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.

Fig. 1

A simplified model of the role of obesity-related inflammation in disease development. Hypertrophied visceral adipocytes secrete MCP-1, recruiting macrophages that secrete inflammatory cytokines including IL-6 and TNF-α. These enter the systemic circulation and stimulate the production of CRP. These inflammatory molecules contribute to peripheral cellular dysfunction of the endoplasmic reticulum and mitochondria, resulting in a worsening of insulin resistance that is further exacerbated by low levels of adiponectin and high levels of free fatty acids. In the intima of arteries, inflammatory molecules including CRP activate monocytes, contributing to reactive oxygen species and the oxidation of LDL-C, which is then taken up by macrophages to form lipid-laden foam cells. Further injury remodeling and fibroblast migration contribute to a growing atherosclerotic plaque. CRP, C-reactive protein; IL-6, interleukin-6; LCL-C, low-density lipoprotein cholesterol; MCP-1, monocyte chemoattractant protein-1; TNF-α, tumor necrosis factor-α.

Fig. 2

Prevalence of fibrous plaques at autopsy examination in individuals by age group. As part of the Bogalusa Heart Study, individuals who died of all causes in the region of Bogalusa, Louisiana underwent autopsy examination, including the determination of fibrous plaques in the aorta and coronary arteries. Results shown are from 204 children and adults, separated by age. Reprinted by permission from Berenson et al. [56].