Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

Yang, Lin; Zhang, Zhou; Huang, Gan; Ouyang, Li; Li, Xia; Yan, Xiang

doi:10.3748/wjg.v11.i19.2900

Cited by 33 publications

(27 citation statements)

References 28 publications

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“…Other studies reported that there was a similar decline in C-peptide in 204 consecutive cases followed for 7.4 years, but age at diagnosis and male sex were positively correlated with residual C-peptide at 5 years [45][46][47]. Another study reported that 25% of latent autoimmune diabetes of adults (LADA) subjects had a >50% decrease in fasting C-peptide 18 months after diagnosis, which was significantly greater than in subjects with type 2 diabetes, but children with type 1 diabetes were not included for comparison in the same analysis [48]. Thus, differences in the rate of progression (loss of beta cell responses) in younger vs older individuals with type 1 diabetes have not been found consistently.…”

Section: Insulin Secretion At the Time Of Diagnosis Of Type 1 Diabetesmentioning

confidence: 99%

The rise and fall of insulin secretion in type 1 diabetes mellitus

et al. 2006

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An understanding of the natural history of beta cell responses is an essential prerequisite for interventional studies designed to prevent or treat type 1 diabetes. Here we review published data on changes in insulin responses in humans with type 1 diabetes. We also describe a new analysis of C-peptide responses in subjects who are at risk of type 1 diabetes and enrolled in the Diabetes Prevention Trial-1 (DPT-1). C-peptide responses to a mixed meal increase during childhood and through adolescence, but show no significant change during adult life; responses are lower in adults who progress to diabetes than in those who do not. The age-related increase in C-peptide responses may account for the higher levels of C-peptide observed in adults with newly diagnosed type 1 diabetes compared with those in children and adolescents. Based on these findings, we propose a revised model of the natural history of the disease, in which an age-related increase in functional beta cell responses before the onset of autoimmune beta cell damage is an important determinant of the clinical features of the disease.

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Section: Insulin Secretion At the Time Of Diagnosis Of Type 1 Diabetesmentioning

confidence: 99%

The rise and fall of insulin secretion in type 1 diabetes mellitus

et al. 2006

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“…Some authors agree that a high titer of GAD65Ab is associated with a shorter insulin-free period, whereas others do not support this view (9). However, the presence of multiple b-cell autoantibodies such as GAD65Ab and islet cell antibodies (ICA) (10) or GAD65Ab and IA-2Ab (11) in adult patients diagnosed with T2D is highly correlated with a faster decline of islet function.…”

Section: Introductionmentioning

confidence: 99%

Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults

Maioli¹,

Pes

Delitala³

et al. 2010

European Journal of Endocrinology

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Objective: In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. Design: The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (MZ131; FZ145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. Results: Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (PZ0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (PZ0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (L-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (PZ0.022), female gender (PZ0.036), low body mass index (BMI; PZ0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (PZ0.020). Conclusions: High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

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“…Although, type 1.5 diabetes is believed to be T-cellmediated, studies identifying type 1.5 diabetic patients rely mainly on Abs (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Therefore, in this study, we investigated whether ␤-cell dysfunction was more associated with Abs or T-cell reactivity to islet antigens in patients with type 1.5 diabetes.…”

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confidence: 97%

T-Cell Responses to Islet Antigens Improves Detection of Autoimmune Diabetes and Identifies Patients With More Severe β-Cell Lesions in Phenotypic Type 2 Diabetes

et al. 2007

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Latent autoimmune diabetes in adults or type 1.5 diabetes is considered to be a T-cell-mediated autoimmune disease. However, identification of patients is based commonly on autoantibody (Ab) detection. To determine whether measuring T-cell reactivity to islet proteins compared with measuring Abs improves detection of autoimmune diabetes and how ␤-cell function correlates with T-cell reactivity compared with Ab positivity, we assessed the T-cell proliferative responses and Ab responses (islet cell autoantibodies, insulin autoantibodies, insulinoma-associated protein-2 autoantibodies, and GAD Abs) to islet proteins of 36 phenotypic type 2 diabetic patients. To be considered Ab

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Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

Abstract: The decreasing rate of islet beta cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet beta cell function, and age at onset and BMI could also act as the predictors.

Cited by 33 publications

References 28 publications

The rise and fall of insulin secretion in type 1 diabetes mellitus

The rise and fall of insulin secretion in type 1 diabetes mellitus

Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults

T-Cell Responses to Islet Antigens Improves Detection of Autoimmune Diabetes and Identifies Patients With More Severe β-Cell Lesions in Phenotypic Type 2 Diabetes

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