title: Renal function is associated with peak exercise capacity in adolescents with type 1 diabetes.
abstract: OBJECTIVE
  Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes.
  
  
  METHODS
  Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO2peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR.
  
  
  RESULTS
  Adolescents (15.5 ± 2.2 years of age) with type 1 diabetes (6.3 ± 3.8 years diabetes duration) had reduced VO2peak (31.5 ± 6.3 vs. 36.2 ± 7.9 mL/kg ⋅ min, P = 0.046) and VO2peak/lean kg (43.7 ± 7.0 vs. 51.0 ± 8.6 mL/lean kg ⋅ min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO2peak and VO2peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA1c level, systolic blood pressure, and LDL cholesterol level (β ± SE, VO2peak: -0.19 ± 0.07, P = 0.02; VO2peak/lean kg: -0.19 ± 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex- and Tanner-adjusted VO2peak and VO2peak/lean kg compared with participants in the lowest tertile.
  
  
  CONCLUSIONS
  Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO petter.bjornstad@childrenscolorado.org.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO Center for Women's Health Research, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cree-Green
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Amy
authors.initials: A
authors.lastname: Baumgartner
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.affiliation: Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Cherney
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Center for Women's Health Research, University of Colorado School of Medicine, Aurora, CO Department of Medicine, Divisions of Internal Medicine and Cardiology, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
authors.affiliation: Center for Women's Health Research, University of Colorado School of Medicine, Aurora, CO Department of Medicine, Division of Internal Medicine, Denver VA Medical Center, Denver, CO.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Reusch
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO Center for Women's Health Research, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Nadeau
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001823:Body Composition; D016022:Case-Control Studies; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D017079:Exercise Tolerance; D005260:Female; D005919:Glomerular Filtration Rate; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007668:Kidney / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008078:Cholesterol, LDL; D003404:Creatinine; D055316:Cystatin C; D006442:Glycated Hemoglobin