The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode
Abstract Background Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrap...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-02095-w |
| _version_ | 1797276003573170176 |
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| author | Clementine E. M. Verhulst Julia I. P. van Heck Therese W. Fabricius Rinke Stienstra Steven Teerenstra Rory J. McCrimmon Cees J. Tack Ulrik Pedersen-Bjergaard Bastiaan E. de Galan the Hypo-RESOLVE consortium |
| author_facet | Clementine E. M. Verhulst Julia I. P. van Heck Therese W. Fabricius Rinke Stienstra Steven Teerenstra Rory J. McCrimmon Cees J. Tack Ulrik Pedersen-Bjergaard Bastiaan E. de Galan the Hypo-RESOLVE consortium |
| author_sort | Clementine E. M. Verhulst |
| collection | DOAJ |
| description | Abstract Background Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans. Methods Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP. Results In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia. Conclusion Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019). |
| first_indexed | 2024-03-07T15:22:05Z |
| format | Article |
| id | doaj.art-99ba37f75dd342839a07a50a2f591ca6 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-07T15:22:05Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-99ba37f75dd342839a07a50a2f591ca62024-03-05T17:36:33ZengBMCCardiovascular Diabetology1475-28402024-02-0123111310.1186/s12933-023-02095-wThe impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episodeClementine E. M. Verhulst0Julia I. P. van Heck1Therese W. Fabricius2Rinke Stienstra3Steven Teerenstra4Rory J. McCrimmon5Cees J. Tack6Ulrik Pedersen-Bjergaard7Bastiaan E. de Galan8the Hypo-RESOLVE consortiumDepartment of Internal Medicine, Radboud University Medical CentreDepartment of Internal Medicine, Radboud University Medical CentreDepartment of Endocrinology and Nephrology, Nordsjællands HospitalDepartment of Internal Medicine, Radboud University Medical CentreSection Biostatistics, Department for Health Evidence, Radboud Institute for Health Sciences, RadboudumcSchool of Medicine, University of DundeeDepartment of Internal Medicine, Radboud University Medical CentreDepartment of Endocrinology and Nephrology, Nordsjællands HospitalDepartment of Internal Medicine, Radboud University Medical CentreAbstract Background Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans. Methods Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP. Results In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia. Conclusion Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).https://doi.org/10.1186/s12933-023-02095-wAntecedent hypoglycaemiaClampDiabetesInflammatory responsesHumans |
| spellingShingle | Clementine E. M. Verhulst Julia I. P. van Heck Therese W. Fabricius Rinke Stienstra Steven Teerenstra Rory J. McCrimmon Cees J. Tack Ulrik Pedersen-Bjergaard Bastiaan E. de Galan the Hypo-RESOLVE consortium The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode Cardiovascular Diabetology Antecedent hypoglycaemia Clamp Diabetes Inflammatory responses Humans |
| title | The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| title_full | The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| title_fullStr | The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| title_full_unstemmed | The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| title_short | The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| title_sort | impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode |
| topic | Antecedent hypoglycaemia Clamp Diabetes Inflammatory responses Humans |
| url | https://doi.org/10.1186/s12933-023-02095-w |
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