Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes.
Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes.
复制标题
短期 SGLT2 抑制剂给药不会改变 2 型糖尿病的全身胰岛素清除率。
DOI：
10.3390/biomedicines9091154
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发表时间：
2021-09-03
期刊：
影响因子：
4.7
通讯作者：
Watada H
中科院分区：
文献类型：
--
作者：
Sato M;Tamura Y;Kaga H;Yamasaki N;Kiya M;Kadowaki S;Sugimoto D;Funayama T;Someya Y;Kakehi S;Nojiri S;Satoh H;Kawamori R;Watada H
背景：胰岛素清除率降低可能是肥胖、代谢综合征和非酒精性脂肪性肝病的相对上游异常。既往研究表明，钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）可提高胰岛素清除指标胰岛素- c肽比值，改善代谢参数。我们评估了SGLT2i tofogliflozin对胰岛素代谢清除率（MCRI）的影响，采用高胰岛素正糖钳研究，这是测量全身胰岛素清除率的金标准。方法：研究对象为12名患有2型糖尿病的日本男性。我们在单次给药（n = 12）和8周（n = 9）之前和之后使用高胰岛素正糖钳（胰岛素输注速率，40 mU/m2·min）评估MCRI和组织特异性胰岛素敏感性。在服用tofogliflozin 8周前后，我们还分别使用1h -磁共振波谱和磁共振成像技术测量了肌肉、肝脏和腹部脂肪区异位脂肪。结果：单次给药tofogliflozin后（594.7±67.7 mL/min·m2和608.3±90.9 mL/min·m2, p = 0.61）和8周后（582.5±67.3 mL/min·m2和602.3±67.0 mL/min·m2, p = 0.41） MCRI无变化。8周的治疗显著改善了糖化血红蛋白，降低了体重（1.7%）和皮下脂肪面积（6.4%），而胰岛素敏感性和肌肉和肝脏的异位脂肪没有显著变化。结论：单剂量tofogliflozin或8周后MCRI未发生变化。mci的增加并不预示着体脂的减少或血糖控制的改善。
Background: Decreased insulin clearance could be a relatively upstream abnormality in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Previous studies have shown that sodium-glucose cotransporter 2 inhibitor (SGLT2i) increases insulin–C-peptide ratio, a marker of insulin clearance, and improves metabolic parameters. We evaluated the effects of the SGLT2i tofogliflozin on metabolic clearance rate of insulin (MCRI) with a hyperinsulinemic euglycemic clamp study, the gold standard for measuring systemic insulin clearance. Methods: Study participants were 12 Japanese men with type 2 diabetes. We evaluated MCRI and tissue-specific insulin sensitivity with a hyperinsulinemic euglycemic clamp (insulin infusion rate, 40 mU/m2·min) before and immediately after a single dose (n = 12) and 8 weeks (n = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively, before and after 8 weeks of tofogliflozin. Results: MCRI did not change after a single dose of tofogliflozin (594.7 ± 67.7 mL/min·m2 and 608.3 ± 90.9 mL/min·m2, p = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m2 and 602.3 ± 67.0 mL/min·m2, p = 0.41). The 8-week treatment significantly improved glycated hemoglobin and decreased body weight (1.7%) and the subcutaneous fat area (6.4%), whereas insulin sensitivity and ectopic fat in muscle and liver did not change significantly. Conclusions: MCRI did not change after a single dose or 8 weeks of tofogliflozin. Increased MCRI does not precede a decrease in body fat or improved glycemic control.
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影响因子：
8.2
作者：
Eriksson JW;Lundkvist P;Jansson PA;Johansson L;Kvarnström M;Moris L;Miliotis T;Forsberg GB;Risérus U;Lind L;Oscarsson J
通讯作者：
Oscarsson J
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13.5
作者：
Bril, Fernando;Lomonaco, Romina;Cusi, Kenneth
通讯作者：
Cusi, Kenneth
影响因子：
5.8
作者：
Abdul-Ghani, Muhammad;DeFronzo, Ralph A.
通讯作者：
DeFronzo, Ralph A.
影响因子：
5.8
作者：
Ladwa, Meera;Bello, Oluwatoyosi;Goff, Louise M.
通讯作者：
Goff, Louise M.
影响因子：
4.6
作者：
Kaga H;Tamura Y;Takeno K;Kakehi S;Funayama T;Furukawa Y;Nishitani-Yokoyama M;Shimada K;Daida H;Aoki S;Giacca A;Kanazawa A;Kawamori R;Watada H
通讯作者：
Watada H