Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways
dc.contributor.author | Bowman, P | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Knight, BA | |
dc.contributor.author | Flanagan, SE | |
dc.contributor.author | Leveridge, M | |
dc.contributor.author | Spaull, SR | |
dc.contributor.author | Shields, BM | |
dc.contributor.author | Hammersley, S | |
dc.contributor.author | Shepherd, MH | |
dc.contributor.author | Andrews, RC | |
dc.contributor.author | Patel, KA | |
dc.contributor.author | Hattersley, AT | |
dc.date.accessioned | 2020-01-09T12:09:46Z | |
dc.date.issued | 2019-12-18 | |
dc.description.abstract | Objective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-K ATP -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 tAUC 0-4h 21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC 0-4h 58.1 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 tAUC 0-4h 727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC 0-4h 327 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-K ATP pathways for insulin secretion. Trial registration number NCT02921906. | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.identifier.citation | Vol. 7, article e000721 | en_GB |
dc.identifier.doi | 10.1136/bmjdrc-2019-000721 | |
dc.identifier.grantnumber | 16/0005407 | en_GB |
dc.identifier.grantnumber | 098395/Z/12/Z | en_GB |
dc.identifier.grantnumber | 110082/Z/15/Z | en_GB |
dc.identifier.grantnumber | 105636/Z/14/Z | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/40321 | |
dc.language.iso | en | en_GB |
dc.publisher | BMJ Publishing Group | en_GB |
dc.rights | © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.title | Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-01-09T12:09:46Z | |
dc.description | This is the final version. Available on open access from BMJ Publishing Group via the DOI in this record | en_GB |
dc.description | Data availability statement: All data relevant to the study are included in the article or uploaded as supplementary information. | en_GB |
dc.identifier.journal | BMJ Open Diabetes Research and Care | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-11-11 | |
exeter.funder | ::Diabetes UK | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-12-18 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-01-09T12:06:41Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-01-09T12:09:52Z | |
refterms.panel | A | en_GB |
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This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/