Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.
Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.
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DOI：
10.1111/dom.13224
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Crawford PA
中科院分区：
文献类型：
--
作者：
Polidori D;Iijima H;Goda M;Maruyama N;Inagaki N;Crawford PA
钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂与2型糖尿病（T2 DM）患者的血清酮体水平升高相关。在本分析中，我们评价了1278例接受卡格列净100或200 mg治疗的日本T2 DM患者的血清酮体水平和变异性。两种卡格列净剂量组的酮体浓度平均增加相似，约为2倍。乙酰乙酸和β-羟基丁酸较基线的中位（四分位距）百分比变化分别为62%（0;180）和78%（2;236）。每种血酮测量值的变异性约有三分之二归因于受试者内变异性。血清酮的受试者内变异性高于其他代谢产物。最低应答三分位数中的患者未表现出酮升高。最高应答三分位数中的受试者倾向于男性，基线时空腹血糖水平较高、胰岛素水平较低、T2 DM病程较长。此外，血浆脂肪酸的变化不能完全解释血清酮的变化，表明SGLT 2抑制对肝脏代谢的下游影响有利于生酮。总之，在日本T2 DM患者中，卡格列净引起的血清酮体增加大于其他代谢指标的变化，且变化更大。
Sodium glucose co‐transporter 2 (SGLT2) inhibitors have been associated with increased serum ketone body levels in patients with type 2 diabetes mellitus (T2DM). In the present analysis we evaluated serum ketone body levels and variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2‐fold were seen with both canagliflozin doses. The median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β‐hydroxybutyrate. Approximately two‐thirds of the variability in each ketone measure was attributed to intra‐subject variability. Intra‐subject variability was higher for serum ketones than other metabolites. Patients in the lowest response tertile exhibited no increase in ketones. Those in the highest response tertile tended to be male and have higher fasting plasma glucose levels, lower insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum ketones were not fully explained by changes in plasma fatty acids, suggesting downstream effects of SGLT2 inhibition on hepatic metabolism that favour ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were greater and more variable than changes in other metabolic measures in Japanese patients with T2DM.
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DOI：
10.1111/dom.12848
发表时间：
2017-05
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Yabe D;Iwasaki M;Kuwata H;Haraguchi T;Hamamoto Y;Kurose T;Sumita K;Yamazato H;Kanada S;Seino Y
通讯作者：
Seino Y
影响因子：
37.8
作者：
Kosiborod M;Cavender MA;Fu AZ;Wilding JP;Khunti K;Holl RW;Norhammar A;Birkeland KI;Jørgensen ME;Thuresson M;Arya N;Bodegård J;Hammar N;Fenici P;CVD-REAL Investigators and Study Group*
通讯作者：
CVD-REAL Investigators and Study Group*
影响因子：
29
作者：
Puchalska P;Crawford PA
通讯作者：
Crawford PA
影响因子：
16.2
作者：
Abdul-Ghani, Muhammad;Del Prato, Stefano;DeFronzo, Ralph A.
通讯作者：
DeFronzo, Ralph A.
影响因子：
158.5
作者：
Neal, Bruce;Perkovic, Vlado;Matthews, David R.
通讯作者：
Matthews, David R.