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

2018 ◽  
Vol 57 ◽  
pp. 11-17 ◽  
Author(s):  
Marcelo Maia Pinheiro ◽  
Felipe Moura Maia Pinheiro ◽  
Maria Luisa Trabachin
Author(s):  
Marcelo Maia Pinheiro ◽  
Felipe Moura Maia Pinheiro ◽  
Margareth Afonso Torres

Summary Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission. Learning points: The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production. The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells. Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission. The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.


2002 ◽  
Vol 84 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Ágnes Vatay ◽  
Katalin Rajczy ◽  
Éva Pozsonyi ◽  
Nóra Hosszúfalusi ◽  
Zoltán Prohászka ◽  
...  

2022 ◽  
pp. 150-155
Author(s):  
A. K. Ovsyannikova ◽  
R. B. Galenok ◽  
O. B. Rymar

In the clinical practice of an endocrinologist, verification of the type of diabetes mellitus (DM) in young people is of high clinical significance, since the prescription of treatment depends on this: from the correction of carbohydrate metabolism by a balanced diet to the prescription of oral hypoglycemic drugs and insulin therapy. In rare forms of diabetes mellitus, which include «latent autoimmune diabetes in adults» (LADA), it is not always possible to make a correct diagnosis. This form of diabetes mellitus occupies an intermediate position between type 1 diabetes mellitus and type 2 diabetes mellitus (DM 1 and DM 2) and is often not detected. In this regard, the study of the LADA flow is of great practical importance. Verification of the LADA diagnosis is based on three clinical criteria: adult onset of diabetes; the presence of circulating islet autoantibodies, which distinguishes LADA from T2DM; the absence of an absolute need for insulin when making a diagnosis, which distinguishes LADA from the classic type 1 diabetes mellitus. The main treatment tactics for patients with LADA should be aimed at preserving their own insulin secretion. This requires the timely appointment of insulin therapy. The question of the possibility of using drugs of peripheral action – biguanides and glitazones, which do not cause depletion of β-cells, is discussed, but their effectiveness has not yet been established. The appointment of any secretogens, including sulfonylurea preparations, is contraindicated Quite often, LADA is difficult to diagnose, and the wrong treatment tactics are prescribed. At the moment, there is little data on the effectiveness of different classes of drugs, which leads to further detailed study of this type of diabetes. Currently, there are no special algorithms for LADA treatment


2014 ◽  
Vol 13 (1) ◽  
pp. 73-78
Author(s):  
T. V. Saprina ◽  
T. S. Prokhorenko ◽  
F. E. Lazarenko ◽  
I. N. Vorozhtsova ◽  
N. V. Ryazantseva

Some researchers found that the development of microvascular complications (nephropathy, retinopathy) with latent autoimmune diabetes adults (LADA) occurs much earlier than in type 1 diabetes mellitus. The research devoted to the study of the spectrum and the time of development of microangiopathy in patients with latent autoimmune diabetes of adults, compared to patients with type 1 and 2 diabetes mellitus. Also studied immunological factors (cytokine secretion of mononuclear leukocytes) as one of the possible mechanisms of diabetic angiopathy progression. It has been shown that in LADA, as in patients with type 2 diabetes mellitus, the development of microvascular complications (nephropathy, retinopathy) occurs much earlier than in type 1 diabetes mellitus (after a 4-year course of the disease) due to a sharp decline in the serum concentration of C peptide. Thus in patients with LADA, having microvascular complications in the supernatants of cell cultures of mononuclear leukocytes determined a significant increase in the concentrations of cytokines IL-2, IL-4, TNFα.


2021 ◽  
Vol Volume 14 ◽  
pp. 565-573 ◽  
Author(s):  
Jaquellyne Gurgel Penaforte-Saboia ◽  
Carlos Eduardo Barra Couri ◽  
Natasha Vasconcelos Albuquerque ◽  
Vanessa Lauanna Lima Silva ◽  
Natália Bitar da Cunha Olegario ◽  
...  

2021 ◽  
Vol 24 (1) ◽  
pp. 70-73
Author(s):  
M. R. Ragimov ◽  
D. D. Omelchuk ◽  
L. I. Ibragimova ◽  
O. S. Derevyanko ◽  
T. V. Nikonova

Slowly developing immune-mediated diabetes, often called latent autoimmune diabetes in adults, is characterized by the presence of autoantibodies (ATs) to glutamic acid decarboxylase (GADA), the patient's age at the onset over 35 years, and the absence of the need for insulin therapy for 6-12 months to 6 years from the moment of diagnosis, according to the WHO classification of 2019, refers to hybrid forms of diabetes mellitus (DM). In this article, we present a case history of slowly developing immune-mediated diabetes in a 14-year-old boy who was transferred from metformin monotherapy and a diet with restriction of digestible carbohydrates to the intensified insulin therapy only 4 years after the onset of diabetes mellitus with a glycated hemoglobin (HbA1c) level of less than 6.5% throughout the disease. As a result of the studies, the patient was found to have a homozygous genotype highly predisposing to the development of Type 1 Diabetes Mellitus (T1DM), as well as increased levels of ATs to GADA and tyrosine phosphatase (IA-2A). The initially preserved level of basal C-peptide and the clinical course of the disease in this patient do not allow us to classify this case as a classic variant of the course of Type 1 Diabetes Mellitus.


Author(s):  
Isabel Borges ◽  
Roberto Añez ◽  
Mervin Chavez-Castillo ◽  
Juan Salazar

Adult-onset autoimmune diabetes (AOAD) is clinical form of diabetes with a wide spectrum of genotypical and phenotypical manifestations, which has risen in prominence in recent decades, probably due to greater interest in its pathogenic mechanisms, and increased identification of autoimmune markers. The clinical presentation may vary from type 1 diabetes mellitus to latent autoimmune diabetes in adults, which although clearly distinct from a theoretical viewpoint, may pose various clinical pitfalls in practice. We present the case of a patient with AOAD which featured several diagnostic challenges during follow-up.


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