Celiac Disease and Diabetes

1
Celiac Disease and Diabetes Marian Rewers,
MD, PhD Professor Clinical Director
University of Colorado, School of Medicine
2
Old paradigm - CD is a disease of small intestine

3
New paradigm multi-organ autoimmune disease

• Central nervous system
• ataxia, seizures
• depression

• Skin mucosa
• dermatitis herpetiformis
• aphtous stomatitis
• hair loss

Carditis, cardiomyopathy

• Celiac disease
• villous athrophy
• malnutrition
• malignancies

Hepatitis Cholangitis
Anemia

• Bone
• osteoporosis, fractures
• arthritis
• dental anomalies

• Reproductive
• miscarriage, infertility
• delayed puberty

4
Dermatitis Herpetiformis

• Erythematous macule gt urticarial papule gt tense
  vesicles
• Severe pruritus
• Symmetric distribution
• 90 no GI symptoms
• 75 villous atrophy
• Gluten sensitive

By permission of Dr. A. Fasano
5
Dental Enamel Defects
Involve the secondary dentition
By permission of Dr. C. Catassi
6
Aphtous Stomatitis
By permission of Dr. C. Mulder
7
Osteopenia/OsteoporosisLow bone mineral density
by DEXA in a child with untreated CD
By permission of Dr. S. Mora
8
Occipital Calcification Epilepsy
By permission of Drs. C. Catassi and G, Holmes
9
Entheropathy-Associated T-cell Lymphoma
By permission Dr. G. Holmes
10
Why screening for celiac disease in T1D?

• Significant health problem, multi-organ
  morbidity
• Intestinal diarrhea, distention, vomiting,
  abdominal pain, weight loss
• Extra-intestinal pubertal/growth delay, anemia,
  osteopenia, etc.
• In type 1 diabetes unexplained hypoglycemia
• poor HbA1c

11
Pathomechanism of Celiac Disease
Gluten
T
T
T
T
T cell
T
T
T
ab TCR
HLA-DQ2 or -DQ8
APC
Transaminated gluten peptides
12
Histology of intestinal biopsy in CD Modified
Marsh score
13
TG Index 0.05 0.1 0.25 0.5 0.75
PPV 0.76 0.80 0.89 0.96 1 NPV 1 1 0.75 0.65
0.39
n 12 2 5
21
1.8
Marsh Score
Liu E et al. Clin Gastroenterol Hepatol 2003
14
Prevalence of TG IgA Autoantibodiesin 2,949 T1D
Patients
Age
Rewers M et al. 2004
15
In asymptomatic cases, biopsy should be
recommended at much higher TG levels than the
positivity cutoff () Highlighted columns show
test cutoffs that maximize likelihood of a
positive biopsy
Liu E et al. J Pediatrics 2005494-9
16
A girl that refuses pasta and bread
Pt 38884, Female T1D Dx age 3.9 yr
HLA-DR3/4 DQB10201/0302 Height
Weight
M3b
?
?
?

• TGgt0.5
• TG 0.05-0.05
• TGlt0.05

GFD ?
17
A girl that is trying to catch up Pt
27188, Female T1D Dx age 5.3 yr HLA-DR3/4
DQB10201/0302 Height Weight
?
?
?
?
M3c
?

• TGgt0.5
• TG 0.05-0.05
• TGlt0.05

?
GFD
18
A boy that is falling off the curve Pt
38220, Male T1D Dx age 5.3 yr HLA-DR3/4
DQB10201/0302 Height
Weight
M0

• TGgt0.5
• TG 0.05-0.05
• TGlt0.05

GFD
19
Obese boy with psychiatric problems
Height Weight
Pt 7677, Male T1D Dx age 4.5 HLA-DR 3/3
DQB10201/0201
M3


?


?
?

• TGgt0.5
• TG 0.05-0.05
• TGlt0.05

GFD
20
A perfect girl Pt 1520, Female T1D Dx age
2.3 yr HLA-DR3/4 DQB10201/0302
Height Weight
M3c
?
? TGgt0.5 TGlt0.05
?
?
?


No GFD
21
Recommendations

• All T1D patients should be screened for TG IgA
  at onset and at least bi-annually until age 10,
  or if symptomatic
• In asymptomatic cases, intestinal biopsy should
  be recommended at TG levels predicting positive
  biopsy in over 90 of the patients
• Biopsy should be done after at least 1-2 weeks
  on a high-wheat diet samples must be properly
  oriented and read by a trained pathologist
• Persistent TG IgA and HLA-DQA10501/B10201
  predict progression to CD even if the initial
  biopsy is negative
• GFD should be recommended to all Bx patients
• Insulin dose usually needs to be increased on
  GFD

22
Rewers et al. EMCNA 2004
23
Thank you
M1
1 in 10
TG IgA
GFD
Biopsy
M2
M3