Background: The prevalence of type 2 diabetes (DM) in children is disturbingly increasing
in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of
type 2 DM in children is paramount to devise an effective management plan.
Objective: Discuss the pathophysiology of type 2 DM in children and adolescents
Methods and Results: This is a comprehensive review of the literature on this topic. Type 2 DM in
childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic
predisposition, intrauterine environment, excessive food consumption, continued rapid weight
gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell
dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic
glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and
increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores
the complexity in disease progression.
Conclusion: A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is
essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary
and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.
Keywords: Type 2 diabetes, obesity, insulin resistance, insulin secretion, hyperglycemia, hyperglucagonemia, incretin
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