title: Early diabetic nephropathy: a complication of reduced insulin sensitivity in type 1 diabetes.
abstract: OBJECTIVE
  Diabetic nephropathy (DN) is a major cause of mortality in type 1 diabetes. Reduced insulin sensitivity is a well-documented component of type 1 diabetes. We hypothesized that baseline insulin sensitivity would predict development of DN over 6 years.
  
  
  METHODS
  We assessed the relationship between insulin sensitivity at baseline and development of early phenotypes of DN-microalbuminuria (albumin-creatinine ratio [ACR] ≥30 mg/g) and rapid renal function decline (glomerular filtration rate [GFR] loss >3 mL/min/1.73 m2 per year)-with three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations over 6 years. Subjects with diabetes (n = 449) and without diabetes (n = 565) in the Coronary Artery Calcification in Type 1 Diabetes study had an estimated insulin sensitivity index (ISI) at baseline and 6-year follow-up.
  
  
  RESULTS
  The ISI was lower in subjects with diabetes than in those without diabetes (P < 0.0001). A higher ISI at baseline predicted a lower odds of developing an ACR ≥30 mg/g (odds ratio 0.65 [95% CI 0.49-0.85], P = 0.003) univariately and after adjusting for HbA1c (0.69 [0.51-0.93], P = 0.01). A higher ISI at baseline conferred protection from a rapid decline of GFR as assessed by CKD-EPI cystatin C (0.77 [0.64-0.92], P = 0.004) and remained significant after adjusting for HbA1c and age (0.80 [0.67-0.97], P = 0.02). We found no relation between ISI and rapid GFR decline estimated by CKD-EPI creatinine (P = 0.38) or CKD-EPI combined cystatin C and creatinine (P = 0.50).
  
  
  CONCLUSIONS
  Over 6 years, a higher ISI independently predicts a lower odds of developing microalbuminuria and rapid GFR decline as estimated with cystatin C, suggesting a relationship between insulin sensitivity and early phenotypes of DN.
authors.affiliation: Corresponding author: Petter Bjornstad, petter.bjornstad@childrenscolorado.org.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Diana
authors.initials: D
authors.lastname: Jalal
authors.forename: Michel B
authors.initials: MB
authors.lastname: Chonchol
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D055316:Cystatin C; D007328:Insulin; D003404:Creatinine
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