diagnosing Metabolic Syndrome in an Urban Sri Lankan Population: The Ragama Health Study.

Background. The prevalence of metabolic syndrome (MetS) within individual cohorts varies with the definition used. The aim of this study was to compare the prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri Lankan population and to investigate the characteristics of discrepant cases. Methods. 2985 individuals, aged 35-65 years, were recruited to the study. Anthropometric and blood pressure measurements and laboratory investigations were carried out following standard protocols. Results. Age and sex-adjusted prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions, respectively. IDF criteria failed to identify 21% of men and 7% of women identified by the revised NCEP criteria. The discrepant group had more adverse metabolic profiles despite having a lower waist circumference than those diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan cohort regardless of the definition used. The revised NCEP definition was more appropriate in identifying the metabolically abnormal but nonobese individuals, especially among the males predisposed to type 2 diabetes or cardiovascular disease. Further research is needed to determine the suitability of the currently accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults.

Evaluation of the hypoglycemic and hypolipidemic effects of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin-induced diabetic rats.

Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state.

Crystallization and preliminary X-ray analysis of shikimate dehydrogenase from Escherichia coli.

Shikimate dehydrogenase from Escherichia coli has been crystallized by the vapour-diffusion method using ammonium sulfate as a precipitant. Mass spectrometry confirmed the purity of the enzyme and dynamic light scattering was used to find the appropriate additives to yield a monodisperse enzyme solution. The crystals are monoclinic, space group C2, with unit-cell parameters a = 110.0, b = 139.8, c = 102.6 A, beta = 122.2 degrees (at 100 K). Native crystals diffract to 2.3 A in-house on a rotating-anode X-ray source. The asymmetric unit is likely to contain four molecules, related by 222 symmetry, corresponding to a packing density of 2.86 A(3) Da(-1).

Chemical modification monitored by electrospray mass spectrometry: a rapid and simple method for identifying and studying functional residues in enzymes.

A simple method to identify functional amino acids in enzymes is described. This method is based on the mass spectrometric detection of molecular weight changes as the consequence of chemical modification of enzymes with group-specific reagents. Here we report the use of phenylglyoxal, trinitrobenzene sulfonic acid, tetranitromethane and diethylpyrocarbonate to identify functional amino acid residues. Precise information is obtained about the stoichiometry of reaction, and a relationship between the loss of enzyme activity and the amount of chemical modification is easily established. Modification sites are located by proteolytic digestion of the modified enzyme, followed by peptide mapping based on high-pressure liquid chromatography using an electrospray mass spectrometer as an on-line detector. In comparison with more conventional methods, protein modification is monitored directly without the need to use radioactively or spectrally labelled reagents. The methodology is limited only by the stability of the chemically modified species produced. The method has been used to characterise the active sites of several shikimate pathway enzymes, and the results obtained have been confirmed by site-directed mutagenesis and X-ray crystallography.