Inflammatory Biomarkers in Asian Indian Women with Metabolic Syndrome

Pooja R. Singhania, Garima Gupta, Kasturi Sen Ray

Department of Food Science and Nutrition, S.N.D.T. Women’s University, Mumbai, India.
Department of Food Science and Nutrition, S.N.D.T. Women’s University, Mumbai, India;.
S.V.T. College of Home Science, S.N.D.T. Women’s University, Mumbai, India..

DOI: 10.4236/fns.2013.410133                

Abstract

Cardiovascular diseases (CVD) are the leading cause of mortality necessitating its early detection. The emergence of newer subclinical biomarkers in addition to the known cardiometabolic risk factors may play an important role in early detection of CVD risk. In the present study, 74 adult females (30 - 75 y) with metabolic syndrome (MS) were selected and additional biochemical parameters such as C-reactive protein (CRP) and Homocysteine (Hcy) levels were analyzed. The average body mass index (BMI) and waist circumference of subjects were found to be 30 kg/m² and99 cmrespectively. Mean LDL levels were found to be much higher than normal (139 mg/dl) while the HDL levels were low (41.5 mg/dl). The average fasting blood sugar and insulin levels were within the normal range. However, 40.5% females had serum Hcy levels >13.2 μmol/l and 59.5% women had CRP levels >3 mg/L indicating increased risk of CVD. Higher Hcy levels were associated with hyperinsulinemia (p < 0.01) and hyperglycemia (p < 0.05), indicating predilection for glucose intolerance. CRP levels showed significant negative correlation with HDL (p < 0.05), indicating a predilection for glucose intolerance. The present study reports overall more than 40% MS women are classified as high risk group using the Western standards. Limited data on normal levels of inflammatory biomarkers are available for Asian Indians. The study results indicate the importance of Hcy and CRP values among females having metabolic syndrome, known to be at a high risk of CVD.

Keywords

Metabolic Disorder; Inflammatory Biomarkers; Homocysteine; C-Reactive Protein; Asian Indians; Metabolic Syndrome

1. Introduction

Metabolic syndrome (MS) is defined as a cluster of the most dangerous heart attack risk factors: diabetes and prediabetes, abdominal obesity, high cholesterol and high blood pressure [1]. M. Thiruvagounder et al. (2010) [2] reported that people with MS are about twice as likely to develop cardiovascular disease (CVD) and over four times as likely to develop Type 2 diabetes compared to subjects without metabolic syndrome. Asian Indians have strong predisposition to MS and CVD [3], which has been shown through several studies on Indians living in India [4,5] and abroad [6,7].

Traditional CVD risk factors account for only around 50% of cardiovascular morbidity and mortality [8]. Thus, the importance and utility of newer predictors have been emphasized as an additional means of early detection of CVD risk [9]. These novel markers may be useful in predicting risk in addition to the conventional risk factors [10].

The 20^th century has seen the emergence of substantial evidence to prove homocysteine (primarily atherogenic marker), C-reactive protein and fibrinogen (primarily thrombosis marker) [1,11] as the newer risk factors for CVD amongst Asian Indians.

Homocysteine (Hcy), a homologue of the naturally occurring amino acid cysteine, has been touted as one of the new-age inflammatory markers of CVD risk. In 1969, autopsy of children with homocystinuria revealed presence of severe atherosclerosis demonstrating pathogenic role of homocysteine [12]. Thereafter, the second phase of NHANES III (1991-1994) included study of homocysteine understanding its significance as more than just a marker of vitamin deficiency. A study by R. Carmel et al. (2002) [13] found that Asian Indian population residing in US have significantly higher Hcy levels compared to men from 4 other ethnic groups with 25.6% being hyperhomocysteinemic. They concluded that hyperhomocysteinemia is common among apparently healthy Asian Indian men accompanied by subclinical cobalamin deficiency.

Similarly, P.E. Szmitko et al. (2003) [14] reported that CRP may play a direct active role in the pathogenesis of atherosclerosis through its inflammatory action in blood vessels. C-reactive protein (CRP) is an acute phase reactant that increases in response to systemic inflammation such as infection or tissue injury [15]. Inflammation causes release of cytokines, especially Interlukin-6, which is largely responsible for triggering the production of CRP from the liver. Studies have shown that high sensitivity CRP consistently predicts new coronary events in patients with unstable angina and acute myocardial infarction [16,17].

The normal levels for the Homocysteine and CRP have been calculated for the Western population. The present study has assessed the Homocysteine and CRP level among Asian Indians with metabolic syndrome at risk for CVD and compared the value with the normal data.

2. Material and Methods

2.1. Sample

Female subjects in the age group of 30 - 75 yr were screened for the presence of 3 or more of the following symptoms to be classified as having metabolic syndrome [18]:

·  Waist circumference > 80 cm in women

·  Blood pressure (BP) ≥ 130/85 or medical treatment of previously diagnosed hypertension

·  Triglycerides (TG) ≥ 150 mg/dL

·  Low levels of High Density Lipoprotein (HDL) Cholesterol in women < 50 mg/dL

·  Fasting blood sugar (glucose) ≥ 110 mg/dL A total of 74 female were then enrolled based on written informed consent.

The proposal was approved by the Institutional Ethics committee of Department of Pharmacology, Grant medical College and Sir J.J. Group of Hospitals, Byculla, Mumbai.

The basic information of the subjects such as age, gender, caste was recorded. BMI and waist circumference were measured as per standard protocol.

2.2. Blood Sampling

5 ml of peripheral venous blood was collected by vein puncture using a dry, disposable syringe between 8 AM - 9 AM after an overnight fast (10.5 - 12 hours). Blood was collected in sterile tubes containing EDTA as anticoagulant for plasma separation. For serum separation, blood was collected without EDTA. Plasma and serum were separated by centrifugation at 3000 rpm for 15 min and were stored at 4˚C and used for various biochemical assays.

2.3. Biochemical-Analytical Methods

Glucose: Fasting blood glucose was estimated using the GOD-POD method [19].

Total cholesterol: Serum total cholesterol level was assayed by the kit method of CHOD-PAP with ATCS method [19-22]. Triglyceride: Serum triglyceride level was estimated by using the GPO-POD method with ESPAS [23-27].

HDL-cholesterol: HDL-cholesterol was estimated by the method of HDL precipitating reagent [28-33].

LDL-cholesterol: Serum LDL-cholesterol was estimated from the primary measurements by using the empirical equation of Friedewald et al. 1972 [34].

Serum LDL cholesterol = Total cholesterol – (HDL cholesterol – Triglyceride/5).

C-Reactive Protein: CRP Turbilatex with high sensitivity and specificity was used [35-41].

Homocysteine (Hcy): Automated enzymatic assay for homocysteine [42].

2.4. Statistical Analysis

Numerical data were presented as mean values ± S.D. Pearson’s correlation co-efficient was used to test the magnitude of association between the inflammatory markers and different anthropometric and biochemical tests.

3. Results & Discussion

Subjects with metabolic syndrome were identified based on the guideline provided by modified National Cholesterol Education Program—Adult Treatment Panel III [18] for Asians. These include presence of higher abdominal waist circumference, high blood pressure, hypertriglyceridemia, low HDL cholesterol and. high blood glucose. Individuals exhibiting at least three or more of these parameters simultaneously were selected.

It has been noted that coronary artery disease occurs 10 years earlier among South Asian Indians compared to other populations across the world and develop metabolic abnormalities at a lower body mass index and waist circumference thereby leading to 25% to 50% underestimation of MS prevalence [43].

Table 1 shows the basic demographic profile of the subjects enrolled from the cosmopolitan city Mumbai, India. The average age of the women subjects was 50 years with majority being in obese category as indicated by a higher average BMI. BMI cut-offs for defining “overweight” and obesity in Asian Indians are 23 kg/m² and 25 kg/m² respectively [5].

Conflicts of Interest

The authors declare no conflicts of interest.

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