Pediatric obesity is a major health problem. Insulin resistance (IR), is one of the early complications related to obesity but its role along that process has not been well investigated in children.
 To investigate the role of insulin resistance in the development of obesity related complications (dyslipidemia, inflammatory markers, adipocyte hormones).
 Children who attended the gastroenterology clinic were prospectively recruited. Exclusion criteria included diseases that may affect obesity and metabolic complications. Fasting blood levels for glucose, liver enzymes, insulin, adiponectin, leptin, IL-6, and TNF were measured. Children were divided into groups: obese children with IR (A), obese children without IR (B), and normal weight children without IR (C). The indices were compared among the groups. Results: A total of 69 children were recruited. 26 were in group A, 15 in group B, and 28 in group C. Group A was significantly different in lipid profiles (TG, HDL), liver enzyme (ALT), leptin, adiponectin, and IL-6 compared to the control groups (C). No significant difference was found between groups B and C but for HDL and adipocyte hormones (leptin, adiponectin).
Conclusion: Insulin resistance is crucial in the development of obesity related complications. We suggest that in order to detect early signs of obesity related complications insulin resistance should be measured in every obese child seen by the primary care physician.

Obesity and its associated metabolic, endocrine, and cardio-vascular complications are major health problems in the United States and may result in increased morbidity and mortality later in life.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder in obese children characterized with lipid accumulation in the liver (steatosis). NAFLD may progress to nonalcoholic steatohepatitis (NASH), histologically characterized by steatosis and inflammation and later may advance to cirrhosis. The pathological processes that lead from NAFLD to cirrhosis have not been fully revealed but involvement of dyslipidemia, oxidative damage, adipose tissue hormones, and inflammatory mediators have been suggested. Insulin resistance may be one of the earlier metabolic processes in this pathophysiology.

Metabolic syndrome is described as the association of three or more risk factors including abdominal obesity, dyslipidemia, insulin resistance (IR), high blood pressure and pro-inflammatory state. Insulin resistance is considered as an early occurrence in the development of obesity related complications.

Accumulation of lipids in the liver associated with elevated aminotransferases is a well-known pathological step in the development of fatty liver disease (NAFLD) and NASH. The pathophysiology of this process has been previously described.

Adipose tissue has been considered an active secretory organ modulating various organs including the gastrointestinal tract and the endocrine system [7]. In support of this hypothesis, many endocrine and cytokine receptors were identified in the adipose cells (adipocytes). Some of the proteins secreted by the adipose tissue include adiponectin, resistin, visfatin, leptin as well as few pro-inflammatory cytokines such as: TNF-α and IL-6. Adiponectin is an anti-inflammatory protein with anti-diabetes properties enhancing insulin sensitization, fatty acid oxidation, and increased glucose uptake in the muscles. Adiponectin has negative association with obesity and has emerged as a valuable biomarker for obesity related complications. Leptin is an adipose tissue hormone that has multiple functions including appetite control and insulin regulation  Leptin has pro-inflammatory properties and increases cytokine production such as IL-6 and TNF-α.

Obesity has a crucial role in the development of diabetes and metabolic syndrome. Insulin resistance is one of metabolic syndrome components but its significance in the pathophysiological process leading to obesity related complications has not been well investigated in children. In the present study we investigate the relationship between IR, obesity (BMI), adipose tissue hormones (leptin, adiponectin), and inflammatory cytokines (IL-6, TNF-α) in obese children from West Virginia.

Children between 8 and 18 years of age who attended the pediatric gastroenterology clinic at Marshall University School of Medicine were prospectively recruited for the study. Exclusion criteria included children with various systemic diseases that affect the immune system such as: celiac disease, inflammatory bowel disease, or children with endocrine problems including hypothyroidism, hypocalcemia, children with primary metabolic diseases (dyslipidemia, etc.), or drug induced obesity (steroids). After consent forms were signed by the parent(s) and the child, when appropriate, fasting blood samples were obtained for the following indices: glucose, liver aminotransferases (ALT, AST), lipid profile [Total cholesterol, Triglycerides (TG), HDL, LDL], insulin, inflammatory markers (IL-6, TNF-α), and adipose tissue hormones (Adiponectin, Leptin). Insulin resistance is calculated by using the formula of Homeostasis Model Assessment (HOMA) as previously described (10C-D). Insulin resistance was determined by the HOMA model and values >2.0 were considered positive for IR. Obesity was defined by the CDC BMI growth charts for both genders (≥ 95%). Children were then divided into 3 groups: obese children with IR (Group A); obese children without IR (Group B); and normal weight children without IR (Group C). The study was approved by the Joan C Edwards School of Medicine, Marshall University IRB committee.

With Regards,
Sara Giselle
Associate Managing Editor