Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes

Abstract

The levels of the Arg variant of the ZnT8 autoantibodies are associated with higher levels of stimulated C-peptide after diagnosis of T1D and during follow-up. Carriers of the TT genotype of the SLC30A8 gene predict lower stimulated C-peptide levels 12 months after diagnosis.

Novel enzyme-linked immunosorbent assay for bivalent ZnT8 autoantibodies

“…Skärstrand and coworkers recently reported that the titer of peptide antibodies induced by the immunization of ZnT8-325Arg 15-mer peptide was higher than that by ZnT8-325Trp peptide [9]. Furthermore, it was reported that autoantibodies to ZnT8A variants differ in the prognosis of β cell function [10,11]. Although we and others reported that there is a strong genetic specificity between the ZnT8A variants and the Slc30A8 gene SNPs [3,4], taken together these data highlight the different strength of humoral autoimmune response to the ZnT8 variants, which may be associated with the rate of β cell destruction.…”

Partial Remission Definition: Validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish Children with New-Onset Type 1 Diabetes

“…Clinical, demographic, and HLA‐DQ characteristics together with autoantibody profile of the included patients are listed in Table . The detailed study design for the two cohorts has previously been described by Mortensen et al and Andersen et al . The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish National Committee on Biomedical Research Ethics (Journal number: H‐KA‐04010‐m).…”

“…In the Danish remission study , the children received 6 mL/kg (maximum 360 mL) of BOOST ® Original Drink [237 mL or 8 FL OZ containing 41 g of carbohydrate, 10 g of protein, and 4 g of fat, 240 kcal in all from Novartis Medical Health, Inc. (Minneapolis, MN, USA; http://www.boost.com/nutritional-drinks/boost-original)]. In the Hvidoere cohort , the children received 6 mL/kg (maximum 360 mL), according to DCCT standards , of BOOST ® High Protein Drink [237 mL or 8 FL OZ containing 33 g of carbohydrate, 15 g of protein and 6 g of fat, 240 kcal in all from Novartis Medical Health, Inc. (http://www.boost.com/nutritional-drinks/boost-high-protein)].…”

Tapering decay of β‐cell function in Chinese patients with autoimmune type 1 diabetes: A four‐year prospective study

“…However, because β‐cell function in T1D is profoundly impaired after clinical onset, and patients inevitably become dependent on exogenous insulin, the residual low level of endogenous insulin in T1D is usually overlooked. Clinical studies of T1D have been mostly interventional trials focusing on new‐onset patients who still had considerable endogenous insulin or some prevention studies that followed high‐risk individuals before disease onset . Few studies have specifically investigated the manner of progression of the decline in β‐cell function in patients with overt T1D.…”

“…In other clinical trials, subjects could have detectable initial FCP and non‐fasting C‐peptide concentrations of approximately 400 pM at the time of initial diagnosis . Some individuals from the 2004 to 2005 cohort of the Danish Remission Phase Study and the 2004 to 2013 TrialNet cohorts had stimulated C‐peptide levels of more than 400 pM at >1 year after diagnosis. These findings are evidence of preserved β‐cell function in newly diagnosed patients.…”