title: The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type.
abstract: BACKGROUND
  Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases.
  
  
  METHODS
  These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model.
  
  
  RESULTS
  There was an association between IS and UACR in type 2 diabetes only (beta = -0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3).
  
  
  CONCLUSIONS
  In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.
authors.affiliation: UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, USA. amy_mottl@med.unc.edu.
authors.forename: Amy K
authors.identifier: http://orcid.org/0000-0002-4258-1726
authors.initials: AK
authors.lastname: Mottl
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.affiliation: Department of Epidemiology, School of Public Health, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Dabelea
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Dolan
authors.affiliation: , Santa Barbara, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pettitt
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.affiliation: Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Imperatore
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pihoker
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.|Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
authors.affiliation: Department of Nutrition, University of North Carolina School of Public Health, Chapel Hill, NC, USA.|Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Mayer-Davis
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000209:etiology*; D002648:Child; D003404:Creatinine / Q000652:urine*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000652:urine; D003928:Diabetic Nephropathies / Q000209:etiology / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance; D007677:Kidney Function Tests; D008297:Male; D015999:Multivariate Analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human
keywords: Insulin resistance; Metabolic syndrome; Microalbuminuria; Nephropathy; Urine:albumin creatinine ratio