scholarly journals Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk

Diabetologia ◽  
2006 ◽  
Vol 49 (5) ◽  
pp. 881-890 ◽  
Author(s):  
◽  
P. J. Bingley ◽  
E. A. M. Gale
2012 ◽  
Vol 97 (2) ◽  
pp. 632-637 ◽  
Author(s):  
Anna E. Long ◽  
A. Talia Gooneratne ◽  
Saba Rokni ◽  
Alistair J. K. Williams ◽  
Polly J. Bingley

Context: Antibodies to islet autoantigens are detectable many years before clinical onset of type 1 diabetes and can be used to identify individuals at increased risk of diabetes. Zinc transporter 8 is a recently identified islet autoantigen. Objective: Our aim was to determine whether addition of zinc transporter 8 autoantibodies (ZnT8A) improved prediction of type 1 diabetes in a well-characterized cohort of islet cell antibody (ICA)-positive first-degree relatives. We were particularly interested in the role of ZnT8A in prediction in antibody-positive relatives with intermediate and low overall risk of diabetes. Participants and Methods: ZnT8A were assayed in baseline samples from 526 ICA-positive first-degree relatives randomized in the European Nicotinamide Diabetes Intervention Trial. Antibodies to insulin, glutamate decarboxylase, islet antigen-2 (IA-2A) and IA-2β (IA-2βA), and human leukocyte antigen type had been previously determined. Risk of diabetes was assessed by survival analysis. Results: Of 221 ZnT8A-positive individuals, 113 developed diabetes during follow-up (5-yr cumulative risk, 55%). In multivariate models based on other autoantibodies, ZnT8A improved prediction in relatives at low genetic risk of diabetes (P = 0.030) and over age 20 yr (P = 0.026), but not in those with ICA alone or with one additional autoantibody (P = 0.696), IA-2A-negative relatives (P = 0.361), those at high or intermediate genetic risk, or younger relatives. Conclusions: ZnT8A are useful additional risk markers in relatives at low genetic risk of diabetes and older individuals, but they add relatively little in younger populations because of the precise prediction possible with current autoantibody combinations.


2017 ◽  
Vol 51 (1) ◽  
pp. 1-7 ◽  
Author(s):  
I. Ates ◽  
M. F. Arikan ◽  
K. Erdogan ◽  
M. Kaplan ◽  
M. Yuksel ◽  
...  

Abstract Objective. The aim of the present study was to determine the irisin levels in patients with the type 1 diabetes mellitus (T1DM) and to examine the relation of irisin levels with the inflammation and autoimmunity.Methods. This study included 35 cases diagnosed with T1DM and 36 healthy volunteers. Antiglutamic acid decarboxylase (anti-GAD), islet cell antibody (ICA), and insulin autoantibody levels were measured in patients at the time when they were included into the study and recorded from the patient files. Serum irisin levels were measured by ELISA kit.Results. The median irisin levels were determined higher in T1DM group compared to the control one (6.8 ng/ml vs. 4.8 ng/ml, p=0.022; respectively). Median irisin levels were higher in anti-GAD (p=0.022) and ICA (p=0.044) positive groups compared to negative groups. In T1DM group, irisin levels displayed positive correlation with glycosylated hemoglobin (HbA1c) (r=0.377, p<0.001) and anti-GAD (r=0.392, p=0.020) and negative correlation with creatinine (r=-0390, p=0.021). In multivariate regression model, HbA1c (B±SE: 2.76±17683, p<0.001), and anti-GAD (B±SE: 2.311±0.610, p=0.001) were determined as independent predictors for predicting the irisin levels.Conclusion. In patients with T1DM, which chronic inflammation and autoimmunity take part in their etiopathogenesis, anti-GAD levels were an independent risk factor for the irisin. Th is may suggest that factors such as inflammation and autoimmunity can be effective in the synthesis of irisin.


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