Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function
van Bommel, Erik J M; Ruiter, Danique; Muskiet, Marcel H A; van Baar, Michaël J B; Kramer, Mark H H; Nieuwdorp, Max; Joles, Jaap A; Bjornstad, Petter; van Raalte, Daniël H
(2020) Diabetes Care, volume 43, issue 1, pp. 228 - 234
(Article)
Abstract
OBJECTIVE: Impaired insulin sensitivity is associated with hyperfiltration (i.e., elevated glomerular filtration rate [GFR]) in adolescents with type 2 diabetes (T2D) and adults with prediabetes. Yet, these relationships are based on studies that relied on estimated GFR (eGFR), estimates of insulin sensitivity, or both. We aimed to verify the relationship
... read more
between insulin sensitivity and renal hemodynamic function by gold standard methods in adults with T2D. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp (M value) (glucose infusion rate in mg/kglean/min) and renal hemodynamic function by urinary inulin (GFR) and para-aminohippuric acid (effective renal plasma flow [ERPF]) clearances in participants with T2D without overt kidney disease. Filtration fraction (FF) (GFR/ERPF) was calculated. Relationships between insulin sensitivity and renal hemodynamic parameters were examined by multivariable linear regression. Renal hemodynamic parameters were examined across tertiles of M values. RESULTS: We tested 44 adults with T2D, of whom 77% were male, with mean ± SD age 63 ± 7 years, BMI 31.2 ± 4.0 kg/m2, and HbA1c 7.4 ± 0.6%. Average GFR was 110 ± 26 mL/min, with an FF of 22.1 ± 2.8% and median 24-h urinary albumin excretion of 11.3 mg (interquartile range 5.8-17.0). Average M value was 5.6 ± 2.9 mg/kglean/min. Insulin sensitivity inversely correlated with GFR (r = -0.44, P < 0.01) and FF (r = -0.40, P < 0.01), and these associations remained significant after multivariable adjustments for age, sex, renin-angiotensin system inhibitor use, and HbA1c. In addition, GFR, FF, and urinary albumin excretion were highest in the participants in the lowest M value tertile. CONCLUSIONS: For the first time, we demonstrate that impaired insulin sensitivity is associated with intrarenal hemodynamic dysfunction by gold standard techniques in adults with T2D treated with metformin monotherapy.
show less
Download/Full Text
The full text of this publication is not available.
Keywords: Advanced and Specialised Nursing, Internal Medicine, Endocrinology, Diabetes and Metabolism, Research Support, Non-U.S. Gov't, Journal Article, Research Support, N.I.H., Extramural
ISSN: 0149-5992
Publisher: American Diabetes Association Inc.
Note: Funding Information: Acknowledgments. The authors acknowledge the help of the assistants and technicians who were indispensable in the process of data collection: Jeanette Boerop, Ingrid Knufman, Renée de Meijer, and Sandra Gassman (Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands); Adele Dijk and Nel Willekes-Koolschijn (Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands); and Hiltjo Kuiper (Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands). The authors are very grateful for the patients who volunteered to participate in the study. Funding. P.B. receives salary and research support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (K23 DK116720-01), in addition to research support from JDRF (JDRF 2-SRA-2019-845-S-B, 2-SRA-2018-627-M-B), NIDDK/DiaComp, Thrasher Research Fund, International Society of Pediatric and Adolescent Diabetes, Colorado Clinical & Translational Sciences Institute, and Center for Women’s Health Research at the University of Colorado. Duality of Interest. This trial was funded by AstraZeneca as an investigator-initiated study. M.H.A.M. is a consultant and speaker for Eli Lilly & Company, Sanofi, and Novo Nordisk, with all honoraria paid to his employer (Amsterdam University Medical Center, location VUmc). M.N. received an unrestricted investigator-initiated grant from AstraZeneca on sodium–glucose cotransporter 2 inhibitor and lipid fluxes. P.B. has acted as a consultant for Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. serves on the advisory board of XORTX Therapeutics. D.H.v.R. has acted as a consultant and received honoraria from Boehringer Ingelheim and Lilly, Merck, Novo Nordisk, Sanofi, and AstraZeneca and has received research operating funds from Boehringer Ingelheim–Lilly Diabetes Alliance, AstraZeneca, Merck, and Novo Nordisk, with all honoraria paid to his employer (Amsterdam University Medical Center, location VUmc). No other potential conflicts of interest relevant to this article were reported. Publisher Copyright: © 2019 by the American Diabetes Association. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
(Peer reviewed)