Autoantigen can be used to modulate the immune system and in best case to get tolerance. What/which autoantigen/s? Combinations? Should we combine with antiCD3 and/or TNFalfa-inhibition and/or ? If so, given before , after, or parallell to the auto-antigen treatment? Please argue! Would YOU suggest addition of Vitamin D? Nicotinamide? Omega3 fatty acids? Metformin? or..? We need an open discussion to get forward!
It is indeed a multifactorial condition. Maybe you can find some answers in this paper we recently published. We talk about the cross-talk between various molecular pathways that regulate beta cell proliferation and regeneration. We also published a list of mitogens that may be useful in such a scenario.
The adenosine, adrenergic and opioid pathways in the regulation of insulin secretion, beta cell proliferation and regeneration
Jun 2018, Pancreatology
Thank you for your interesting information!- I understand that nobody has his/her clear vision of what should be done, but if the common aim is to cure and/or prevent Type 1 diabetes I would expect researchers not to keep their ideas secret but to participate in an open discussion. Looking forward to more answers!
Though a long list of cytokines & supplements been shared, I interpret autoimmunity related predicted beta cell damage is difficult to predict especially once the genetic factor, unlike T2DM is,only in less than 50% especially in clinics.
I do appreciate the roles of these mentioned triggers( though not in whole some) & I also interpret a single study would be difficult to get the answers on that. Furthermore, these chemicals effect few & not all. Like hypovitaminosis D is almost endemic but not all get type 1 diabetes.
Lastly, pancreatic transplant may be better hope in these patients.
Limitations: Your question has many components & I guess I need to see more especially with regards to pathways...
We propose to use sitagliptin plus vitamin D3 to preserve beta cells in new-onset Type 1 diabetes. This combination could has effects on immune system as well as in the beta cells. Time to start the treatment maybe be the most important. See in: Article Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vit...
I feel GLP-1 better because of longer half-lives and greater reduction in A1c. Plus can be given over a period of week to months so avoids daily injections.
I, in person am not clear about the cause to effect relationship between association of vitamin D and and diabetes. i interpret vitamin D is deficient in many metabolic disorders but then there are so many normal people who are found to be randomly deficient of vitamin D.
So hypovitaminosis D as a supplement in diabetes seems less evidence based. However, life style changes especially exercise and eating healthy and reducing weight generally helps diabetes and can be then linked with vitamin D.
If any specified randomized controlled trials taking care of associated metabolic and life style factors about vit D and others are available, they would be interesting. Please share f you find any.
Regards
DPP-4 inhibitors by its effects in immune system and on beta cells.
While both have near similar effects to cause more GLP-1 availability, and better as not associated with hypoglycemia, still i will GLP-1 agonist show better performance in causing:
1-More reduction in A1c
2- Higher reduction in FPG and PPG
3- Increased weight loss
4- While both drugs improve associated metabolic effects but GLP-1 slightly perform better than DPP-IV inhibitors as they reduce lipids and blood pressure slightly more.
5- GLP-1 agonist have longer half-life
I am attaching a reference, which points which should help in selecting a drug for an individual patient:
http://clinical.diabetesjournals.org/content/30/1/3
Finally i feel both drugs are yet not recommended as first line treatment for diabetes.
Regards
Thanks, but I am less interested in the pure metabolic effects, and more interested in possible effects on the immune process ( where DPP-4 inhibitors may (?) have better profile,) , and beta cell proliferation ( where GLP-1 may be best?)
GLP-1 has some immune effects,mainly on NK cells, but DPP-inhibitors has much more, on cytokines, B and T lymphocytes, NK cells, macrophages and dentritic cells. Besides that has effects on beta cells too. In type 1 diabetes mellitus we need seek what best dose. The time to start is in the diagnosis.
First of all, I salute you for your crusade for beta cell preservation in Type 1 diabetes. As of now, a multi-pronged approach with combination therapy that may comprise an antigen, a Teff-depleting agent, and a Tregs-boosting agent (vitamin D) does appear to be the right choice.
The slower decline of residual beta cell function with prolonged vitamin D supplementation does occur and has been documented by several papers. And because vitamin D is really an inexpensive addition to immune interventions, there is no substantial reason why it should not be part of the combined approaches to beta cell preservation.
The other arguments in favour of vitamin D as one arm of combination therapy were discussed in the letter (attached for others' reference) that I wrote to your comprehensive review published in 'Drugs' in 2016. Meanwhile we conducted another study on vitamin D supplementation for 1 year (accepted for publication) and the results were better than our previous 6-month supplementation study.
Best wishes,
Devi Dayal
Dear Devi
It was a well-summarized account of the actual question asked. So salutes to you as well. Excuse me for my knowledge gap but Just one question:
What do you mean by "Teff-depleting agent"?
Regards
Dear Devi Dayal,
I agree with you. Vitamin D has good immunomodulatory effects, but higher doses should be used in the future. DPP4-inhibitors the 2nd drug coud be the best option because its effects in immune system as well as in beta cells. The Teff-depleting agent is difficult even in bone marrow transplantation with stem cells, besides having no effects on beta-cell functions.
We should initiate beta cell preservation treatment immediately in the diagnosis of diabetes, when peptide C levels are still positive. Time and dose!
Thanks Dr Sikandar.
Teff-depletion/induction of unresponsiveness is employed to restore the balance between regulatory and effector T cells (Teff). Several drugs such as Teplizumab, otelixizumab, alefacept etc have been tried for this in the past.
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