Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus
Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus
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DOI：
10.1152/ajprenal.00555.2014
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发表时间：
2015-01-15
影响因子：
4.2
通讯作者：
Cherney, David Z. I.
中科院分区：
文献类型：
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作者：
Lytvyn, Yuliya;Skrtic, Marko;Cherney, David Z. I.
血浆尿酸（普阿）与2型糖尿病患者的代谢、心血管和肾脏异常相关，但在1型糖尿病（T1 D）中了解较少。我们的目的是比较T1 D患者与健康对照（HC）在正常血糖和高血糖期间的普阿水平和尿酸排泄分数（FEUA）。在T1 D患者（n = 66）中评价了钳夹正常（葡萄糖4-6 mmol/l）和高血糖（9-11 mmol/l）期间的PUA、FEUA、血压（BP）、肾小球滤过率（GFR-菊粉）和有效肾血浆流量（ERPF-对氨基马尿酸盐），在HC患者（n = 41）中评价了正常期间的PUA、FEUA、血压（BP）、肾小球滤过率（GFR-菊粉）和有效肾血浆流量（ERPF-对氨基马尿酸盐）。为了区分高血糖与糖尿增加的影响，在钠葡萄糖协同转运蛋白2（SGLT 2）抑制8周之前和之后，在T1 D患者亚组中评价了钳夹正常期间的参数。T1 D患者的普阿低于HC患者（228 +/- 62 vs. 305 +/- 75 μ mol/l，P < 0.0001）。在T1 D中，高血糖进一步降低了普阿（228 +/- 62至199 +/- 65 μ mol/l，P < 0.0001），同时伴随着FEUA增加（7.3 +/- 3.8至11.6 +/- 6.7，P < 0.0001）。T1 D患者普阿水平与SBP呈正相关（P = 0.029），与ERPF（P = 0.031）和GFR（P = 0.028）呈负相关。抑制SGLT 2诱导糖尿后，同时维持钳夹正常，普阿降低（P < 0.0001），FEUA增加（P < 0.0001）。T1 D患者的普阿低于HC患者，与SBP呈正相关，与GFR和ERPF呈负相关。糖尿而不是高血糖增加T1 D患者的尿酸尿。未来的研究检查降尿酸治疗的效果应该考虑环境湿度的影响，环境湿度会引起重要的尿酸排泄效应。
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 mu mol/l, P < 0.0001). In T1D, hyperglycemia further decreased PUA (228 +/- 62 to 199 +/- 65 mu mol/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.