Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways. Issue 1 (18th December 2019)

• Record Type: Journal Article
• Authors: Bowman, Pamela; McDonald, Timothy J; Knight, Bridget A; Flanagan, Sarah E; Leveridge, Maria; Spaull, Steve R; Shields, Beverley M; Hammersley, Suzanne; Shepherd, Maggie H; Andrews, Robert C; Patel, Kashyap A; Hattersley, Andrew T
• Is Part Of: BMJ open diabetes research and care. Volume 7:Issue 1(2019)
• Publication Date: 2019-12-18
• Subjects: permanent Neonatal Diabetes -- SU (Sulfonylurea) -- insulin secretion -- physiology; Diabetes -- Periodicals; 616.462005
• DOI: 10.1136/bmjdrc-2019-000721
• Languages: English
• ISSNs: 2052-4897

Abstract

Abstract : 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 tAUC0-4h 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 tAUC0-4h 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 tAUC0-4h 727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC0-4h 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-KATP pathways for insulin secretion. Trial registration number: NCT02921906 .