Screening for neonatal diabetes at day 5 of life using dried blood spot glucose measurement

Timothy J McDonald, Rachel E Besser, Mandy Perry, Tarig Babiker, Bridget A Knight, Maggie H Shepherd, Sian Ellard, Sarah E Flanagan, Andrew T Hattersley, Timothy J McDonald, Rachel E Besser, Mandy Perry, Tarig Babiker, Bridget A Knight, Maggie H Shepherd, Sian Ellard, Sarah E Flanagan, Andrew T Hattersley

Abstract

Aims/hypothesis: The majority of infants with neonatal diabetes mellitus present with severe ketoacidosis at a median of 6 weeks. The treatment is very challenging and can result in severe neurological sequelae or death. The genetic defects that cause neonatal diabetes are present from birth. We aimed to assess if neonatal diabetes could be diagnosed earlier by measuring glucose in a dried blood spot collected on day 5 of life.

Methods: In this retrospective case-control study we retrieved blood spot cards from 11 infants with genetically confirmed neonatal diabetes (median age of diagnosis 6 [range 2-112] days). For each case we also obtained one (n = 5) or two (n = 6) control blood spot cards collected on the same day. Glucose was measured on case and control blood spot cards. We established a normal range for random glucose at day 5 of life in 687 non-diabetic neonates.

Results: All 11 neonates with diabetes had hyperglycaemia present on day 5 of life, with blood glucose levels ranging from 10.2 mmol/l to >30 mmol/l (normal range 3.2-6.0 mmol/l). In six of these neonates the diagnosis of diabetes was made after screening at day 5, with the latest diagnosis made at 16 weeks.

Conclusions/interpretation: Neonatal diabetes can be detected on day 5 of life, preceding conventional diagnosis in most cases. Earlier diagnosis by systematic screening could lead to prompt genetic diagnosis and targeted treatment, thereby avoiding the most severe sequelae of hyperglycaemia in neonates.

Keywords: Blood spots; Glucose; Neonatal diabetes; Newborn; Screening.

Conflict of interest statement

Data availability

All data are available on request from the authors.

Funding

TJM is an NIHR HEE funded Clinical Senior Lecturer. SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number: 105,636/Z/14/Z). ATH and SE are Wellcome Trust Senior Investigators. ATH is an NIHR Senior Investigator and MHS is supported by the NIHR Exeter Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

TJM, REB, MP and ATH contributed to the conception and design, acquisition, analysis and interpretation of data, and writing the manuscript. TB and BAK contributed to the acquisition, analysis and interpretation of data, and reviewed the manuscript. MHS, SE and SEF contributed to the acquisition of data, drafting the article and revising it. All authors approved the final version. TJM is the guarantor of this work.

Figures

Fig. 1
Fig. 1
Stability of blood spot glucose stored at room temperature (dotted black line/squares), in a fridge (4°C, solid black line/triangles) and in a freezer (−20°C, dashed line/circles) over 14 days. Blood taken from 20 volunteers. Data presented as mean percentage of baseline at each time point, with error bars representing the 95% CI
Fig. 2
Fig. 2
Graph showing projected glucose (adjusted for degradation with time) in Guthrie blood spots collected at day 5 of life for participants with neonatal diabetes and paired control samples collected on the same day

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Source: PubMed

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