Pathogenesis of insulin resistance and glucose intolerance in childhood obesity

Abstract

Obesity during childhood is a key driver of the development of insulin resistance. This is mainly due to two mechanisms-lipid partitioning patterns favoring greater deposition of fat in the intra-abdominal compartment and within insulin-responsive tissues (such as the skeletal muscle and liver) and fat tissue-derived cytokine secretion which affects whole-body metabolism. Both cause impairment of insulin signal transduction pathways manifesting as whole-body insulin resistance, necessitating a compensatory beta cell response in order to maintain euglycemia. This resistance results in increased fasting hepatic glucose production, reduced postprandial muscle glucose uptake, and enhanced adipose tissue lipolysis. Failure to develop such beta cell response over time results in prediabetic conditions (such as impaired fasting glucose and impaired glucose tolerance) and may advance to overt type 2 diabetes.