Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes
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...
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1154 |
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| author | Motonori Sato Yoshifumi Tamura Hideyoshi Kaga Nozomu Yamasaki Mai Kiya Satoshi Kadowaki Daisuke Sugimoto Takashi Funayama Yuki Someya Saori Kakehi Shuko Nojiri Hiroaki Satoh Ryuzo Kawamori Hirotaka Watada |
| author_facet | Motonori Sato Yoshifumi Tamura Hideyoshi Kaga Nozomu Yamasaki Mai Kiya Satoshi Kadowaki Daisuke Sugimoto Takashi Funayama Yuki Someya Saori Kakehi Shuko Nojiri Hiroaki Satoh Ryuzo Kawamori Hirotaka Watada |
| author_sort | Motonori Sato |
| collection | DOAJ |
| description | 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/m<sup>2</sup>·min) before and immediately after a single dose (<i>n</i> = 12) and 8 weeks (<i>n</i> = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using <sup>1</sup>H-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·m<sup>2</sup> and 608.3 ± 90.9 mL/min·m<sup>2</sup>, <i>p</i> = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m<sup>2</sup> and 602.3 ± 67.0 mL/min·m<sup>2</sup>, <i>p</i> = 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. |
| first_indexed | 2024-03-10T07:52:04Z |
| format | Article |
| id | doaj.art-345cd8f6668b42e494610487fec43725 |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:04Z |
| publishDate | 2021-09-01 |
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| series | Biomedicines |
| spelling | doaj.art-345cd8f6668b42e494610487fec437252023-11-22T12:07:49ZengMDPI AGBiomedicines2227-90592021-09-0199115410.3390/biomedicines9091154Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 DiabetesMotonori Sato0Yoshifumi Tamura1Hideyoshi Kaga2Nozomu Yamasaki3Mai Kiya4Satoshi Kadowaki5Daisuke Sugimoto6Takashi Funayama7Yuki Someya8Saori Kakehi9Shuko Nojiri10Hiroaki Satoh11Ryuzo Kawamori12Hirotaka Watada13Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSportology Center, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanSportology Center, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanClinical Research Center, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanBackground: 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/m<sup>2</sup>·min) before and immediately after a single dose (<i>n</i> = 12) and 8 weeks (<i>n</i> = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using <sup>1</sup>H-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·m<sup>2</sup> and 608.3 ± 90.9 mL/min·m<sup>2</sup>, <i>p</i> = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m<sup>2</sup> and 602.3 ± 67.0 mL/min·m<sup>2</sup>, <i>p</i> = 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.https://www.mdpi.com/2227-9059/9/9/1154SGLT2 inhibitorinsulin clearanceinsulin resistanceectopic fathyperinsulinemic euglycemic clamp |
| spellingShingle | Motonori Sato Yoshifumi Tamura Hideyoshi Kaga Nozomu Yamasaki Mai Kiya Satoshi Kadowaki Daisuke Sugimoto Takashi Funayama Yuki Someya Saori Kakehi Shuko Nojiri Hiroaki Satoh Ryuzo Kawamori Hirotaka Watada Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes Biomedicines SGLT2 inhibitor insulin clearance insulin resistance ectopic fat hyperinsulinemic euglycemic clamp |
| title | Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes |
| title_full | Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes |
| title_fullStr | Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes |
| title_full_unstemmed | Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes |
| title_short | Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes |
| title_sort | short term sglt2 inhibitor administration does not alter systemic insulin clearance in type 2 diabetes |
| topic | SGLT2 inhibitor insulin clearance insulin resistance ectopic fat hyperinsulinemic euglycemic clamp |
| url | https://www.mdpi.com/2227-9059/9/9/1154 |
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