Fortuna Danielle, McCloskey Laura J, Stickle Douglas F
Jefferson University Hospitals, Philadelphia, PA 19107, USA.
Jefferson University Hospitals, Philadelphia, PA 19107, USA.
Clin Chim Acta. 2016 Jan 15;452:138-41. doi: 10.1016/j.cca.2015.11.010. Epub 2015 Nov 10.
Renal reabsorption of 1,5-anhydroglucitol (AG) is competitively inhibited by elevated glucose and leads to depleted plasma AG in diabetes. Plasma AG recovery in diabetes normally correlates with improved glycemic control. However, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors (e.g., canagliflozin) to treat diabetes by inhibition of renal glucose reabsorption can negate this correlation, via an indirect effect (increase of renal filtrate glucose concentration) to inhibit AG reabsorption by sodium-glucose co-transporter 4 (SGLT4). Conversely, then, AG measurement might be useful as an independent marker for SGLT2 inhibitor activity.
Using an AG mass balance model, we analyzed literature data on plasma AG before and after initiation of canagliflozin therapy (CT) to quantitatively characterize the effect of CT on AG reabsorption.
According to model calculations, modest decreases (<5%) in fractional reabsorption of AG account for the drastic decrease in [AG] observed during CT. Decreases are predicted to be rapid (t1/2<3days) after CT initiation.
CT negates the usual premise of AG measurement (that [AG] should increase with improved glycemic control). However, according to model calculations, a substantial and likely rapid effect of CT on [AG] means that AG measurement might provide an early marker for CT activity.
1,5 - 脱水葡萄糖醇（AG）的肾脏重吸收受到升高的葡萄糖竞争性抑制，导致糖尿病患者血浆AG水平降低。糖尿病患者血浆AG恢复正常通常与血糖控制改善相关。然而，使用钠 - 葡萄糖协同转运蛋白2（SGLT2）抑制剂（如卡格列净）通过抑制肾脏葡萄糖重吸收来治疗糖尿病，可通过间接作用（增加肾滤液葡萄糖浓度）抑制钠 - 葡萄糖协同转运蛋白4（SGLT4）对AG的重吸收，从而消除这种相关性。相反，AG测量可能作为SGLT2抑制剂活性的独立标志物。
使用AG质量平衡模型，我们分析了卡格列净治疗（CT）开始前后血浆AG的文献数据，以定量表征CT对AG重吸收的影响。
根据模型计算，AG重吸收率适度降低（<5%）导致CT期间观察到的[AG]急剧下降。预计CT开始后下降迅速（t1/2<3天）。
CT否定了AG测量的通常前提（即[AG]应随血糖控制改善而增加）。然而，根据模型计算，CT对[AG]有显著且可能迅速的影响，这意味着AG测量可能为CT活性提供早期标志物。
