Type 1 Diabetes

Karen S. Penko, MD
Fellow, Pediatric Endocrinology
September 2005
 PREP Content Specifications
• 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 497 mg/dl
Venous pH 7.396
Bicarb 27 mmol/l
UA 150 mg/dl ketones, + glucose
Serum acetone Negative
Electrolytes 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
• Polyuria, Polydipsia
• Nocternal enuresis
• Polyphagia
• Weight loss
• Fatigue, weakness
• Blurry vision
• Ketoacidosis: abdominal pain, nausea,
vomiting, mental status changes
 Epidemiology
• 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 Honeymoon
Mass

100% Islet loss

“Diabetes threshold”
 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
• 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 • Lilly
– NovoLog (aspart) – Humalog (lispro)
– NovoLog Mix 70/30 – Humalog Mix 75/25
– Novolin R – Humulin R
– Novolin N – Humulin N
– Novolin 70/30 – Humulin 70/30
• Sanofi-Aventis – Humulin 50/50
– Lantus (glargine) • 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
75
Breakfast Lunch Dinner
Plasma insulin (µU/ml)

50

Dawn
phenomenon
25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 NPH and Regular
75
Breakfast Lunch Dinner
Plasma insulin (µU/ml)

50
R R

N N
25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 NPH and Regular

2/3 NPH
AM 2/3
1/3 Regular

½ NPH (2/3)
PM 1/3
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
• AM blood glucoses → Evening NPH
• Lunch → AM Regular
• Dinner → AM NPH
• Bedtime → PM Regular
 Basal/Bolus
Breakfast Lunch Dinner

Aspart Aspart Aspart

Plasma insulin

or or or
Lispro Lispro Lispro

Glargine

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 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
• 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
• 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
• 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
• Retinopathy
• Nephropathy
• Neuropathy
• Cardiovascular disease

• Prevention by optimal glucose control

 Diabetes Control and
Complications Trial
Conventional Therapy Intensive Therapy
• 1-2 injections/day • ≥3 injections/day
• Mean A1c 9% • 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:
– 76% for retinopathy
– 54% for nephropathy
– 69% for neuropathy
– 41% for macrovascular disease
• Adverse events
– Hypoglycemia
– Weight gain
 Case 1 – Follow-up visit
• Home from college on break
• Insulin requirement 0.5 units/kg/day
• Physical exam
• Monitoring for complications
 Physical Exam
• 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
– 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
• Hemoglobin A1c - 6.0%
• Ophthalmology exam – no retinopathy
• TSH, FT4 – normal
• Lipids – cholesterol 143
• Urine microalbumin - negative
 Hemoglobin A1c
A1C BG

• Reflects blood 6 135

glucose over the past 7 170
3 months
• Goal <7 for adults 8 205
<7.5% for teens 9 240
<8% for 6-12 y/o
10 275
7.5-8.5% for <6 y/o
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
• 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
• 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
• 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 intermediate-
acting 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 intermediate-
acting 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