Heterogeneous phenotypes of insulin resistance and its implications for defining metabolic syndrome in Asian Indian adolescents

Abstract

Objective

To assess the phenotypic correlations of insulin resistance with obesity and its relationship with the metabolic syndrome in Asian Indian adolescents.

Design and subjects

We analyzed clinical, anthropometric (body mass index [BMI], waist circumference [WC]) and laboratory (fasting blood glucose [FBG], lipids and fasting serum insulin) data from 793 subjects (401 males and 392 females) aged 14–19 years randomly selected from Epidemiological Study of Adolescents and Young (ESAY) adults (n = 1447). The percentile cut-offs for 14–19 years age from ESAY cohort were used for defining abnormal values of variables. We devised three sets of definitions of metabolic syndrome by including BMI and fasting insulin levels with other defining variables.

Results

Nearly 28.9% of adolescents had fasting hyperinsulinemia despite normal values of BMI, WC, FBG, lipids, and blood pressure. Remarkably, NCEP criteria with appropriate percentile cut-off points for Asian Indian adolescents identified metabolic syndrome in only six (0.8%) subjects. Inclusion of both BMI and WC in the definition resulted in increase in the prevalence of metabolic syndrome to 4.3%. With inclusion of hyperinsulinemia, the prevalence of metabolic syndrome increased to 4.2% (from 0.8%) in the modified NCEP definition, 5.2% (from 0.9%) when BMI was substituted for WC, and 10.2 (from 4.3%) when both BMI and WC were included.

Conclusions

Our data show marked heterogeneity of phenotypes of insulin resistance and poor value of NCEP definition to identify metabolic syndrome. We propose that BMI and fasting insulin should be evaluated in candidate definitions of metabolic syndrome in Asian Indian adolescents.

Introduction

Associations and presentations of insulin resistance are heterogeneous. The magnitude of insulin resistance varies by three-fold in the individuals with normal glucose tolerance [1]. Further, although obesity is considered to be a forerunner and an essential component of metabolic syndrome, resistance to insulin-mediated glucose uptake may occur in ∼25% of non-obese individuals with normal glucose tolerance [1].

Several definitions of metabolic syndrome are available; initially by the World Health Organization (WHO) [2], and later by Expert Committee of National Cholesterol Education Program (NCEP, Adult Treatment Panel III) [3] and by others [4]. However, ambiguities have been identified in these definitions. First, although insulin resistance is believed by many investigators to be the central pathophysiological feature of metabolic syndrome, the NCEP definition has rarely been scientifically correlated against measures of insulin resistance in population-based studies. Further, direct or surrogate measure of insulin resistance has not been included as one of the defining variable in the NCEP definition. Second, the cut-off points of waist circumference (as included in NCEP definition) and body mass index (BMI) (as included in the WHO definition) have been defined using data from white Caucasians but may not be suitable for Asian ethnic groups who have different anthropometric characteristics [5], [6], [7]. For defining overweight in Asian populations, a cut-off point of 23 kg/m² instead of 25 kg/m² has been recently suggested [7], since the increased risk for morbidities such as type 2 diabetes mellitus (T2DM) and hypertriglyceridemia manifest at a lower range of BMI (22–25 kg/m²) [8]. Similarly, investigators opine that lower cut-off points of waist circumference for defining abdominal obesity might be more suitable for Asians than those suggested by NCEP [9], [10]. Overall, Asians are shorter and thinner than white Caucasians and most of them would be considered non-obese by the currently accepted criteria but they have higher amount of body fat, truncal fat and abdominal adiposity [11], [12]. Importantly, insulin resistance is widely prevalent in Asian Indians and its magnitude is higher than white Caucasians, substantially contributed by anthropometric features [13], [14]. Overall, it appears that the current definitions might not be appropriate for identifying Asian Indians with metabolic syndrome. Taking cognizance of these data, we have recently evaluated several candidate definitions of metabolic syndrome for adult Asian Indians [15].

Metabolic abnormalities associated with insulin resistance are known to occur during the childhood and adolescence that may increase the risk of T2DM in adults. Despite growing realization that primary prevention of T2DM requires vigorous lifestyle measures to tackle metabolic syndrome in early life, currently no satisfactory definition for identification of metabolic syndrome in children and adolescents is available. A modified version of NCEP definition of metabolic syndrome was used by Cook et al. [16] and de Ferranti et al. [17] to analyze prevalence of metabolic syndrome in adolescents from the cross-sectional data available from the Third National Health and Nutrition Survey (NHANES, 1988–1994, and 1998–2002, respectively).

It is important to characterize and prevent metabolic syndrome in Asian Indians at a young age, since this ethnic group is highly predisposed to develop insulin resistance, T2DM, and coronary heart disease. We recently showed a high prevalence of fasting hyperinsulinemia and low adiponectin levels in a representative random sample of post-pubertal urban Asian Indian children [18], [19]. However, identification and characterization of metabolic syndrome, and its correlation with fasting hyperinsulinemia/insulin resistance are important issues that have not been investigated in Asian Indian children. Investigations of these issues would lead to optimal definition of metabolic syndrome in Asian Indians and other Asian ethnic groups, and pave way for rational application of population-based preventive strategies.

We hypothesized that insulin resistance is highly prevalent in Asian Indian adolescents and its phenotypic correlations with various components of metabolic syndrome are varied and heterogeneous. To investigate these issues, we analyzed clinical, anthropometric, and biochemical data of 793 adolescents from a population-based study in urban north India.