title: Insulin resistance, cystatin C, and mortality among older adults.
abstract: OBJECTIVE
  Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes.
  
  
  METHODS
  We performed a cohort study of 3,138 Cardiovascular Health Study participants (age ≥ 65 years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR).
  
  
  RESULTS
  A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6-41) and 11% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4-43) and 4% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models.
  
  
  CONCLUSIONS
  Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship.
authors.affiliation: University of Washington, Seattle, Washington, USA. deboer@u.washington.edu
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.forename: Michel B
authors.initials: MB
authors.lastname: Chonchol
authors.forename: Linda F
authors.initials: LF
authors.lastname: Fried
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism* / Q000401:mortality* / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D055316:Cystatin C / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D009026:Mortality / Q000639:trends; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism* / Q000401:mortality* / Q000503:physiopathology; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D055316:Cystatin C; D014280:Triglycerides; D002097:C-Reactive Protein