Assessment of Apo-B and TG/HDL-C Ratio as Indicators of Insulin Resistance in Patients with Metabolic Syndrome

The aim of the present study was to assess Apolipoprotein B (Apo-B) and Triglyceride/High Density Lipoprotein Cholesterol (TG/HDL-C) ratio as indicators of insulin resistance (IR) with Homeostasis Model of assessment of insulin resistance (HOMA IR)) in metabolic syndrome patients . Study Design: Observational and prospective. Place and Duration of Study: The study was carried out in Department of Biochemistry and Department of Medicine, MGM Medical College, Navi-Mumbai from March 2012 to June 2013. Methodology: Total 110 normal subjects and patients were recruited in the study after obtaining informed written consent. They were divided in to two groups. Group I was healthy controls (n=50) and Group II included subjects with MS (n=60) as per NCEP ATP III criteria. Anthropometric measurements & biochemical analysis was performed in all subjects. IR was defined by HOMA IR. Simple & multiple regression analysis were used to obtain relationship between IR (HOMA IR) using TG/HDL-C (model -1) and Apo-B (Model- 2) as independent variables. Result: There were statistically significant differences in anthropometric, glycemic and lipid parameters between the control and study group (p<0.0001).The regression model between HOMA IR and TG/HDL-C ratio showed a positive correlation, (r=0.29, p < 0.05). HOMA IR & Apo-B also showed a significantly positive correlation (0. 41, p < 0.001). But combined multivariate analysis indicated that Apo-B is a better predictor of IR compared to TG/HDL-C ratio. Conclusion: We concluded in our study that Apo-B may be a better predictor of IR than TG/HDL-C and hence could be adopted in routine laboratory practice as a lipid marker for prediction of insulin resistance (IR) in metabolic syndrome patients at an early stage. Keywords: Insulin resistance; Apo B; metabolic syndrome; Insulin resistance indicators; lipid

Contribution of allelic variability in prostate specific antigen (PSA) & androgen receptor (AR) genes to serum PSA levels in men with prostate cancer.

Background & objectives: Wide variability in serum prostate specific antigen (PSA) levels exists in malignant conditions of the prostate. PSA is expressed in normal range in 20 to 25 per cent of prostate cancer cases even in presence of high grade Gleason score. This study was aimed to assess the influence of genetic variants exhibited by PSA and androgen receptor (AR) genes towards the variable expression of PSA in prostate cancer. Methods: Pre-treatment serum PSA levels from 101 prostate cancer cases were retrieved from medical record. PSA genotype analysis in promoter region and AR gene microsatellite Cytosine/Adenine/Guanine (CAG) repeat analysis in exon 1 region was performed using DNA sequencing and fragment analysis techniques. Results: A total of seven single nucleotide polymorphisms (SNPs) in the PSA promoter region were noted. Only two SNPs viz., 158G/A (P<0.001) in the proximal promoter region and -3845G/A (P<0.001) in enhancer region showed significant association with serum PSA levels. The carriers of homozygous GG genotype (P<0.001) at both of these polymorphic sites showed higher expression of PSA whereas homozygous AA genotype (P<0.001) carriers demonstrated lower PSA levels. The combination effect of PSA genotypes along with stratified AR CAG repeats lengths (long, intermediate and short) was also studied. The homozygous GG genotype along with AR long CAG repeats and homozygous AA genotype along with AR short CAG repeats at position -3845 and -158 showed strong interaction and thus influenced serum PSA levels. Interpretation & conclusions: The genetic variants exhibited by PSA gene at positions -3845G/A and -158G/A may be accountable towards wide variability of serum PSA levels in prostate cancer. Also the preferential binding of G and A alleles at these polymorphic sites along with AR long and short CAG repeats may contribute towards PSA expression.

TG/HDL-C Ratio: A Surrogate Marker of Insulin Resistance in Patients with Metabolic Syndrome.

Insulin resistance (IR) is hallmark of metabolic syndrome. It is important to identify IR as it is the early stage before development of diabetes mellitus. The standard method to measure insulin resistance is the euglycemic clamp technique, which is laborious. Hence, a number of surrogate measures like homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio have been developed. Both of the former involve calculations, while TG/HDL ratio may be readily available for clinicians. Therefore, this study was undertaken to assess whether TG/HDL-C ratio serves as a better predictive marker of IR. Objectives: The aim of the present study was to evaluate the triglyceride/HDL-C ratio as a surrogate marker of IR in metabolic syndrome patients. Materials and methods: Total 110 patients were recruited in the study after obtaining informed written consent. They were divided into two groups. Group I included healthy controls (n = 50) and subjects with metabolic syndrome (MS) (n = 60) as per NCEP ATP III criteria were included in group II. Anthropometric measurements and biochemical analysis was performed in all subjects. Results: There was statistically significant difference in anthropometric, glycemic and lipid parameters in control and study group (p < 0.0001). The regression model between HOMA-IR and TG/HDL-C ratio showed was positive correlation (r = 0.29, p = 0.01) while between QUICKI and TG/HDL-C ratio showed negative correlation (r = –0.37, p = 0.002). Conclusion: We report in our study that TG/HDL-C can be adopted in routine laboratory practice as a surrogate marker for prediction of insulin resistance. So that patients with metabolic syndrome may be beneficial at an early stage.

Brachial Artery Flow Mediated Vasodilatation Changes in Endothelium Due to Hyperuricemia in Type 2 Diabetes Mellitus.

Aim: This study aims to evaluate serum uric acid levels and assess its effect on endothelial dysfunction by measuring flow mediated vasodilatation (FMD) of brachial artery in type 2 diabetes mellitus. Study Design: Observational and prospective Place and Duration of Study: The study was carried out in Department of Biochemistry and Department of Radiology, MGM Medical College, Navi-Mumbai from August 2010 to 2012 Methodology: Total 90 patients were selected and divided in to three groups. Group I (n=30) – Controls, Group II A & B (n=60) –Diabetic patients without & with hyperuricemia (HUA). All subjects were examined by high resolution ultrasound to measure FMD. Serum uric acid and nitric oxide (NO) levels along with other biochemical parameters were estimated. Result: Group II B showed significantly increased serum uric acid levels (p<0.001) along with decreased levels of serum NO (p< 0.0001) and decreased vasodilatation when measured by FMD. (p<0.001). Conclusion: The FMD of brachial artery along with serum NO levels are reduced in patients of type 2 diabetes mellitus with HUA. Uric acid may be a contributing factor to endothelial dysfunction in type 2 diabetes. Such endothelial damage may be preventable by regularly monitoring uric acid levels and pharmacologically treating HUA.

A pilot study on the use of serum glyoxalase as a supplemental biomarker to predict malignant cases of the prostate in the PSA range of 4-20 ng/ml.

Background & objectives: Serum prostate specific antigen (PSA) though most commonly used for diagnosis of prostate cancer lacks specificity. This study was aimed at exploring the use of serum glyoxalase as a supplemental biomarker to differentiate between malignant vs non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml. Methods: Serum glyoxalase and PSA were measured in 92 men (30 control, 31 cases of benign prostate hyperplasia (BPH) and 31 cases of adenocarcinoma of prostate). Of the latter group, 11 cases of prostate cancer in the PSA range of 4-20 ng/ml were included for studying the diagnostic utility of combination of both serum PSA and glyoxalase. Results: In prostate cancer cases with PSA in the range of 4-20 ng/ml, the glyoxalase was found to be 233.3 ± 98.6 μmol/min while for the non-malignant group it was 103.1 ± 19.7 μmol/min. A cut-off of 19.2 ng/ml PSA showed sensitivity of 9 per cent, specificity of 96.7 per cent, positive predictive value (PPV) of 50 per cent and negative predictive value (NPV) of 75 per cent. A serum glyoxalase cut-off of 141 μmol/min showed sensitivity of 81.8 per cent, specificity of 100 per cent, PPV of 100 per cent and NPV of 93.9 per cent. Further, ROC analysis showed a significant difference in the area under curve (AUC) for glyoxalase as compared to serum PSA (0.92 vs 0.57; P<0.001). Interpretation & conclusions: Serum glyoxalase appears to be predictive of prostate cancer in the PSA range of 4-20 ng/ml. Studies with larger number of participants would be required to confirm this finding.