Whole-body insulin clearance in people with type 2 diabetes and normal kidney function: Relationship with glomerular filtration rate, renal plasma flow, and insulin sensitivity

Autor: Michaël J.B. van Baar, Erik J.M. van Bommel, Mark M. Smits, Daan J. Touw, Max Nieuwdorp, Reinier W. ten Kate, Jaap A. Joles, Daniël H. van Raalte
Přispěvatelé: Experimental Vascular Medicine, Vascular Medicine, ACS - Diabetes & metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), Groningen Research Institute for Asthma and COPD (GRIAC), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Internal medicine, AGEM - Endocrinology, metabolism and nutrition
Rok vydání: 2022
Předmět:
Zdroj: Journal of diabetes and its complications, 36(4):108166. Elsevier Inc.
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 36(4):108166. ELSEVIER SCIENCE INC
van Baar, M J B, van Bommel, E J M, Smits, M M, Touw, D J, Nieuwdorp, M, ten Kate, R W, Joles, J A & van Raalte, D H 2022, ' Whole-body insulin clearance in people with type 2 diabetes and normal kidney function : Relationship with glomerular filtration rate, renal plasma flow, and insulin sensitivity ', Journal of Diabetes and its Complications, vol. 36, no. 4, 108166 . https://doi.org/10.1016/j.jdiacomp.2022.108166
Journal of Diabetes and its Complications, 36(4):108166. Elsevier Inc.
ISSN: 1056-8727
Popis: OBJECTIVE: Kidney insulin clearance, proposed to be the main route of extra-hepatic insulin clearance, occurs in tubular cells following glomerular filtration and peritubular uptake, a process that may be impaired in people with type 2 diabetes (T2D) and/or impaired kidney function. Human studies that investigated kidney insulin clearance are limited by the invasive nature of the measurement. Instead, we evaluated relationships between whole-body insulin clearance, and gold-standard measured kidney function and insulin sensitivity in adults with T2D and normal kidney function.RESEARCH DESIGN AND METHODS: We determined insulin, inulin/iohexol and para-aminohippuric acid (PAH) clearances during a hyperinsulinemic-euglycemic clamp to measure whole-body insulin clearance and kidney function. Insulin sensitivity was expressed by glucose infusion rate (M value). Associations between whole-body insulin clearance, kidney function and insulin sensitivity were examined using univariable and multivariable linear regressions models.RESULTS: We investigated 44 predominantly male (77%) T2D adults aged 63 ± 7, with fat mass 34.5 ± 9 kg, lean body mass 63.0 ± 11.8 kg, and HbA1c 7.4 ± 0.6%. Average whole-body insulin clearance was 1188 ± 358 mL/min. Mean GFR was 110 ± 22 mL/min, mean ERPF 565 ± 141 mL/min, and M value averaged 3.9 ± 2.3 mg/min. Whole-body insulin clearance was positively correlated with lean body mass, ERPF and insulin sensitivity, but not with GFR. ERPF explained 6% of the variance when entered in a nested multivariable linear regression model op top of lean body mass (25%) and insulin sensitivity (15%).CONCLUSIONS: In adults with T2D and normal kidney function, whole-body insulin clearance was predicted best by lean body mass and insulin sensitivity, and to a lesser extent by ERPF. GFR was not associated with whole-body insulin clearance. In contrast to prior understanding, this suggests that in this population kidney insulin clearance may not play such a dominant role in whole-body insulin clearance.
Databáze: OpenAIRE
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