title: Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.
abstract: Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. kbritton@partners.org
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Britton
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: Evan L
authors.initials: EL
authors.lastname: Thacker
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005260:Female; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin