TY - JOUR
T1 - Homeostasis model assessment of insulin resistance and survival in patients with diabetes and acute coronary syndrome
AU - Stähli, Barbara E.
AU - Nozza, Anna
AU - Schrieks, Ilse C.
AU - Buse, John B.
AU - Malmberg, Klas
AU - Mellbin, Linda
AU - Neal, Bruce
AU - Nicholls, Stephen J.
AU - Rydén, Lars
AU - Svensson, Anders
AU - Wedel, Hans
AU - Weichert, Arlette
AU - Lincoff, A. Michael
AU - Grobbee, Diederick E.
AU - Tardif, Jean Claude
AU - Schwartz, Gregory G.
N1 - Funding Information:
Disclosure Summary: The AleCardio trial was funded by F. Hoffmann-La Roche (Basel, Switzerland). B.E.S. received research grants from the Gottfried and Julia Bangerter-Rhyner Foundation, the Novartis Foundation for Medical-Biomedical Research, and the Swiss National Science Foundation. J.B.B. received research grants from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GI Dynamics, Intarcia, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Orexigen, Sanofi, Scion NeuroStim, Takeda, and Theracos, has ownership interest in PhaseBio, and is a consultant/advisory board member of Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, Elycylex, F. Hoffman-LaRoche, GI Dynamics, Lexicon, Merck, Metavention, Novo Nordisk, Orexigen, PhaseBio, Quest, Takeda, and vTv Therapeutics. K.M. is employed by Roche and Vicore Pharma. B.N. received research grants from Abbvie, Dr. Reddy’s Laboratories, Janssen, Roche, and Servier and honoraria from Abbott, AstraZeneca, Novartis, Pfizer, Roche, and Servier. S.J.N. received research grants from Anthera, Amgen, AstraZeneca, Cerenis, Eli Lilly, F. Hoffmann-La Roche, InfraReDx, LipoScience, Novartis, Resverlogix, and Sanofi-Regeneron and is a consultant/advisory board member of Abbott, Amgen, AstraZeneca, Atheronova, Boehringer Ingelheim, CSL Behring, Esperion, LipoScience, Merck, Novartis, Omthera, Pfizer Roche, Sanofi-Aventis, and Takeda. L.R. received research grants from AFA Insurance Company, Bayer AG, Karolinska Institutet Funds, Roche, the Swedish Diabetes Association, and the Swedish Heart Lung Foundation and honoraria from AstraZeneca, Bristol-Myers Squibb, Roche, and Sanofi-Aventis. A.S. is employed by F. Hoffmann-La Roche and has ownership interest in F. Hoffmann-La Roche. H.W. received honoraria from AstraZeneca, Roche, and Pfizer. A.W. is employed by F. Hoffmann-La Roche. A.M.L. and D.E.G. received research grants from F. Hoffmann-La Roche. J.-C.T. received research grants from Amarin, Eli Lilly, Isis, Merck, Pfizer, Roche, Sanofi-Aventis, Servier, and DalCor and honoraria from Servier. G.G.S. received research support from Cerenis, Resverlogix, The Medicines Company, F. Hoffmann-La Roche, and Sanofi. The remaining authors have nothing to disclose.
Publisher Copyright:
Copyright © 2018 Endocrine Society.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Objective: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain.Design: The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter.Results: In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events.Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.
AB - Objective: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes. Whether the degree of insulin resistance predicts adverse outcomes in patients with type 2 diabetes and acute coronary syndrome (ACS) is uncertain.Design: The Effect of Aleglitazar on Cardiovascular Outcomes after Acute Coronary Syndrome in Patients with Type 2 Diabetes Mellitus trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with type 2 diabetes and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR; n = 4303) or the change in HOMA-IR on assigned study treatment (n = 3568) was related to the risk of death or major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models. Because an inverse association of HOMA-IR with N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been described, we specifically examined effects of adjustment for the latter.Results: In unadjusted analysis, twofold higher baseline HOMA-IR was associated with lower risk of death [hazard ratio (HR): 0.79, 95% CI: 0.68 to 0.91, P = 0.002]. Adjustment for 24 standard demographic and clinical variables had minimal effect on this association. However, after further adjustment for NT-proBNP, the association of HOMA-IR with death was no longer present (adjusted HR: 0.99, 95% CI: 0.83 to 1.19, P = 0.94). Baseline HOMA-IR was not associated with major adverse cardiovascular events, nor was the change in HOMA-IR on study treatment associated with death or major adverse cardiovascular events.Conclusions: After accounting for levels of NT-proBNP, insulin resistance assessed by HOMA-IR is not related to the risk of death or major adverse cardiovascular events in patients with type 2 diabetes and ACS.
KW - Acute Coronary Syndrome/etiology
KW - Aged
KW - Diabetes Mellitus, Type 2/complications
KW - Female
KW - Homeostasis
KW - Humans
KW - Hypoglycemic Agents/therapeutic use
KW - Insulin/therapeutic use
KW - Insulin Resistance
KW - Male
KW - Middle Aged
KW - Natriuretic Peptide, Brain/blood
KW - Oxazoles/therapeutic use
KW - Peptide Fragments/blood
KW - Proportional Hazards Models
KW - Risk Assessment/methods
KW - Risk Factors
KW - Survival Analysis
KW - Thiophenes/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85050071780&partnerID=8YFLogxK
U2 - 10.1210/jc.2017-02772
DO - 10.1210/jc.2017-02772
M3 - Article
C2 - 29659887
AN - SCOPUS:85050071780
SN - 0021-972X
VL - 103
SP - 2522
EP - 2533
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -