Insulin secretion, sensitivity, and kidney function in young persons with type 2 diabetes

Abstract

<p dir="ltr">Objective: β-cell dysfunction and insulin resistance magnify risk for kidney injury in type 2 diabetes. The relationship between these factors and intraglomerular hemodynamics and kidney oxygen availability in youth with type 2 diabetes remains sparsely explored. Research Design and Methods: Fifty youth with type 2 diabetes (age: 16±2 years, diabetes duration: 2.3±1.8 years, 60% female, HbA1c: 6.4 [5.9, 7.6]%, body mass index (BMI): 36.4±7.4kg/m2, urine albumin-to-creatinine ratio (UACR): 10.3 [5.9, 58.0]mg/g), 21 controls with obesity (OC) (age: 16±2 years, 29% female, BMI: 37.6±7.4kg/m2), and 20 controls in normal weight category (NWC) (age: 17±3 years, 70% female, BMI: 22.5±3.6kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow (RPF), kidney MRI for oxygenation, hyperglycemic clamps for insulin secretion (acute c-peptide response to glucose [ACPRg]) and disposition index (DI, x103 mg/kg lean/min), and dual-energy X-ray absorptiometry for body composition. Results: Youth with type 2 diabetes exhibited lower DI (0.6 [0.0, 1.6] vs. 3.8 [2.4, 4.5] x103 mg/kg lean/min, p<0.0001) and ACPRg (0.6 [0.3, 1.4] vs. 5.3 [4.3, 6.9] nmol/L, p<0.001), and higher UACR (10.3 [5.9, 58.0] vs. 5.3 [3.4, 14.3]mg/g, p=0.003), and intraglomerular pressure (77.8±11.5 vs. 64.8±5.0 mmHg, p<0.001) compared to OC. Youth with type 2 diabetes and OC had higher GFR and kidney oxygen availability (relative hyperoxia) than NWC. DI associated inversely with intraglomerular pressure and kidney hyperoxia. Conclusion: Youth with type 2 diabetes demonstrated severe β-cell dysfunction that associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OC youth.</p>