One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus

Asseldonk, Edwin J.P. van; Poppel, P.C.M. van; Ballak, Dov B.; Stienstra, Rinke; Netea, Mihai G.; Tack, Cees J.

doi:10.1016/j.clim.2015.06.003

Cited by 57 publications

(37 citation statements)

References 25 publications

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“… The effects of the treatments were not, however, what the investigators expected: single‐agent anti‐IL‐1 therapy did not prevent a decline in β‐cell function, as measured by the level of a stimulated C‐peptide . Notably, treatment with anakinra decreased systemic inflammation and improved insulin sensitivity in the insulin‐resistant patients with T1D, who had no residual β‐cell function, a result that was mirrored by improved glucose control and decreased insulin needs …”

Section: Classical Cytokines With Proinflammatory Rolesmentioning

confidence: 60%

Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets

et al. 2020

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Cytokines play crucial roles in orchestrating complex multicellular interactions between pancreatic β cells and immune cells in the development of type 1 diabetes (T1D) and are thus potential immunotherapeutic targets for this disorder. Cytokines that can induce regulatory functions—for example, IL‐10, TGF‐β and IL‐33—are thought to restore immune tolerance and prevent β‐cell damage. By contrast, cytokines such as IL‐6, IL‐17, IL‐21 and TNF, which promote the differentiation and function of diabetogenic immune cells, are thought to lead to T1D onset and progression. However, targeting these dysregulated cytokine networks does not always result in consistent effects because anti‐inflammatory or proinflammatory functions of cytokines, responsible for β‐cell destruction, are context dependent. In this review, we summarise the current knowledge on the involvement of well‐known cytokines in both the initiation and destruction phases of T1D and discuss advances in recently discovered roles of cytokines. Additionally, we emphasise the complexity and implications of cytokine modulation therapy and discuss the ways in which this strategy has been translated into clinical trials.

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Section: Classical Cytokines With Proinflammatory Rolesmentioning

confidence: 60%

Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets

et al. 2020

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“…Of note, 39 weeks after withdrawal of IL-1Ra, insulin secretion was still preserved and CRP levels remained decreased, suggesting that IL-1 antagonism has long-lasting effects [10], possibly because of an interruption of the vicious cycle of IL-1 β autoinduction [11]. Twelve independent follow-up clinical studies have confirmed that IL-1 antagonism may improve insulin secretion or sensitivity and glycaemia [12]: ten in patients with type 2 diabetes, one in obese, insulinresistant, non-diabetic individuals with the metabolic syndrome [13] and one in insulin-resistant patients with type 1 diabetes [14].…”

Section: Il-1βmentioning

confidence: 99%

Multiple benefits of targeting inflammation in the treatment of type 2 diabetes

Donath

2016

Diabetologia

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The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti-inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch,

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“…Anakinra and canakinumab were each examined as a potential treatment for recent onset type 1 diabetes by the same group in 2013 and were found to have no effect on SCP, HbA1c, or insulin dose [102•]. A small study with no control group found that a short course of anakinra in overweight patients with type 1 diabetes resulted in modestly improved HbA1c and fasting glucose [103]. …”

Section: Diabetes-specific Effects Of Rheumatologic Immune Modulatorsmentioning

confidence: 99%

Immune-Modulating Therapy for Rheumatologic Disease: Implications for Patients with Diabetes

et al. 2016

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Immune modulators used to treat rheumatologic disease have diverse endocrine effects in patients with diabetes. Providers should be aware of these effects given that diabetes and rheumatologic disease overlap in prevalence and cardiovascular morbidity. In patients with type 1 diabetes, clinical trials have demonstrated that immune modulators used early in the disease can improve pancreatic function, though their efficacy in adults with longstanding autoimmune diabetes is unknown. In patients with type 2 diabetes, hydroxychloroquine is an effective antihyperglycemic and may be preferred for rheumatologic use in patients with difficult glycemic control. In patients without diabetes, hydroxychloroquine and tumor necrosis factor (TNF) inhibitors have been found to decrease diabetes incidence in observational studies. Additionally, dapsone and sulfasalazine alter erythrocyte survival resulting in inaccurate HbA1c values. These multifaceted effects of immune modulators create a need for coordinated care between providers treating patients with diabetes to individualize medication selection and prevent hypoglycemic events. More research is needed to determine the long-term outcomes of immune modulators in patients with diabetes.

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One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus

Cited by 57 publications

References 25 publications

Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets

Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets

Multiple benefits of targeting inflammation in the treatment of type 2 diabetes

Immune-Modulating Therapy for Rheumatologic Disease: Implications for Patients with Diabetes

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