Early Insulin Resistance, Type 2 Diabetes, and Treatment Options in Childhood

Abstract

Background T2D (Type 2 Diabetes) represents just the tip of the iceberg of the complex metabolic alterations associated with obesity and other clinical conditions associated to impaired adipose tissue storage. Summary Available data have suggested the presence of a continuous spectrum of metabolic alterations developed in the progression from IR to T2D, most of which are likely preventable through the early characterization of all the multiple risk factors involved. Therefore, the complete characterization of the natural history of the disease and the major modifiable factors represents a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life. This review will focus on the main components defining the risk of IR and T2D in childhood with a specific focus on the main aspects of treatment options available in children and adolescents. Key messages Impaired adipose tissue storage documented in obesity results in a continuous spectrum of metabolic alterations ranging from IR to T2DM. These metabolic alterations are mostly likely preventable through the early characterization of all the multiple risk factors involved. The complete characterization of the disease and of the major modifiable factors represent a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life.

Insulin resistance relates to DKA severity and affects insulin requirement in children with type 1 diabetes at onset

“…Taken together, these results suggest a progressive worsening of insulin sensitivity state ranging from mild to severe DKA state. It is well known that insulin levels during a fasting state and after an oral glucose load differs significantly according to insulin sensitivity, having subjects with insulin resistance (e.g., obese children or subject with lipodystrophies) significantly higher values 17,25 . Similarly, it is well known that values of glucose/insulin ratio in a fasting state significantly and inversely reflects insulin sensitivity 26 .…”

Amino Acid-Related Metabolic Signature in Obese Children and Adolescents

“…The increase in BMI-SDS was greater in children aged 2–6 years. In addition, they smartly demonstrated that overweight and obesity presented in 11.2% of those with normal weight in the pre-pandemic period and obesity presented in 21.4% of those with overweight in the pre-pandemic period [ 40 ]. Taken together, these results and further confirming data reported in the very near future will strongly highlight the relevant and global burden of childhood obesity and its related parallel increase of metabolic complications.…”

Insulin resistance in children

“…A family history positive for hypertension, CVD, T2DM or gestational diabetes, diagnosis of polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD) and evidence of acanthosis nigricans and visceral adiposity are other risk factors [44 ▪ ]. Gender influences IR prevalence, in particular girls have demonstrated to be more insulin resistant than boys, although after puberty males are at higher risk than females to develop IR [45].…”