Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways
Objective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-ri...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-05-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/7/1/e000721.full |
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| author | Pamela Bowman Timothy J McDonald Bridget A Knight Sarah E Flanagan Maria Leveridge Steve R Spaull Beverley M Shields Suzanne Hammersley Maggie H Shepherd Robert C Andrews Kashyap A Patel Andrew T Hattersley |
| author_facet | Pamela Bowman Timothy J McDonald Bridget A Knight Sarah E Flanagan Maria Leveridge Steve R Spaull Beverley M Shields Suzanne Hammersley Maggie H Shepherd Robert C Andrews Kashyap A Patel Andrew T Hattersley |
| author_sort | Pamela Bowman |
| collection | DOAJ |
| description | Objective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM.Research design and methods 5 adults with sulfonylurea-treated KCNJ11 PNDM and five age, sex and body mass index-matched controls without diabetes had a high-carbohydrate and high-protein/fat meal on two separate mornings. Insulin(i) and glucose(g) were measured at baseline then regularly over 4 hours after the meal. Total area under the curve (tAUC) for insulin and glucose was calculated over 4 hours and compared between meals in controls and KCNJ11 cases.Results In controls, glucose values after carbohydrate and protein/fat were similar (median glucose tAUC0-4h21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC0-4h58.1 vs 31.3 mmol/L, p=0.04). These different glycemic responses reflected different patterns of insulin secretion: in controls, insulin secretion was greatly increased after carbohydrate versus protein/fat (median insulin tAUC0-4h727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC0-4h327 vs 378 pmol/L, p=0.50).Conclusions Individuals with sulfonylurea-treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to glucose levels, consistent with a dependence on non-KATP pathways for insulin secretion.Trial registration number NCT02921906. |
| format | Article |
| id | doaj-art-a0b332d2815f4f22a19fcc037e8b775a |
| institution | OA Journals |
| issn | 2052-4897 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-a0b332d2815f4f22a19fcc037e8b775a2025-08-20T02:35:47ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000721Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathwaysPamela Bowman0Timothy J McDonald1Bridget A Knight2Sarah E Flanagan3Maria Leveridge4Steve R Spaull5Beverley M Shields6Suzanne Hammersley7Maggie H Shepherd8Robert C Andrews9Kashyap A Patel10Andrew T Hattersley11Exeter NIHR Clinical Research Facility, Exeter, Devon, UK3 Department of Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UKNIHR Exeter Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UKDepartment of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UKRoyal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UKExeter NIHR Clinical Research Facility, Exeter, Devon, UKInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UKInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UKInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UKInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UKInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UKDepartment of Clinical and Biomedical Sciences, University of Exeter Faculty of Health and Life Sciences, Exeter, UKObjective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM.Research design and methods 5 adults with sulfonylurea-treated KCNJ11 PNDM and five age, sex and body mass index-matched controls without diabetes had a high-carbohydrate and high-protein/fat meal on two separate mornings. Insulin(i) and glucose(g) were measured at baseline then regularly over 4 hours after the meal. Total area under the curve (tAUC) for insulin and glucose was calculated over 4 hours and compared between meals in controls and KCNJ11 cases.Results In controls, glucose values after carbohydrate and protein/fat were similar (median glucose tAUC0-4h21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC0-4h58.1 vs 31.3 mmol/L, p=0.04). These different glycemic responses reflected different patterns of insulin secretion: in controls, insulin secretion was greatly increased after carbohydrate versus protein/fat (median insulin tAUC0-4h727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC0-4h327 vs 378 pmol/L, p=0.50).Conclusions Individuals with sulfonylurea-treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to glucose levels, consistent with a dependence on non-KATP pathways for insulin secretion.Trial registration number NCT02921906.https://drc.bmj.com/content/7/1/e000721.full |
| spellingShingle | Pamela Bowman Timothy J McDonald Bridget A Knight Sarah E Flanagan Maria Leveridge Steve R Spaull Beverley M Shields Suzanne Hammersley Maggie H Shepherd Robert C Andrews Kashyap A Patel Andrew T Hattersley Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways BMJ Open Diabetes Research & Care |
| title | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways |
| title_full | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways |
| title_fullStr | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways |
| title_full_unstemmed | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways |
| title_short | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways |
| title_sort | patterns of postmeal insulin secretion in individuals with sulfonylurea treated kcnj11 neonatal diabetes show predominance of non katp channel pathways |
| url | https://drc.bmj.com/content/7/1/e000721.full |
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