Download Around 65000 children aged below 15 years develop type 1

Introduction:
Around 65,000 children aged below 15 years develop type 1
diabetes each year all over the world (1). The incidence is rising, with
some reports show a well recognised higher increases to children below 5
years (2). About 80% of patients below 15 years who are diagnosed with
type 1 diabetes have DKA at diagnosis, DKA at presentation ranges from
12.8% to 80% (3). This study aimed to identify clinical presentation and
criteria of type 1 diabetes in children below 5 years.
Methods:
This cohort study was conducted in the Diabetes Endocrine and
Metabolism Paediatrics Unit at the Children's Hospital of Cairo
University (DEMPU). Over a period of 6 months, thirty infants and
toddlers (age less than 5 years) presenting with newly diagnosed diabetes,
based on recent ISPAD guidelines (4), were included.
Informed parents approval and consent was obtained before inclusion
of the subjects to the study for the collection of clinical data and
withdrawal of blood samples.
Thorough history taking, clinical and laboratory evaluation at
presentation were done.
Patients were subdivided into 3 subgroups based on the age at
presentation
 Group 1: < 6 months ( NDM) (4).
 Group 2: 6months to < 2 years
 Group 3: ≥2 to ≤5 years
All data were tabulated and statistically analyzed using SPSS
statistical software. Descriptive statistics including mean, standard
deviations, minimum, maximum and range for numerical data; and
frequency and percentages for non-numerical data. For subgroup
analysis and comparison, student’s t- test was used to compare
quantitative variables; and Chi-square test for qualitative variables.
Statistical significance was considered at p value < 0.05.
Results:
Demographic data:
The studied children were 15 (50%) males and 15 (50%) females with
M/F ratio 1. Their age ranged from 2 to 77 months with a median of 24
months. Twenty-two (73.3%) children had history of diabetes in the family.
Positive consanguinity was present in 17/30 (56.7%) children. Four families
had 2 diabetic offspring, of whom two families (50%) had positive
consanguinity (table 1).
Identifiable environmental risk factors:
Nineteen (63.3%) children had no identifiable risk factors while 11
(36.6%) showed environmental triggers. Stress was the most identified
triggering risk factor in the form of maternal pregnancy and labour or
family troubles which was found in 7 patients (23%) (table 2). Early
introduction of cow's milk (before the age of 4 months) was detected in 3
children as a risk factor. The majority had no identifiable risk factor.
Mode of presentation:
Twelve patients presented with DKA (40%), 16 (53.3%) presented
with classic symptoms in the form of polyuria, ploydipsia and weight loss
and 2 were accidently discovered during routine workup for other
conditions (figure 1). The duration of symptoms, for symptomatic cases,
before diagnosis ranged from 2 to 60 days with median of 14 days.
Glucose level at presentation ranged from (210 to 1875 mg/dl) mean
540.1±300.8 mg/dl and median 505 mg/dl (table 3).
Of the 12 patients who presented with DKA; none were mild, 5/12
(41.7%) were of moderate severity and 7/12 (58.3%) were severe. The
lowest PH was 6.8; lowest HCO3 was 2.2 mEq/dl. They received
intravenous insulin infusion over a period ranging from 12 to 72 hrs with
a median of 12 hrs at a dose of (0.05- 0.1 IU/kg/hour), then they were
shifted to S.C. insulin. Nine patients (80%) were admitted to ICU < 2
days, and 4 patients (20%) >2 days.
Among the patients presented with DKA, no significant correlation
was found between blood glucose level and age at presentation, duration
of symptoms, HCO3 or PH (p>0.05). However, there was a negative
correlation between initial blood glucose level and age at presentation
with marginal significance (p=0.051) (table 4, figure 2).
Dividing the patients into subgroups:
The 30 patients were classified into 3 groups according to age at
presentation (figure 3).
 Group 1: included 6 (20%) infants who aged < 6 mo at the onset
of diabetes, neonatal diabetes (NDM) .
 Group 2: included 9 (30%) children who aged 6 mo to 2 yrs at the
onset of diabetes.
 Group 3: included 15 (50%) children who aged 2-5 yrs at the
onset of diabetes.
Group 1: 6 infants with neonatal diabetes:
They included 6 patients. Three males and 3 females. Mean age at
presentation was 2.5 months. Five infants (83.3%) had positive
consanguinity. Five infants (83.3%) had history of DM in the family, 3
patients (50%) had positive family history for neonatal diabetes and one
patient had a sibling with diagnosed diabetes at the age of 9 months.
Positive consanguinity was present in 5 patients (83.3%). None of the
siblings have had definitive molecular diagnosis.
Groups 2 (infants) and 3 (toddlers):
The following set table and figures illustrate a comparison between
groups 2 and 3 as regards clinical and laboratory data.
Frequency of DKA was higher in group 2, 5/9 (55%), than in group 3,
5/15 (33%). DKA was also more severe in group 2 than group 3. Four out
of five cases presented with DKA of group 2 were severe DKA (80%),
while only one case (20%) of five patients presenting with DKA of group
3 presented with severe DKA. Group 3 showed a female sex
predominance, however, the difference was not statistically significant
(p=0.7) (figure 4, table 6).
Shorter mean duration of symptoms (polyuria and polydipsia) before
presentation for group 2 (12 days ) versus 20 days for group 3 and the
difference was not statistically significant (p=0.1). Blood glucose levels
between both groups were comparable. For group 2, ranged between 221750 mg/d, median blood glucose level is 570 mg/dl. Group 3 blood
glucose levels ranges were 350- 750 mg/dl with median of 510 mg/ dl
and the difference was not statistically significant (p=0.8)
Discussion:
Studying the demographic data:
 Sex distribution:
In the present study, male to female ratio was 1: 1. This is similar to
general reports about incidence of type 1 diabetes being equal. As
reported by Soltesz, (5), male to female ratio is 1:1 in most populations.
In Egypt, Small studies in Cairo university over children attending
DEMPU were done over (29 children diagnosed with diabetes before the
age of 2.5 years, 96 children with type 1 diabetes, and 86 children with
diabetes) reported male to female ratio of (1.4, 0.7, and 1.15 respectively)
(6, 7, 8 (N.d.)).
A previous, large study done over children with diabetes in Nile
Delta and Northern Egypt, which reviewed data about newly diagnosed
children over the period between 1 January 1994 and 31 December 2011
who were admitted to Mansoura University Children’s Hospital or were
beneficiaries from Health Insurance services, showed total numbers for
female and male patients were 891 (55.7%) and 709 (44.3%),
respectively and the female/male ratio was 1.3 in favour of girls (9).
 Family history:
In the present study, family history of diabetes (type 1 and/or type
2) was reported in 22 (73.3%) children. This study also detected 4
families, each of them had 2 diabetic offspring (26% of patients belong to
diabetic family). These cases had their diabetes before 5 years of age.
This was comparable to the results of a previous Turkish study
which reported all cases diagnosed with T1DM was made in a 0-14-year
age group in the course of one year time starting on 1 June 2010 and
ending on 31 May 2011 in the city of Diyar bakr . Twenty-five patients
(61%) of total of 41 patients had T1DM or T2DM in their family history
(10).
 Consanguinity:
In the current study, high rate of positive consanguinity was present:
17/30 (56.7%) children.
In Egypt, several studies were carried out to determine the incidence
of consanguineous mating in the general population. The recent reports
say that consanguineous marriage is still high in Egypt (35.3%),
especially among first cousins (86%) (11).
Studying clinical data:
 Predisposing factors:
In the current study the most frequently encountered predisposing
factor was the familial stress in 7 children (23%), whether maternal
pregnancy, giving birth and in one patient the separation from father and
several familial troubles was reported. The 2nd most common identifiable
risk factor was early introduction of cow's milk in 3 children (10%).
Consumption of canned juices and canned meat products on daily bases
was identified in 1 (3.3%) patient.
Family stress is reported in several studies as a risk factor,
particularly in the year preceding the diagnosis (5).
N-Nitroso compounds that is used in diet such as processed meat
products, was shown to be significantly associated with higher incidence
of type 1 diabetes in many studies. Several clinical studies reported strong
relation between early introduction of cow's milk and type 1 diabetes
(12).
Mode of presentation:
 DKA:
In the present study, 40% of the patients presented with DKA. With
the blood glucose level at presentation inversely proportional to their age
with marginal significance (p=0.051). DKA frequency was 55.6% in
children below 2 years (group 2) versus 33.3% in those between 2-5 years
(group 3). Most of DKA patients <2 suffered severe form (4/5, 80%),
while only (1/5, 20%) patient >5 years suffered severe DKA. Only one
patient had fulminate fungal sinusitis as a complication and suffered
another attack of DKA during the follow up period.
In a previous study in DEMPU, DKA frequency at presentation
among 96 patients with T1DM with mean age at onset 5.3 years was
41.7%. This was in the year 2009 (7(N.d.)). However, in another study in
the year 2012, on 46 patients with T1DM who were below 2 years at time
of diagnosis the frequency of DKA at presentation was as high as 87%.
This was significantly higher (p= 0.0001) than patients over 5 years at
onset (27.5%) (8 (N.d.)).
According to Wolfsdorf et al. (13), wide geographic variability in the
DKA rates at presentation; rates inversely correlate with the incidence of
type 1 diabetes in the region. Frequencies varies from 15–70% in Europe
and North America. DKA at diagnosis has a higher incidence in younger
children (<2 yr of age).
In one large study based on data from DanDiabKids, a Danish
national diabetes register for children which provides clinical and
biochemical data on patients with type 1 diabetes diagnosed in 1996–
2009, prevalence of DKA at diagnosis in children between 0-5 years was
reported to be 25.3% and the highest of all age groups. The study also
observed that very young children (<2 years) had an undesirably high
prevalence of DKA (48.3%), comparable with register studies from
Sweden, Finland and Germany (39.5–54.9%) (14).
Conclusions and Recommendations:
 Diabetes in children below 5 years is still representing a potential
life threatening condition. DKA is frequently the first presentation.
 Increase awareness of childhood diabetes, and the possibility of
neonatal presentation in general population and among general
medical practitioners.
 Higher index of suspicion is required to diagnose diabetes early in
the disease before severe decompensation.
 Endocrinologist should pay special care to newly diagnosed cases
below 5 years. They should be aware of the higher risks of
fluctuating blood glucose.
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