Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune diabetes in adults in the future

Pinheiro, Marcelo Maia; Pinheiro, Felipe Moura Maia; Trabachin, Maria Luisa

doi:10.1016/j.intimp.2018.02.003

Cited by 18 publications

(13 citation statements)

References 99 publications

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“…However, some case studies showed a potential efficacy of cholecalciferol in combination with the DPP-4 inhibitor sitagliptin in sustaining clinical remission in new-onset T1D [203], as well as insulin independence in LADA [204]. The rationale for such combination therapy in autoimmune diabetes may essentially consist in the synergism between the DPP-4 inhibition-mediated effects on pancreatic endocrine cells (reduction in glucagon secretion from alfa cells, increase in insulin secretion from beta cells, and potential stimulation of beta-cell proliferation) and the immunomodulatory effects exerted by both vitamin D and DPP-4 [205]. Nonetheless, future prospective studies are needed to confirm this hypothesis.…”

Section: Cholecalciferol In Combination With Anti-inflammatory Ormentioning

confidence: 99%

Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

et al. 2019

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Type 1 diabetes (T1D) is a chronic autoimmune disease leading to immune-mediated destruction of pancreatic beta cells, resulting in the need for insulin therapy. The incidence of T1D is increasing worldwide, thus prompting researchers to investigate novel immunomodulatory strategies to halt autoimmunity and modify disease progression. T1D is considered as a multifactorial disease, in which genetic predisposition and environmental factors interact to promote the triggering of autoimmune responses against beta cells. Over the last decades, it has become clear that vitamin D exerts anti-inflammatory and immunomodulatory effects, apart from its well-established role in the regulation of calcium homeostasis and bone metabolism. Importantly, the global incidence of vitamin D deficiency is also dramatically increasing and epidemiologic evidence suggests an involvement of vitamin D deficiency in T1D pathogenesis. Polymorphisms in genes critical for vitamin D metabolism have also been shown to modulate the risk of T1D. Moreover, several studies have investigated the role of vitamin D (in different doses and formulations) as a potential adjuvant immunomodulatory therapy in patients with new-onset and established T1D. This review aims to present the current knowledge on the immunomodulatory effects of vitamin D and summarize the clinical interventional studies investigating its use for prevention or treatment of T1D.

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Section: Cholecalciferol In Combination With Anti-inflammatory Ormentioning

confidence: 99%

Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

et al. 2019

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“…This might be particularly applicable for individuals with atherosclerotic disease, heart failure or renal impairment who should not be excluded from the benefits of the new agents. There is also preliminary evidence that the combined administration of DPP‐4 inhibitors and vitamin D to individuals with LADA might have beneficial effects on beta‐cell function, probably as a result of additive immunoregulatory and anti‐inflammatory actions 50 ; yet, this hypothesis remains to be confirmed in clinical studies.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

Treating latent autoimmune diabetes in adults in the era of cardiovascular outcomes trials: Old dog should learn new tricks

2021

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Background Latent autoimmune diabetes in adults (LADA) is characterised by pathophysiological and clinical heterogeneity. Hence, the optimal treatment strategy for this type of diabetes remains a clinical challenge. Aim To discuss the potential of a modern therapeutic approach for LADA in the context of the novel findings of cardiovascular outcomes trials and stress the controversies surrounding LADA and the barriers in the effective management of people with this type of diabetes. Methods We performed a literature search in major biomedical databases in order to retrieve relevant literature. The results of key studies, along with the authors' clinical experience and perspective, are summarised and discussed in this narrative, mini review article. Results Insulin remains the primary treatment choice in individuals with low C‐peptide levels. Although cardiovascular outcomes trials have mainly recruited participants with type 2 diabetes, recent data suggest that the cardiorenal protective properties of the new therapies are even present in people without diabetes and thus, the extrapolation of their results on LADA individuals sounds reasonable. Therefore, sodium–glucose co‐transporter 2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists should be considered for the management of people with preserved insulin production being at high cardiovascular risk. The risk of diabetic ketoacidosis with SGLT2is requires increased vigilance by treating physicians. Conclusions Individualisation, preservation of beta‐cell mass and function and cardiorenal protection are the new challenges in LADA therapy.

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“…Over the last few years, our group and other authors showed a potential therapeutic role of dipeptidyl peptidase-4 inhibitors (DPP-4i) and/or vitamin D in prolonging the clinical remission phase and preserving the residual beta-cell function in patients with autoimmune diabetes [59][60][61][62][63][64][65][66][67][68][69]. This review aims to provide a comprehensive overview of the anti-inflammatory and immunomodulatory properties of vitamin D and DPP-4i, as well as their potential synergistic effects in preserving residual beta-cell function in autoimmune diabetes, including both T1D and LADA.…”

Section: Heterogeneity Of Autoimmune Diabetesmentioning

confidence: 99%

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

Pinheiro

Diniz

et al. 2021

International Immunopharmacology

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Type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) represent the most common types of autoimmune diabetes and are characterized by different age of onset, degrees of immune-mediated destruction of pancreatic beta cells and rates of disease progression towards insulin dependence. Several immunotherapies aimed to counteract autoimmune responses against beta cells and preserve beta-cell function are currently being investigated, particularly in T1D. Preliminary findings suggest a potential role of combination therapy with vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors (VIDPP-4i) in preserving beta-cell function in autoimmune diabetes. This manuscript aims to provide a comprehensive overview of the immunomodulatory properties of vitamin D and DPP-4 inhibitors, as well as the rationale for investigation of their combined use as an immunomodulation therapy for autoimmune diabetes.

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Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune diabetes in adults in the future

Cited by 18 publications

References 99 publications

Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

Treating latent autoimmune diabetes in adults in the era of cardiovascular outcomes trials: Old dog should learn new tricks

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

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