Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: A need for screening tools to target interventions

Abstract

Cardiovascular disease (CVD) and type 2 diabetes mellitus have their roots in childhood, particularly in obese children and adolescents, raising important opportunities for early lifestyle intervention in at-risk individuals. However, not all obese individuals are at the same risk for disease progression. Accurate screening of obese adolescents may identify those in greatest need for intensive intervention to prevent or delay future disease. One potential screening target is obesity-related inflammation, which contributes to insulin resistance, metabolic syndrome, and CVD. In adults, the inflammatory marker high-sensitivity C-reactive protein (hsCRP) has utility for risk stratification and treatment initiation in individuals of intermediate CVD risk. In adolescents, hsCRP shares many of the associations of hsCRP in adults regarding the degree of insulin resistance, metabolic syndrome, and carotid artery media thickness. However, long-term data linking increased hsCRP levels—and increased insulin or decreased adiponectin—in childhood to adult disease outcomes are lacking at this time. Future efforts continue to be needed to identify childhood clinical and laboratory characteristics that could be used as screening tests to predict adult disease progression. Such tests may have utility in motivating physicians and patients’ families toward lifestyle changes, ultimately improving prevention efforts.

Introduction

The increasing incidence of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) worldwide has raised interest in means of early identification of risk and preventative treatment in those with multiple risk factors [1]. A major factor in the increase in these adult chronic diseases has been the obesity epidemic: compared with those of normal weight, adults who are obese have a 50% to 75% increased risk of CVD over 3- to 14-y periods [2], whereas obesity starting in childhood carries a higher risk of adult CVD and T2DM [3]. These risks make childhood obesity a logical target for intervention. Nevertheless, not all obese individuals carry the same risk for future disease, which is encapsulated in the concept of the “healthy obese,” a subset of obese children and adults who do not exhibit increases in CVD risk factors [4], [5]. In addition, outside of intensive lifestyle interventions as part of research protocols, attempts at weight loss for children and adolescents in clinical settings have been modest [6], [7], [8]. This raises a question about the need for tools to identify risk for future disease—tools that could be used to trigger more intensive intervention in a subset of children at higher risk.

Currently, there are few evidence-based tools available for use in risk stratification in pediatrics. Such tools could end up being factors related to the underlying processes that connect obesity to future disease. One set of such processes is the metabolic syndrome (MetS), a cluster of CV factors, including central obesity (as assessed by increases in waist circumference), hypertension, increased fasting blood glucose, high levels of triacylglycerols, and low high-density lipoprotein cholesterol [9], [10], [11]. MetS itself represents a potential screening tool for risk in adolescents [12] but is not widely used clinically, likely because of its complexity of use, requiring that patients have increases above specific cutoff values in at least three of the five components of MetS [13]. In this sense—if possible—a single blood test would likely represent an easier clinical tool. A further drawback is that MetS exhibits racial/ethnic differences in its accuracy [14].

Another important target for risk-related screening is obesity-related inflammation. One inflammation-associated screening tool that is used for risk stratification in adults is high-sensitivity C-reactive protein (hsCRP). Higher levels of hsCRP have been linked to risk for CVD and T2DM in adults [15], [16], [17], [18], [19], [20], [21], although no such long-term data are available in adolescents. In this review, I will consider the processes underlying the connections among obesity, inflammation, and adult disease; the data for hsCRP as a screening tool for future CVD and T2DM in adults; and data regarding obesity-related inflammation in children. Using this as background, I will consider multiple potential screening tools that in the future may be used to identify obese adolescents at highest risk for future CVD and T2DM.