Insulin-resistance in paediatric age: Its magnitude and implications

Abstract

Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.

The crucial role and mechanism of insulin resistance in metabolic disease

“…More importantly, since many molecular pathways are involved in energy homeostasis and metabolism, IR is the result of a certain number of mutations in multiple genes, such as those related to type 4 glucose transporter (GLUT4), glucokinase, and Peroxisome proliferator-activated receptor (PPAR) nuclear receptor family, among others ( 90 , 91 ). Mutations in lipid metabolic pathways, such as mutations in adipocyte-derived hormones such as leptin, adiponectin, resistin or their receptors, mutations in peroxisome proliferator-activated receptors α, γ, and δ, mutations in the lipoprotein lipase gene, and other mutations in genes related to adipose tissue formation can affect the development of glycolipid metabolism and IR ( 92 ). For example, the mutation of AKT2/PKBβ in cultured cells may disrupt insulin signaling and inhibit AKT/PKB co-expression ( 93 ).…”

Association of cardiometabolic risk factors with insulin resistance in overweight and obese children

“…Insulin receptor mutations as a genetic factor may lead to IR. These mutations can induce the formation of abnormal glucose transporter 4 molecules or stimulate autoantibody production against insulin receptors [ 32 ]. Also, mutations in the lipid pathway have a significant role in the development of IR These mutations occurs in the peroxisomal proliferator-activated receptors (α, γ, δ), mutations in the adipocyte-derived hormones and their receptors such as leptin or adiponectin, mutation in the lipoprotein lipase gene, and other genes which are related with adipose tissue formation [ 33 ].…”

Not Only Metabolic Complications of Childhood Obesity

“…By definition, insulin resistance (IR) is a state of reduced response to insulin of target tissues with normal or elevated serum insulin levels and is the reciprocal of insulin sensitivity [ 7 ]. It is one of the earliest and most serious changes in hormonal balance in obesity, regardless of the age at which overweight occurs, and its prevalence in the pediatric population is estimated at 11.5% (according to some studies, even up to 44%) [ 10 ]. The consequence of IR is chronic, compensatory hyperinsulinemia allowing for maintenance of the required biological effect in the form of obtaining proper glucose levels while reducing the suppression of glucose production in the liver [ 11 ].…”