title: Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.
abstract: OBJECTIVE
  Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding.
  
  
  METHODS
  Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention.
  
  
  METHODS
  Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m(-2) ; 29 m/6f).
  
  
  METHODS
  Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate (eGFR) from the modification of diet in renal disease (MDRD), insulin sensitivity/glucose disposal rate (GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels.
  
  
  RESULTS
  Both eGFR and Ccr increased with overfeeding (P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity (P = 0.003). Fasting glucose concentration was not affected (P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding (r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point.
  
  
  CONCLUSIONS
  These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess.
authors.affiliation: Laboratory of Human Physiology, Pennington Biomedical Research Center, Baton Rouge, LA, USA.|School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Covington
authors.affiliation: Laboratory of Human Physiology, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: Laboratory of Human Physiology, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Redman
authors.affiliation: Laboratory of Human Physiology, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Johannsen
authors.affiliation: Laboratory of Human Physiology, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Ravussin
mesh_terms: D000328:Adult; D003404:Creatinine / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006963:Hyperphagia / Q000503:physiopathology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male
chemical_list: D008055:Lipids; D003404:Creatinine; D005947:Glucose
keywords: end-stage renal disease; glomerular filtration rate; insulin resistance; type 2 diabetes