1. Philippe Froguel, MD, PhD
froguel@good.ibl.fr

2. 1980-2013 a road that ignored
personalized diabetic medicine, far
from any precision treatment
v In 1980 overweight diabetic patients were
treated differently than normal weight patients.
v Today all diabetics receive metformin and if
(when) doesn’t work there is no agreed
guidelines.
v The road is dominated by drug company new
products.

3. You said personalized metabolic medicine ?

4. T2D Genetic dissection

5. >2% of diabetic cases have a monogenic cause

7. Role of the ATP-sensitive
potassium channel subunits Kir6.2 and ABCC8/
SUR1 in insulin secretion
KATP channels close
Membrane
depolarization
Ca2+ influx
Insulin secretion
ATP/ADP
Glucose entering
Gloyn et al., N Eng J Med, 2004
Babenko et al., N Eng J Med, 2006
SUR1 = sulfonylurea receptor

8. => >95% patients with a mutation in a potassium channel gene
can be successfully switched from insulin injections to more
efficient oral sulfonylurea treatment.
ABCC8 (SUR1) is the sulfonylurea
receptor
Sulfonylureas

11. Until
Today:
sequencial
gene
after
gene
screening
(Sanger)
2013:
Targeted
Resequencing
of
all
known
diabetes
genes
Microdroplet
based
PCR
and
Next
Generation
Sequencing
(Raindance)

13. ü In every child with diabetes before 6
months of life
ü In every diabetic child proven negative
for insulin or gad antibodies (markers for
type 1 diabetes)

14. Shields et al, Diabetologia, 2012,

16. Intérêt clinique du diagnostic des formes
monogéniques de diabète
La médecine personnalisée du diabète
existe et peut conduire à la “guérison”
définitive de l’hyperglycémie
En 2014 la révolution du séquençage du
génome permet le diagnostic
étiologique de tous les diabètes
“atypiques”

17. T2D is a systemic disease

18. And interaction
Genes
Environment
Gene 4
Gene 3
Gene 5
Gene 13
Gene 9
Gene 12
Gene 11
Gene 8
Gene 7
Gene 10Gene 6
Gene 2 Gene 14
Gene 1 Gene n
Epistatic
interaction
between genes?
Low
penetrance

20. Elucidation of causes of
diabetes in families/
patients
Diabetes genetic
modeling
T2D Genetic Modellng

22. How to pave the route
towards Personalized Diabetic Medicine ?
Bio bank
Somatic stem cells from
PBMC
Generation of iPS derived
cells and for patients’ beta
cells/hepatocytes/muscle

24. Repaired
iPSCs
Non-­‐repaired
iPSCs

28. ¡ Les
nouvelles
méthodologies
génétiques
permettent
une
caractérisation
génétique
des
diabètes
familiaux
et
améliorent
leur
prise
en
charge
¡ Le
séquençage
du
génome
et
les
cellules
souches
reprogrammées
permettent
d’avancer
vers
une
véritable
médecine
personnalisée
des
diabètes
et
de
leurs
complications

29. Martine Vaxillaire
Amelie Bonnefond
Bernadette Neve
Loic Yengo
Inga
Prokopenko
Mario
Falchi
François
Pattou
Bart
Staels
Beverley
Balkau
Michel
Marre
Guillaume
Charpentier
Ralf
Jockers