| 1. |
- Berryman, Meghan A., et al.
(författare)
-
Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut
- 2023
-
Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
-
Forskningsöversikt (refereegranskat)abstract
- Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator. Graphical representation of central hypothesis.
|
|
| 2. |
- Ceriello, Antonio, et al.
(författare)
-
Diabetes as a case study of chronic disease management with a personalized approach: The role of a structured feedback loop
- 2012
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:1, s. 5-10
-
Forskningsöversikt (refereegranskat)abstract
- As non-communicable or chronic diseases are a growing threat to human health and economic growth, political stakeholders are aiming to identify options for improved response to the challenges of prevention and management of non-communicable diseases. This paper is intended to contribute ideas on personalized chronic disease management which are based on experience with one major chronic disease, namely diabetes mellitus. less thanbrgreater than less thanbrgreater thanDiabetes provides a pertinent case of chronic disease management with a particular focus on patient self-management. Despite advances in diabetes therapy, many people with diabetes still fail to achieve treatment targets thus remaining at risk of complications. Personalizing the management of diabetes according to the patients individual profile can help in improving therapy adherence and treatment outcomes. This paper suggests using a six-step cycle for personalized diabetes (self-)management and collaborative use of structured blood glucose data. E-health solutions can be used to improve process efficiencies and allow remote access. Decision support tools and algorithms can help doctors in making therapeutic decisions based on individual patient profiles. Available evidence about the effectiveness of the cycles constituting elements justifies expectations that the diabetes management cycle as a whole can generate medical and economic benefit.
|
|
| 3. |
- Dedrick, Sandra, et al.
(författare)
-
The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis
- 2020
-
Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 11
-
Forskningsöversikt (refereegranskat)abstract
- Type 1 Diabetes (T1D) is regarded as an autoimmune disease characterized by insulin deficiency resulting from destruction of pancreatic beta-cells. The incidence rates of T1D have increased worldwide. Over the past decades, progress has been made in understanding the complexity of the immune response and its role in T1D pathogenesis, however, the trigger of T1D autoimmunity remains unclear. The increasing incidence rates, immigrant studies, and twin studies suggest that environmental factors play an important role and the trigger cannot simply be explained by genetic predisposition. Several research initiatives have identified environmental factors that potentially contribute to the onset of T1D autoimmunity and the progression of disease in children/young adults. More recently, the interplay between gut microbiota and the immune system has been implicated as an important factor in T1D pathogenesis. Although results often vary between studies, broad compositional and diversity patterns have emerged from both longitudinal and cross-sectional human studies. T1D patients have a less diverse gut microbiota, an increased prevalence of Bacteriodetes taxa and an aberrant metabolomic profile compared to healthy controls. In this comprehensive review, we present the data obtained from both animal and human studies focusing on the large longitudinal human studies. These studies are particularly valuable in elucidating the environmental factors that lead to aberrant gut microbiota composition and potentially contribute to T1D. We also discuss how environmental factors, such as birth mode, diet, and antibiotic use modulate gut microbiota and how this potentially contributes to T1D. In the final section, we focus on existing recent literature on microbiota-produced metabolites, proteins, and gut virome function as potential protectants or triggers of T1D onset. Overall, current results indicate that higher levels of diversity along with the presence of beneficial microbes and the resulting microbial-produced metabolites can act as protectors against T1D onset. However, the specifics of the interplay between host and microbes are yet to be discovered.
|
|
| 4. |
- Ludvigsson, Johnny
(författare)
-
Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route
- 2020
-
Ingår i: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - : MDPI. - 1422-0067. ; 21:5
-
Forskningsöversikt (refereegranskat)abstract
- Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.
|
|
| 5. |
- Ludvigsson, Johnny
(författare)
-
Combination therapy for preservation of beta cell function in Type 1 diabetes: New attitudes and strategies are needed!
- 2014
-
Ingår i: Immunology Letters. - : Elsevier. - 0165-2478 .- 1879-0542. ; 159:1-2, s. 30-35
-
Forskningsöversikt (refereegranskat)abstract
- In several diseases where the immune system plays an important role there has been a tremendous progress in treatment efficacy during the last decades. Based on necessary basic science these improvements are results of rapid, numerous and open-minded clinical trials where pieces of positive results step by step have been added into treatment schemes. Treatment of Type 1 diabetes has certainly improved but too slowly. It has been difficult to convince the scientific community of opinions which among non-professionals have been regarded as common sense such as the value of normal blood glucose and preservation of insulin secretion. Lack of motivation to participate in clinical trials has slowed down progress, as well as too narrow views on both pathogenesis of Type 1 diabetes and how studies should be designed to test therapeutic interventions. Studies in experimental animals can create and support hypothesis for human conditions but must not delay clinical trials too long. There is already evidence enough for intervention trials where immune suppression is combined with antigen treatment, beta cell protection, anti-inflammatory treatment, and efforts to stimulate beta cell regeneration. Regimens should be elaborated and first tried in those groups of patients where response can be expected to be best, and thereafter adjusted to increase efficacy step-wise, and in broader patient categories.
|
|
| 6. |
|
|
| 7. |
- Ludvigsson, Johnny
(författare)
-
Farmakoterapi vid typ 1-diabetes
- 2015
-
Ingår i: BestPractice. - : BestPractice ApS. - 1329-1874. ; 5:14, s. 27-31
-
Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
|
|
| 8. |
- Ludvigsson, Johnny
(författare)
-
GAD65: a prospective vaccine for treating Type 1 diabetes?
- 2017
-
Ingår i: Expert Opinion on Biological Therapy. - : TAYLOR & FRANCIS LTD. - 1471-2598 .- 1744-7682. ; 17:8, s. 1033-1043
-
Forskningsöversikt (refereegranskat)abstract
- Introduction: In spite of modern techniques, the burden for patients with type 1 diabetes (T1D) will not disappear and T1D remains a life-threatening disease causing severe complications and increased mortality. We have to learn how to preserve residual insulin secretion or even increase beta cell regeneration. This would give a milder disease, simpler treatment and perhaps even cure. Thus, there are good reasons to try therapies that may preserve beta cell function.Areas covered: In this review the author reviews the literature and registered ongoing trials using GAD-alum put in relation to the high number of published different immune interventions.Expert opinion: GAD-alum treatment is safe, tolerable and easy for the patients and healthcare. It seems probable that treatment with GAD65-alum 20 mu g sc can preserve residual beta cell function in T1D, but efficacy needs to be improved. This may be achieved by the use of combination therapies and new approaches for administration.
|
|
| 9. |
- Ludvigsson, Johnny
(författare)
-
Glutamic acid decarboxylase immunotherapy for type 1 diabetes
- 2022
-
Ingår i: Current Opinion in Endocrinology, Diabetes & Obesity. - : LIPPINCOTT WILLIAMS & WILKINS. - 1752-296X .- 1752-2978. ; 29:4, s. 361-369
-
Forskningsöversikt (refereegranskat)abstract
- Purpose of review To describe recent development of an autoantigen (GAD) treatment towards well tolerated and efficacious precision medicine in type 1 diabetes. Recent findings Although subcutaneous GAD-alum treatment failed to reach primary endpoint in a phase III trial, metanalyses showed a 97% probability of efficacy, and clear efficacy in patients carrying Hyman Leucoycte Antigen (HLA) DR3DQ2. Efforts have been made to improve efficacy by trying combination therapies with vitamin D + Ibuprofen resp vitamin D + Etanercept (TNF-alpha inhibition), without any breakthrough until the administration of GAD-alum was changed from subcutaneous to intralymphatic. With a very small dose of GAD-alum (4 mu g) given into an inguinal lymph three times with 1 month interval, the efficacy in patients with HLADR3DQ2 has been impressive, with significantly better beta cell preservation than patients who got placebo in a double-blind randomized trial, and clinical efficacy with more patients in partial remission (IDAA1c < 9) and larger proportion of patients with CGM-measured blood glucose Time In Range (TIR), significantly correlated to the C-peptide values. The treatment has been easy for patients and healthcare without treatment-related risk or adverse events. Intralymphatic GAD-alum treatment in type 1 diabetes patients carrying HLA DR3DQ2 seems to be an attractive immune intervention.
|
|
| 10. |
- Ludvigsson, Johnny
(författare)
-
Insulin Adverse Events
- 2020
-
Ingår i: Pediatric Endocrinology Reviews. - : MEDICAL MEDIA. - 1565-4753. ; 17, s. 183-190
-
Forskningsöversikt (refereegranskat)abstract
- The negative consequencies of diabetes treatment are traditionally regarded as caused by a disastrous treatment rather than adverse events of the insulin preparations. However, hypoglycemia, changes at the injection site (lipatrophy, lipoma), insulin allergy, obesity and increased risk of certain forms of cancer can easily be regarded as adverse events of the drug, and needle -phobia, psychological problems, increased risk of suicide are adverse events related to insulin and its administration. Also macroongiopathy and even microangiopathy to some extent can be regarded as adverse events as the most crucial part of the treatment of Type 1 diabetes is the insulin treatment. There is still room for improvments of insulin as a drug. We need insulins with more predictable absorption and kinetics, leading to more stable near-normal blood glucose, less risk of hypoglycemia, less effect in periphery and more effect on the liver, and less risk of vascular complications, obesity, cancer.
|
|
