Pharmacogénétique et médecine personnalisée du diabète
 
What are the effects of mutations in MC4R on Obesity bariatric surgery outcome ?
EEEEEEEEEEEEEEEEEE EEEEEEEEEE Obesity Surgery success rate is diminished by MC4R mutations
6th of October 2011
<ul><li>The number of copies of the 16p11.2 region predicts BMI  </li></ul>deletion duplication Dosage normal Walters, Nat...
5% of diabetic cases have a monogenic cause Monogenic T2D is due to primary  -cell dysfunction…
Role of the ATP-sensitive  potassium channel subunits  Kir6.2  and  ABCC8/SUR1  in insulin secretion K ATP  channels close...
Most KCNJ11/ABCC8 NDM patients can be switched from insulin to oral anti diabetic drug sulfonylurea   NDM patients newly t...
 
 
>95% of Type 2 Diabetes cases are polygenic And interaction   Genes  Environment Environment Gene 4 Gene 3 Gene 5 Gene 13 ...
“ The optimal management of type 2 diabetes should take into consideration the heterogeneity of the disorder which require...
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RRC 2011 : Pharmacogénétique et médecine personnalisée du diabète

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  • Environmental compenent - sedentary lifestyle
  • RRC 2011 : Pharmacogénétique et médecine personnalisée du diabète

    1. 1. Pharmacogénétique et médecine personnalisée du diabète
    2. 3. What are the effects of mutations in MC4R on Obesity bariatric surgery outcome ?
    3. 4. EEEEEEEEEEEEEEEEEE EEEEEEEEEE Obesity Surgery success rate is diminished by MC4R mutations
    4. 5. 6th of October 2011
    5. 6. <ul><li>The number of copies of the 16p11.2 region predicts BMI </li></ul>deletion duplication Dosage normal Walters, Nature,  Jacquemont, Nature, 2011 <ul><ul><li>Food intake control </li></ul></ul>
    6. 7. 5% of diabetic cases have a monogenic cause Monogenic T2D is due to primary  -cell dysfunction…
    7. 8. Role of the ATP-sensitive potassium channel subunits Kir6.2 and ABCC8/SUR1 in insulin secretion K ATP channels close Membrane depolarization Ca 2+ 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. 9. Most KCNJ11/ABCC8 NDM patients can be switched from insulin to oral anti diabetic drug sulfonylurea NDM patients newly treated with glibenclamide n=28 Success : n =27 96.4% Failure n = 1 3.6% Glibenclamide alone n=24 89% Insulin + glibenclamide n = 3 11%
    9. 12. >95% of Type 2 Diabetes cases are polygenic And interaction Genes Environment Environment Gene 4 Gene 3 Gene 5 Gene 13 Gene 9 Gene 12 Gene 11 Gene 8 Gene 7 Gene 10 Gene 6 Gene 2 Gene 14 Gene 1 Gene n Epistatic interaction between genes? Low penetrance Type 2 Diabetes
    10. 13. “ The optimal management of type 2 diabetes should take into consideration the heterogeneity of the disorder which requires individualized therapies tailored to patient's individual needs” “

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