Insulin Secretion, Sensitivity, and Kidney Function in Young Individuals With Type 2 Diabetes
Petter Bjornstad, Ye Ji Choi, Carson Platnick, Susan Gross, Phoom Narongkiatikhun, Isabella Melena, Lauryn Remmers, Madison Baca, Grant Schutte, Tyler Dobbs, Tim Vigers, Laura Pyle, Lynette Driscoll, Kalie L. Tommerdahl, Jessica Kendrick, Helen C. Looker, Allison Dart, David Z.I. Cherney, Daniël H. van Raalte, Anand Srivastava, Luping Li, Pottumarthi V. Prasad, Pierre‐Jean Saulnier, Robert G. Nelson, Richard J. Johnson, Kristen J. Nadeau, Bjornstad Lab, Nicholas Becker, KYLA C. BEST, Carissa Birznieks, Michelle Bui, Diego S. Carrasco, Daniel Casillas, Maureen Flynn, Audrey Gruszcynski, Lucy Hall, Madeline Harbour, Melissa Leroux, Kelly Nash, Nhung Nguyen, Emily Sell, Callyn Rountree-Jablin
Abstract
OBJECTIVE: β-Cell dysfunction and insulin resistance magnify the risk of 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 incompletely explored. RESEARCH DESIGN AND METHODS: Fifty youth with type 2 diabetes (mean age ± SD 16 ± 2 years; diabetes duration 2.3 ± 1.8 years; 60% female; median HbA1c 6.4% [25th, 75th percentiles 5.9, 7.6%]; BMI 36.4 ± 7.4 kg/m2; urine albumin-to-creatinine ratio [UACR] 10.3 [5.9, 58.0] mg/g) 21 control participants with obesity (OCs; age 16 ± 2 years; 29% female; BMI 37.6 ± 7.4 kg/m2), and 20 control participants in the normal weight category (NWCs; age 17 ± 3 years; 70% female; BMI 22.5 ± 3.6 kg/m2) underwent iohexol and p-aminohippurate clearance to assess glomerular filtration rate (GFR) and renal plasma flow, kidney MRI for oxygenation, hyperglycemic clamp for insulin secretion (acute C-peptide response to glucose [ACPRg]) and disposition index (DI; ×103 mg/kg lean/min), and DXA 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] × 103 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 with OCs. Youth with type 2 diabetes and OCs had higher GFR and kidney oxygen availability (relative hyperoxia) than NWCs. DI was associated inversely with intraglomerular pressure and kidney hyperoxia. CONCLUSIONS: Youth with type 2 diabetes demonstrated severe β-cell dysfunction that was associated with intraglomerular hypertension and kidney hyperoxia. Similar but attenuated findings were found in OCs.