Hypoglycemia-induced changes in complement pathways in type 2 diabetes
<p>Background and aims An association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would...
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2021
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| _version_ | 1864513517735903232 |
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| author | Abu Saleh Md Moin (6189512) |
| author2 | Manjula Nandakumar (1545811) Ilhame Diboun (3522413) Ahmed Al-Qaissi (9975173) Thozhukat Sathyapalan (704787) Stephen L. Atkin (6684368) Alexandra E. Butler (6189536) |
| author2_role | author author author author author author |
| author_facet | Abu Saleh Md Moin (6189512) Manjula Nandakumar (1545811) Ilhame Diboun (3522413) Ahmed Al-Qaissi (9975173) Thozhukat Sathyapalan (704787) Stephen L. Atkin (6684368) Alexandra E. Butler (6189536) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abu Saleh Md Moin (6189512) Manjula Nandakumar (1545811) Ilhame Diboun (3522413) Ahmed Al-Qaissi (9975173) Thozhukat Sathyapalan (704787) Stephen L. Atkin (6684368) Alexandra E. Butler (6189536) |
| dc.date.none.fl_str_mv | 2021-12-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.athplu.2021.11.002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Hypoglycemia-induced_changes_in_complement_pathways_in_type_2_diabetes/25713759 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Hypoglycemia Type 2 diabetes Complement proteins Proteomics |
| dc.title.none.fl_str_mv | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Background and aims An association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would be elevated in response to hypoglycemia in type 2 diabetes (T2D) through the inflammatory response. Methods A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycemia with blood sampling at baseline, hypoglycemia and post-hypoglycemia; SOMAscan proteomic analysis of complement pathway-related proteins, cytokines and inflammatory proteins was undertaken. Results At baseline: Complement C2 (p < 0.05) and Factor B (p < 0.05) were elevated in T2D. At hypoglycemia: Complement C2 (p < 0.05) and Factor B (p < 0.01) remained elevated, whilst Factor I became elevated (p < 0.05) in T2D; Complement C4b became elevated in controls (p < 0.05). In the post-hypoglycemia follow up period, Complement C2, Factor B and Factor I remained elevated in T2D; in addition, Factor D, Factor H and mannose-binding protein C showed elevations in T2D, whilst properdin, complement C3b, Factor H-related protein 5, complement C1q and decay-accelerating factor (DAF) showed elevations in controls. Granger causality analysis showed that inflammatory proteins appeared to drive complement protein changes in T2D; conversely, in controls, complement proteins drove inflammatory protein changes. Conclusions Baseline elevations in C2 and Factor B indicate upregulation of the complement pathway in T2D. Changes in complement pathway-related protein levels in response to hypoglycemia suggest both intrinsic and alternative pathway activation at 2-h that appears driven by the underlying inflammation in T2D and could contribute to a cardiovascular event. ClinicalTrials.gov NCT03102801. Date of registration April 6, 2017, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03102801?term=NCT03102801&draw=2&rank=1.</p><h2>Other Information</h2> <p> Published in: Atherosclerosis Plus<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.athplu.2021.11.002" target="_blank">https://dx.doi.org/10.1016/j.athplu.2021.11.002</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d11c31acb6c7dcfeefb2f5559267ca7a |
| identifier_str_mv | 10.1016/j.athplu.2021.11.002 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25713759 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Hypoglycemia-induced changes in complement pathways in type 2 diabetesAbu Saleh Md Moin (6189512)Manjula Nandakumar (1545811)Ilhame Diboun (3522413)Ahmed Al-Qaissi (9975173)Thozhukat Sathyapalan (704787)Stephen L. Atkin (6684368)Alexandra E. Butler (6189536)Biomedical and clinical sciencesClinical sciencesHypoglycemiaType 2 diabetesComplement proteinsProteomics<p>Background and aims An association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would be elevated in response to hypoglycemia in type 2 diabetes (T2D) through the inflammatory response. Methods A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycemia with blood sampling at baseline, hypoglycemia and post-hypoglycemia; SOMAscan proteomic analysis of complement pathway-related proteins, cytokines and inflammatory proteins was undertaken. Results At baseline: Complement C2 (p < 0.05) and Factor B (p < 0.05) were elevated in T2D. At hypoglycemia: Complement C2 (p < 0.05) and Factor B (p < 0.01) remained elevated, whilst Factor I became elevated (p < 0.05) in T2D; Complement C4b became elevated in controls (p < 0.05). In the post-hypoglycemia follow up period, Complement C2, Factor B and Factor I remained elevated in T2D; in addition, Factor D, Factor H and mannose-binding protein C showed elevations in T2D, whilst properdin, complement C3b, Factor H-related protein 5, complement C1q and decay-accelerating factor (DAF) showed elevations in controls. Granger causality analysis showed that inflammatory proteins appeared to drive complement protein changes in T2D; conversely, in controls, complement proteins drove inflammatory protein changes. Conclusions Baseline elevations in C2 and Factor B indicate upregulation of the complement pathway in T2D. Changes in complement pathway-related protein levels in response to hypoglycemia suggest both intrinsic and alternative pathway activation at 2-h that appears driven by the underlying inflammation in T2D and could contribute to a cardiovascular event. ClinicalTrials.gov NCT03102801. Date of registration April 6, 2017, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03102801?term=NCT03102801&draw=2&rank=1.</p><h2>Other Information</h2> <p> Published in: Atherosclerosis Plus<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.athplu.2021.11.002" target="_blank">https://dx.doi.org/10.1016/j.athplu.2021.11.002</a></p>2021-12-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.athplu.2021.11.002https://figshare.com/articles/journal_contribution/Hypoglycemia-induced_changes_in_complement_pathways_in_type_2_diabetes/25713759CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257137592021-12-01T00:00:00Z |
| spellingShingle | Hypoglycemia-induced changes in complement pathways in type 2 diabetes Abu Saleh Md Moin (6189512) Biomedical and clinical sciences Clinical sciences Hypoglycemia Type 2 diabetes Complement proteins Proteomics |
| status_str | publishedVersion |
| title | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| title_full | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| title_fullStr | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| title_full_unstemmed | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| title_short | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| title_sort | Hypoglycemia-induced changes in complement pathways in type 2 diabetes |
| topic | Biomedical and clinical sciences Clinical sciences Hypoglycemia Type 2 diabetes Complement proteins Proteomics |