Type 1 Diabetes
Karen S. Penko, MD
Fellow, Pediatric Endocrinology
September 2005
PREP Content Specifications
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Recognize signs/symptoms
Know how to treat type 1 diabetes
Know the value of hemoglobin A1c
Know the natural history
Counsel patients on self-management
Differentiate Somogyi & dawn
phenomena
PREP Content Specifications
• Know how to manage sick days
• Know the long-term complications
• Know importance of blood glucose
control in preventing long-term
complications
• Recognize the association with other
autoimmune disorders
Gary Hall Jr.
Olympic swimming
medalist
Type 1 diabetes
Case 1
• 18 y/o white male, father pages on-call
peds endo:
– Polyuria, polydipsia x 1 week
– 16 y/o brother has type 1 diabetes
– Using brother’s supplies, BG “high”, large
urine ketones
– What should we do?
• Leaving for college next week
At WRAMC ED
Serum glucose
Venous pH
Bicarb
UA
Serum acetone
Electrolytes
497 mg/dl
7.396
27 mmol/l
150 mg/dl ketones, + glucose
Negative
Na 133, K 4.2, Cl 94, BUN 14,
creat 0.8
Diagnostic Criteria
• Symptoms of diabetes and a casual
plasma glucose 200 mg/dl, OR
• Fasting plasma glucose 126 mg/dl, OR
• 2-hour plasma glucose 200 mg/dl during
an oral glucose tolerance test.
• In the absence of unequivocal
hyperglycemia, these criteria should be
confirmed by repeat testing on a different
day.
Presenting Signs/Symptoms
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Polyuria, Polydipsia
Nocternal enuresis
Polyphagia
Weight loss
Fatigue, weakness
Blurry vision
Ketoacidosis: abdominal pain, nausea,
vomiting, mental status changes
Epidemiology
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Prevalence 1:300
Peak age of diagnosis: 11-13 y/o
Risk for sibling: 6%
Risk for monozygotic twin: 50%
Risk for offspring: 2-10%, higher side if
father has diabetes
• Highest incidence: Finland, Sardinia
Pathophysiology
• Autoimmune destruction of pancreatic cell
• Antibodies:
– Islet cell
– Insulin
– Anti-glutamic acid decarboxylase 65
• T-cell mediated
• Lymphocytic infiltration
Pathophysiology
• Genetic susceptibility
– Association with HLA DR3/4, DQ 2/8 alleles
• Environmental triggers
– Viruses: congenital rubella, coxsackievirus,
enterovirus, mumps
– Early exposure to cow’s milk
Progression to Type 1 DM
Autoimmune markers
(ICA, IAA, GAD)
Autoimmune destruction
Islet
Cell
Mass
Honeymoon
“Diabetes threshold”
100% Islet loss
Associated Autoimmune
Disorders
• Thyroid (Hashimoto’s, Graves’): 5-10%
• Celiac Disease: 6%
• Addison’s disease: <1%
Nicole Johnson
Miss America 1999
Type 1 diabetes
Management
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Diabetes team
Insulin
Diet
Exercise
Psychological support
Banting and Best
1923 Nobel Prize for
discovery and use of
insulin in the
treatment of IDDM
The Miracle of Insulin
Patient J.L., December 15, 1922
February 15, 1923
Insulin Preparations - US
• Novo Nordisk
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–
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NovoLog (aspart)
NovoLog Mix 70/30
Novolin R
Novolin N
Novolin 70/30
• Sanofi-Aventis
– Lantus (glargine)
• Lilly
–
–
–
–
–
–
Humalog (lispro)
Humalog Mix 75/25
Humulin R
Humulin N
Humulin 70/30
Humulin 50/50
• Lente, Ultralente
have been
discontinued
Treatment with Insulin
• Total daily requirement:
– 0.5-1 unit/kg/day
– 1.5 units/kg/day during puberty
• Typical Regimens
– NPH and Regular
– Basal/Bolus: glargine and Novolog/Humalog
Insulin Delivery
• Vials and syringes
• Pens
• Insulin pump
Physiological Serum Insulin
Secretion Profile
Plasma insulin (µU/ml)
75
Breakfast
Lunch
Dinner
50
Dawn
phenomenon
25
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
NPH and Regular
Plasma insulin (µU/ml)
75
Breakfast
50
Lunch
R
R
N
N
25
4:00
Dinner
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
NPH and Regular
2/3 NPH
AM 2/3
PM 1/3
1/3 Regular
½ NPH (2/3)
½ Regular (1/3)
NPH and Regular
• Regular insulin given 30 min prior to a
meal
• NPH dose often given at bedtime
• Prescribed amount of carbs at
meals/snacks
NPH and Regular
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AM blood glucoses → Evening NPH
Lunch → AM Regular
Dinner → AM NPH
Bedtime → PM Regular
Basal/Bolus
Breakfast
Lunch
Plasma insulin
Aspart
or
Lispro
Dinner
Aspart
or
Aspart
or
Lispro
Lispro
Glargine
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Basal/Bolus
• Basal: glargine, 50% total daily dose
• Bolus: NovoLog or Humalog
– Insulin to carbohydrate ratio
– Correction
BG – target
Correction factor
Basal/Bolus
• I:CHO = 450/total daily insulin dose =
amount of carbs 1 units will cover
• Correction Factor: “1700 rule” =
1700/TDD
• Glargine can not be mixed with any other
insulins
Basal/Bolus
• Glargine dose limited by which blood
sugar?
– 2 AM and breakfast
• Which blood sugar is affected by the
I:CHO ratio?
– 2 hour post-prandial
NPH and Regular
• Advantages
– 2-3 shots per day
– “Easier” – less carb counting and
calculations
• Disadvantages
– Strict dietary plan
– Less flexible
– Less physiologic
Basal/Bolus
• Advantages
– More physiologic
– More flexible
– Less hypoglycemia
• Disadvantages
– More labor-intensive (CHO counting, insulin
calculations)
– At least 4 injections per day
Diet
• Healthy, balanced diet
– 50-60% total calories from carbohydrate
– <30% fat
– 10-20% protein
• Carbohydrate counting
• No forbidden foods - moderation
• Eating too much will not cause ketosis
Exercise
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Increases sensitivity to insulin
Helps control blood sugar
Lowers cardiovascular risk
Blood sugar usually decreases but may
initially increase
• Hypoglycemia may occur during,
immediately after, or 8-24 hours later
Exercise
• Check blood sugar before, during, after
• Always have snacks available
• May need extra snacks or decreased
insulin (learn from experience)
– Usually 15 gm CHO for every 30 min
vigorous exercise
• Do not exercise if ketones are present
Psychosocial Support
• Every newly diagnosed family should
meet with a psychologist
• Guilt
• Anger
• Fear
• Denial
• Depression
Case 1: Special Concerns for
College Students
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Independence
Dining hall food
Alcohol – lowers blood sugar
Roommate aware of diabetes, glucagon
Airline travel – prescription labels
Case 1
• Discharged after teaching complete on
– Glargine and Humalog
– 0.7 units/kg/day
• 3 weeks after diagnosis blood sugars
begin going low
• What is going on?
Honeymoon Phase
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Educate that it may happen
Diabetes is not cured!
Occurs within first 3 months of diagnosis
Insulin requirements <0.5 units/kg/day
Lasts weeks to up to 2 years
Resolution of glucotoxicity, recovery of
residual β-cell function
Case 1
• Blood glucoses continue to be so low that
pt takes himself off all insulin
• Normal blood glucoses for 5 months off
insulin
• Blood glucoses begin to rise
• Homesickness
• Depression
Long Term Complications
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Retinopathy
Nephropathy
Neuropathy
Cardiovascular disease
• Prevention by optimal glucose control
Diabetes Control and
Complications Trial
Conventional Therapy
• 1-2 injections/day
• Mean A1c 9%
Intensive Therapy
• ≥3 injections/day
• Mean A1c 7%
• 1983-1993, early termination given results
• Intensive therapy delays onset and progression
of long-term complications in type 1 diabetes
Diabetes Control and
Complications Trial
• Intensive therapy reduced risk by:
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76% for retinopathy
54% for nephropathy
69% for neuropathy
41% for macrovascular disease
• Adverse events
– Hypoglycemia
– Weight gain
Case 1 – Follow-up visit
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Home from college on break
Insulin requirement 0.5 units/kg/day
Physical exam
Monitoring for complications
Physical Exam
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Height, weight, BP
Pubertal progression
Thyroid
Abdomen
Shot sites - lipohypertrophy
Feet
Medical alert tag
Necrobiosis Lipodica
Prayer Sign
Limited joint
mobility
Associated with:
poor control,
increased risk of
retinopathy,
nephropathy
Monitoring
• Hemoglobin A1c – every 3 months
• Celiac screen – at diagnosis and if ssx
• Annually
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TSH
Ophthalmology exam - after 10 and 3-5 yrs disease
Urine microalbumin - after 10 and 5 yrs disease
Lipid panel - puberty, unless fam hx, q5 years if
normal
– Influenza vaccine
Case 1
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Hemoglobin A1c - 6.0%
Ophthalmology exam – no retinopathy
TSH, FT4 – normal
Lipids – cholesterol 143
Urine microalbumin - negative
Hemoglobin A1c
• Reflects blood
glucose over the past
3 months
• Goal <7 for adults
<7.5% for teens
<8% for 6-12 y/o
7.5-8.5% for <6 y/o
A1C
BG
6
135
7
170
8
205
9
240
10
275
11
310
12
345
Case 1
• 1 year after diagnosis, remains diligent
about sending blood sugars
• Insulin requirements 0.5 units/kg/day
• A1c 5.9%
• Interested in the insulin pump
Insulin Pump Candidates
• Highly motivated
• Willing to perform frequent blood
glucose monitoring
• Good control on basal/bolus regimen
• Proficient at carbohydrate counting
• Proficient at adjusting insulin doses with
I:CHO and correction factor
Insulin Pump
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Only NovoLog or Humalog insulin
Hourly basal rate:
1. 80% of total daily insulin dose
2. Divided by 2
3. Divide by 24
•
Same I:CHO and correction factor
Insulin Pump
• Advantages
– Mimics physiologic pancreatic secretion
– Lifestyle
– Accurate dosing
– Less hypoglycemia
• Disadvantages
– No depot to protect from DKA
– Labor intensive
– Expensive
Jason Johnson
Detroit Tigers
Pitcher
Type 1 diabetes
diagnosed age 11
Wears insulin pump
on field
Case 2
• 9 y/o male with type 1 diabetes for 4
years
• NPH and Regular insulin 2 shots per day
• Total insulin dose = 0.8 units/kg/day
• Relatively high AM numbers
Case 2
B
L
D
HS
200
110
106
120
220
97
102
115
198
105
132
110
241
99
96
122
Case 2
• What is going on?
• What additional information do you
want?
• 2AM blood sugar is 122
• Dawn phenomenon
• To correct: Move evening NPH to
bedtime
Case 2
• What if 2AM blood sugar was 59?
• Somogyi phenomenon – rebound
hyperglycemia after hypoglycemia
• Treatment: decrease evening NPH
Mary Tyler Moore
Type 1 diabetes
Case 3
• 13 y/o black female, 2 week h/o polyuria,
polydipsia, 16 lb weight loss
• Overweight, BMI 97%
• Acanthosis nigricans on neck
• 2 grandparents have type 2 diabetes
Case 3
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Initial glucose – 634 mg/dl
Bicarb – 18 mmol/l
UA >80 mg/dl ketones
Serum ketones – negative
• Type 1 or type 2?
Risk Factors for Type 2
• Obesity
• Acanthosis nigricans
• Family history
• Maternal gestational diabetes
Case 3
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Islet cell antibodies – positive
Anti-GAD 65 – positive
Insulin antibodies – negative
C-peptide - <0.5
• Type 1
Sick Day Management
• Never omit insulin
• Insulin requirements are often greater
with illness
• Hypoglycemia may be a problem,
especially in younger children
• Test blood sugars every 2-4 hours
• Check urine ketones
Sick Day Management
• Drink plenty of fluids (1 cup per hour)
– Sugar-containing liquids for hypoglycemia
• Need extra insulin to clear ketones
– NPH/R: extra 20% of total dose as R q4
hours
– Basal/bolus: correction dose q3 hours +
additional 20% of calculated correction
• ED for persistent vomiting
Halle Berry
Actress
Type 1 diabetes
New Directions: Inhaled Insulin
PREP Questions
Question
Which of the following statements regarding the
development of type 1 diabetes is true?
A. Administration of parenteral insulin to those at risk
has been proven to decrease the likelihood of
developing diabetes
B. HLA typing has not been shown to be useful in
determining the risk of developing diabetes
C. Most patients have complete destruction of the beta
cells, with no residual function at the time of diagnosis.
D. The presence of antibodies against islet cells and
insulin can be predictive of the risk of developing
diabetes.
Answer
• D. The presence of antibodies against islet
cells and insulin can be predictive of the
risk of developing diabetes.
Question
Which of the following statements regarding insulin
therapy is true?
A. Inhaled insulin is not effective in children.
B. Insulin pump therapy should be reserved for
noncompliant adolescent patients.
C. Insulin therapy should be discontinued temporarily
during the “honeymoon” period.
D. Rapid-acting insulin is beneficial because it decreases
glycosylated hemoglobin levels over time.
E. Use of rapid-acting insulin can decrease postprandial
hyperglycemia and night-time hypoglycemia.
Answer
• E. Use of rapid-acting insulin can
decrease postprandial hyperglycemia and
night-time hypoglycemia.
Question
• You are seeing a 9 y/o boy who was
diagnosed with type 1 diabetes 2 years
ago. He currently receives 2 daily
injections of short- and intermediateacting insulin. As part of your
evaluation, you ask to see his blood
glucose diary. You note that most of his
readings over the last month have been
around 200 mg/dL. His mother is
unwilling to try a pump at this point.
Question
Which of the following management options is best?
A. Increase the evening dose of short-acting insulin.
B. Increase the morning dose of intermediate-acting
insulin.
C. Increase the morning dose of short-acting insulin.
D. Obtain a hemoglobin A1c level, and if it is normal,
continue the current insulin regimen.
E. Split the evening dose to administer intermediateacting insulin at bedtime.
Answer
• E. Split the evening dose to administer
intermediate-acting insulin at bedtime.
SSG Mark Thompson
Deployed to Iraq with Type 1 Diabetes
Resources
• www.childrenwithdiabetes.com
• Clinical Practice Recommendations:
January Diabetes Care, ADA website
• American Diabetes Association
• Juvenile Diabetes Research Foundation