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Background: Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes., Methods: Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms., Results: Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide., Conclusions: WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective To establish a new standard for measurement islet autoantibodies by electrochemiluminescence (ECL) assay and to discuss its applications for type 1 diabetes mellitus (T1DM) prediction and diagnosis. Methods ECL assay was used to measure serum levels of glutamic acid decarboxylase antibody (GADA65), insulin autoantibody (IAA) and protein tyrosine phosphatase antibody (IA-2A) in 124 healthy volunteers, 180 T1DM patients, and 180 type 2 diabetes mellitus (T2DM) patients. Patients admitted in Sir Run Run Hospital, Nanjing Medical University from December 2016 to June 2018 with diagnosis of T1DM or T2DM were enrolled in the study. Healthy volunteers were recruited from students in Nanjing Medical University. The serum antibody level was represented as antibody index. The positive cut-off limit for each antibody was defined as 99% of the indicated antibody index from healthy volunteers. The chi-square test was used to analyze the positivity of GADA65, IAA, IA-2A of T1DM and T2DM patients detected by ECL method. Results The cut-off points for GADA65, IAA and IA-2A were 0.047, 0.009 and 0.0029 respectively by ECL methods. The intra-assay coefficients of variation (CV) for GADA65, IAA and IA-2A were 1.88% - 8.30%, 1.39% - 3.40%, 1.23% - 3.17% respectively, and the inter-assay CV were 3.9%-7.3%, 2.7%-9.8%, 2.2%-7.4% respectively. The repeatability of the result was 99.8%. The positivity of GADA65, IAA, IA-2A were 52% (94/180), 45% (81/180), 21% (39/180) respectively in T1DM patients and were 2.2% (4/180), 2.2% (4/180), 2.2% (4/180) respectively in T2DM patients. There were statistic significances in positivity between T1DM and T2DM for all three antibodies (χ²=113.57, 32.35, 91.31, all P<0.001). The positive ratio of GADA65 and IA-2A detected by ECL or radio-binding assay shows no difference. Conclusion The ECL assay has high sensitivity, specificity and repeatability and could be used for the prediction and diagnosis of T1DM. [ABSTRACT FROM AUTHOR]