Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial.
Cardiovasc Diabetol
; 22(1): 176, 2023 07 12.
Article
em En
| MEDLINE
| ID: mdl-37438734
ABSTRACT
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 rate17.8% 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Nefropatias Diabéticas
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cardiovasc Diabetol
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos