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.