Diabetes: complications

1
Diabetes complications
2
Non-myeloablative Stem Cell Transplantation (NST)
for New Onset Diabetes

• Preservation of insulin producing b-islet cell
  mass by halting immune destruction

3
Pathophysiology of T1DM
100
?-Cell Mass
30
20
10
Time from Clinical Diagnosis
Pozzilli P, et al. Diabetes Care 2001 24
1460-67
4
Non-myeloablative Stem Cell protocol for
autoimmune diseases Type 1 diabetes Mellitus
Infusion PBSC
Conditioning
Mobilization
Post Transplant
Day 0
Cyclophosphamide rATG / MP

• Cycloposphamide
• G-CSF

• G-CSF

5
Hematopoietic stem cell (immune) stem cell
6
Bone Marrow Transplantation Unit School of
Medicine of Ribeirão Preto University of São
Paulo, Brazil And Division of
Immunotherapy Northwestern University Chicago,
IL, USA
Autologous hematopoietic stem cell
transplantation for early onset type 1 diabetes
mellitus J Voltarelli, C Couri, M Oliveira, A
Stracieri, D Moraes, M Coutinho, K Malmegrim, M
Foss-Freitas, B Simões, M Foss, R Burt
7
Why perform the study in Brazil ?Por que faz
protocolo em Brasil?
8
(No Transcript)
9
Initial study HSCtransplant in 15 patients with
type Idiabetes mellitus

• Principal investigators JC Voltarelli, Ribeirão
  Preto, Brazil Richard Burt, NWU, Chicago, USA
• Inclusion criteria
• 14-35 years old
• An established diagnosis of type 1 diabetes
  mellitus
• (with positive anti-GAD antibody)
• lt6 weeks of diagnosis (first hyperglicemia)

N 15, Dec/03-Set/06, 14-31 y old (mean
19.5) Follow-up 1-33 months (median 13 mo)
10
Time Course of Hemoglobin A1c Levels
11
Time Course of Hemoglobin A1c Levels
12
Summary initial stem cell study for type 1
diabetes

• First time in history of T1D that patients have
  normal blood sugar (HgbA1C) and are drug free
• Critique Insulin independence was a normal
  honeymoon period

13
Follow-up study on 23 patients with type 1
diabetes

• Focus on C-peptide

14
(No Transcript)
15
(No Transcript)
16
Time course peak stimulated C-peptide levels,
period free form insulin and period of use of
sitagliptin in 2 patients
Patient No 2
Patient No 2
Peak stimulated C-peptide levels (nmol/L)
Patient No 4
Peak stimulated C-peptide levels (nmol/L)
Horizontal blue lines schematicaly indicates
period insulin-free and gray tint indicates
period using sitagliptin 100mg/day
17
So, (aside tight glucose control) preservation
of ?-cell mass is another important target in the
management of T1DM and prevention of its related
complications
DCCT. Ann Intern Med. 1998 128 517-523
18
Chicago Thank you
Stem cell transplant for Type 1 Diabetes
randomized trial is approved by Northwestern
University IRB, now awaiting FDA approval.
19
HSCT for type I diabetes mellitus-Sao Paulo
Brasil / Chicago Illinois