Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians (CURES-113)
Introduction
Obesity represents a state of increase in adipose tissue mass due to the increase in the number and size of adipocytes [1]. Adipose tissue is now recognized as an active endocrine organ which secretes a vast array of adipocytokines involved in the local and systemic regulation of numerous metabolic and inflammatory processes in an autocrine and paracrine manner [2]. Dysregulated endocrine function of the adipose tissue triggers obesity associated chronic low-grade inflammation and contributes to the development of obesity related metabolic disorders including insulin resistance, type 2 diabetes and atherosclerosis [3].
Asian Indians have an increased propensity to abdominal adiposity, which could be more strongly related to insulin resistance [4]. Increased intra abdominal fat/trunk fat/visceral fat is more detrimental than higher total body fat or generalized obesity in producing metabolic abnormalities [5]. Asian Indians also have an increased susceptibility to T2DM and coronary artery disease (CAD) in comparison with Caucasians and other ethnic groups [4], [6]. We have previously demonstrated that visceral fat was significantly correlated with body mass index, waist circumference, sagittal abdominal diameter and blood pressure and cardiovascular risk factors [7].
Adiponectin is an adipokine with insulin sensitizing and anti-inflammatory activities. The PIVUS study done in a population of elderly adults has shown that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis [8]. Another adipose tissue hormone leptin has been proposed to be involved in the neuroendocrine regulation of adiposity and its metabolic sequelae and is shown to be associated with total body fat [9]. Visfatin is an adipocytokine recently discovered in 2005 with potentially important effects on glucose metabolism and atherosclerosis and is supposed to contribute to the complex inter-correlation between adiposity, glucose metabolism and vascular disease [10]. There is a close association with inflammation and insulin resistance and hs-CRP, an inflammatory marker associated with insulin resistance and dysglycemic conditions, including the cardiometabolic syndrome and incident type 2 diabetes [11]. Increased visceral adipose tissue levels have been shown to be a determinant co-variable of the association between high hs-CRP concentrations and alteration in the metabolic profile in post menopausal women [12]. TNF-alpha has been shown to play a pivotal role in orchestrating the cytokine cascade in diabetes [13] and their levels have been shown to be associated with visceral fat [14]. Oxidative stress plays an important role in initiation and progression of diabetes and cardiovascular risk and oxidized LDL, one of the markers of oxidative stress shown to be associated with visceral fat accumulation in healthy obese men [15], and Gletsu-Miller et al. [16] have suggested that adipose tissue mass contributes to oxidative stress. Although alterations in circulating levels of adipocytokines in diabetes are well documented, the contribution of subcutaneous and visceral fat depots to the circulating pool of adipocytokines and IR is less explored particularly in non-Europeans and relatively less obese populations.
Thus ,the aims of the present study are the following: 1. to examine the differences in body fat distributions in different stages of glucose intolerance, 2. to study the association of adipocytokines (adiponectin, leptin, visfatin), inflammatory markers (hs-CRP and TNF-alpha) and oxidative stress marker (oxidized LDL) with the different fat depots. 3. to look at the association of insulin resistance and carotid intimal media thickness with the different fat depots. The study of the adipocytokines and inflammatory markers in visceral fat assumes significance in the context that Asian Indians have more visceral fat accumulation for a given BMI than the other populations and studying these associations would pinpoint the specific metabolic sequences operating in the fat depots that contribute to increased diabetes and cardiovascular risk in Asian Indians.
Section snippets
Research design and methods
Study subjects were recruited from the Chennai Urban Rural Epidemiological Study (CURES), an ongoing epidemiological study conducted on a representative population (aged ≥ 20 years) of Chennai (formerly Madras), the fourth largest city in India. The methodology of the study has been published elsewhere [17]. Briefly, in phase 1 of the urban component of CURES, 26,001 individuals were recruited based on a systematic random-sampling technique; details of the sampling are described on our website (//www.drmohansdiabetes.com/
Results
Table 1 shows the clinical and the biochemical characteristics of the study subjects. Subjects with IGT and diabetes were significantly older than the NGT subjects. Hence, age adjustment was done for all the variables. However, as the sex ratio was equal in all three groups, no adjustment for gender was done. Waist circumference (p < 0.001), systolic blood pressure (p < 0.002), fasting plasma glucose (p < 0.001), glycated hemoglobin (p < 0.024), total cholesterol (p < 0.001), triglycerides (p < 0.001) and
Discussion
The study makes the following important observations: 1. A progressive increase in visceral fat and total abdominal fat but not subcutaneous fat is observed with increasing glucose intolerance, i.e., from NGT to IGT to diabetes. 2. There was a linear increase in insulin resistance with increasing quartiles of visceral fat but not subcutaneous fat. 3. An increase in the pro-inflammatory cytokines (TNF-alpha and hs-CRP), adipocytokine (visfatin) and oxidative stress marker (OX-LDL) and a decrease
Conflict of interests
There is none to declare.
Source of funding
There is none to declare.
Author contributions
VM conceived and designed the experiments. KI, ARM and JS performed the experiment and analyzed the data and are responsible for the integrity of the data.
Acknowledgments
We acknowledge the Chennai Wellingdon Corporate Foundation which supported the CURES field studies. KI & JS acknowledge the Lady-Tata Junior Research Fellowship. This is the 113rd paper from the CURES.
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