Assessing Diagnostic Accuracy of Serum Holotranscobalamin (Active-B12) in Comparison with Other Markers of Vitamin B12 Deficiency.

About 15-40% India is Vitamin B12 deficient (commonly diagnosed by total Vitamin B12) but, as only holoTC (active form) is taken up by body cells, thus measuring holoTC is more reflective of Vitamin B12 status than the former. We aimed to assess diagnostic accuracy of serum holoTC in comparison with total Vitamin B12 and total Homocysteine (HCY) as indicator of serum Vitamin B12 status. 217 human subjects (99 males and 118 females) ranging from 17 to 83 years were divided into Vitamin B12 deficient (n = 70), borderline (n = 100) and sufficient groups (n = 47) who were further assessed for markers of Vitamin B12 deficiency-holoTC, HCY, Mean Corpuscular Volume (MCV), Folate, heamoglobin and creatinine. Samples were analysed using Siemens Advia Centaur Xpi. Total Vitamin B12 deficient group had - 84.3% holoTC deficient; 15.7% holoTC sufficient; 72.9% with elevated HCY; 27.1% with normal HCY; 11.4% with megaloblastic anaemia. Borderline group had - 34% holoTC deficient; 28% elevated HCY. A strong positive correlation was found between Total Vitamin B12 and holoTC (r = 0.754, p = <0.001) but strong negative correlation existed between holoTC and HCY (r = - 0.471, p = <0.001). Concordance between Total Vit B12 and HCY (Kappa index = 0.51, p < 0.001); between holoTC and HCY (Kappa index = 0.52, p = <0.001) were statically significant but the latter had a better sensitivity and specificity. Also, statically significant association exists between Total Vitamin B12 and holoTC with HCY (p = <0.001). Therefore, it is ascertained that Active Vitamin B12 assay is a better test and can be considered as an early marker of vitamin B12 deficiency.

Vitamin-D deficiency and its association with breast feeding among children at 1 year of age in an urban community in South India.

CONTEXT: High prevalence of Vitamin D deficiency is reported among healthy infants, children and adolescents. Maternal Vitamin-D deficiency, poor vitamin-D content of breast milk even in Vitamin-D replete mothers, exclusive breastfeeding without Vitamin-D supplementation and inadequate sunlight exposure are important risk factors for Vitamin D deficiency in infants. AIM: To determine the prevalence of hypovitaminosis-D and its relation with breast feeding and childhood illness among healthy infants at 1 year of age. SETTINGS AND DESIGN: A prospective cohort study was conducted among the infants in an urban community in south India. METHODS AND MATERIAL: A total of 495 children were followed up at 1 year of age. Clinical history, anthropometric measurements, and serum blood samples for vitamin-D were obtained. The effects of breastfeeding duration and infections on Vitamin-D status were assessed by univariate and multivariate analysis. RESULTS: The prevalence of Vitamin D deficiency was 22% in these infants. Univariate analysis showed risk of hypovitaminosis-D in children breast fed for more than 6 months (p 0.02); however, multivariate analysis did not prove an association. Other risk factors analysed were not significantly associated with Hypovitaminosis D. CONCLUSION: The prevalence of hypovitaminosis-D in this study was low compared to previous studies from India. This study emphasizes the issue of hypovitaminosis-D in otherwise normal children. Routine Vitamin-D supplementation for antenatal women and infants may be needed to overcome this public health problem.

Anthropometric measurements for the prediction of the metabolic syndrome: a cross-sectional study on adolescents and young adults from southern india.

OBJECTIVES: To determine which anthropometric measurement correlates best with the metabolic abnormalities associated with the metabolic syndrome in adolescents and young adults. DESIGN: Cross-sectional study. SETTING: Schools, high schools and universities. PARTICIPANTS: 1359 adolescents and young adults aged 14-25 years. MAIN OUTCOME MEASURES: Anthropometric predictors of metabolic abnormalities as classified by International Diabetes Federation definition. RESULTS: The waist circumference (OR 1.56, 95% CI 1.0 to 2.43: p≤0.01) and the abdominal skin fold thickness (OR 1.44, 95% CI 1.02 to 2.04, p≤0.01) above the third quintile cut-offs were found to be significantly associated with metabolic abnormalities. The sensitivity of either one of these measurements in predicting metabolic abnormalities was 66.1% with a negative predictive value of 82.8%. Hyperglycaemia was significantly associated with an abdominal skin fold thickness over the fourth quintile alone (OR 1.63, 95% CI 1.24 to 2.1). All the anthropometric measurements correlated well with elevated triglycerides and hypertension. CONCLUSIONS: In a large community-based cross-sectional survey of subjects aged 14-25 years, the waist circumference and the abdominal skin fold thickness are important predictors of the metabolic abnormalities associated with metabolic syndrome. This simple clinical tool may help in a primary care setting to identify subjects who require a further biochemical evaluation and would considerably reduce the cost of unwarranted testing.

Accuracy of filter paper method for measuring glycated hemoglobin.

BACKGROUND AND OBJECTIVES: Glycated hemoglobin (HbA1c) provides an accurate and reliable method to assess the glycemic control in patients with Diabetes. Its measurement is limited by the inconvenience of sample collection that requires venipuncture, sample handling and storage factors. The aim of this study was to assess the feasibility of using a dried capillary blood spot on a filter paper to estimate HbA1c, to check its stability at room temperature and to compare these values with the venous sample HbA1c by Turbidimetric Inhibition Immunoassay (TINA, Tina-quant HbA1c II). METHODS: Venous blood samples of seventy eight patients with Type 1 or type 2 diabetes, were collected in EDTA containing vacutainers. Stability of HbA1c was studied in capillary blood samples blotted on to Whatman number 1 filter paper and stored at room temperature, for the first 20 patients enrolled in the study. After establishing the stability over a ten day period, HbA1c values obtained on the capillary blood spots were compared with those obtained from the venous blood samples of the remaining 58 patients. RESULTS: Glycated hemoglobin is found to be stable in dried capillary blood spots on filter paper till the 10th day, stored at room temperature. It however, shows an inherent variability of +/- 15%, which falls within the permissible variability (18%) of the quality control material. Seventy nine percent of the capillary HbA1c values were found to fall within this range. With linear regression, we derived the relationship between filter paper and venous HbA1c values. The regression equation was as follows: Cap.HbA1c = 0.95 (Ven.HbA1c) + 1.4. The filter paper results were highly correlated with the venous sample values (r = 0.889, p < 0.01). CONCLUSION: Measurement of glycated hemoglobin in dried blood spots on filter paper gives reliable and reproducible results. In our study, the mean capillary sample HbA1c value was 12% higher compared to the venous sample HbA1c values. Therefore a higher normal range may have to be used for interpreting the dried blood spot capillary blood HbA1c values.

Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease.

Most studies aiming to detect associations of genetic variation with common complex diseases, e.g. coronary heart disease (CHD) have been performed in populations with a western lifestyle but it is unclear whether associations detected in one geographic group exist also in others. We here have determined lipoprotein(a) levels and apo(a) K-IV-2 repeat genotypes in CHD patients (N=254) and controls (N=480) from two Asian Indian populations (Tamil Nadu and New Delhi). In both populations and also in the pooled dataset median Lp(a) levels were significantly elevated in the patients (27.4 mg/dl) compared with the controls (17.6 mg/dl). Apo(a) K-IV-2 allele frequencies were not different between the CHD patients and controls and thus did not explain the increased Lp(a) levels in CHD patients. Contrary to what has recently been observed in Black and White men short (K-IVor=30) apo(a) alleles were all associated with higher Lp(a) levels in the patients. Accordingly relative risk (estimated as odds ratio) for CHD rose continuously with increasing Lp(a) but was independent of apo(a) allele length. Together with previous studies our results indicate that the relation between apo(a) genotypes, Lp(a) levels, and CHD may be heterogeneous across ethnic groups and that it depends on the genetic architecture of the Lp(a) trait in a given population whether an association of K-IV-2 repeat length with CHD exists or not.

Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease.

BACKGROUND: Plasma lipoprotein (a) levels in the Indian population are varied; this study was undertaken to determine the relationship between plasma lipoprotein (a) levels and their phenotypes in a group of south Indian patients with coronary artery disease. METHODS AND RESULTS: A total of 104 patients with angiographically proven coronary artery disease were compared with 104 age- and sex-matched controls with no risk factors such as hypertension, diabetes and smoking. Lipoprotein (a) levels were measured by an in-house ELISA method and its phenotyping was done by SDS agarose gel electrophoresis. Plasma lipoprotein (a) levels were significantly elevated in patients with coronary artery disease as compared to controls (33.4+/-26.1 mg/dl v. 21.4+/-12.8 mg/dl; p<0.01). Lipoprotein (a) phenotyping showed that low-molecular weight isoforms were found only in 19.2% of the patients with coronary artery disease and their plasma lipoprotein (a) levels were significantly elevated compared to coronary artery disease patients with higher molecular weight isoforms (50.9+/-34.2 mg/dl v. 29.24+/-20.06 mg/dl; p<0.001). CONCLUSIONS: Plasma lipoprotein (a) levels are significantly elevated in patients with coronary artery disease as compared to controls. The commoner phenotype in a South Indian population is the larger apolipoprotein (a). in which the lipoprotein (a) levels are lower. Hence the contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our population, if any, is modest.

Low apolipoprotein A-IV plasma concentrations in men with coronary artery disease.

OBJECTIVES: The objective of this study was to evaluate the relation between apolipoprotein A-IV (apoA-IV) plasma concentrations and coronary artery disease (CAD). BACKGROUND: Experimental in vitro and in vivo studies favor apoA-IV to be protective against the development of atherosclerosis. Mice that overexpress either human or mouse apoA-IV demonstrated a significant reduction of aortic atherosclerotic lesions compared with control mice. Data on apoA-IV plasma concentrations and CAD in humans are lacking. METHODS: We determined in two independent case-control studies of a Caucasian and an Asian Indian population whether apoA-IV plasma concentrations are related to the presence of angiographically assessed CAD. RESULTS: Plasma apoA-IV levels were significantly lower in 114 male Caucasian subjects with angiographically defined CAD when compared with 114 age-adjusted male controls (10.2 +/-3.8 mg/dL vs. 15.1 +/- 4.0 mg/dL, p < 0.001). Logistic regression analysis indicated that the association between apoA-IV levels and CAD was independent of the high-density lipoprotein cholesterol and triglyceride concentrations. The inverse relationship between plasma levels of apoA-IV and the presence of CAD was confirmed in an independent sample of 68 male Asian Indians with angiographically documented CAD and 68 age-matched controls. CONCLUSIONS: The results of this cross-sectional study demonstrate for the first time an association between low apoA-IV concentrations and CAD in humans and suggest that apoA-IV may play an antiatherogenic role in humans.

Correlation of serum prostate specific antigen levels and bone scintigraphy in carcinoma prostate.

Serum prostate specific antigen (PSA) has been suggested as an accurate means of monitoring prostate cancer. An analysis of PSA levels and bone scan findings was carried out in a heterogeneous group of patients with a view to determine whether PSA can accurately predict bone metastases in carcinoma prostate. Of the 48 patients studied, all 10 untreated cases had elevated PSA levels, eight having bone metastases. In 29 cases on follow-up after treatment of the primary, 10 out of 11 cases with normal PSA had a negative bone scan. In the nine who received hormonal therapy, the PSA levels were generally lower than others in the study group. Two out of four with normal PSA had bone metastases. In 26 cases with positive bone scans, 23 had elevated PSA levels (mean 109.9 ng ml-1). Among 22 patients who had normal bone scans, all 10 with high PSA were found to have soft tissue disease which could explain the elevated PSA. In those with normal PSA, 12 out of 15 patients had negative scans. PSA has fairly high sensitivity (86.5%) and negative predictive value (80%). But it suffers from low specificity (54.5%) and low positive predictive value (69.7%) for bone metastases. In an untreated patient with elevated PSA, a bone scan may be required to exclude bone metastases, whereas during follow-up after treatment, a normal PSA level may obviate a "routine" bone scan.