Abstract | OBJECTIVE: DESIGN: We studied 761 individuals with KATP- hyperinsulinism and 862 probands with hyperinsulinism of unknown aetiology diagnosed before 6 months of age. All were referred as part of routine clinical care. METHODS: We compared the clinical features of KATP- hyperinsulinism and unknown hyperinsulinism cases. We performed logistic regression and receiver operator characteristic (ROC) analysis to identify the features that predict KATP- hyperinsulinism. RESULTS: Higher birth weight, diazoxide unresponsiveness and diagnosis in the first week of life were independently associated with KATP- hyperinsulinism (adjusted odds ratio: 4.5 (95% CI: 3.4-5.9), 0.09 (0.06-0.13) and 3.3 (2.0-5.0) respectively). Birth weight and diazoxide unresponsiveness were additive and highly discriminatory for identifying KATP- hyperinsulinism (ROC area under the curve for birth weight 0.80, diazoxide responsiveness 0.77, and together 0.88, 95% CI: 0.85-0.90). In this study, 86% born large for gestation and 78% born appropriate for gestation and who did not respond to diazoxide treatment had KATP- hyperinsulinism. In contrast, of those individuals born small for gestation, none who were diazoxide responsive and only 4% of those who were diazoxide unresponsive had KATP- hyperinsulinism. CONCLUSIONS: Individuals with hyperinsulinism born appropriate or large for gestation and unresponsive to diazoxide treatment are most likely to have an ABCC8 or KCNJ11 mutation. These patients should be prioritised for genetic testing of KATP channel genes.
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Authors | Thomas I Hewat, Daphne Yau, Joseph C S Jerome, Thomas W Laver, Jayne A L Houghton, Beverley M Shields, Sarah E Flanagan, Kashyap A Patel |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 185
Issue 6
Pg. 813-818
(Oct 30 2021)
ISSN: 1479-683X [Electronic] England |
PMID | 34633981
(Publication Type: Journal Article)
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Chemical References |
- ABCC8 protein, human
- KATP Channels
- Kir6.2 channel
- Potassium Channels, Inwardly Rectifying
- Sulfonylurea Receptors
- Diazoxide
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Topics |
- Birth Weight
- Congenital Hyperinsulinism
(diagnosis, genetics)
- Diazoxide
(administration & dosage)
- Female
- Humans
- Infant, Newborn
- KATP Channels
(genetics)
- Male
- Mutation
- Potassium Channels, Inwardly Rectifying
(genetics)
- Sulfonylurea Receptors
(genetics)
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