Reversibility of brain glucose kinetics in type 2 diabetes mellitus
Aims/hypothesis We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1 H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA 1c normalise intracerebral glucose levels. Methods Eight individuals...
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| Veröffentlicht in: | Diabetologia 2022-05, Vol.65 (5), p.895-905 |
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| creator | Sanchez-Rangel, Elizabeth Gunawan, Felona Jiang, Lihong Savoye, Mary Dai, Feng Coppoli, Anastasia Rothman, Douglas L. Mason, Graeme F. Hwang, Janice Jin |
| description | Aims/hypothesis
We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by
1
H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA
1c
normalise intracerebral glucose levels.
Methods
Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m
2
and HbA
1c
84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent
1
H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.
Results
Following the intervention, mean ± SD HbA
1c
decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (
p
=0.006), with minimal weight changes (
p
=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (
p |
| doi_str_mv | 10.1007/s00125-022-05664-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8960594</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2644218152</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-e7150cc99e88fda0de30ad5a6cc9ee3ae8e9b39746b5d12b3c7ea64d54542de83</originalsourceid><addsrcrecordid>eNp9kUtLw0AUhQdRbK3-ARcScOMmOu8kG0GKLygIouBumExu69Q0qTNJIf_eqan1sXA1zD3fPTOHg9AxwecE4-TCY0yoiDGlMRZS8rjbQUPCWbhymu6i4VqPSSpfBujA-znGmAku99GACcoTLJMhGj_CCpy3uS1t00X1NMqdtlU0K1tTe4jebAWNNT4Ks6ZbQkSjwuocGvDRAsqw1PpDtDfVpYejzTlCzzfXT-O7ePJwez--msSGJ7yJISECG5NlkKbTQuMCGNaF0DLMAJiGFLKcZQmXuSgIzZlJQEteCC44LSBlI3TZ-y7bfAGFgapxulRLZxfadarWVv1WKvuqZvVKpZnEIuPB4Gxj4Or3FnyjFtabkEJXULdeUckkEYIIEtDTP-i8bl0V4gWKc0pSImigaE8ZV3vvYLr9DMFq3ZHqO1KhI_XZkerC0snPGNuVr1ICwHrAB6magft--x_bD9epnm4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2644218152</pqid></control><display><type>article</type><title>Reversibility of brain glucose kinetics in type 2 diabetes mellitus</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Sanchez-Rangel, Elizabeth ; Gunawan, Felona ; Jiang, Lihong ; Savoye, Mary ; Dai, Feng ; Coppoli, Anastasia ; Rothman, Douglas L. ; Mason, Graeme F. ; Hwang, Janice Jin</creator><creatorcontrib>Sanchez-Rangel, Elizabeth ; Gunawan, Felona ; Jiang, Lihong ; Savoye, Mary ; Dai, Feng ; Coppoli, Anastasia ; Rothman, Douglas L. ; Mason, Graeme F. ; Hwang, Janice Jin</creatorcontrib><description>Aims/hypothesis
We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by
1
H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA
1c
normalise intracerebral glucose levels.
Methods
Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m
2
and HbA
1c
84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent
1
H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.
Results
Following the intervention, mean ± SD HbA
1c
decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (
p
=0.006), with minimal weight changes (
p
=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (
p
<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (
p
=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA
1c
(
r
= 0.71,
p
=0.048).
Conclusion/interpretation
These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control.
Trial registration
ClinicalTrials.gov
NCT03469492.
Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-022-05664-y</identifier><identifier>PMID: 35247067</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Blood Glucose - metabolism ; Blood Glucose Self-Monitoring ; Brain - metabolism ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Female ; Glucose ; Glucose metabolism ; Glucose monitoring ; Glucose transport ; Glycated Hemoglobin - metabolism ; Human Physiology ; Humans ; Hyperglycemia ; Hypoglycemic Agents - therapeutic use ; Internal Medicine ; Kinetics ; Magnetic resonance spectroscopy ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Neurology</subject><ispartof>Diabetologia, 2022-05, Vol.65 (5), p.895-905</ispartof><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022</rights><rights>2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.</rights><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-e7150cc99e88fda0de30ad5a6cc9ee3ae8e9b39746b5d12b3c7ea64d54542de83</citedby><cites>FETCH-LOGICAL-c474t-e7150cc99e88fda0de30ad5a6cc9ee3ae8e9b39746b5d12b3c7ea64d54542de83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-022-05664-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-022-05664-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35247067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sanchez-Rangel, Elizabeth</creatorcontrib><creatorcontrib>Gunawan, Felona</creatorcontrib><creatorcontrib>Jiang, Lihong</creatorcontrib><creatorcontrib>Savoye, Mary</creatorcontrib><creatorcontrib>Dai, Feng</creatorcontrib><creatorcontrib>Coppoli, Anastasia</creatorcontrib><creatorcontrib>Rothman, Douglas L.</creatorcontrib><creatorcontrib>Mason, Graeme F.</creatorcontrib><creatorcontrib>Hwang, Janice Jin</creatorcontrib><title>Reversibility of brain glucose kinetics in type 2 diabetes mellitus</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by
1
H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA
1c
normalise intracerebral glucose levels.
Methods
Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m
2
and HbA
1c
84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent
1
H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.
Results
Following the intervention, mean ± SD HbA
1c
decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (
p
=0.006), with minimal weight changes (
p
=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (
p
<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (
p
=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA
1c
(
r
= 0.71,
p
=0.048).
Conclusion/interpretation
These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control.
Trial registration
ClinicalTrials.gov
NCT03469492.
Graphical abstract</description><subject>Adult</subject><subject>Blood Glucose - metabolism</subject><subject>Blood Glucose Self-Monitoring</subject><subject>Brain - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Glucose monitoring</subject><subject>Glucose transport</subject><subject>Glycated Hemoglobin - metabolism</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Internal Medicine</subject><subject>Kinetics</subject><subject>Magnetic resonance spectroscopy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Neurology</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtLw0AUhQdRbK3-ARcScOMmOu8kG0GKLygIouBumExu69Q0qTNJIf_eqan1sXA1zD3fPTOHg9AxwecE4-TCY0yoiDGlMRZS8rjbQUPCWbhymu6i4VqPSSpfBujA-znGmAku99GACcoTLJMhGj_CCpy3uS1t00X1NMqdtlU0K1tTe4jebAWNNT4Ks6ZbQkSjwuocGvDRAsqw1PpDtDfVpYejzTlCzzfXT-O7ePJwez--msSGJ7yJISECG5NlkKbTQuMCGNaF0DLMAJiGFLKcZQmXuSgIzZlJQEteCC44LSBlI3TZ-y7bfAGFgapxulRLZxfadarWVv1WKvuqZvVKpZnEIuPB4Gxj4Or3FnyjFtabkEJXULdeUckkEYIIEtDTP-i8bl0V4gWKc0pSImigaE8ZV3vvYLr9DMFq3ZHqO1KhI_XZkerC0snPGNuVr1ICwHrAB6magft--x_bD9epnm4</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Sanchez-Rangel, Elizabeth</creator><creator>Gunawan, Felona</creator><creator>Jiang, Lihong</creator><creator>Savoye, Mary</creator><creator>Dai, Feng</creator><creator>Coppoli, Anastasia</creator><creator>Rothman, Douglas L.</creator><creator>Mason, Graeme F.</creator><creator>Hwang, Janice Jin</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220501</creationdate><title>Reversibility of brain glucose kinetics in type 2 diabetes mellitus</title><author>Sanchez-Rangel, Elizabeth ; Gunawan, Felona ; Jiang, Lihong ; Savoye, Mary ; Dai, Feng ; Coppoli, Anastasia ; Rothman, Douglas L. ; Mason, Graeme F. ; Hwang, Janice Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-e7150cc99e88fda0de30ad5a6cc9ee3ae8e9b39746b5d12b3c7ea64d54542de83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Blood Glucose - metabolism</topic><topic>Blood Glucose Self-Monitoring</topic><topic>Brain - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Glucose monitoring</topic><topic>Glucose transport</topic><topic>Glycated Hemoglobin - metabolism</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Internal Medicine</topic><topic>Kinetics</topic><topic>Magnetic resonance spectroscopy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Neurology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanchez-Rangel, Elizabeth</creatorcontrib><creatorcontrib>Gunawan, Felona</creatorcontrib><creatorcontrib>Jiang, Lihong</creatorcontrib><creatorcontrib>Savoye, Mary</creatorcontrib><creatorcontrib>Dai, Feng</creatorcontrib><creatorcontrib>Coppoli, Anastasia</creatorcontrib><creatorcontrib>Rothman, Douglas L.</creatorcontrib><creatorcontrib>Mason, Graeme F.</creatorcontrib><creatorcontrib>Hwang, Janice Jin</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanchez-Rangel, Elizabeth</au><au>Gunawan, Felona</au><au>Jiang, Lihong</au><au>Savoye, Mary</au><au>Dai, Feng</au><au>Coppoli, Anastasia</au><au>Rothman, Douglas L.</au><au>Mason, Graeme F.</au><au>Hwang, Janice Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversibility of brain glucose kinetics in type 2 diabetes mellitus</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2022-05-01</date><risdate>2022</risdate><volume>65</volume><issue>5</issue><spage>895</spage><epage>905</epage><pages>895-905</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by
1
H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA
1c
normalise intracerebral glucose levels.
Methods
Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m
2
and HbA
1c
84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent
1
H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.
Results
Following the intervention, mean ± SD HbA
1c
decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (
p
=0.006), with minimal weight changes (
p
=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (
p
<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (
p
=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA
1c
(
r
= 0.71,
p
=0.048).
Conclusion/interpretation
These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control.
Trial registration
ClinicalTrials.gov
NCT03469492.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35247067</pmid><doi>10.1007/s00125-022-05664-y</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2022-05, Vol.65 (5), p.895-905 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8960594 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adult Blood Glucose - metabolism Blood Glucose Self-Monitoring Brain - metabolism Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - drug therapy Female Glucose Glucose metabolism Glucose monitoring Glucose transport Glycated Hemoglobin - metabolism Human Physiology Humans Hyperglycemia Hypoglycemic Agents - therapeutic use Internal Medicine Kinetics Magnetic resonance spectroscopy Male Medicine Medicine & Public Health Metabolic Diseases Middle Aged Neurology |
| title | Reversibility of brain glucose kinetics in type 2 diabetes mellitus |
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