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

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posted on 2023-12-28, 03:27 authored by Petter Bjornstad, Ye Ji Choi, Carson Platnick, Susan Gross, Phoom Narongkiatikhun, Isabella Melena, Lauryn Remmers, Mayra Baca, Grant Schutte, Tyler Dobbs, Tim Vigers, Laura Pyle, Lynette Driscoll, Kalie Tommerdahl, Jessica Kendrick, Helen C Looker, Allison Dart, David Cherney, Daniel H van Raalte, Anand Srivastava, Luping Li, Pottumarthi Prasad, Pierre Saulnier, Robert G Nelson, Richard J Johnson, Kristen J Nadeau

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.

Funding

This work was supported by the NIH/NIDDK K23 DK116720, as well as Boettcher Foundation. P.B. receives salary and research support from NIDDK (DK132399, DK129211, DK129720, DK116720), NHLBI (HL165433), JDRF (3-SRA-2022-1097-M-B, 3-SRA-2022-1230-M-B, 3-SRA-2022-1243-M-B, 3-SRA-2023-1373-M-B), American Heart Association (20IPA35260142), and American Diabetes Association (7-23-ICTST2DY-08, 7-23-ICTST2DY-01).

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