Etiology of Insulin Resistance in Youth with Type 2 Diabetes

Abstract

Type 2 diabetes (T2DM), historically an adult disease, is now increasingly prevalent in obese youth. Poor diet and increased sedentary behavior contribute to the increasing rates of obesity in youth, yet not all obese children develop T2DM. In general, T2DM is characterized by both insulin resistance (IR) and pancreatic beta-cell insufficiency. In children, IR is related to elevated body mass index (BMI) and pubertal hormones, along with abnormal fat partitioning, elevated free fatty acids, inflammation, and/or mitochondrial dysfunction. Hyperglycemia and T2DM develop when the pancreas cannot match the increased insulin demands resulting from IR. Unique to youth, IR varies with stage of pubertal development, and some children may have resolution of hyperglycemia post-puberty once the IR of puberty resolves. Further understanding of IR, the progression to T2DM in youth, and later outcomes as adults will help direct future therapies and interventions for youth at risk.

Prepubertal Adiposity, Vitamin D Status, and Insulin Resistance

“…35 It has also been reported that in obese children, pancreatic β-cell insulin secretion may be unable to respond to the increased demands imposed by puberty, resulting in inadequate regulation of blood glucose levels. 36 We here suggest that this dysregulation may be augmented in children with the combined condition of central obesity and suboptimal-25(OH)D status. These 7 4 This work does not include data for the full sample of the primary (GOCS) study.…”

Management of diabetes mellitus in children and adolescents: engaging in physical activity

“…Adolescents with T2DM have impaired exercise capacity even when compared to obese controls without diabetes (23). Insulin resistance in T2DM has been thought to be related to a combination of excess lipid production and mitochondrial dysfunction (24,25). Obesity is associated with the presence of increased free © Translational Pediatrics.…”

“…Excessive free fatty acid production also leads to an increase in reactive oxygen species, which affects mitochondrial function (24). The presence of reactive oxygen species also effects adequate insulin secretion from the beta-cells from the pancreas (24).…”

“…Excessive free fatty acid production also leads to an increase in reactive oxygen species, which affects mitochondrial function (24). The presence of reactive oxygen species also effects adequate insulin secretion from the beta-cells from the pancreas (24). Regular physical activity leads to an overall improvement in insulin sensitivity with a reduction in baseline insulin levels (26).…”

Management of Depression in Adolescents with Type 2 Diabetes Mellitus

“…While the pathophysiology of T2D in adolescents is similar to that of adults with insufficient insulin production from pancreatic beta-cells and insulin resistance, the comorbidities in young diabetes may be more aggressive than in adults [20]. Serious comorbidities are also seen earlier in the patient's life because of the longer duration of the T2D and uncontrolled blood glucose [21].…”