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A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women

AIM: The voltage‐gated potassium channel K(v)11.1 is important for repolarizing the membrane potential in excitable cells such as myocytes, pancreatic α‐ and β‐cells. Moxifloxacin blocks the K(v)11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose r...

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Autores principales: Juhl, Christian R., Burgdorf, Josephine, Knudsen, Cecilie, Lubberding, Anniek F., Veedfald, Simon, Isaksen, Jonas L., Hartmann, Bolette, Frikke‐Schmidt, Ruth, Mandrup‐Poulsen, Thomas, Holst, Jens J., Kanters, Jørgen K., Torekov, Signe S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10087839/
https://www.ncbi.nlm.nih.gov/pubmed/36054143
http://dx.doi.org/10.1111/dom.14851
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author Juhl, Christian R.
Burgdorf, Josephine
Knudsen, Cecilie
Lubberding, Anniek F.
Veedfald, Simon
Isaksen, Jonas L.
Hartmann, Bolette
Frikke‐Schmidt, Ruth
Mandrup‐Poulsen, Thomas
Holst, Jens J.
Kanters, Jørgen K.
Torekov, Signe S.
author_facet Juhl, Christian R.
Burgdorf, Josephine
Knudsen, Cecilie
Lubberding, Anniek F.
Veedfald, Simon
Isaksen, Jonas L.
Hartmann, Bolette
Frikke‐Schmidt, Ruth
Mandrup‐Poulsen, Thomas
Holst, Jens J.
Kanters, Jørgen K.
Torekov, Signe S.
author_sort Juhl, Christian R.
collection PubMed
description AIM: The voltage‐gated potassium channel K(v)11.1 is important for repolarizing the membrane potential in excitable cells such as myocytes, pancreatic α‐ and β‐cells. Moxifloxacin blocks the K(v)11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose regulation and secretion of glucoregulatory hormones in young people with and without moxifloxacin, a drug known to block the K(v)11.1 channel. MATERIALS AND METHODS: The effect of moxifloxacin (800 mg/day for 4 days) or placebo on glucose regulation was assessed in a randomized, double‐blind, crossover study of young men and women (age 20‐40 years and body mass index 18.5‐27.5 kg/m(2)) without chronic disease, using 6‐h oral glucose tolerance tests and continuous glucose monitoring. RESULTS: Thirty‐eight participants completed the study. Moxifloxacin prolonged the QTcF interval and increased heart rate. Hypoglycaemia was more frequently observed with moxifloxacin, both during the 8 days of continuous glucose monitoring and during the oral glucose tolerance tests. Hypoglycaemia questionnaire scores were higher after intake of moxifloxacin. Moxifloxacin reduced the early plasma‐glucose response (AUC(0‐30 min)) by 7% (95% CI: −9% to −4%, p < .01), and overall insulin response (AUC(0‐360 min)) decreased by 18% (95% CI: −24% to −11%, p < .01) and plasma glucagon increased by 17% (95% CI: 4%‐33%, p = .03). Insulin sensitivity calculated as the Matsuda index increased by 11%, and MISI, an index of muscle insulin sensitivity, increased by 34%. CONCLUSIONS: In young men and women, moxifloxacin, a drug known to block the K(v)11.1 channel, increased QT interval, decreased glucose levels and was associated with increased muscle insulin sensitivity and more frequent episodes of hypoglycaemia.
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spelling pubmed-100878392023-04-12 A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women Juhl, Christian R. Burgdorf, Josephine Knudsen, Cecilie Lubberding, Anniek F. Veedfald, Simon Isaksen, Jonas L. Hartmann, Bolette Frikke‐Schmidt, Ruth Mandrup‐Poulsen, Thomas Holst, Jens J. Kanters, Jørgen K. Torekov, Signe S. Diabetes Obes Metab Original Articles AIM: The voltage‐gated potassium channel K(v)11.1 is important for repolarizing the membrane potential in excitable cells such as myocytes, pancreatic α‐ and β‐cells. Moxifloxacin blocks the K(v)11.1 channel and increases the risk of hypoglycaemia in patients with diabetes. We investigated glucose regulation and secretion of glucoregulatory hormones in young people with and without moxifloxacin, a drug known to block the K(v)11.1 channel. MATERIALS AND METHODS: The effect of moxifloxacin (800 mg/day for 4 days) or placebo on glucose regulation was assessed in a randomized, double‐blind, crossover study of young men and women (age 20‐40 years and body mass index 18.5‐27.5 kg/m(2)) without chronic disease, using 6‐h oral glucose tolerance tests and continuous glucose monitoring. RESULTS: Thirty‐eight participants completed the study. Moxifloxacin prolonged the QTcF interval and increased heart rate. Hypoglycaemia was more frequently observed with moxifloxacin, both during the 8 days of continuous glucose monitoring and during the oral glucose tolerance tests. Hypoglycaemia questionnaire scores were higher after intake of moxifloxacin. Moxifloxacin reduced the early plasma‐glucose response (AUC(0‐30 min)) by 7% (95% CI: −9% to −4%, p < .01), and overall insulin response (AUC(0‐360 min)) decreased by 18% (95% CI: −24% to −11%, p < .01) and plasma glucagon increased by 17% (95% CI: 4%‐33%, p = .03). Insulin sensitivity calculated as the Matsuda index increased by 11%, and MISI, an index of muscle insulin sensitivity, increased by 34%. CONCLUSIONS: In young men and women, moxifloxacin, a drug known to block the K(v)11.1 channel, increased QT interval, decreased glucose levels and was associated with increased muscle insulin sensitivity and more frequent episodes of hypoglycaemia. Blackwell Publishing Ltd 2022-09-12 2023-01 /pmc/articles/PMC10087839/ /pubmed/36054143 http://dx.doi.org/10.1111/dom.14851 Text en © 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Juhl, Christian R.
Burgdorf, Josephine
Knudsen, Cecilie
Lubberding, Anniek F.
Veedfald, Simon
Isaksen, Jonas L.
Hartmann, Bolette
Frikke‐Schmidt, Ruth
Mandrup‐Poulsen, Thomas
Holst, Jens J.
Kanters, Jørgen K.
Torekov, Signe S.
A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title_full A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title_fullStr A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title_full_unstemmed A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title_short A randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
title_sort randomized, double‐blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10087839/
https://www.ncbi.nlm.nih.gov/pubmed/36054143
http://dx.doi.org/10.1111/dom.14851
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