Bacillus Calmette-Gurin (BCG) vaccination

and childhood diabetes in the

Qubec Birth Cohort on Immunity and Health (QBCIH)
M-C Rousseau, M El-Zein, F Conus, L Legault, M-E Parent

40th Annual Conference, ISPAD

Toronto, Canada
September 5, 2014

Presenter Disclosure Information

Marie-Claude Rousseau

No conflict of interest to disclose.

Background
Type 1 diabetes: chronic autoimmune process -cell destruction
BCG prevents diabetes in non-obese diabetic (NOD) mice
[e.g., Harada, 1990; Qin & Singh, 1997; DaRosa, 2013]

BCG non-specific immune stimulation (TH1 lymphocytes)

Potential mechanism
Stimulation

BCG

Prevention?

TH1
Lymphocytes

Diabetes

IL-1, IL-2, IFN-,

TNF-

T reg

Effect of BCG on diabetes development in humans

No association
[Blom, 1991; Dahlquist, 1995; Parent, 1997; Wadsworth, 1997; Hummel, 2000]

Harmful effects
autoantibodies (IA-2A) in newborns
[Wahlberg, 2003]

Accelerated progression from autoimmunity to diabetes

[Huppmann, 2005]

Objectives
To investigate whether a non-specific immune stimulation
in early age has a protective effect on childhood diabetes.
1. Is the occurrence of diabetes lower among BCG
vaccinated children?
2. Does age at BCG vaccination matter?
3. Are there differences according to sex?

Study design and data

Qubec Birth Cohort on Immunity and Health (QBCIH)
Linkage of provincial administrative databases
Subjects born in the province of Qubec (Canada) in 1974 at 32
weeks of gestation
Data
Birth and death registries (1974-1994)
Quebec BCG Vaccination Registry (1974-1994)
2010 Healthcare Registration File (1983-1994)
Physician billing claims (1983-1994)
Hospitalization data (1987-1994)

Variable definitions and analyses

Diabetes
Diagnostic code ICD-9: 250
National Diabetes Surveillance System (NDSS) definition
2 medical visits in 2 years or 1 hospitalization
BCG vaccination
1) - Not vaccinated
- Vaccinated

2)

- Not vaccinated
- Vaccinated within 1st year of life
- Vaccinated after age 1

Statistical Analyses
Cox proportional hazards regression: hazard ratios (HR) and 95%
confidence intervals (CI)
Adjustment for sex, perinatal and socioeconomic characteristics,
and history of allergic diseases

BCG vaccination status in study population

QBCIH

BCG
information

Vaccination
status

Yes
Available

81,496

Age at
vaccination
1 year old
34,870 (92.3%)

37,760 (46.4%)

81,407

No
Not available
89

43,647 (53.6%)

> 1 year old

2890 (7.7%)

Cohort characteristics (n=81,407)

51% males
76% appropriate or large birth weight for gestational age
70% living in urban areas

Diabetes prevalence
0.38% (310 subjects)
No difference by BCG vaccination status or by sex

Association between BCG vaccination and diabetes

Diabetes
n

Crude HR
(95% CI)

Adjusted HR
(95% CI)

Not vaccinated

163

Ref

Ref

Vaccinated

147

1.04 (0.83-1.30)

0.97 (0.77-1.23)

Not vaccinated

163

Ref

Ref

1 year old

130

1.00 (0.79-1.26)

0.92 (0.73-1.17)

> 1 year old

17

1.58 (0.96-2.60)

1.21 (0.94-1.56)

N=81,407
BCG vaccination status

Age at BCG vaccination

Models adjusted for sex, birth weight for gestational age, number of older siblings,
maternal age at child birth, census-based family income, area of residence, parents
place of birth, and presence of concomitant allergies.

Results did not differ by sex

Discussion
Results were the same using another definition of diabetes
4 physician claims in 2 yrs
[Guttmann, 2010]

A therapeutic rather than prophylactic effect?

Clinical remission of newly diagnosed diabetics (small n)
[Shehadeh, 1994]

Decreased autoimmunity in long-term diabetics (very small n)

[Faustman, 2012]

Conclusion
In the largest study ever to address this hypothesis, we did not
observe a protective effect of BCG vaccination on occurrence of
childhood diabetes

Funding

Institutions