The University of Southampton
University of Southampton Institutional Repository

Prematurity and genetic testing for neonatal diabetes

Prematurity and genetic testing for neonatal diabetes
Prematurity and genetic testing for neonatal diabetes
BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants.

METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ?37 weeks.

RESULTS: A genetic etiology was found in 97/146 (66%) preterm infants compared with 501/604 (83%) born ?37weeks, P < .0001. Chromosome 6q24 imprinting abnormalities (27% vs 12%, P = .0001) and GATA6 mutations (9% vs 2%, P = .003) occurred more commonly in preterm than term infants while mutations in KCNJ11 were less common (21 vs 34%, P = .008). Preterm patients with an identified mutation were diagnosed later than those without an identified mutation (median [interquartile range] 35 [34 to 36] weeks vs 31 [28 to 36] weeks, P < .0001). No difference was seen in other clinical characteristics of preterm patients with and without an identified mutation including age of presentation, birth weight, and time to referral.

CONCLUSIONS: Patients with neonatal diabetes due to a monogenic etiology can be born preterm, especially those with 6q24 abnormalities or GATA6 mutations. A genetic etiology is more likely in patients with less severe prematurity (>32 weeks). Prematurity should not prevent referral for genetic testing as 37% have a potassium channel mutation and as a result can get improved control by replacing insulin with sulphonylurea therapy.
0031-4005
1-9
Besser, R.E.J.
a3a3f059-d3b4-4c05-b305-e61d1a9c4198
Flanagan, S.E.
1713096d-47b2-427d-980f-3c3450a743dd
Mackay, D.G.J.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Shepherd, M.H.
984b3baa-2eef-4c18-9082-91d00cb61c3a
Shields, B.M.
9bda2f85-4434-4dd8-9f3d-03b051785c4f
Ellard, S.
e83de653-52c7-4706-9ddf-da5047a1cef5
Hattersley, A.T.
c555d835-dd08-415c-be14-26940d5c582d
Besser, R.E.J.
a3a3f059-d3b4-4c05-b305-e61d1a9c4198
Flanagan, S.E.
1713096d-47b2-427d-980f-3c3450a743dd
Mackay, D.G.J.
588a653e-9785-4a00-be71-4e547850ee4a
Temple, I.K.
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Shepherd, M.H.
984b3baa-2eef-4c18-9082-91d00cb61c3a
Shields, B.M.
9bda2f85-4434-4dd8-9f3d-03b051785c4f
Ellard, S.
e83de653-52c7-4706-9ddf-da5047a1cef5
Hattersley, A.T.
c555d835-dd08-415c-be14-26940d5c582d

Besser, R.E.J., Flanagan, S.E., Mackay, D.G.J., Temple, I.K., Shepherd, M.H., Shields, B.M., Ellard, S. and Hattersley, A.T. (2016) Prematurity and genetic testing for neonatal diabetes. Pediatrics, 138 (3), 1-9. (doi:10.1542/peds.2015-3926). (PMID:27540106)

Record type: Article

Abstract

BACKGROUND: Hyperglycemia in premature infants is usually thought to reflect inadequate pancreatic development rather than monogenic neonatal diabetes. No studies, to our knowledge, have investigated the prevalence of monogenic forms of diabetes in preterm infants.

METHODS: We studied 750 patients with diabetes diagnosed before 6 months of age. We compared the genetic etiology and clinical characteristics of 146 preterm patients born <37 weeks and compared them with 604 born ?37 weeks.

RESULTS: A genetic etiology was found in 97/146 (66%) preterm infants compared with 501/604 (83%) born ?37weeks, P < .0001. Chromosome 6q24 imprinting abnormalities (27% vs 12%, P = .0001) and GATA6 mutations (9% vs 2%, P = .003) occurred more commonly in preterm than term infants while mutations in KCNJ11 were less common (21 vs 34%, P = .008). Preterm patients with an identified mutation were diagnosed later than those without an identified mutation (median [interquartile range] 35 [34 to 36] weeks vs 31 [28 to 36] weeks, P < .0001). No difference was seen in other clinical characteristics of preterm patients with and without an identified mutation including age of presentation, birth weight, and time to referral.

CONCLUSIONS: Patients with neonatal diabetes due to a monogenic etiology can be born preterm, especially those with 6q24 abnormalities or GATA6 mutations. A genetic etiology is more likely in patients with less severe prematurity (>32 weeks). Prematurity should not prevent referral for genetic testing as 37% have a potassium channel mutation and as a result can get improved control by replacing insulin with sulphonylurea therapy.

Text
RBESSER Preterm paper Pediatrics 2015.doc - Accepted Manuscript
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 14 June 2016
e-pub ahead of print date: 1 September 2016
Published date: September 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 399864
URI: https://eprints.soton.ac.uk/id/eprint/399864
ISSN: 0031-4005
PURE UUID: 9ed19ad8-58dc-46b1-adcc-d1ca3a7059e8
ORCID for D.G.J. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

Catalogue record

Date deposited: 02 Sep 2016 09:10
Last modified: 06 Jun 2018 12:54

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×