Incidence of Diabetes and Effect of Breast Feeding

1
Incidence of Diabetes and Effect of Breast
Feeding

• Bruce Buckingham, M.D.

2
Worldwide Incidence of Type 1 Diabetes in
Children lt 14 Years, by Sex
Karvonen et al., Diabetes Care, 23, 2000
3
Type 1 diabetes in Finland
Incidence /100,000 children age 0-14
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Finland Type 1 Diabetes Incidence 1965-1996 (32
years)Relative Percent Increase
Diabetes Care 221066-1070
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An Epidemic of Type 2 Diabetes

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The Changing Face of Diabetes in Youth
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Type 2 by Ethnicity, the Barbara Davis Center
Experience
Dabelea
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Types of Childhood Diabetes in Different Ethnic
Groups Is This True?
American Indians
Whites
Other ethnicities
Dabelea
9
Lifetime Risk of Developing Diabetes for Children
Born in 2000
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Effect of Diabetes on Lifespan

• A man diagnosed with diabetes at age 40 will die
  12 years sooner, and a woman will die 14 years
  sooner

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Figure 1 Diabetes Death Rates by Sex California,
1980-1986
14
(By Okace if Residence)
13
Male
12
AGE-ADJUSTED DEATH RATE
Total
11
Female
10
9
8
7
Note Rates are per 100,000 Population ICD-9
code 250. Source Table 1.
0
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Natural History of Type 1 Diabetes
CELLULAR (T CELL) AUTOIMMUNITY
LOSS OF FIRST PHASE INSULIN RESPONSE (IVGTT)
GLUCOSE INTOLERANCE (IGTT)
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Possible Environmental Triggers

• Cows Milk
• Wheat Protein
• 3-omega fatty acids
• Vitamin D

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Possible Environmental Triggers cont.

• Viral infections
• Congenital Rubella
• Enteroviruses
• Lack of exposure to viral infections
• Toxins

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Breast Feeding and Diabetes

• Breast feeding delays the introduction of Cows
  milk protein

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Cow milk protein

• First foreign proteins entering infant gut
• Major proportion of infant diet for considerable
  length of time
• BSA Bovine Serum Albumin
• BLG ß-Lactoglobulin
• Casein

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Intact Cows Milk Causes Diabetes in Rodent
Models of Diabetes
Elliott/Martin BB rats Diabetologia 26297, 1984
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Epidemiological Findings

• Increased incidence of diabetes in countries with
  increased milk consumption
• Scott, AJCN 51489-491, 1990

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An Association Milk and Diabetes
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Relative risk for IDDMrelative to cow milk
consumption
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Cows Photo
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Les Vaches/ Cows
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Children and skinny Cow
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B-Casein in Cows Milk

• A1 b-casein is diabetogenic in animal studies,
  and A2 casein is not
• B b-casein is diabetogenic
• Both A1 and B b-casein are cleaved by intestinal
  enzymes to b-casomorphin-7, which may be
  diabetogenic

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Incidence of Diabetes and A1 B beta-Casein
Consumption By County
Diabetologia 42 292,1999
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Case Controlled Studies

• 1.38 to 1.5 (odds ratio) increased incidence of
  diabetes in individuals who were not breast fed
  or ceased breast feeding within 4 months after
  birth
• Gerstein, DC 1713, 1994
• Norris, Epidemiology 787, 1996

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Case Controlled Studies cont.

• Studies rely on long-term recall of infant
  feeding practices

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DAISY Interviews and Clinical
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DAISY study case controlled ADA 2002, poster
950
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TRIGR Hypothesis

• Weaning to an extensively hydrolyzed infant
  formula will decrease the incidence of type 1
  diabetes mellitus, as it does in all relevant
  animal models for the disease.

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TRIGR Pilot 3-yr Follow-up Results Seroconversion
to
1 Autoantibody
p0.043
n173
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TRIGR Design

• Multicenter, International
• Double blind, Placebo controlled
• Randomized
• Prospective
• Intervention

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TRIGR Sample Size

• 2,730 infants to receive intervention
• 95 Confidence level
• 80 Statistical power

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TRIGR Sample Size cont.

• 40 Reduction of Type 1 diabetes by 10 years
• 20 Dropout rate
• 10 Exclusive breastfeeding to 6 months

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TRIGR Randomization

• Immediately after birth
• Coordinated in Helsinki

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TRIGR Randomization cont.

• HLA screening
• Filter paper blood spot (cord or heelstick)
• Results available in 4-5 days
• 45 will have high risk genotype and continue in
  study

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TRIGR Intervention

• All mothers who participate in TRIGR will be
  counseled and supported to exclusively breastfeed
  for at least the first six months
• If they need to begin formula feeding, they will
  be randomly assigned to a casein hydrolysate or a
  formula containing intact cows milk protein.

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TRIGR Intervention

• Study formula
• Enfamil flavor masked by addition of 20
  Nutramigen
• Both nutritionally complete and meet FDA
  standards for infant diet

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TRIGR Summary

• First primary prevention trial for Type 1
  diabetes
• If intervention effective, can be applied to
  general population (90 of new cases)

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Contact Information for the TRIGR Study in
California

• Web Site http//www.trigr.org/
• California
• Uday Devaskar, M.D., PI,   
• Phone [phone]
• UCLA