Type 1 Diabetes

1
Type 1 Diabetes

• Karen S. Penko, MD
• Fellow, Pediatric Endocrinology
• September 2005

2
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

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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

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Gary Hall Jr. Olympic swimming medalist Type 1
diabetes
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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 brothers supplies, BG high, large urine
  ketones
• What should we do?
• Leaving for college next week

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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

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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.

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Presenting Signs/Symptoms

• Polyuria, Polydipsia
• Nocternal enuresis
• Polyphagia
• Weight loss
• Fatigue, weakness
• Blurry vision
• Ketoacidosis abdominal pain, nausea, vomiting,
  mental status changes

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Epidemiology

• Prevalence 1300
• 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

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Pathophysiology

• Autoimmune destruction of pancreatic ?-cell
• Antibodies
• Islet cell
• Insulin
• Anti-glutamic acid decarboxylase 65
• T-cell mediated
• Lymphocytic infiltration

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Pathophysiology

• Genetic susceptibility
• Association with HLA DR3/4, DQ 2/8 alleles
• Environmental triggers
• Viruses congenital rubella, coxsackievirus,
  enterovirus, mumps
• Early exposure to cows milk

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Progression to Type 1 DM
Autoimmune markers (ICA, IAA, GAD)
Autoimmune destruction
Islet Cell Mass
Honeymoon
100 Islet loss
Diabetes threshold
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Associated Autoimmune Disorders

• Thyroid (Hashimotos, Graves) 5-10
• Celiac Disease 6
• Addisons disease lt1

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Nicole Johnson Miss America 1999 Type 1 diabetes
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Management

• Diabetes team
• Insulin
• Diet
• Exercise
• Psychological support

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Banting and Best 1923 Nobel Prize for discovery
and use of insulin in the treatment of IDDM
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The Miracle of Insulin
February 15, 1923
Patient J.L., December 15, 1922
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c. 1923
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Insulin Preparations - US

• Novo Nordisk
• 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

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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

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Insulin Delivery

• Vials and syringes
• Pens
• Insulin pump

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Physiological Serum Insulin Secretion Profile
75
Breakfast
Lunch
Dinner
50
Plasma insulin (µU/ml)
Dawn phenomenon
25
400
800
1200
1600
2000
2400
400
800
Time
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NPH and Regular
75
Breakfast
Lunch
Dinner
50
R
R
Plasma insulin (µU/ml)
N
N
25
400
800
1200
1600
2000
2400
400
800
Time
24
NPH and Regular
2/3 NPH 1/3 Regular
AM 2/3
½ NPH (2/3) ½ Regular (1/3)
PM 1/3
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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

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NPH and Regular

• AM blood glucoses ? Evening NPH
• Lunch ? AM Regular
• Dinner ? AM NPH
• Bedtime ? PM Regular

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Basal/Bolus
Breakfast
Lunch
Dinner
Aspart Aspart Aspart
or
or
or
Lispro Lispro Lispro
Plasma insulin
Glargine
400
1600
2000
2400
400
800
1200
800
Time
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Basal/Bolus

• Basal glargine, 50 total daily dose
• Bolus NovoLog or Humalog
• Insulin to carbohydrate ratio
• Correction

BG target Correction factor
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Basal/Bolus

• ICHO 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

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Basal/Bolus

• Glargine dose limited by which blood sugar?
• 2 AM and breakfast
• Which blood sugar is affected by the ICHO ratio?
• 2 hour post-prandial

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NPH and Regular

• Advantages
• 2-3 shots per day
• Easier less carb counting and calculations
• Disadvantages
• Strict dietary plan
• Less flexible
• Less physiologic

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Basal/Bolus

• Advantages
• More physiologic
• More flexible
• Less hypoglycemia
• Disadvantages
• More labor-intensive (CHO counting, insulin
  calculations)
• At least 4 injections per day

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Diet

• Healthy, balanced diet
• 50-60 total calories from carbohydrate
• lt30 fat
• 10-20 protein
• Carbohydrate counting
• No forbidden foods - moderation
• Eating too much will not cause ketosis

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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

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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

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Psychosocial Support

• Every newly diagnosed family should meet with a
  psychologist
• Guilt
• Anger
• Fear
• Denial
• Depression

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Case 1 Special Concerns for College Students

• Independence
• Dining hall food
• Alcohol lowers blood sugar
• Roommate aware of diabetes, glucagon
• Airline travel prescription labels

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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?

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Honeymoon Phase

• Educate that it may happen
• Diabetes is not cured!
• Occurs within first 3 months of diagnosis
• Insulin requirements lt0.5 units/kg/day
• Lasts weeks to up to 2 years
• Resolution of glucotoxicity, recovery of residual
  ß-cell function

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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

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Long Term Complications

• Retinopathy
• Nephropathy
• Neuropathy
• Cardiovascular disease
• Prevention by optimal glucose control

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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

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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

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Case 1 Follow-up visit

• Home from college on break
• Insulin requirement 0.5 units/kg/day
• Physical exam
• Monitoring for complications

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Physical Exam

• Height, weight, BP
• Pubertal progression
• Thyroid
• Abdomen
• Shot sites - lipohypertrophy
• Feet
• Medical alert tag

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Necrobiosis Lipodica
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Prayer Sign Limited joint mobility Associated
with poor control, increased risk of
retinopathy, nephropathy
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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

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Case 1

• Hemoglobin A1c - 6.0
• Ophthalmology exam no retinopathy
• TSH, FT4 normal
• Lipids cholesterol 143
• Urine microalbumin - negative

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Hemoglobin A1c

• Reflects blood glucose over the past 3 months
• Goal lt7 for adults
• lt7.5 for teens
• lt8 for 6-12 y/o
• 7.5-8.5 for lt6 y/o

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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

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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 ICHO
  and correction factor

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Insulin Pump

• Only NovoLog or Humalog insulin
• Hourly basal rate
• 80 of total daily insulin dose
• Divided by 2
• Divide by 24
• Same ICHO and correction factor

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Insulin Pump

• Advantages
• Mimics physiologic pancreatic secretion
• Lifestyle
• Accurate dosing
• Less hypoglycemia
• Disadvantages
• No depot to protect from DKA
• Labor intensive
• Expensive

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Jason Johnson Detroit Tigers Pitcher Type 1
diabetes diagnosed age 11 Wears insulin pump on
field
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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

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Case 2
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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

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Case 2

• What if 2AM blood sugar was 59?
• Somogyi phenomenon rebound hyperglycemia after
  hypoglycemia
• Treatment decrease evening NPH

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Mary Tyler Moore
Type 1 diabetes
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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

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Case 3

• Initial glucose 634 mg/dl
• Bicarb 18 mmol/l
• UA gt80 mg/dl ketones
• Serum ketones negative
• Type 1 or type 2?

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Risk Factors for Type 2

• Obesity
• Acanthosis nigricans
• Family history
• Maternal gestational diabetes

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Case 3

• Islet cell antibodies positive
• Anti-GAD 65 positive
• Insulin antibodies negative
• C-peptide - lt0.5
• Type 1

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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

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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

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Halle Berry
Actress Type 1 diabetes
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CGMS
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New Directions Inhaled Insulin
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PREP Questions
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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.

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Answer

• D. The presence of antibodies against islet cells
  and insulin can be predictive of the risk of
  developing diabetes.

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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.

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Answer

• E. Use of rapid-acting insulin can decrease
  postprandial hyperglycemia and night-time
  hypoglycemia.

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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.

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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.

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Answer

• E. Split the evening dose to administer
  intermediate-acting insulin at bedtime.

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SSG Mark Thompson
Deployed to Iraq with Type 1 Diabetes
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Resources

• www.childrenwithdiabetes.com
• Clinical Practice Recommendations January
  Diabetes Care, ADA website
• American Diabetes Association
• Juvenile Diabetes Research Foundation