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Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration
Author(s) -
Covington J. D.,
Bray G. A.,
Redman L. M.,
Johannsen D. L.,
Ravussin E.
Publication year - 2015
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12377
Subject(s) - medicine , renal function , endocrinology , glomerular hyperfiltration , creatinine , insulin , diabetes mellitus , glucose clamp technique , diabetic nephropathy , insulin resistance , insulin sensitivity
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. Design 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. Subjects Thirty‐five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m −2 ; 29 m/6f). Measurements 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.