NEONATAL

DIABETES:
Current Trends in Diagnosis and Management
Melissa Andrews Rearson, MSN, CRNP • Heather McKnight-Menci, MSN, CRNP • Linda Steinkrauss, MSN, CRNP

Abstract
The purpose of this article is to describe diabetes diagnosed during the first 6 months of life.
Neonatal diabetes, also known as congenital diabetes, presents a unique set of challenges for the
pediatric healthcare provider. Neonatal diabetes is not type 1 diabetes. While the etiology of type
1 diabetes is multifactorial and includes genetic and environmental factors, neonatal diabetes is
strictly a genetic condition. Management of children with neonatal diabetes, treatment of the dis-
ease, psychosocial considerations for the family, and nursing care required for this population are
all included in this article. Unique issues related to the diagnosis of a genetic mutation resulting
in a defect in the potassium channel are also discussed.
Key words: Diabetes mellitus; Genetic diseases; Inborn; Infant; Insulin.

January/February 2011 MCN 17

Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 eonatal diabetes is defined as uncontrolled hyper-
N
glycemia that requires treatment with insulin and
has an onset in the first 6 months of life (Vaxil-
laire, Bonnefond, & Froguel, 2009). It occurs in
approximately 1 in 300,000 to 500,000 live births
(Cave, Polak, Drunet, Denamur, & Czernichow,
2000; Sagen et al., 2004) and can be either permanent or
transient. Some have proposed the term “congenital dia-
betes” because some of these cases occur after the
4-week neonatal period, but “neonatal diabetes” remains the
conventional term. A vast majority of cases of neonatal
diabetes are genetically determined by a gene mutation
and are, therefore, not autoimmune (Craig, Hattersley, &
Donaghue, 2009). Type 1 diabetes, the more familiar form
of diabetes, is an autoimmune disease determined by
both genetic and environmental factors and is not termed
neonatal diabetes. Although it is possible that a child un-
der 6 months of age could have type 1 diabetes, this is
extremely rare, and less than 1% of children with type 1
diabetes present in infancy (Hattersley, Burining, Shield,
Njolstad, & Donaghue, 2009). This article focuses on the
diagnosis, classification, and treatment of children with
neonatal diabetes. Caring for a child with neonatal dia-
betes presents unique challenges to the healthcare team
and the caregiver. Based on the type of genetic mutation,
many children with neonatal diabetes can be treated with
an oral hypoglycemic agent. The identification of infants
who are candidates for treatment with oral agents will also
be discussed.
Diagnosis of Diabetes in Infancy
The majority of the cases of neonatal diabetes present
with intrauterine growth restriction, failure to thrive,
decreased subcutaneous fat, and low or undetectable
C-peptide levels—a marker of insulin reserve (Fösel,
1995). Babies with neonatal diabetes are small for gesta-
tional age (SGA) because of insulin deficiency in utero;
insulin is an important growth factor without which op-
timal growth cannot occur. Additional presenting signs
of neonatal diabetes include increased thirst, polyuria,
dehydration, and failure to thrive (DeLeon & Stanley,
2008). Parents often report that their child is “soaking
the crib” or “soaking through diapers suddenly.” Parents
may initially not seek medical attention for what they
think may be a normal occurrence in an infant; parents
may attribute increased urination to overhydration or
may think it is a variation of normal. In addition, because
of the rarity of this disorder, healthcare providers may
not suspect diabetes during infancy; diabetes in very
young children is often misdiagnosed, and babies are
significantly more likely to present with severe diabetic
ketoacidosis because of a delayed diagnosis (Pawłowicz,
Birkholz, Niedz´wiecki, & Balcerska, 2009).
Diagnosis of diabetes may initially be suspected based
on signs of polydipsia, polyuria from parent report but
ketones may or may not be present (Ozlu, Tyker, &
Yuksel, 2006). A metabolic panel will show elevated
glucose levels; persistent blood glucose levels of >150 to
18 volume 36 | number 1
Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
200 mg/dl are diagnostic of diabetes in an infant (DeLeon
& Stanley, 2008).
Differentiating Type 1 Diabetes
and Neonatal Diabetes
Although most infants who present with diabetes have
congenital diabetes, the diagnosis of type 1 diabetes must
be explored to be excluded (Murphy, Ellard, & Hatters-
ley, 2008). Type 1 diabetes is an autoimmune condition
that is typically diagnosed after the neonatal period in
children and young adults. Autoimmune conditions
occur because antibodies attack the islet cells (insulin-
producing cells) of the pancreas. Although the etiology
of type 1 diabetes is multifactorial and includes ge-
netic and environmental factors, neonatal diabetes is
strictly a genetic condition. Children or adults who de-
velop type 1 diabetes have a genetic predisposition that
is exacerbated by associated, yet unproven, environmen-
tal factors that include viruses, cow’s milk, and nitrosa-
mines (Borchers, Uibo, & Gershwin, 2010). Many genes
are involved in type 1 diabetes, making this a polygenic
condition; type 1 diabetes cannot be tied to a specific
gene mutation or mutations. Type 1 diabetes is differen-
tiated from other types of diabetes by the presence of
autoantibodies including GAD 65, insulin antibodies,
and ICA 512.
Neonatal Diabetes
Neonatal diabetes may take one of two forms, depending
on the permanence of hyperglycemia: transient neonatal
diabetes mellitus (TNDM) or permanent neonatal dia-
betes mellitus (PNDM).
Transient Neonatal Diabetes
TNDM is thought to be a result of a combination of mu-
tations on chromosome 6 (Temple & Mackay, 2010). It
is characterized by an early onset and remission of insulin
requirement by 18 months of age. Babies with PNDM
and TNDM share the characteristic of being SGA. In
TNDM, however, once catch-up growth has occurred,
insulin is no longer required (DeLeon & Stanley, 2008).
TNDM most commonly presents with hyperglycemia in
the first week of life.
Most infants with TNDM will not have diabetes auto-
antibodies, but will have a low C-peptide at diagnosis,
indicating that their pancreas is not able to secrete insulin
(endogenous insulin) (Temple, Gardner, Mackay, Barber,
Robinson, & Shield, 2000). Infants having TNDM will
have resolution of hyperglycemia in infancy, but may
need insulin again during adolescence or pregnancy
(Greeley Tucker, Worrell, Skowron, Bell, & Philipson,
2010). This is most common during a time of physical
change or stress when the body demands more insulin to
keep blood glucose levels in a normal range (DeLeon &
Stanley, 2008). The potential for recurrence of diabetes
later in life makes long-term follow-up essential for babies
with transient neonatal diabetes. If there is a recurrence,
diet management can initially be used, but most children
January/February 2011
will then go on to require insulin with then progress normally for successful
uncertain response to oral hypoglycemic insulin secretion: Figure 1 details these
agents (Hattersley et al., 2009). five steps (Sperling, 2006). A genetic mu-
tation on the KCNJ11 or ABCC8 genes
Permanent Neonatal leads to an inability of the potassium
channel to properly close in response to
Diabetes glucose influx. This interference in the
Diagnosis and management of PNDM, β-cell pathway prevents the appropriate
characterized by hyperglycemia that de- secretion of insulin and causes PNDM
velops during the first 6 months of life (Aguilar-Bryan & Bryan, 2010; Sagen
and does not resolve, present further et al., 2004). Sulfonylureas are effec-
challenges because of the ongoing need tive in treating this type of diabetes as
for insulin therapy. Insulin is required they prevent the KATP channel from per-
daily, with doses ultimately increasing manently staying open, allowing se-
rather than decreasing. Diabetes auto- Because of the rarity cretion of the insulin normally made by
antibodies and C-peptide levels will be the body.
absent in infants with PNDM. PNDM
of this disorder, nurses
results from a mutation in the potassium may not suspect Treatment Options for
(KATP) channel of the insulin-producing
cells. The specific mutation prohibits in- diabetes during Neonatal Diabetes
sulin secretion in the β cells (Murphy et Insulin
al., 2008). Murphy et al. (2008) state infancy; diabetes in Treatment with insulin therapy should
that while most infants with PNDM will begin immediately after diabetes is diag-
have only diabetes from this gene muta-
very young children is nosed by an elevated hemoglobin A1c
tion, up to 20% will also have neurologi- often misdiagnosed, (normal <5.9%) or persistent hypergly-
cal complications such as Developmental cemia (blood glucose >150). Insulin is
delay, Epilepsy, and Neonatal Diabetes and babies are often delivered initially by an insulin in-
(collectively termed “DEND”). DEND can fusion that gives healthcare providers
occur along a spectrum of severity, from significantly more the ability to titrate doses depending on
mild developmental delay to more severe likely to present blood glucose levels. Once transitioned
(Hattersley & Ashcroft, 2005). Infants from the initial insulin infusion, injec-
with mutations in KCNJ11 and ABCC81 with severe diabetic tions of a basal insulin (Lantus/insulin
(genes that encode the KATP channel) can be glargine—Aventis or Levemir/insulin
treated successfully with oral sulfonyl- ketoacidosis because detemir—Novo Nordisk) or Neutral
ureas that will manage hyperglycemia Protamine Hagedorn (NPH) insulin may
without an increase in hypoglycemia
of a delayed diagnosis. be started. Basal insulin, which can often
(Pearson et al., 2006). last 24 hours in adults, is often divided
into twice-daily dosing in young chil-
dren and infants to provide an adequate basal effect
Genetics of Neonatal Diabetes (DeLeon & Stanley, 2008). The pharmacological action
When diabetes is diagnosed in the first week of life, it is of NPH is variable in different individuals, and with a
not possible to determine whether the infant has TNDM peak time of 4 to 6 hours; this makes dosing this type
or PNDM by clinical evaluation. Genetic testing is of insulin with feedings difficult. Humalog (insulin
therefore imperative for making a diagnosis. Testing for lispro—Eli Lilly) and Novolog (insulin aspart—Novo
gene mutations in IPF1, GCK, KCNJ11, INS, and ABCC Nordisk) should be used cautiously, as peak action can
should be done as part of the initial laboratory evalua- cause significant hypoglycemia even in very small doses
tion (Murphy et al., 2008). There is a commercially avail- (DeLeon & Stanley, 2008). Similar to insulin use in older
able panel of these specific tests for DNA sequencing to children with type 1 diabetes, insulin to carbohydrate
identify gene mutations for neonatal diabetes. Compa- ratios can be used by caregivers to calculate a bolus in-
nies that perform this testing typically test one gene at a sulin dose. Additionally, a ratio of insulin dose to blood
time and continue to test additional genes until a muta- glucose level can be used for high blood glucose correc-
tion is identified. Because this testing can cost more tion. These ratios, when used for small infants requiring
than $5,000, prior authorization from the insurance little insulin per day translate into very small doses that
company is often required (Athena Diagnostics Client can be difficult to measure in a standard insulin syringe
Price List, 22 February, 2010). (Casella, Mongilio, Plotnick, Hesterberg, & Long,
The physiology of KATP channel mutation in patients 1993). Caregivers can only reliably measure in half-unit
with PNDM is important for nurses to understand. First, increments using a BD Ultra-Fine II Insulin Syringe 3/10
in normal β-cell function, glucose influx into the β cell cc with half-unit markings. Some families report the abil-
stimulates insulin release. A cascade of five steps must ity to affect blood sugars by giving a “heavy” or “light”

January/February 2011 MCN 19

Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 half, based on lesser or more amounts of carbohydrate
and blood correction factor. Blood glucose is affected by
a great variety of variables, however, and hyperglycemia
and hypoglycemia are both difficult to control. Casella et
al. (1993) suggest using diluted insulin if doses required
are less than 2 units to avoid dosing error.
Dilute insulin
Dilute insulin may be utilized to ease measurement of in-
sulin doses for small children (Stickelmeyer, Graf, Frank,
Ballard, & Storms, 2000). The usual dilution used for
insulin is a 1:10 concentration, allowing for more speci-
ficity with measurement. Although dilute insulin does al-
low for exact measurement, it can also lead to confusion
for healthcare providers about dosing. The utilization
of 1 unit/10 ml allows for greater ease in drawing up the
small doses required by infants. For example, an infant
may be prescribed 0.2 units of insulin. A standard U-100
insulin preparation (100 units/1 ml) would require that
0.2 units be measured into an insulin syringe, a virtually
impossible task when the smallest marking on an insulin
syringe is 0.5 units. When using dilute U-10 insulin, how-
ever, 0.2 units of standard U-100 insulin may be obtained
by drawing up to the 2-unit line on an insulin syringe.
Although this provides better accuracy, it can also lead to
dosing errors. Many healthcare providers are not famil-
iar with dilute insulin, and communicating with the
caregiver requires clear differentiation between standard
FIGURE 1. Five Steps for Successful Insulin Secretion
1. Glucose influx causes an increase in the ATP/ADP ratio
2. Resulting in closure of the KATP channel
3. The β cell membrane depolarizes
4. Causing an influx of positively charged calcium
5. Stimulating insulin release
G6P = glucose-6-phosphate
Normal Insulin Release Pathway in the Beta Cell
K+
KATP Channel 3
SUR1+Klr6.2
Ca++
2
K+
ATP/ADP
1 Hyperinsulinism in Infants and
Glucose G6P
Beta Cell
20 volume 36 | number 1
MCN0111_Neonatal_120_Amit.indd 20
Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
U-100 preparations and the dilute U-10 preparation.
In addition to documenting the insulin dilution used,
families can help to improve safety by carefully inform-
ing any provider working with them that their child is
using dilute U-10 insulin and that each “mark on the
syringe” is 1/10 unit.
Orders concerning dilute insulin should clearly state
the dose to be given (0.2 units), that dilute insulin is to be
utilized, and the amount of dilute insulin to be drawn
up in the syringe (2 units). Dilute insulin should be pre-
pared by a pharmacist who is familiar with the dilution
technique. Due to instability issues, dilute insulin loses its
potency more quickly than standard insulin, and should
be discarded 30 days after preparation (Stickelmeyer et
al., 2000). For this reason, parents cannot obtain a sup-
ply for longer than 1 month at a time. Along with insulin
use, caregivers can be shown how to carefully monitor
blood glucose levels and be taught to respond to chang-
ing levels with problem solving about feeding and insulin
administration. Caregivers should monitor blood glucose
levels through the night and frequently through the day,
being aware that most infants do not exhibit symptoms
of hypoglycemia. The risk of hypoglycemia, which may
affect the developing brain, is frightening for families
and healthcare providers alike. In the future, continuous
glucose monitors, now only approved for use in children
7 and older, may provide caregivers with another way to
frequently monitor changes in blood glucose levels.
Ca++
4
Insulin
5 Adapted and reprinted with per-
mission from Stanley, C. A. (1997).
children. Pediatric Clinics of North
America, 44(2), 363-373. Elsevier Lim-
ited VAT # GB 494 6272 12.
January/February 2011
09/12/10 11:56 PM
Feeding and insulin glucose testing would also dramatically
Counting carbohydrates and planning lessen. Treatment with oral agents mark-
dietary intake for an infant with diabetes edly decreases the complexity of diabe-
require participation from all team mem- tes management in infants. The use of
bers on the child’s care team. A registered sulfonylureas in infants is still a relative-
dietitian can assist the family and other ly new treatment modality and must be
healthcare providers in determining car- approached with caution. Once the di-
bohydrate content of breast milk, for- agnosis of permanent neonatal diabetes
mula, and eventually solid foods as they caused by KATP channel defects has been
are introduced. As rapid-acting insulin is established through genetic testing, par-
most commonly dosed based on carbo- ents can be informed that insulin may be
hydrate content, it is important that insu- replaced by a sulfonylurea. Substitution
lin boluses be paired with feedings, and of insulin with the sulfonylurea should
that carbohydrate intake is measured as take place gradually under the direction
accurately as possible. For example, a Dilute insulin can of a medical team experienced with the
common rule for evaluating the insulin-to- ease measurement use of these medications in infants. The
carbohydrate ratio is to divide 500 by use of sulfonylureas in infancy is cur-
the total daily insulin dose. If the infant is of insulin doses for rently off-label, and parents should be
requiring about 3 units of insulin in a 24- fully informed and sign consent for the
hour period, divide 500 by 3. This results small children. Using change in treatment. Hospital admission
in 166—the insulin-to-carbohydrate ra- is recommended for close monitoring of
tio would be 1 unit of insulin for 166 g 1 unit per 10 ml these patients, and hospital and outpatient
of carbohydrate. Using a U-10 dilution allows for greater protocols have been developed (Pearson
of insulin, each 0.1 unit of insulin would et al., 2006).
then cover 16 g of carbohydrate—the ease in drawing up
total carbohydrate in 10 oz of milk. Rapid-
acting insulin is given not only for carbo- the small doses. Assessment of Blood
hydrate ingestion but also for correcting Glucose Control
high blood glucoses. For blood glucose Evaluation of blood glucose records is
correction, the 1,800 rule is applied: di- usually the easiest way to determine
vide 1,800 by the total daily insulin dose. In this case, day-to-day fluctuations in blood glucose levels in infants
divide 1,800 by 3 and get 600. Each unit of insulin would with neonatal diabetes. Trends can be seen at specific
decrease the blood glucose by 600 mg/dl. Using U-10 times of the day, after specific meals or feeding times or in
dilute insulin, each 0.1 unit would decrease the blood relation to illness or other change in the daily activity.
glucose by 60 mg/dl, a more manageable amount (Walsh, For an infant, morning blood glucose levels do not
Roberts, Bailey, & Varma, 2003). often reflect fasting because many infants feed during
the night. Instead, a morning blood glucose level may in-
Oral Sulfonylureas dicate how a nighttime feed is covered with basal insulin
The recent discovery of the fact that the KATP channel or a bolus dose of rapid-acting insulin. If healthcare
mutation caused permanent neonatal diabetes has led to providers can maintain a consistent schedule of feeding,
the use of glyburide, an oral sulfonylurea in the treatment it is easier to determine whether trends in blood glucose
of hyperglycemia. Sulfonylurea drugs bind to the chan- levels exist.
nel, resulting in closure and release of endogenous insu- Determining goals for blood glucose levels can be
lin (Hattersley & Ashcroft, 2005). This treatment is not challenging as well. Normal blood glucose levels range
used until the results of genetic testing are available, between 70 and 110 mg/dl. The safety margin between
however, which may take 6 to 8 weeks. The 6- to 8-week normal and low blood glucose levels is close, however,
waiting period for laboratory results is difficult for both so traditionally, blood glucose levels have been allowed
parents and healthcare providers (Catz et al., 2005) as to run as high as 200 mg/dl to prevent hypoglycemia. A
the parents cope with the stressors of having a sick infant safe target range for glucose levels for infants is 100 to
requiring insulin and worry about the possibility of a 180 mg/dl before feeding and 110 to 200 mg/dl at sleep
genetic mutation causing diabetes, which would change times, as recommended by the American Diabetes
the treatment modality for their infant. During this peri- Association (Silverstein et al., 2005).
od multiple insulin injections and blood glucose tests Hemoglobin A1c measures long-term glucose control
should be carried out despite the possibility that the di- and should be measured every 3 months. For a child
agnosis of KATP channel mutation would guide the pro- younger than 6 years, the American Diabetes Association
vider to prescribe oral sulfonylurea to replace the insulin recommends that the hemoglobin A1c level be between
injections. 7.5% and 8.5% to optimize good blood glucose control
If the genetic diagnosis of permanent neonatal diabe- while being cautious about hypoglycemia (Silverstein et
tes is made, treatment with sulfonylureas and blood al., 2005).

January/February 2011 MCN 21

Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Clinical Implications
There is a great deal for nurses to learn about diagnosis
and management of neonatal diabetes. Nurses play a sig-
nificant role in supporting families as they learn about
the disease, and struggle to manage the stress, which ac-
companies having a sick infant. Parents who have only
recently learned the skills of newborn care are suddenly
expected to learn the skills of being a healthcare provider
for their own child: giving insulin as needed and monitor-
ing blood glucose throughout the day and night (Strei-
sand et al., 2008). Parents need to be taught about the
dangers of hypoglycemia and hyperglycemia in their
infants, and about the complicated dosing calculations
for insulin in small infants. Infants have varying sleep/
wake and eating schedules, adding to the complications
of trying to achieve consistently safe blood glucose levels.
Fussiness can be correctly interpreted as normal in the
infant, but it may also be caused by hypoglycemia or
hyperglycemia, requiring more frequent blood glucose
testing than might be necessary in an older child. All of
these factors contribute to incredibly difficult transitions
for the family, and are further challenges for the nurses
caring for the infants and families.
Managing infants with diabetes requires a skilled pe-
diatric endocrine team with experience in diagnosis and
management of diabetes in this young age group, with
professional nurses who are both learned and compas-
sionate in their care. ✜
Melissa Andrews Rearson, MSN, CRNP, is a Pediatric
Nurse Practitioner, Children’s Hospital of Philadelphia/
Division of Endocrinology and Diabetes. She can be
reached via e-mail at rearson@email.chop.edu
Heather McKnight-Menci, MSN, CRNP, is a Pediatric
Nurse Practitioner, Children’s Hospital of Philadelphia/
Division of Endocrinology and Diabetes.
Linda Steinkrauss, MSN, CRNP, is a Pediatric Nurse
Practitioner, Children’s Hospital of Philadelphia/Divi-
sion of Endocrinology and Diabetes.
The authors have disclosed that they have no financial
relationships related to this article.
DOI:10.1097/NMC.0b013e3181fc06cd
References
Aguilar-Bryan, L., & Bryan, J. (2010). Neonatal diabetes mellitus. Endo-
crine Reviews, 29(3), 265-291. doi:10.1210/er.2007-0029
Borchers, A. T., Uibo, R., & Gershwin, M. E. (2010). The geoepidemi-
ology of type 1 diabetes. Autoimmunity Review, 9(5), 355-365.
doi:10.1016/j.autrev.2009.12.003
Casella, S. J., Mongilio, M. K., Plotnick, L. P, Hesterberg, M. P., & Long,
C. A. (1993). Accuracy and precision of low-dose insulin administra-
tion. Pediatrics, 91(6), 1155-1157.
Catz, D. S., Green, N. S., Tobin, J. N., Lloyd-Puryear, M. A., Kyler,
P., Umemoto, A. Wolman, F. (2005). Attitudes about genetics in
underserved, culturally diverse populations. Community Genetics,
8(3), 161-172. doi:10.1159/000086759
For 38 additional continuing nursing education articles on
neonatal topics, go to nursingcenter.com/ce
22 volume 36 | number 1
Copyright © 2010 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cave, H., Polak, M., Drunet, S., Denamur, E., & Czernichow, P. (2000).
Refinement of the 6q chromosomal region implicated in transient
neonatal diabetes. Diabetes, 49, 108-113. doi:10.2337/diabetes.
49.1.108
Craig, M. E., Hattersley, A., & Donaghue, K. C. (2009). Definition, epide-
miology and classification of diabetes in children and adolescents.
Pediatric Diabetes, 10(Suppl. 12), 3-12. doi:10.1111/j.1399-5448.
2009.00568.
DeLeon, D., & Stanley, C. (2008). Permanent neonatal diabetes melli-
tus. Gene Reviews, 1-26. Retrieved from http://www.ncbi.nlm.nih.
gov/pubmed/19952737
Fösel, S. (1995). Transient and permanent neonatal diabetes. European
Journal of Pediatrics, 154(12), 944-948. doi:10.1007/BF01958635
Greeley, S. A., Tucker, S. E., Worrell, H. I., Skowron, K. B., Bell, G. I., &
Philipson, L. H. (2010). Update in neonatal diabetes. Current Opin-
ion in Endocrinology, Diabetes, and Obesity, 17(1), 13-19.
Hattersley, A. T., & Ashcroft, F. M. (2005). Activating mutation in Kir6.2
and neonatal diabetes: New clinical syndromes, new scientific in-
sights and new therapy. Perspective in Diabetes, 54(9), 2503-2513.
Hattersley, A., Burining, J., Shield, J., Njolstad, P., & Donaghue, K.C.
(2009). The diagnosis and management of monogenic diabetes in
children and adolscents. Pediatric Diabetes, 10 (Suppl. 12), 33-42.
doi:10.1111/ j.1399-5448.2009.00571.x
Murphy, R., Ellard, S., & Hattersley, A. (2008, April). Clnical implications
of a molecular genetic classificiation of monogenic beta-cell diabe-
tes. Nature Clinical Practice Endocrinology & Metabolism, 4, 200-213.
doi:10.1038/ncpendmet0778
Ozlu, F., Tyker, F., & Yuksel, B. (2006). Neonatal diabetes mellitus. Indian
Pediatrics, 43(7), 642-645.
Pawłowicz, M., Birkholz, D., Niedz´ wiecki, M., & Balcerska A. (2009, De-
cember). Difficulties or mistakes in diagnosing type 1 diabetes in
children?—demographic factors influencing delayed diagnosis.
Pediatric Diabetes, 10(8), 542-549.
Pearson, E. R., Flechtner, I., Njolstad, P. R., Malecki, M. T., Flanagan, S.
E., Larkin, B. Hattersley, A. T. (2006). Switching from insulin to oral
sulfonylureas in patients with diabetes due to Kir6.2 mutations.
New England Journal of Medicine, 355, 467-477. doi:10.1056/NEJ-
Moa061759
Sagen, J. V., Raeder, H., Hathout, E., Shahadeh, N., Gundmuddson, K,
Baevre, H. Njolstad. (2004). Permanent neonatal diabetes due to
mutations in KCNJ11 encoding Kir6.2: Patient characteristics and
initial response to sulfonylurea therapy. Diabetes, 53, 2713-2718.
doi:10.2337/diabetes.53.10.2713
Silverstein, J., Klingensmith, G., Copeland, K., Plotnick, L., Kaufman, F.,
Laffel, L. Clark, N. (2005). Care of children and adolescents with
type 1 diabetes: A statement of the American Diabetes Association.
Diabetes Care, 28, 186-212. doi:10.2337/diacare.28.1.186
Sperling, M. A. (2006). ATP-Sensitive potassium channels—neonatal
diabetes mellitus and beyond. New England Journal of Medicine,
335(5), 507-510.
Stickelmeyer, M. P., Graf, C. J., Frank, B. H., Ballard, R. L., & Storms,
S. M. (2000, May). Stability of U-10 and U-50 dilutions Lispro.
Diabetes Technology & Therapeutics, 2(1), 61-66. doi:10.1089/
152091599316757
Streisand, R., Mackey, E. R., Elliot, B. M., Mednick, L., Slaughter, I. M.,
Turek, J., & Austin, A. (2008). Parental anxiety and depression as-
sociated with caring for a newly diagnosed with type 1 diabetes:
Opportunities for education and counseling. Patient Education and
Counseling,73(2), 333-338.
Temple, I. K., Gardner, R. J., Mackay, D. J., Barber, J. C., Robinson, D. O.,
& Shield, J. P. (2000). Transient neonatal diabetes, widening the
understanding of the etiopathogenesis of diabetes. Diabetes, 49,
1359-1366.doi:10.2337/diabetes.49.8.1359
Temple, I. K., & Mackay, D. J. G. (2010). Diabetes mellitus, 6q24-related
transient neonatal. In R. A. Pagon, T. C. Bird, C. R. Dolan, & K. Ste-
phens (Eds.), GeneReviews (Internet). Seattle, WA: University of
Washington, Seattle. PMID: 20301706
Vaxillaire, M., Bonnefond, A., & Froguel, P. (2009). Breakthroughs in
monogenic diabetes genetics: From pediatric forms to young adult-
hood diabetes. Pediatric Endocrinology Reviews, 6(3), 405-417.
Walsh, J., Roberts, R., Bailey, T., & Varma, C. B. (2003). Using Insulin.
San Diego: Torrey Pines Press.
January/February 2011