Hyperleptinemia and Hypoadiponectinemia in Extreme Pediatric Obesity

Abstract

Background: Adiponectin and leptin, adipokines associated with metabolic syndrome, type 2 diabetes, and cardiovascular disease, have not been well characterized in extreme pediatric obesity. Therefore, levels were compared in youth that were extremely obese (EO) to normal weight (NW), overweight (OW), and obese (OB) youth. Methods: Leptin, adiponectin, body mass index (BMI), blood pressure, fasting glucose, insulin, and lipids were obtained in 277 children and adolescents (age 13.4 -2.6 years; 152 boys). Participants were classified into four BMI groups (NW, OW, OB, EO). Variables were compared across groups using analysis of covariance (ANCOVA) adjusted for gender, age, and race. Results: Risk factors generally worsened across BMI groups. EO had significantly higher levels of leptin than OB (P < 0.0001), OW (P < 0.0001), and NW (P < 0.0001). Leptin was higher in OB compared to OW (P < 0.005) and NW (P < 0.0001) and higher in OW compared to NW (P < 0.0001). Adiponectin levels in EO did not significantly differ from OB or OW but were significantly lower than NW (P < 0.0001). Adiponectin was not significantly different among the OB, OW, and NW groups. Conclusions: Leptin was markedly elevated in EO children and adolescents, suggesting that this subset of obese youth may be at particularly high risk of future weight gain and potentially reduced response to weight-loss interventions.

Severe Obesity in Children and Adolescents: Identification, Associated Health Risks, and Treatment Approaches

“…Other studies have reported that severe pediatric obesity, compared with milder forms of adiposity and normal weight, is associated with higher levels of blood pressure, 9,10,12,13,15 dyslipidemia, 9,10,12,13,15 oxidative stress, 15 inflammation, 11,15,18 cardiorespiratory deconditioning (low fitness level) and poor pulmonary function, 9 clustering of cardiometabolic risk factors, 8,14 arterial stiffness, 17 increased carotid artery intima-media thickness, 11 and endothelial dysfunction/activation. 11,12,16,17 Perhaps most striking are the markedly elevated levels of inflammation that have been demonstrated in severe pediatric obesity.…”

“…12,13,15,18,[77][78][79][80] Impaired glucose tolerance, a strong predictor of future development of T2DM in obese youth, is prevalent among children and adolescents with severe obesity. 77,78,81 In a study of >700 severely obese children of European decent, insulin resistance and insulin secretion were associated with 2-hour postprandial glucose levels.…”

“…6,[8][9][10][11][12][13][14][15][16][17][18] Tracking of adiposity from childhood into adulthood is much stronger in the severely obese, 6 and high body mass index (BMI) in childhood is associated with increased risk of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and premature death. [19][20][21][22][23][24][25][26][27][28][29] Unfortunately, many of the treatment approaches commonly used with some success in overweight and obese youth are less effective in those with severe obesity.…”

The obese child in the Intensive Care Unit. Update

“…30,31 Leptin plays an immunomodulatory role 32 and develops, in these patients, a low-grade chronic inflammation, 33 w h i c h i s a s s o c i a t e d w i t h m a c r o p h a g e infiltration into adipose tissue. This leads to increased proinflammatory cytokine levels, such as tumor necrosis factor-α, interleukin-1b, interleukin-6, and this situations contributes to insulin resistance 34 and a reduced immune and metabolic reservoir.…”

Comparison of inflammation and oxidative stress levels by the severity of obesity in prepubertal children

“…3 Other data further suggested that compared to overweight and obese children and adolescents, youth with severe obesity have a much more adverse cardiometabolic risk factor profiles and are more likely to develop diabetes and cardiovascular diseases at a younger age. 4,5 Inflammation and oxidative stress associated with childhood obesity appears to be central to the development of insulin resistance and atherosclerosis, and may be important in the pathogenesis of other comorbid conditions. 6 A previous study documented that obese children with upper quartiles of C-reactive protein (CRP) and oxidative stress markers were more likely to have metabolic syndrome and abnormal lipid profiles, suggesting that inflammation and oxidative stress are interrelated, and might be associated with harmful health effects.…”