Clinical manifestation and islet β-cell function of a subtype of latent autoimmune diabetes in adults (LADA): positive for T cell responses in phenotypic type 2 diabetes

Liang, Huiying; Cheng, Ying; Tang, Wei; Cui, Qiuyan; Yuan, Jianmin; Huang, Gan; Yang, Lin; Zhang, Zhou

doi:10.1007/s00592-019-01391-w

Cited by 12 publications

(8 citation statements)

References 28 publications

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“…The lowest value (0.5) was substituted if the mean number of spots in negative control wells was zero 12 . A response is considered positive when stimulation index >3.2 for GAD and stimulation index >6.3 for CP, respectively 11 base on the best cut‐off selection by receiver operating characteristic plot analysis. The endotoxin contents were low in GAD65 and CP (both negative in limulus lysate assay).…”

Section: Methodsmentioning

confidence: 99%

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Diagnostic value of combined islet antigen‐reactive T cells and autoantibodies assays for type 1 diabetes mellitus

Tang

Liang

Cheng

et al. 2020

J of Diabetes Invest

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Aims/Introduction Type 1 diabetes mellitus is a T cell‐mediated autoimmune disease. However, the determination of the autoimmune status of type 1 diabetes mellitus relies on islet autoantibodies (Abs), as T‐cell assay is not routinely carried out. This study aimed to investigate the diagnostic value of combined assay of islet antigen‐specific T cells and Abs in type 1 diabetes mellitus patients. Materials and Methods A total of 54 patients with type 1 diabetes mellitus and 56 healthy controls were enrolled. Abs against glutamic acid decarboxylase (GAD), islet antigen‐2 and zinc transporter 8 were detected by radioligand assay. Interferon‐γ‐secreting T cells responding to glutamic acid decarboxylase 65 and C‐peptide (CP) were measured by enzyme‐linked immunospot. Results The positive rate for T‐cell responses was significantly higher in patients with type 1 diabetes mellitus than that in controls (P < 0.001). The combined positive rate of Abs and T‐cell assay was significantly higher than that of Abs assay alone (85.2% vs 64.8%, P = 0.015). A significant difference in fasting CP level was found between the T+ and T– groups (0.07 ± 0.05 vs 0.11 ± 0.09 nmol/L, P = 0.033). Furthermore, levels of fasting CP and postprandial CP were both lower in the Ab−T+ group than the Ab−T− group (fasting CP 0.06 ± 0.05 vs 0.16 ± 0.12 nmol/L, P = 0.041; postprandial CP 0.12 ± 0.13 vs 0.27 ± 0.12 nmol/L, P = 0.024). Conclusions Enzyme‐linked immunospot assays in combination with Abs detection could improve the diagnostic sensitivity of autoimmune diabetes.

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Section: Methodsmentioning

confidence: 99%

“…ELISPOT assay IFN-c-secreting T-cell responses to GAD65 and CP were determined by ELISPOT, as described previously 11 . In brief, human peripheral blood mononuclear cells were separated within 4 h of blood collection by density gradient centrifugation with a lymphocyte separation medium (Sigma, St. Louis, MO, USA).…”

Section: Participantsmentioning

confidence: 99%

Diagnostic value of combined islet antigen‐reactive T cells and autoantibodies assays for type 1 diabetes mellitus

Tang

Liang

Cheng

et al. 2020

J of Diabetes Invest

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“…Type 2 diabetes (T2D) is a metabolic disease of increasing incidence fuelled by obesity and ageing demographics [ 1 ]. Corresponding to > 80% of the less common type 1 diabetes (T1D) cases [ 2 ], latent autoimmune diabetes of adults (LADA) bears close clinical similarity with type 2 diabetes [ 3 , 4 ]. Thus, T2D and LADA patients receive an initial treatment with oral hypoglycaemic agents (OHA), which leads to variable results ranging from the attenuation to the progression of the phenotype [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Sarnobat

Moffett

Flatt

et al. 2021

J Endocrinol Invest

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Aims Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets. Methods Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100 mg/kg), thiazolidinedione rosiglitazone (10 mg/kg), or sulfonylurea tolbutamide (20 mg/kg) for 10 days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence. Results The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet β-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of α-cells and β-cell apoptosis with tolbutamide; increased relative number of β-cells and bi-hormonal insulin + glucagon + cells with metformin. These effects were accompanied by normalisation of food and fluid intake with only minor effects on glycaemia at the low doses of the agents employed. Conclusions Our data suggest that metformin and rosiglitazone attenuate the depletion of the β-cell pool in the streptozotocin-induced diabetes, whereas tolbutamide exacerbates the β-cell apoptosis, but is likely to protect β-cells from chronic hyperglycaemia by directly elevating insulin secretion.

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“…Rolandsson et al (62) noted that type 2 diabetes patients with antigen-specific reactive T cells and no autoantibodies were termed as T-LADA (Ab-T+). T-LADA (Ab-T+) patients have worse b-cell function distinct from classic type 2 diabetes (Ab-T-) (63). The latest study also indicated that T cell-mediated autoimmunity plays an important role in b-cell destruction and worse glycemic control (64), implying that altered proportions and functional defects of T-cell subsets are an important cause of autoimmunity in LADA.…”

Section: Cellular Immunitymentioning

confidence: 99%

Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy

et al. 2022

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Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease sharing some phenotypic, genetic, and immunological features with both type 1 and 2 diabetes. Patients with LADA have a relatively slow autoimmune process and more residual islet β-cell function at onset, allowing a time window to protect residual islet β cells and delay or inhibit disease progression. It is crucial to discover various heterogeneous factors affecting islet β-cell function for precise LADA therapy. In this review, we first describe the natural history of LADA. Thereafter, we summarize β-cell function-related heterogeneous factors in LADA, including the age of onset, body mass index, genetic background, and immune, lifestyle, and environmental factors. In parallel, we evaluate the impact of current hypoglycemic agents and immune intervention therapies for islet β-cell protection. Finally, we discuss the opportunities and challenges of LADA treatment from the perspective of islet β-cell function protection.

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Clinical manifestation and islet β-cell function of a subtype of latent autoimmune diabetes in adults (LADA): positive for T cell responses in phenotypic type 2 diabetes

Cited by 12 publications

References 28 publications

Diagnostic value of combined islet antigen‐reactive T cells and autoantibodies assays for type 1 diabetes mellitus

Diagnostic value of combined islet antigen‐reactive T cells and autoantibodies assays for type 1 diabetes mellitus

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy

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