Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus.
Plasma uric acid (PUA) is associated with metabolic, cardiovascular, and renal abnormalities in patients with type 2 diabetes but is less well understood in type 1 diabetes (T1D). Our aim was to compare PUA levels and fractional uric acid excretion (FEUA) in patients with T1D vs. healthy controls (HC) during euglycemia and hyperglycemia. PUA, FEUA, blood pressure (BP), glomerular filtration rate (GFR-inulin), and effective renal plasma flow (ERPF-paraaminohippurate) were evaluated in patients with T1D (n = 66) during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (9-11 mmol/l), and in HC (n = 41) during euglycemia. To separate the effects of hyperglycemia vs. increased glycosuria, parameters were evaluated during clamped euglycemia in a subset of T1D patients before and after sodium glucose cotransporter 2 (SGLT2) inhibition for 8 wk. PUA was lower in T1D vs. HC (228 ± 62 vs. 305 ± 75 μmol/l, P < 0.0001). In T1D, hyperglycemia further decreased PUA (228 ± 62 to 199 ± 65 μmol/l, P < 0.0001), which was accompanied by an increase in FEUA (7.3 ± 3.8 to 11.6 ± 6.7, P < 0.0001). In T1D, PUA levels correlated positively with SBP (P = 0.029) and negatively with ERPF (P = 0.031) and GFR (P = 0.028). After induction of glycosuria with SGLT2 inhibition while maintaining clamped euglycemia, PUA decreased (P < 0.0001) and FEUA increased (P < 0.0001). PUA is lower in T1D vs. HC and positively correlates with SBP and negatively with GFR and ERPF in T1D. Glycosuria rather than hyperglycemia increases uricosuria in T1D. Future studies examining the effect of uric acid-lowering therapies should account for the impact of ambient glycemia, which causes an important uricosuric effect.
Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada;
Yuliya
Y
Lytvyn
Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada;
Marko
M
Škrtić
Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada;
Gary K
GK
Yang
Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada; and.
Paul M
PM
Yip
Division of Endocrinology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Bruce A
BA
Perkins
Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; david.cherney@uhn.ca.
David Z I
DZ
Cherney
D000328:Adult; D001559:Benzhydryl Compounds; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000652:urine*; D005260:Female; D005960:Glucosides; D006029:Glycosuria / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000652:urine; D008297:Male; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014527:Uric Acid / Q000097:blood* / Q000652:urine*; D055815:Young Adult
D001559:Benzhydryl Compounds; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014527:Uric Acid; C570240:empagliflozin
hyperglycemia; uricosuria