Diabetes Care Volume 40, October 2017 e147

Lisa R. Letourneau,1 David Carmody,2

Diabetes Presentation in Infancy: High Kristen Wroblewski,3
Risk of Diabetic Ketoacidosis Anna M. Denson,1 May Sanyoura,1
Diabetes Care 2017;40:e147–e148 | https://doi.org/10.2337/dc17-1145 Rochelle N. Naylor,1,4
Louis H. Philipson,1 and
Siri Atma W. Greeley1,4

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Diabetes in childhood has been associ- mutation subtypes based on socioeco- age of diagnosis found in our study. This
ated with increased morbidity and mor- nomic status (P = 0.19), race/ethnicity delay may be related to the challenge
tality, but the risks for diabetes in infancy (P = 0.36), or sex (P = 0.07). KCNJ11- of diagnosing diabetes in infants who
remain unclear. Cases with onset of hy- related diabetes was the most common cannot communicate symptoms and in
perglycemia in the first 6 months of life form of infancy-onset diabetes (37.5%, whom polydipsia and polyuria may not
consist predominantly of monogenic dia- n = 33), followed by “Unknown” (likely be readily apparent and could even be
betes, whereas type 1 autoimmune dia- type 1 diabetes) (21.6%, n = 19); 14% reassuring to clinicians. Presentation
betes accounts for the majority of cases (n = 12) had transient neonatal diabetes. characteristics were different by muta-
beyond this threshold. Regardless of eti- Median age at diabetes diagnosis was tion subtype, therefore this information
ology, diabetes symptoms tend to be dif- 10.4 weeks and was significantly different (in addition to genetic testing) may help
ficult to recognize in an infant, putting by mutation subtype (Table 1). When to guide providers when making clinical
patients at increased risk for delays in di- grouped into permanent versus tran- decisions. Continuing to educate pediat-
agnosis, which may lead to higher blood sient diabetes, diagnosis age was signifi- ric providers about the many ways that
glucose levels and diabetic ketoacidosis cantly lower in the transient group infants can present with diabetes may
(DKA) at presentation. Here, we report a (median 15.2 weeks vs. 0.43 weeks, P , help to diagnose cases more efficiently
high degree of morbidity among a cohort 0.001). The most commonly reported signs/ and ultimately decrease the frequency
of subjects with infancy-onset diabetes. symptoms were polyuria (n = 32), tachypnea of DKA at diagnosis. Further study is
We examined diagnosis records from (n = 31), flu-like symptoms (n = 30), tired- needed to develop effective strategies
88 cases with diabetes onset #13 months ness/weakness (n = 28), dehydration (n = to reduce morbidity and mortality in this
of age collected through the University 27), and “not acting right” (n = 26). Blood vulnerable population.
of Chicago Monogenic Diabetes Registry glucose, pH, bicarbonate, HbA1c, and DKA
(1). We assessed laboratory values and were dependent on mutation subtype
sign/symptoms, and if a causal mutation (Table 1). Overall frequency of DKA was Acknowledgments. The authors would like to

e-LETTERS – OBSERVATIONS
for diabetes was detected, participants 66.2% (Table 1), and odds of DKA in- recognize the student research assistants who
were subdivided by similar mutation sub- creased with age at diagnosis (odds ratio contributed to data entry on this project: Janu
Arun (Chicago Medical School, Rosalind Franklin
types. Data were managed using REDCap per 1 month increase 1.23 [95% CI 1.04, 1.45]). University), Ade Ayoola (University of Chicago),
electronic data capture tools and ana- In this studydthe largest of its kindd Monica Lanning (University of Chicago), Maddie
lyzed using Stata version 14 (StataCorp, DKA was more frequent than in other McLaughlin (Purdue University), Kiran Munir
2015). early-onset U.S. studies (2,3) or other co- (Chicago Medical School, Rosalind Franklin Uni-
The majority of participants were male horts of patients with neonatal diabetes versity), Sai Talluru (Johns Hopkins University),
and Kandace Williamson (University of Chicago).
(n = 46, 52%), Caucasian (n = 55, 63%), and (4,5). One reason for this may be a delay The authors thank all the clinicians providing care
living in the United States (n = 83, 94%). in diagnosis, which is reflected in the for patients within the Monogenic Diabetes Reg-
There was no significant difference across increased likelihood of DKA at a later istry (http://monogenicdiabetes.uchicago.edu).

1
Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, Chicago, IL
2
Department of Endocrinology, Singapore General Hospital, Singapore
3
Department of Public Health Sciences, The University of Chicago, Chicago, IL
4
Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, The University of Chicago, Chicago, IL
Corresponding author: Siri Atma W. Greeley, [email protected].
Received 8 June 2017 and accepted 19 July 2017.
© 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and
the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
e148 Diabetes Presentation in Infancy Diabetes Care Volume 40, October 2017

They are most grateful to all of the patients and

†Statistically significant by Wilcoxon rank sum test, Kruskal-Wallis test, or Fisher exact test. Because of limited sample sizes, pairwise comparisons were not performed. ‡Data available from 73 participants. §Data available
All data presented as median (interquartile range) unless otherwise specified. T1D, type 1 diabetes; NA, not available. *In most cases, the mutation subtype was not reported in the medical record but rather was available
for each case through the Monogenic Diabetes Registry data. Mutation subtypes were grouped according to functional similarities. All participants in the “Unknown” category did not have an identifiable monogenic
families who participated in this study.

,0.001†
,0.001†

,0.001†
P value

0.005†
0.02†

0.04†

cause of diabetes at the time of data analysis. Some of these participants had positive diabetes autoantibodies, and thus likely had autoimmune type 1 diabetes. “Total” category represents pooled participants.
Funding. This work was supported by an
investigator-initiated grant from Novo Nordisk;
grants from the National Institutes of Health

8.8 [73] (6.9–9.8) ([52–84]) 9.9 [85] (8.3–12.2) ([67–110])

National Institute of Diabetes and Digestive

from 49 participants. |Data available from 58 participants. ¶Data available from 27 participants; HbA1c ,6 months are underestimated owing to fetal hemoglobin. #Data available from 71 participants.
and Kidney Diseases (R01DK104942, DRTC

7.08 (6.98–7.31)
P30DK020595, and K23DK094866 [to S.A.W.G.]),

10.4 (5.2–26.5)
618 (477–800)
7.7 (4.1–14.0)

7.0 (5.0–18.8)
the National Institutes of Health National Center

47 (66.2)
88 (100)
Total*
for Advancing Translational Sciences (CTSA
UL1TR000430), and the American Diabetes Asso-
ciation (1-11-CT-41 and 1-17-JDF-008); and gifts
from the Kovler Family Foundation.
Duality of Interest. No conflicts of interest rele-
vant to this article were reported.
Author Contributions. L.R.L. wrote the manu-
Unknown (likely T1D)*

script and collected, analyzed, and interpreted

42.6 (37.4–50.4)

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10.9 (6.7–17.9)

7.08 (7.0–7.27)

data. D.C. contributed to study design and

736 (526–840)

5.0 (4.0–10.4)
19 (21.6)

14 (87.5)
interpreted data. K.W. provided biostatistical
analysis and interpreted data. A.M.D. conducted
the literature review and collected, analyzed, and
interpreted data. M.S. provided genetic testing
support and interpreted data. R.N.N. contributed
to study design and interpreted data. L.H.P. de-
signed the study, provided administrative
7.11 (6.9–7.31)
21.1 (20.0–21.8) 13.0 (6.0–20.0) 16.0 (7.0–25.0)
920 (342–1,600) 411 (355–467)
GATA6/PDX1*

3.2 (2.2–4.2)

and material support, and obtained funding.

9.1 (0–18.3)
2 (2.3)

S.A.W.G. designed the study; collected, analyzed,

1 (50)
NA

and interpreted data; provided administrative

and material support; obtained funding; and
supervised the study. All authors reviewed and
edited the manuscript, contributed to discussion,
FOXP3/IL2RA*

6.95 (6.9–7.0)
14.8 (0–22.2)

and approved the final manuscript. S.A.W.G. is

3.3 (3.2–6.6)

4.9 [30]
3 (100)
3 (3.4)

the guarantor of this work and, as such, had full

access to all the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis.
7.43 (7.39–7.46)
408 (300–502)

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Number of participants,

Age at diagnosis, weeks

HbA1c, % [mmol/mol]¶
Bicarbonate, mmol/L|
Current age, years

Glucose, mg/dL‡

DKA, n (%)#
n (%)

pH§