Download Pediatric Diabetes

Diabetes in Children:
Diagnosis and Management
L. Kurt Midyett, MD
Endocrinologist
Jacobson & McElliott Diabetes and Endocrinology Center
St. Luke’s Health System
Kansas City
Disclosures
• Advisory Board – Abbott Diabetes
• Advisory Board – Insulet Corporation
Introduction
• Kurt Midyett, MD
– Trained in both pediatric and adult medicine
– I currently practice a St. Luke’s Hospital (South and
Plaza)
– I am particularly interested in working with patients
who are transitioning between adult and pediatric
care
– Type 1 diabetes and the technology used in the
management of diabetes is one of my major clinical
focuses
– My wife, Eleanor, and I live in Shawnee and have four
boys ages 11, 15,18, 21 who keep us busy!
Objectives
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Epidemiology
Diagnosis and Laboratory Evaluation
Education
Treatment
Insulin Pumps & Glucose Sensors
Other Medications
Future Therapies
EPIDEMIOLOGY
Epidemiology
• Prevalence of total diabetes among people under 20 years of age, United
States, 2009
•
– About 208,000 Americans under age 20 are estimated to have diagnosed
diabetes, approximately 0.25% of that population.
In 2008—2009, the annual incidence of diagnosed diabetes in youth was
estimated at 18,436 with type 1 diabetes, 5,089 with type 2 diabetes.
– Each year, more than 13,000 young people are diagnosed with type 1
diabetes.
– Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes
(adults & children).
Source: American Diabetes Association
Epidemiology
• Racial and ethnic background varies
– Up to 30 new cases per 100,000 in Finland
– Only 1 per 100,000 in Japan
• Annual incidence in United States is approximately 12 to 15
cases per 100,000 of the childhood population
• Male to female ratio close to 1:1
• Age of presentation peaks at 5-7 years of age and also at
puberty
Proportion of type 1 and type 2
diabetes among 15–19 year olds in
SEARCH by race/ethnicity.
David J. Pettitt et al. Dia Care 2014;37:402-408
SEARCH for Diabetes in Youth Study
• Estimated that about 15,000 units are
diagnosed annually with type 1 diabetes
• About 3,700 are diagnosed annually with type
2 diabetes
SEARCH for Diabetes in Youth Study
• Worldwide, the prevalence of type 1 diabetes
and children and young adults has doubled in
the past 25 years and is expected to double
again in the next 15-20 years.
• In 2001, SEARCH estimated that there were
approximately 154,000 youth under the age of
20 years with diabetes and in 2010 the
estimated number of youths with diabetes
was 215,000
SEARCH for Diabetes in Youth Study
• The incidence of T2DM among non-Hispanic
whites 10 to 19 years of age was 3.0/100,000
person-years compared to 15.7/100,000 personyears in African American youth.
• Comparing age groups, T2DM was most prevalent
in youth 15 to 19 years of age, with the greatest
incidence noted in the American Indian subgroup
at 49.4/100,000 person-years.
• A higher incidence was also observed in females
than in males.
Epidemiology
• DKA occurs in 25% to 40% of children with new-onset type 1
diabetes.
• Frequency of DKA is increased in very young children.
• In children with established diabetes, DKA occurs at a rate of
1% to 8% per year.
– Mainly due to missed insulin injections (31%)
• Mortality rates low, 1% for DKA
– But majority caused by cerebral edema (62-87%)
Number of Deaths for Hyperglycemic Crises as
Underlying Cause, United States, 1980–2009
http://www.cdc.gov/diabetes/statistics/complications_national.htm
Death Rates for Diabetic Ketoacidosis as
Underlying Cause per 100,000 Diabetic
Population, By Age, United States, 1980-2009
http://www.cdc.gov/diabetes/statistics/complications_national.htm
Differences in Diabetes in Children
Pediatric Diabetes 2014: 15 (Suppl. 20): 4–17
Global mean
annual incidence
rates of type 1
diabetes in
children and
adolescents
aged 0–14yr.
Pediatric Diabetes 2014: 15 (Suppl. 20): 4–17
DIAGNOSIS AND LABORATORY
EVALUATION
Diagnosis
• Diabetes in young people usually presents
with characteristic symptoms such as
– polyuria, polydipsia, nocturia, enuresis, weight
loss (which may be accompanied by polyphagia),
and blurred vision.
– Impairment of growth and susceptibility to certain
infections may also accompany chronic
hyperglycemia.
Diagnosis
• If symptoms are present,
– urinary ‘dipstick’ testing for glycosuria and
ketonuria, or measurement of glucose and
ketones using a bedside glucometer, provides a
simple and sensitive screening tool.
– If the blood glucose level is elevated, then prompt
referral to a center with experience in managing
children with diabetes is essential.
Criteria for the Diagnosis of Diabetes
Any one of the following is diagnostic:
1. HbA1c ≥6.5%
2. FPG ≥7.0 mmol/L (126 mg/dL)
3. 2-hr plasma glucose ≥11.1 mmol/L (200 mg/dL) during
an OGTT
4. Symptoms of hyperglycemia and a random plasma
glucose ≥11.1 mmol/L (200 mg/dL)
Diabetes Care Volume 39, Supplement 1, January 2016
New-Onset Type 1 Diabetes
– Goals
• Establish diagnosis
• Triage patient
• Determine if treatment needed immediately
New-Onset Type 1 Diabetes
• Classic symptoms
– Polyuria
– Polydipsia
– Weight loss
• Most patients have been having symptoms for several days to
weeks before diagnosis
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Important clues can include enuresis in a previously toilet-trained child
Recurrent yeast infections or “UTIs” in girls
Persistent “asthma” in a young child
Acute abdominal pain, vomiting
New-Onset Type 1 Diabetes
• Weight loss very common
– Average healthy 10 year old has a caloric intake of ~2000
kcal with 50% derived from carbohydrates. With
development of diabetes, daily losses of water and glucose
may be as much as 5 L and 250 g, respectively. This
represents 1000 calories lost in urine, or 50% of average
daily intake.
New-Onset Type 1 Diabetes
• However…
– Since obesity has become such a problem in the pediatric
population, many of the children with new-onset Type 1
diabetes don’t fit the classic picture of thin and
emaciated.
– If you are taking in 3000-4000 kcal a day, one’s weight loss
is not as severe!
New-Onset Type 1 Diabetes
• Laboratory evaluation
– Most important is simply a basic metabolic profile
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Glucose
Bicarbonate
Na+
K+
BUN/Cr
New-Onset Type 1 Diabetes
• Clinical evaluation
– How sick is this patient?
– Vital signs, evidence of Kussmaul breathing?
– Degree of dehydration, weight loss
– What do the labs show?
• Bicarb <10, usually very sick
• 10-15, moderate DKA
• >15, most patients are in this range
New-Onset Type 1 Diabetes
• What can be done in my office?
– Capillary blood glucose (glucometer)?
– Urine dipstick?
– Electrolytes?
– IV fluids?
Laboratory Evaluation
• Diabetes-associated autoantibodies:
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Glutamic acid decarboxylase 65 autoantibodies (GAD)
Tyrosine phosphatase-like insulinoma antigen 2 (IA2)
insulin autoantibodies (IAA)
β- cell-specific zinc transporter 8 autoantibodies
(ZnT8).
• The presence of one of more of these antibodies
confirms the diagnosis of type 1 diabetes
Diagnosis of Type 2 Diabetes
• Results from the 2007 to 2008 NHANES found
that among children 6 to 11 years of age,
obesity rates increased from 6.5% in 1976 to
1980 to 16.9% in 2007 to 2008.
• NHANES data from 2009 to 2010 indicate the
percentage of children and adolescents 2 to
19 years of age defined as obese or
overweight was approximately 33%
Diagnosis of Type 2 Diabetes
• Children presenting with Type 2 diabetes may
have classic symptoms of polyuria and polydipsia,
but many may not. Therefore,
– Children who have BMI in the 85th to 95th percentile
with a family history, signs of insulin resistance (e.g.,
acanthosis nigricans), or comorbidities of insulin
resistance (e.g., hypertension, dyslipidemia, polycystic
ovarian syndrome, and others) are considered high
risk and should be screened for T2DM.
– Children with a BMI >95th percentile should be
screened, regardless.
J Pediatr Pharmacol Ther. 2015 Jan-Feb; 20(1): 4–16.
EDUCATION
Chronic Care Model
Bodenheimer T, et al. Improving primary care for patients with chronic illnesses: The
Chronic Care Model. Part 2 JAMA 2002;288:1909-1914.
Diabetes Education
• Intensive diabetes education at the time of
diagnosis is critical to the success of the patient
and family
– There is a great deal of initial information that can be
quite overwhelming to both the patient and their
family and this necessitates ongoing education
especially in the first year with multiple follow-up
educational goals.
– Referral to a diabetes center capable of
comprehensive diabetes education is a requirement
Barriers to Achieving Target A1c
• Underutilization of team support
– Physicians cannot single-handedly do everything that
is needed for aggressive, comprehensive diabetes
management.
• Diabetes care can be improved by means of a team
approach, providing support through non-physician
healthcare professionals such as diabetes educators either
within or outside the physician's office.
• Benefits of multidisciplinary team care include improved
glycemic control, increased follow-up, higher patient
satisfaction, lower risk of complications, and better QOL.
• However, team support is not always readily available and,
when available, is often not utilized.
American Journal of Managed Care, 2010
TREATMENT
A1c Targets
American Diabetes Association1
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A1C < 7.0%
Pre-prandial: 90-130 mg/dl
Post-prandial: <180 mg/dl
American Association of Clinical Endocrinologists2
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A1c <6.5%
Pre-prandial: <110 mg/dl
Post-prandial: <140 mg/dl
International Diabetes Federation3
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A1c <7.5%
Pre-prandial: 90-145 mg/dl
Post-prandial 90-180 mg/dl
1. Diabetes Care Volume 39, Supplement 1, January 2016
2. AACE/ACE Diabetes Guidelines, Endocr Pract. 2015;21(Suppl 1)
3. Global IDF/ISPAD Guideline for Diabetes in Childhood and Adolescence 2012
Pediatric Glycemic Targets
2005 American Diabetes Association Guidelines for Children
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Toddlers and preschoolers (<6 yrs.)
– A1c >7.5% but <8.5%
– Pre-prandial: 100-180 mg/dl.
– Post-prandial: 110-200 mg/dl.
School age (6-12 yrs.)
– A1c <8%
– Pre-prandial: 90-180 mg/dl.
– Post-prandial: 100-180 mg/dl.
Adolescents and young adults (13-19 yrs.)
– A1c <7.5%
– Pre-prandial: 90-130 mg/dl.
– Post-prandial: 90-150 mg/dl.
2016 ADA Guidelines
Insulin Treatment
• Generally accepted that multiple daily injections
of insulin (MDI) is the most appropriate regimen
for insulin initiation in children with newly
diagnosed Type 1 diabetes
• Basal (long-acting) insulin
– Glargine(Lantus), Detemir(Levemir)
• Bolus (short-acting) insulin
– Lispro(Humalog), Aspart(Novolog), Glulisine(Apidra)
Insulin Initiation
• For newly diagnosed children:
– Approximately 0.5-1 unit/kg/d
– 50% of this total is given as basal insulin
– Mealtime insulin is calculated after diabetes
education based on an insulin to carbohydrate
ratio. (e.g. 1 unit for every 15 grams of CHO) given
before all meals and snacks.
Insulin Treatment
• The “correct” dose of insulin is that which
achieves the best attainable glycemic control
for an individual child or adolescent without
causing obvious hypoglycemia problems
– Prepubertal children 0.7–1.0 Units/kg/d
– During puberty, requirements may rise
substantially above 1.2 Units/kg/d and even up to
2 Units/kg/d.
Approach to initial and subsequent
treatment of youth with type 2 diabetes
Pediatric Diabetes 2014: 15 (Suppl. 20): 26–46
FDA approved medications for
children with Type 2 diabetes
• Metformin (Glucophage) >10 years of age
• 500-1000 mg PO bid
• Glimepiride (Amaryl) >8 years of age
• 1-4 mg PO qd
• Rosiglitazone (Avandia) >10 years of age
• 2-4 mg PO qd
• Piolglitazone (Actos) >15 years of age
• 15-30 mg PO qd
• Exenatide (Byetta) > 15 years of age
• 2.5-5 mcg SC bid
INSULIN PUMPS & GLUCOSE
SENSORS
Where we have come from….
Early Glucose Meters
Ames Reflectance Meter
Introduced in early 1970s
Minimed Medtronic 530G
Minimed Medtronic 670G
Unique features:
Has the ability to automatically
decrease or increase insulin basal
rates based on glucose date from
sensor
FDA approved 10/16- available
May 2017
Tandem t:slim
Unique features:
Touch screen
Rechargable battery
Animas
Omnipod
Unique features:
Tubeless
Disposable
Waterproof
Dexcom G5 Continuous Glucose Monitor
Dexcom Continous Glucose Sensor
Animas Vibe
Animas Vibe is
combination of
the Animas
pump and
Dexcom CGM.
Freestyle Libre
Unique features:
Factory calibrated
Worn for two weeks
Currently only
available in Europe
Submission made to
FDA
OTHER MEDICATIONS
Other medications
• Expect for exenitide (Byetta) the medications
discussed in this section are not currently
approved for use in the pediatric patient with
diabetes
• However, there is ongoing research interest in
regard to the potential benefits for improving
glucose control in adolescents with either
Type 1 or Type 2 diabetes
Are there other therapies that can be
used to treat T1DM?
• Symlin (pramlintide) is a synthetic version of a
natural hormone, amylin. Amylin is produced in
the beta cells of the pancreas like insulin and
patients with T1DM become deficient in amylin
due to immunologic damage of the beta cells
– Pramlintide lowers the glucose rise after meals
• resulting in modestly lower A1c levels.
• It slows down the stomach emptying into the intestine, so
food gets held longer in the stomach that leaves a person
feeling full after a meal, which helps promote weight loss, as
well as keeping blood glucose low.
• Pramlintide also works by suppressing the release of yet
another hormone, glucagon.
Symlin
• Is the only other therapy besides insulin that is
approved by the FDA for the use in people with T1DM
• Symlin requires an injection before meals
– The two biggest side effects are mild nausea and low blood
sugars
• The dosing range can be very small and requires a “trial
and error” approach
• Some have discussed giving Symlin before a meal and
the insulin after
• While beneficial, the difficultly in dosing and the side
effects have not made it very popular
Afrezza
• Afrezza is a newer
inhaled insulin that was
approved by the FDA in
the past year.
• The doses come in 4
unit, 8 unit, and 12 unit
“packs”
• The insulin is inhaled at
meals or if there is
evidence of
hyperglycemia
Afrezza
• The device is very small and easy to use
• Before is can be prescribed it requires a
pulmonary function test.
• Some patients have found Afrezza to be very
helpful in reducing high blood sugars
– But there has been some concern about the precision
of the dosing since it only comes in 4, 8, or 12 units
• Uncertain future (Sanofi-Aventis will no longer
market)
Incretin hormone
• Incretin hormone is a hormone from the gut that
stimulates the release of insulin when someone
eats food
• The discovery of this hormone led to the
development of a class of medicines called GLP-1.
Glucagon-like Polypeptide act similarly to incretin
and help stimulate the release of insulin
– GLP-1 comes from the same gene as glucagon, it
stimulates insulin and it suppresses glucagon
• A 2010 study in Diabetes Care reported that giving exenatide
(Byetta) to adolescents with type 1 diabetes reduced blood
glucose after meals, even with a lower insulin dose
GLP-1 therapy
• A 2013 study in Diabetes Research and Clinical Practice
found that people with type 1 needed less insulin while
taking exenatide (Byetta) or sitagliptin (Januvia)
– Januvia is another class of medicines, known as DPP-4
inhibitors, that works to keep the GLP-1 levels high
• Types of GLP-1
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Exenatide (Byetta) twice daily injection
Exenatide (Bydureon) long acting once weekly injection
Liraglutide (Victoza) once daily injection
Dulaglutide (Trulicity) long acting once weekly injection
DPP-4 inhibitors
• These are medicines are taken as a pill once daily
– Sitagliptin (Januvia)
– Saxagliptin (Onglyza)
– Linagliptin (Tradjenta)
• They have proven to be safe in people with T2DM
• Their effect on A1c has not been shown to be
dramatic
• Not much of a push to use in people with T1DM
SGLT-2 inhibitors
• This is a newer class of medicine that has been
approved to treat people with T2DM
• This medicine works to release extra sugars in the
urine.
• There has been interest in using this medication
in people with T1DM since it works in a
completely different fashion by causing release of
sugars in the urine (previously all other medicines
for diabetes (except insulin) worked by
stimulating insulin release from the body which is
something that people with T1DM can’t do.
SGLT-2 inhibitors
• Canagliflozin (Invokana) 100mg or 300mg pill taken
once daily
• Dapagliflozin (Farxiga) 5mg or 10 mg pill taken once
daily
• Empagliflozin (Jardiance) 10mg or 25mg pill taken
once daily
– These medicines have generally proven to be safe
• The most common side effect can be more frequent urination
which can lead to dehydration
• Some women can be at a greater risk for a yeast infection when
taking this type of medicine
SGLT-2 inhibitors
• There has been some recent controversy about this type of
medicine
– There have been reports that they “cause” diabetic ketoacidosis
(DKA)
• The only way to develop DKA is to not have enough insulin, but when
taking this medicine some people have stop taking, or have reduced
their insulin too much, which then can lead to ketosis or DKA
• There has also been talk about this type of medicine causing kidney
problems
– It is not thought that the medicine causes kidney problems, but some people
with diabetes already have kidney problems and this medicine needs to be
used more cautiously in this group of people
• There are currently a number of studies looking into the
benefits of this type of medicine in people with T1DM
Other therapies
• ….. Unfortunately, to date we have not found
other medical therapies that can be proven to
help control blood sugars in people with diabetes
• Intensive insulin therapy with an insulin pump
can provide the best opportunity to deliver
insulin in the most precise and flexible manner
currently possible
• Continuous glucose monitors can provide
important information that then can help further
refine insulin dosing.
Other therapies
• The boring things such as eating a specific meal plan
and learning how certain foods affect blood sugars are
always important
• Understanding how stress can impact blood sugars is
also very important
• Of course, the goal is a cure. Meaning a process that
restores complete insulin regulation to one’s body
– Until that time we will always be looking for anything that
can compliment our current treatment strategies and
make it easier to control blood sugars
FUTURE THERAPIES
“Bionic Pancreas”
•
MONDAY, June 16, 2014 (Presented at the ADA Scientific meeting in San Francisco)
– The "bionic pancreas" -- a device that uses a sophisticated computer program working in
concert with several diabetes management devices -- successfully managed blood sugar
levels in its first real-world trials on adults and children with type 1 diabetes.
– "It's difficult for people who don't live with type 1 diabetes to understand how much
work it is. It's such a burden. But, everyone in the trial said that burden was all lifted.
The device is inherently automated -- it's diabetes without the numbers," said study
senior author Edward Damiano, an associate professor in the department of biomedical
engineering at Boston University. Damiano understands the issue more keenly than
most, as he is the father of a 15-year-old son with type 1 diabetes.
“Bionic Pancreas”
• Here's how the bionic pancreas can help.
– It contains two hormones -- insulin and glucagon. Insulin lowers blood sugar and
glucagon can raise blood sugar quickly.
– The current version of the bionic pancreas had two insulin pumps one that delivered
small doses of insulin and the second for glucagon.
– The device also included a smartphone with an app that contained the computer
program to control the pumps.
– The phone also wirelessly communicated with a continuous glucose monitor that
constantly reported blood sugar levels.
• They used an iPhone, Dexcom CGM, and 2 Tandem insulin pumps
“Bionic Pancreas”
Thank you
[email protected]