Insulin resistance and type 2 diabetes in children

Abstract

Type 2 diabetes (T2D) is an emerging health risk in obese children and adolescents. Both environmental (lack of physical activity, excess nutritional intake, sedentary lifestyle) and genetic factors contribute to this global epidemic. The growing prevalence of T2D in youth is also associated with a consistently increased incidence of metabolic and cardiovascular complications. Insulin resistance (IR), i.e., whole-body decreased glucose uptake in response to physiological insulin levels, determines impaired glucose homeostasis and it is recognized as cardinal trigger of T2D and cardiovascular disease in both adults and children. In particular, IR and beta-cell dysfunction lead to the persistent hyperglycemia which characterizes T2D. Indeed, both pathological states influence each other and presumably play a crucial, synergistic role in the pathogenesis of T2D, although the precise mechanisms are not completely understood. However, beta-cell dysfunction and IR induce impaired glucose metabolism, thus leading to the progression to T2D. Therefore, understanding the mechanisms correlated with the decline of beta-cell function and IR is crucial in order to control, prevent, and treat T2D in youth. This review focuses on the current knowledge regarding IR and T2D in children and adolescents and showcases interesting opportunities and stimulating challenges for the development of new preventative approaches and therapeutic strategies for young patients with T2D.

Keywords: Child; Insulin; Insulin resistance; Obesity; Pancreas; Type 2 diabetes.

Fig. 1.

Pathophysiology of type 2 diabetes. PC1, proprotein convertase 1; POMC, pro-opiomelanocortin; MC4, melanocortin 4; PPAR-γ, peroxisome proliferator-activated receptor gamma; TCF7L2, transcription factor 7 like 2; IGF2BP2, insulin-like growth factor 2 mRNA binding protein 2; CDKAL1, CDK5 regulatory subunit associated protein 1 like 1; HHEX, hematopoietically expressed homeobox; HNF1A, HNF1 homeobox A; IR, insulin resistance.