Warum können wir bis jetzt weder Typ 1 noch Typ 2 Diabetes heilen?

Warum können wir bis jetzt weder Typ 1 noch Typ 2 Diabetes heilen?

Warum können wir bis jetzt weder
Typ 1 noch Typ 2 Diabetes heilen?
Marc Y Donath
Typ 1 Diabetes:
Weil wir die Krankheit nicht verstehen!!!!
1. Histology
2. Clinical studies
3. Genetic
4. Polyglandular autoimmune syndrome
1. Histology
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<10% infiltrated islets
15 CD45+ cells (background, 7)
Exocrine and endocrine
Similar at onset of the disease
≠ Other auto‐immune disease
≠ NOD
2. Clinical studies
• Ciclosporin: no real blinding, borderline
significant, no effect on HbA1c
• No immune treatment stopped the
progression
• Last remaining “autoimmune” disease without
specific treatment
3. Genetic
• HLA genotype favours an autoimmune
aetiology
But
• Chromosomal region encodes hundreds of
genes, which may also be involved in β cell
demise by other mechanisms
• Inheritance has low penetrance
4. Polyglandular autoimmune syndrome
(Hashimoto's thyroiditis, adrenal insufficiency, vitiligo
and coeliac disease. )
• No obvious molecular similarity between the
affected tissues
• But secretory cells
 Primary shared defect in secretory dysfunction ?
 Secondary event with excessive auto‐antigen presentation ?
Typ 2 Diabetes:
Weil das Leben immer mit dem Tod endet!
(precipitation of an aging disease)
Lifestyle
Ist McDonald wirklich so böse?
Rimonabant
(Acomplia)
•CB1 receptor blockade of the endocannabinoid
system
•Weight loss & improvement of glycaemia
BUT….
Mesolimbic system: the anatomic basis of the reward system
Drogen legalisieren
Lernen mit Drogen umzugehen:
Essen macht glücklich!
???
???
Steroids 77 (2012) 323–331
N Engl J Med 2012 Oct 18;367(16):1562-4
Exercise improves
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Well beeing
Glucose uptake in muscles
Insulin production (cross-talk muscle-islet)
Body weight (?)
Diabetes is chronic &
progressive
ß-cell
Islet Inflammation in Type 2 Diabetes:
M.Y. Donath 13:465-76; 2014
Clinical studies using IL-1 antagonism to treat patients with type 2 diabetes
Canakinumab (anti-IL-1β) Anti-inflammatory Thrombosis Outcomes Study
(CANTOS)
•10,000 participants over 4 years
•Primary Endpoint: cardiovascular events
•Secondary Endpoints: new onset Diabetes, diabetes progression…
Phase 2 Study of Gevokizumab in Patients With Diabetic Nephropathy
•370 patients for 52 weeks
•Primary Endpoint: glomerular filtration rate