Long Term Metabolic Complications of Childhood Obesity

Charles J. Glueck MD, Jewish Hospital 5/4/09 update

Summary

Childhood risk factors for adult cardiovascular disease (CVD) track during childhood, track into adulthood, and are associated with adult obesity and centripetal obesity, hypertension, high triglycerides (TG), low HDL cholesterol (HDL-C), high LDL cholesterol (LDL-C) impaired fasting glucose, and type 2 diabetes mellitus. When three of the following 5 CVD risk factors are present (centripetal obesity, high TG, low HDL-C, high systolic and/or diastolic blood pressure, impaired fasting glucose) childhood metabolic syndrome can be diagnosed, and is associated with premature CVD in young adulthood (Figure 1).  Particularly for obesity, childhood risk factors are amplified by low socioeconomic status in black girls more than any other gender-race group.  

It is hard to discern whether heritable insulin resistance and resultant hyperinsulinemia, amplified by consequent obesity, is the pre-eminent explanatory variable for adult obesity, impaired fasting glucose, and type 2 diabetes mellitus (T2DM), or whether obesity comes first, and subsequently increases insulin resistance, and hyperinsulinemia, which in turn, increase obesity with a feedback cycle which increases insulin resistance and hyperinsulinemia. It is possible that there are heritable antecedents for both insulin resistance and obesity, often in the same individual, and that these interact in a feedback loop which worsens both insulin resistance and obesity, and the subsequent development of metabolic syndrome and increased CVD events in adulthood (Figure 1)  Most obese, insulin resistant individuals do not develop T2DM, maintaining normal glucose tolerance by increasing insulin secretion enough to compensate for insulin resistance. The superimposition of obesity-related insulin resistance on a beta cell with genetically limited ability to compensate by increasing insulin secretion may be the fundamental pathological sequence of events.  On the other hand, although this issue is hotly debated, IR may not necessarily be an essential component of T2DM, even though most patients with T2DM have some degree of insulin resistance. Models to predict which children are at increased risk for impaired fasting glucose IFG) and T2DM could provide diagnostic and therapeutic insights into the etiologic relationships of insulin resistance IR to IFG and T2DM.The most common endocrine syndrome in women, polycystic ovary syndrome (PCOS), which affects ~ 6  % of white and 8-10% of black and Hispanic adolescent girls, has its genesis in insulin resistance and hyperinsulinemia. PCOS in adults is associated with increased CVD, mediated through associated obesity and morbid obesity, hyperinsulinemia, impaired fasting glucose, gestational diabetes and T2DM, high TG, high LDL-C, and low HDL cholesterol (HDL-C) (Figure 1). Obesity augments polycystic ovary syndrome, increases the likelihood of gestational diabetes both in PCOS and non-PCOS women, and increases the risk of late teen and young adult T2DM. Understanding of the conjoint roles of childhood hyperinsulinemia and obesity should illuminate approaches to deal simultaneously with both, with a goal of preventing or ameliorating cardiovascular events, T2DM, hypertension, and obesity in adulthood (Figure 1).