Altered T‐cell subsets and transcription factors in latent autoimmune diabetes in adults taking sitagliptin, a dipeptidyl peptidase‐4 inhibitor: A 1‐year open‐label randomized controlled trial

Wang, Xia; Yang, Lin; Cheng, Ying; Zheng, Peilin; Hu, Jingping; Huang, Gan; Zhang, Zhou

doi:10.1111/jdi.12873

Cited by 22 publications

(41 citation statements)

References 31 publications

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“…As a cell surface antigen, CD26 has a costimulatory function on T-cell activation and proliferation ( 52 ). Our group’s recent study implied that sitagliptin could modulate cellular immunity by increasing the proportion of T helper 2 cells, decreasing the proportion of T helper 17 cells in LADA patients and down-regulating the messenger RNA expression of T box expressed in T cells and related orphan receptor C in LADA patients ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…Two prespecified primary outcomes were chosen: (1) the change in β-cell function by the standardized mixed-meal tolerance test (MMTT) at 6, 12, 18, and 24 months of the study; and (2) the change in β-cell function with hyperglycemic clamp and insulin sensitivity with HEC in 12 LADA patients at 12 and 24 months. Secondary parameters included glycemic control measured by HbA1c and possible immunomodulatory effects on T-cell subsets and transcription factors, which have been published elsewhere ( 10 ).…”

Section: Methodsmentioning

confidence: 99%

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Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

Yang

Liang

Liu

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. Objective To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. Design and Setting A randomized controlled trial at the Second Xiangya Hospital. Patients and Interventions Fifty-one patients with LADA were randomized to sitagliptin + insulin group (SITA group) or insulin alone group (CONT group) for 24 months. Main Outcome Measures Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP) and updated homeostatic model assessment of β-cell function (HOMA2-B) were deterrmined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. Results During the 24-month follow-up, there were no significant changes in β-cell function in SITA group, whereas the levels of 2hCP and △CP in CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in SITA group than in CONT group. At 24 months, first-phase insulin secretion was improved in SITA group by hyperglycemia clamp, which was higher than in CONT group (P<0.001), while glucose metabolized(M), insulin sensitivity index and M over logarithmical insulin ratio in HEC were increased in SITA group (all P<0.01 vs. baseline), which were higher than in CONT group. Conclusions Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

Yang

Liang

Liu

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…As already mentioned, there is emerging evidence linking therapy with DPP‐4 inhibitors to down‐regulation of autoimmunity 41 and preservation of beta‐cell mass and function in people with LADA 42 . Their good safety and tolerability profiles should be also taken into consideration.…”

Section: Methodsmentioning

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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“…Peripheral blood samples were taken on days 3, 5, 7, 14, 27, and 53 after the abortion, and flow cytometry was used to determine the distribution of the lymphocyte subsets present. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Paque density-gradient ( 34 ). The fresh separated PBMCs were used for flow cytometry analysis.…”

Section: Methodsmentioning

confidence: 99%

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

Deng

Qiu

et al. 2021

Front. Immunol.

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The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion. The expression of HMGB1, TLR4, Nf-κB, AQP4, IL-2, IL-4, IL-6, and TNF-α in the fetal membrane and placenta was compared between the patient with pregnancy-related ADEM and a woman with a normal pregnancy using Real-time qPCR and western blotting (WB). The patient was diagnosed with ADEM in the early stage of pregnancy after showing limb weakness symptoms. In the third month of gestation, the symptoms worsened, with a disturbance of consciousness and breathing. After the abortion, the patient relapsed with vertigo and visual rotation. Analysis of lymphocyte subsets by flow cytometry showed that B lymphocytes increased, while natural killer T lymphocytes decreased. WB and Real-time qPCR showed that the expression levels of HMGB1, TLR4, Nf-κB, AQP4, and IL-6 in the fetal membrane and placenta were higher in the patient with pregnancy-related ADEM than in the woman with a normal pregnancy, while those of IL-2 were lower in the patient than in the woman with a normal pregnancy. The local immune changes and the activation of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface may be related to the pathogenesis of ADEM.

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Altered T‐cell subsets and transcription factors in latent autoimmune diabetes in adults taking sitagliptin, a dipeptidyl peptidase‐4 inhibitor: A 1‐year open‐label randomized controlled trial

Abstract: The data confirmed that sitagliptin altered the phenotype of T cells and downregulated the expression of T-BET and RORC in LADA patients, and ameliorated glycemic control in LADA patients.

Cited by 22 publications

References 31 publications

Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

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

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

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