Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization
Aims Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐actin...
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| Veröffentlicht in: | British journal of clinical pharmacology 2003-03, Vol.55 (3), p.246-251 |
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| creator | Robinson, Robert T. C. E. Harris, Nigel D. Ireland, Robert H. Lindholm, Anders Heller, Simon R. |
| description | Aims
Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.
Methods
A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4–6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter‐regulatory hormones.
Results
The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h−1 kg−1, IAsp mean ± s.d. 1.22 ± 0.32 l h−1 kg−1). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P |
| doi_str_mv | 10.1046/j.1365-2125.2003.01726.x |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1884218</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>BCP1726</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5006-f6f227804a56f02f27de56c445d437a0d4661df3a136b3d343df113a6096c9cd3</originalsourceid><addsrcrecordid>eNqNUctuEzEUtRCIpoVfQN6wzNSv8cwsQIKIl1QJFrC2bvxoHHnskZ1pG1bwB3wjX8JMEzWwY3WvdB7XPgchTElFiZCX24pyWS8ZZXXFCOEVoQ2T1d0jtHgAHqMF4UQua1bTM3ReypYQyqmsn6IzyiQnXSMW6Ocq9QNk2Pkbi61zVu9wcngz9hBxSWFcB4t9LGPwEUM0p71Msh0ehxTxZj-k67DXYHsPv3_88tGM2hoMYWdn6xTLpMMasvGgcbZDCpD993voGXriIBT7_Dgv0Lf3776uPi6vPn_4tHpztdQ1mb7hpGOsaYmAWjrCHGuMraUWojaCN0CMkJIax2EKYM0NF9w4SjlI0kndacMv0OuD7zCue2u0jbsMQQ3Z95D3KoFX_yLRb9R1ulG0bQWj7WTQHgx0TqVk6x60lKi5FrVVc_pqTl_Ntaj7WtTdJH3x9-2T8NjDRHh5JEDREFyGqH058YTkTdN1E-_VgXfrg93_9wPU29WXeeN_AGbMrhY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>Alma/SFX Local Collection</source><creator>Robinson, Robert T. C. E. ; Harris, Nigel D. ; Ireland, Robert H. ; Lindholm, Anders ; Heller, Simon R.</creator><creatorcontrib>Robinson, Robert T. C. E. ; Harris, Nigel D. ; Ireland, Robert H. ; Lindholm, Anders ; Heller, Simon R.</creatorcontrib><description>Aims
Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.
Methods
A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4–6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter‐regulatory hormones.
Results
The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h−1 kg−1, IAsp mean ± s.d. 1.22 ± 0.32 l h−1 kg−1). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 ± 0.01 to 4.87 ± 0.48 nm, P < 0.001, IAsp, 0.24 ± 0.01 to 4.99 ± 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 ± 0.3 to 4.2 ± 0.2 mm, P < 0.001, IAsp, 4.2 ± 0.3 to 4.2 ± 0.3 mm, P < 0.001).
Conclusions
Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia‐induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1046/j.1365-2125.2003.01726.x</identifier><identifier>PMID: 12630974</identifier><identifier>CODEN: BCPHBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adolescent ; Adult ; Arrhythmias, Cardiac - etiology ; Arrhythmias, Cardiac - prevention & control ; Biological and medical sciences ; Diabetic Angiopathies - drug therapy ; Diabetic Angiopathies - physiopathology ; Drug toxicity and drugs side effects treatment ; Electrophysiology ; Epinephrine - blood ; Glucagon - blood ; human insulin ; Humans ; hypoglycaemia ; Hypoglycemia - chemically induced ; Insulin - adverse effects ; Insulin - analogs & derivatives ; Insulin Aspart ; Male ; Medical sciences ; Norepinephrine - blood ; Pharmacodynamics ; Pharmacology. Drug treatments ; Potassium - blood ; Toxicity: cardiovascular system ; Ventricular Function ; ventricular repolarization</subject><ispartof>British journal of clinical pharmacology, 2003-03, Vol.55 (3), p.246-251</ispartof><rights>2003 INIST-CNRS</rights><rights>2003 Blackwell Publishing Ltd 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5006-f6f227804a56f02f27de56c445d437a0d4661df3a136b3d343df113a6096c9cd3</citedby><cites>FETCH-LOGICAL-c5006-f6f227804a56f02f27de56c445d437a0d4661df3a136b3d343df113a6096c9cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1365-2125.2003.01726.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1365-2125.2003.01726.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14637799$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12630974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robinson, Robert T. C. E.</creatorcontrib><creatorcontrib>Harris, Nigel D.</creatorcontrib><creatorcontrib>Ireland, Robert H.</creatorcontrib><creatorcontrib>Lindholm, Anders</creatorcontrib><creatorcontrib>Heller, Simon R.</creatorcontrib><title>Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>Aims
Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.
Methods
A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4–6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter‐regulatory hormones.
Results
The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h−1 kg−1, IAsp mean ± s.d. 1.22 ± 0.32 l h−1 kg−1). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 ± 0.01 to 4.87 ± 0.48 nm, P < 0.001, IAsp, 0.24 ± 0.01 to 4.99 ± 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 ± 0.3 to 4.2 ± 0.2 mm, P < 0.001, IAsp, 4.2 ± 0.3 to 4.2 ± 0.3 mm, P < 0.001).
Conclusions
Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia‐induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Arrhythmias, Cardiac - etiology</subject><subject>Arrhythmias, Cardiac - prevention & control</subject><subject>Biological and medical sciences</subject><subject>Diabetic Angiopathies - drug therapy</subject><subject>Diabetic Angiopathies - physiopathology</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Electrophysiology</subject><subject>Epinephrine - blood</subject><subject>Glucagon - blood</subject><subject>human insulin</subject><subject>Humans</subject><subject>hypoglycaemia</subject><subject>Hypoglycemia - chemically induced</subject><subject>Insulin - adverse effects</subject><subject>Insulin - analogs & derivatives</subject><subject>Insulin Aspart</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Norepinephrine - blood</subject><subject>Pharmacodynamics</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium - blood</subject><subject>Toxicity: cardiovascular system</subject><subject>Ventricular Function</subject><subject>ventricular repolarization</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUctuEzEUtRCIpoVfQN6wzNSv8cwsQIKIl1QJFrC2bvxoHHnskZ1pG1bwB3wjX8JMEzWwY3WvdB7XPgchTElFiZCX24pyWS8ZZXXFCOEVoQ2T1d0jtHgAHqMF4UQua1bTM3ReypYQyqmsn6IzyiQnXSMW6Ocq9QNk2Pkbi61zVu9wcngz9hBxSWFcB4t9LGPwEUM0p71Msh0ehxTxZj-k67DXYHsPv3_88tGM2hoMYWdn6xTLpMMasvGgcbZDCpD993voGXriIBT7_Dgv0Lf3776uPi6vPn_4tHpztdQ1mb7hpGOsaYmAWjrCHGuMraUWojaCN0CMkJIax2EKYM0NF9w4SjlI0kndacMv0OuD7zCue2u0jbsMQQ3Z95D3KoFX_yLRb9R1ulG0bQWj7WTQHgx0TqVk6x60lKi5FrVVc_pqTl_Ntaj7WtTdJH3x9-2T8NjDRHh5JEDREFyGqH058YTkTdN1E-_VgXfrg93_9wPU29WXeeN_AGbMrhY</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Robinson, Robert T. C. E.</creator><creator>Harris, Nigel D.</creator><creator>Ireland, Robert H.</creator><creator>Lindholm, Anders</creator><creator>Heller, Simon R.</creator><general>Blackwell Science Ltd</general><general>Blackwell Science</general><general>Blackwell Science Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>200303</creationdate><title>Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization</title><author>Robinson, Robert T. C. E. ; Harris, Nigel D. ; Ireland, Robert H. ; Lindholm, Anders ; Heller, Simon R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5006-f6f227804a56f02f27de56c445d437a0d4661df3a136b3d343df113a6096c9cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Arrhythmias, Cardiac - etiology</topic><topic>Arrhythmias, Cardiac - prevention & control</topic><topic>Biological and medical sciences</topic><topic>Diabetic Angiopathies - drug therapy</topic><topic>Diabetic Angiopathies - physiopathology</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Electrophysiology</topic><topic>Epinephrine - blood</topic><topic>Glucagon - blood</topic><topic>human insulin</topic><topic>Humans</topic><topic>hypoglycaemia</topic><topic>Hypoglycemia - chemically induced</topic><topic>Insulin - adverse effects</topic><topic>Insulin - analogs & derivatives</topic><topic>Insulin Aspart</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Norepinephrine - blood</topic><topic>Pharmacodynamics</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium - blood</topic><topic>Toxicity: cardiovascular system</topic><topic>Ventricular Function</topic><topic>ventricular repolarization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Robinson, Robert T. C. E.</creatorcontrib><creatorcontrib>Harris, Nigel D.</creatorcontrib><creatorcontrib>Ireland, Robert H.</creatorcontrib><creatorcontrib>Lindholm, Anders</creatorcontrib><creatorcontrib>Heller, Simon R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robinson, Robert T. C. E.</au><au>Harris, Nigel D.</au><au>Ireland, Robert H.</au><au>Lindholm, Anders</au><au>Heller, Simon R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2003-03</date><risdate>2003</risdate><volume>55</volume><issue>3</issue><spage>246</spage><epage>251</epage><pages>246-251</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><coden>BCPHBM</coden><abstract>Aims
Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid‐acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function.
Methods
A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 mm for 30 min and reduced to 2.5 mm after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4–6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter‐regulatory hormones.
Results
The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h−1 kg−1, IAsp mean ± s.d. 1.22 ± 0.32 l h−1 kg−1). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 ± 0.01 to 4.87 ± 0.48 nm, P < 0.001, IAsp, 0.24 ± 0.01 to 4.99 ± 0.48 nm, P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 ± 0.3 to 4.2 ± 0.2 mm, P < 0.001, IAsp, 4.2 ± 0.3 to 4.2 ± 0.3 mm, P < 0.001).
Conclusions
Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia‐induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12630974</pmid><doi>10.1046/j.1365-2125.2003.01726.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Arrhythmias, Cardiac - etiology Arrhythmias, Cardiac - prevention & control Biological and medical sciences Diabetic Angiopathies - drug therapy Diabetic Angiopathies - physiopathology Drug toxicity and drugs side effects treatment Electrophysiology Epinephrine - blood Glucagon - blood human insulin Humans hypoglycaemia Hypoglycemia - chemically induced Insulin - adverse effects Insulin - analogs & derivatives Insulin Aspart Male Medical sciences Norepinephrine - blood Pharmacodynamics Pharmacology. Drug treatments Potassium - blood Toxicity: cardiovascular system Ventricular Function ventricular repolarization |
| title | Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization |
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