Introduction
Adipose tissue is a highly insulin-responsive organ that largely contributes to both glucose and lipid metabolism.1 Impairment of insulin action on the adipose tissue, herein termed as adipose tissue insulin resistance, is an important contributor to systemic insulin resistance2 and is a major risk factor for metabolic diseases, including diabetes,3 4 non-alcoholic steatohepatitis5 6 and cardiovascular disease (CVD).7 The current gold standard of measuring adipose tissue insulin sensitivity is the multistep pancreatic clamp technique that accurately determines lipolysis fluxes by employing tracer dilution techniques during continuous intravenous insulin infusion.8 However, the utilization of this method has been restricted by its technical complexity and expensive cost. In recent years, a simplified measurement method has been well established by calculating the adipose tissue insulin resistance index (Adipo-IRI) from the plasma concentrations of fasting insulin and fasting free fatty acids (FFA), which was found to be well correlated with a 50% suppression of lipolysis (IC50) as measured by the multistep pancreatic clamp technique (r=0.86).9 10 To demonstrate feasibility of this method, the Adipo-IRI has been used in several population studies.4 6 7
Some basic molecular studies supported by animal studies have well documented that hypertrophy and hyperplasia of adipocytes can induce inflammation as a major underlying cause of insulin resistance of adipose tissue.11–14 To our knowledge, there were only limited population-based studies that have assessed the relationship between obesity and adipose tissue insulin resistance. Several recent studies have examined the differences of Adipo-IRI across the spectrum from normal weight to obesity as defined by body mass index (BMI), which demonstrated that the Adipo-IRI in young15 16 and adult4 obese subjects was about twofold higher than normal weight subjects. Obesity is a highly heterogeneous condition whereby fat is distributed in different regions of the body, which can be assessed by various anthropometric measurements or indicators. These anthropometric indicators include BMI, neck circumference (NC), waist circumference (WC) and waist/hip ratio (WHR), which have been used to measure total, upper or abdominal obesity, respectively. Several studies have indicated that abdominal (WC/WHR) and upper body (NC) obesity were either similar or stronger indicators of metabolic diseases than general obesity (ie, BMI).17–19 When the utilization of WC was not applicable in some clinical situations, such as pregnancy, ascites and abdominal tumors, the NC could be used as a more convenient clinical alternative. Therefore, more detailed information about the relationship of obesity to adipose tissue insulin resistance is needed, such as what anatomical forms of obesity are most closely related to adipose tissue insulin resistance? The predictive value and contribution of obesity to adipose tissue insulin resistance in the general population are also unclear. Elucidation of such important questions could be useful in understanding how obesity influences adipose tissue insulin resistance on a population level, which could therefore provide a direct basis for choosing the adipose tissue to target when treating metabolic disorder.
In this study, we have systemically examined the association of the distinct forms of anatomical obesity as defined by various anthropometric indicators with adipose tissue insulin resistance; and we also determined which anthropometric indicators have better predictive value for adipose tissue insulin resistance. Furthermore, we also assessed the contribution of obesity to adipose tissue insulin resistance.