Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes

Area of Science:

• Pediatric Endocrinology
• Nephrology
• Metabolic Disorders

Background:

• Type 2 diabetes in youth is linked to increased kidney injury risk.
• Beta-cell dysfunction and insulin resistance are key contributors.
• The impact on kidney hemodynamics and oxygenation in adolescents is not well understood.

Purpose of the Study:

• To investigate the relationship between beta-cell function, insulin resistance, and kidney parameters in youth with type 2 diabetes.
• To compare these parameters with obese and normal-weight controls.

Main Methods:

• Fifty youth with type 2 diabetes, 21 obese controls, and 20 normal-weight controls were studied.
• Methods included clearance studies for GFR and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion and disposition index (DI), and DXA for body composition.

Main Results:

• Youth with type 2 diabetes had significantly lower DI and acute C-peptide response to glucose (ACPRg), and higher urine albumin-to-creatinine ratio (UACR) and intraglomerular pressure compared to obese controls.
• Both type 2 diabetes and obese groups showed higher GFR and kidney oxygen availability (relative hyperoxia) than normal-weight controls.
• Lower DI correlated with higher intraglomerular pressure and kidney hyperoxia.

Conclusions:

• Adolescents with type 2 diabetes exhibit severe beta-cell dysfunction.
• This dysfunction is associated with intraglomerular hypertension and kidney hyperoxia.
• Obese controls showed similar, though less pronounced, alterations.