Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial.

Autor: Mohebi R; Cardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA., Liu Y; Cardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA., Hansen MK; Janssen Research Development, LLC, Spring House, Montgomery, PA, USA., Yavin Y; Janssen Research Development, LLC, Spring House, Montgomery, PA, USA., Sattar N; BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Pollock CA; Kolling Institute, Royal North Shore Hospital University of Sydney, Sydney, NSW, Australia., Butler J; University of Mississippi Medical Center, Jackson, MS, USA.; Baylor Scott & White Institute, Dallas, TX, USA., Jardine M; The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia.; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.; Concord Repatriation General Hospital, Sydney, NSW, Australia., Masson S; Roche Diagnostics International, Rotkreuz, Switzerland., Heerspink HJL; Department Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, The Netherlands., Januzzi JL Jr; Cardiology Division, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. jjanuzzi@partners.org.; Heart Failure and Biomarker Trials, Baim Institute for Clinical Research, Boston, MA, USA. jjanuzzi@partners.org.
Jazyk: angličtina
Zdroj: Cardiovascular diabetology [Cardiovasc Diabetol] 2023 Jul 12; Vol. 22 (1), pp. 176. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1186/s12933-023-01916-2
Abstrakt: Background: The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes.
Methods: Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes.
Results: Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09-2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14-2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00-2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09-2.26; P; 0.01).
Conclusions: These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes.
Trial Registration: CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.
(© 2023. The Author(s).)
Databáze: MEDLINE
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