Type 1 and Type 2 Diabetes
in Pediatric Practice
Chirag R. Kapadia, MD
Division of Endocrinology, Phoenix Children’s Hospital
Clinical Assistant Professor, U of A College of Medicine
Presentation outline – Pediatric Diabetes
• Type 1 Diabetes Pathophysiology
• Type 2 Diabetes Pathophysiology
• Pathophysiology beyond Insulin
– Local effects
– Gut-Brain Signaling
• Type 1 Diabetes Insulin Treatment
• Standard Subcutaneous Insulin Regimens
• Insulin Pumps
•
•
•
•
Type 2 Diabetes Treatment Regimens in Pediatrics
Technology and Devices
Newer therapies on the horizon for pediatric diabetes
Common pharmaceutical and insulin issues
1
Type 1 Diabetes – Beta Cell Destruction
Eisenbarth, GS. Primer:
Imunology/Autoimmunity. from
Eisenbarth, GS & Lafferty, KJ.
(Eds.) Oxford University Press:
New York. 1996. Type I Diabetes:
Molecular, Cellular, and Clinical
Immunology
Type 1 Diabetes – Gradual onset
Jasinski, JM. Drugs Today
2005, 41(2): 141
2
DKA
www.deo.ucsf.edu/.../dia
betic-ketoacidosis.html
3
Type 2 Diabetes Pathophysiology
Type 2 Diabetes Pathophysiology
Update in
pathofysiology of
diabetes: Insulin
resistance, β-cell
dysfunction, and
sustained
glycaemic
control.
Prof. Bernard
Charbonnel,
Nantes, France,
presented at
CDMC, oct 08,
Brussels
In T2DM
in children,
B-cell
defects
play a
larger role
4
T2DM in children: greater severity, beta cell
destruction plays a greater role than in adults, and
there is a greater chance of needing insulin
• More than 30% of pediatric Type 2 Diabetes patients
may be Antibody positive (Kaufman FR, Endocrinology
and Metabolism Clinics - Volume 34, Issue 3 (September
2005)
• Only 10% can be managed with lifestyle and diet alone
• Grinstein,Muzumdar,Saenger, DiMartino-Nardi, Horm
Res 2003;60:121-126. African Americans/Hispanic: 20%
need insulin 5 years post-diagnosis
• The results of a survey of 130 clinical practices of
members of the Lawson Wilkins Pediatric Endocrine
Society reported in 2000 that 48% of subjects were
treated with insulin and 44% with oral agents
Gut peptides with influence on appetite, weight, glucose
glucagon
amylin
Modified for presentation
5
Diabetes complications (and a note on diagnosis)
http://www.roche.com/pages/facets/3/diabetes_2.jpg
Type 1 Diabetes Treatment
• Goals for glucose control vary by age
• Very young children and infants: Safety
first; avoid DKA and severe hypoglycemia
• Ages 5 to 12: Gradual tightening of
control; A1c targets around 8%
• Greater than 12: A1c target 7%; 6.5% OK
if can avoid severe hypoglycemia
• Glucose variability also found to play a
role in macrovascular disease
6
www.pakhealth.info/basics-insulin/
Common insulin regimens
• “Intensive management” – Lantus or Levemir once or
twice a day to provide basal rate. Short acting insulin
such as Humalog, Novolog, Apidra with meals. Very
flexible in terms of meal times/amounts.
• “NPH plus short acting” – NPH/short acting at breakfast,
dinner; NPH at bedtime. Avoid lunch shot; but requires
strict dietary adherence.
• 70/30 or 75/25 twice a day – used in T2DM; or used in
T1DM patients who have difficulty doing more intensive
management or shots, or the uninsured. This regimen
can work well in T2DM; in T1DM, it’s just a way to get by
w/o a disaster.
• Insulin pumps – more on this later
7
Insulin – side effects
• I’m sure everyone here knows this, but patients don’t.
Insulin does not cause:
–
–
–
–
Need for dialysis
Problems with eyes
Nerve problems
These are all from poor diabetes control!
• It does cause:
– Hypoglycemia
– Some weight gain
• Recently in news: Lantus- cancer link. Lantus binds tightly
to certain growth factors. Some speculation that it may
cause existing cancer cells to grow more quickly.
However, risk remains unproven at this time; if it does
exist, it is very small; even Sanofi’s competitors, when they
come to our office, state that they doubt there is much to
be worried about.
Insulin Emergencies:
Hypoglycemia
• The rule of 15: 15 grams CHO, recheck in 15
minutes, repeat until sugar >80
– Glucose tablets – 4 tabs
– 4 to 5 ounces of apple juice, soda, etc.
• Dizzy, passing out, seizure, can’t take PO:
– Glucose gel – rub on buccal mucosa/gums. One tube
is 15 grams CHO
– Cake gel – a cheaper version of glucose gel
– Glucagon: 0.5 mg for <7 years of age, 1.0 mg for >7
years of age. Intramuscular, subcutaneous, or IV
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Type 2 Diabetes – Insulin use
• Lantus – The official ADA guideline does not
advocate polypharmacy in terms of oral agents
in T2DM. Instead, if metformin alone fails to
achieve goals, suggest adding/titrating lantus;
add short-acting insulin if this also fails.
• 70/30 or 75/25– These are widely used in
T2DM. It is a mixed insulin, used twice/day.
Can be very effective in T2DM, when some
insulin production does remain.
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Technology: Insulin Pens
•Some operate only on full units; others can dispense ½ units. Some
have loadable cartridges; others are pre-filled and disposable.
Manufacturers moving more and more to prefilled.
•Many insurance plans require prior authorization for pens
•Can be very economical in pediatrics, when doses are smaller (3 ml,
not 10 ml, in each pen; insulin must be discarded 1 month after
opening)
Technology – Insulin Pumps
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Insulin pump regimens
www.deo.ucsf.edu/.../graph_pump_regimen.gif
Technology – More devices
•
•
•
•
•
•
Blood glucose meters
Ketone strips, Ketone Meters
Test strips, lancets
Glucowatch or similar: not indicated in peds
CGMS
A few patients with needle phobia are using a
device called a J-tip:
Injects SQ using high-pressure
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So, that’s what’s in use, right now.
But, as they told us in medical
school, only 50% of what we tell
you will still be valid in a few years.
The problem is, we don’t know
which 50%. So what’s coming in
Pediatric Diabetes? Let’s go back
to our enteroendocrine slide
Gut peptides with influence on appetite, weight, glucose
glucagon
amylin
Modified for presentation
12
GLP-1
Barnett,Drugs Today 2005, 41(9): 563
GLP-1 Receptor Agonist (Exenetide)
• Stimulates first and later phase
insulin release
• Delays gastric emptying
• Decreases food intake
• Indicated as adjuvant to
metformin, sulfonylureas, or
insulin
• May eventually have some use
in T1DM also
• Rarely used as monotherapy,
though can lower A1c when
used this way
• SEs include nausea (50%,
does improve with time, CNS
effect), diarrhea (13%),
Hypoglycemia when in combo
with other drugs (10 to 20%).
• Sporadic reports of acute
pancreatitis with this drug are a
concern
• Not yet in pediatrics (in trial)
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DPP-IV inhibitors
• DPP-IV hydrolyzes GLP-1 in 23 minutes
• Therefore inhibiting DPP-IV
enhances action of
endogenous GLP-1
• Also it can be given orally,
instead of subcutaneously
• Examples: Sitagliptin,
Vildagliptin
• Also being used in
combination with Metformin
(example = Januvia)
• Not yet in pediatrics (in trial,
high hopes for T2DM, maybe
even in T1DM)
Amylin/Amylin Analogues
Not yet in pediatrics – but hopes for both T1DM and T2DM in peds
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There is more hope for these newer oral
agents, even though some old standbys are
rarely used in Peds:
• Sulfonylureas
• TZD’s (TODAY study has been studying
use, some potential for more use in future)
• Acarbose
In fact unless it was a teenager who is
nearly an adult, I would question using any
of these in a pediatric patients
Greater focus on long-term complications
• Statin therapy – only Pravastatin approved
in pediatrics as of yet
• Microvascular Kidney disease – Generally
ACE-Inhibitors are used for early
microalbuminuria
• Blood Pressure Management – Generally
ACE-Inhibitors are used in diabetic
patients
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Common pharmaceutical issues
• Insulin dose not written specifically –
sometime this is intentional
• Insulin vials or pens for use at schools
• Prior authorization needed for the higher
amounts of test strips or other diabetes
technology used in Type 1 DM, vs. T2DM
Common misunderstandings
• If your blood sugar is 300, it’s because you missed
medications or don’t take care of your diabetes properly
– Not always true in Type 1 Diabetes
• He has Type 1 Diabetes, but I saw him eating that cake.
Unbelievable how they don’t take care of themselves!
– In T1DM, you should eat a normal, healthy diet. Occasional – not
frequent – sugary snacks are OK (twice a week)
• If you have Type 2 diabetes and end up needing insulin,
it means you were non-compliant
– Maybe…but maybe not
• Herbal medications are more ‘natural’ than Insulin or oral
diabetes drugs
– These drugs are almost all patterned after human hormones
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