Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents

Area of Science:

• Metabolic research
• Adolescent endocrinology
• Prediabetes pathophysiology

Background:

• Obesity in youth is a growing concern, often associated with metabolic dysfunction and increased risk of type 2 diabetes.
• Prediabetes, characterized by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), represents a critical window for intervention.

Purpose of the Study:

• To elucidate the specific metabolic abnormalities differentiating isolated IFG, isolated IGT, and combined IFG/IGT in obese adolescents.
• To identify the underlying mechanisms of insulin resistance and impaired insulin secretion in these prediabetic states.

Main Methods:

• Utilized hyperinsulinemic-euglycemic and hyperglycemic clamps, alongside glucose-stimulated insulin secretion modeling.
• Analyzed glucose and C-peptide concentrations in obese adolescents with normal glucose tolerance (NGT), IFG, IGT, and IFG/IGT.
• Assessed body composition using dual-energy x-ray absorptiometry.

Main Results:

• Reduced peripheral insulin sensitivity was observed in IGT and IFG/IGT groups, but not in the IFG group compared to NGT.
• Increased basal hepatic insulin resistance index was significant across IFG, IGT, and IFG/IGT groups.
• Progressive decline in glucose sensitivity of first-phase insulin secretion was noted in IFG, IGT, and IFG/IGT, with a defect in second-phase secretion specific to the IFG/IGT group.

Conclusions:

• In obese youth, IFG is primarily associated with impaired first-phase insulin secretion and hepatic insulin sensitivity.
• IGT is characterized by more severe peripheral insulin resistance and reduced first-phase insulin secretion.
• Combined IFG/IGT presents with profound insulin resistance and an additional defect in second-phase insulin secretion.