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Objective To observe the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of brittle diabetes. Methods Ten patients with brittle diabetes who were treated in the Department of Endocrinology of Sir Run Run Hospital, Nanjing Medical University from July 2017 to December 2019 were enrolled. After a 4-week run-in period, patients began WMT treatment. At baseline (T0), 1 week post WMT (T1W), 1 month post WMT (T1M), and 3 months post WMT (T3M), the following clinical data were collected: indicators of self-blood glucose monitoring (SMBG), insulin dose, glycated hemoglobin A1c, blood glucose and C peptide during standard steamed bread meal test, blood lipids, the occurrence of hypoglycemia and adverse events. Continuous glucose monitoring was conducted at T0 and T1W, and diabetes treatment satisfaction questionnaire was conducted at T0 and T1M. Paired t test, Wilcoxon matched-pairs signed rank test, Fisher exact test, One-way analysis of variance (ANOVA) test or Kruskal-Wallis test were used for data analysis. Results The insulin dose began to decrease from T1W, with the most significant decrease at T1M (P<0.05). The SMBG showed that the fasting and 2-hour postprandial blood glucose, mean of blood glucose, standard deviation of blood glucose, coefficients of variation of blood glucose values, mean amplitude of glycemic excursions, the largest amplitude of glycemic excursions, episodes of hypoglycemia, low blood glucose index (LBGI) and the mean absolute difference daytime blood glucose after WMT treatment were significantly decreased than T0 (P<0.05). In addition, continuous blood glucose monitoring data showed that the percentage of timewith glucose values ≤3.9 mmol/L and the percentage of timewith glucose values≥11.1 mmol/L at T1W were significantly reduced compared with T0 [1.46% (0.06%, 3.08%) vs 0 (0, 0.18%), 21.95% (16.02%, 44.68%) vs 5.52% (0.57%, 19.93%), respectively, both P<0.05], while the percentage of time in glucose target range was significantly increased [(44.36±25.24)% vs (74.40± 19.13)%, P<0.05]. There was no significant difference in serum C peptide and blood lipid before and after treatment (all P>0.05). No serious adverse events occurred during treatment and follow-up. Up to T3M, the overall effective rate of treatment reached 70% (7/10), with a statistically significant difference compared with T0 (P<0.05 or P<0.01). The total score of WMT treatment satisfaction was significantly increased compared with T0 [(26.0±2.0) vs (18.0±2.0) points, t=9.847, P<0.01]. Conclusion WMT for the treatment of brittle diabetes is considered to be both safe and efficient with a high patient satisfaction rate. [ABSTRACT FROM AUTHOR]

Objective To explore the interaction of T cell and insulinoma-associated protein 2 (IA-2) conformation and peptide primary sequence on B and T lymphocyte. Methods We designed and synthesized four types of IA-2 epitope peptides, parental β-fold structure IA-2843-855 peptide, α-helical IA-2843-855 peptide (conformation variability), random coil IA-2843-855 peptide (sequence variance) and further β-fold structure IA-2843-855 peptide which incorporated three hydrophobic amino acid. Patients who were diagnosed as type 1 diabetes mellitus (T1DM, n=12) within 1 year and with high titer IA-2 autoantibodies, T2DM (n=12) and healthy control(n=12) were recruited from the second hospital of Jilin university. Their peripheral blood mononuclear cell (PBMC) cells were stimulated with four types of IA-2843-855 antigens（10 μg/ml）and nonspecific mitogen PHA (5 μg/ml) was added as positive control. Cellular proliferation was expressed as the stimulation index(SI). The suspensions collected from culture medium after centrifuged were used to test the levels of cytokines interleukin (IL)-2 and IL-4. T-test was used to compare the means between groups. Results The SI of T1DM stimulated by parental β-fold structure IA-2843-855 peptide, the α-helical IA-2843-855 peptide, the random coil IA-2843-855 peptide and the further β-fold structure IA-2843-855 peptide were significantly higher than those in T2DM(1.33 ± 0.05 vs 1.13 ± 0.06, 1.27 ± 0.06 vs 1.19 ± 0.05, 1.31± 0.07 vs 1.21± 0.05, 1.20± 0.07 vs 1.11± 0.05, respectively,t=-11.6--2.71,P<0.05), and also significantly higher than that in the healthy group (t=-12.6--2.12,P<0.05). The IL-4 level of T1DM stimulated by the four types of IA-2843-855 peptide were significantly lower than that in T2DM and the healthy group(t=2.43-11.75, all P<0.05). The IL-2 level of T1DM stimulated by the four types of IA-2843-855 peptide were significantly higher than that in T2DM and the healthy group(t=-7.20--2.14, all P<0.05).The IL-2 level stimulated by the further β-fold structure of IA-2843-855 peptide and IL-4 cytokines level was lower than the other three peptides(t=-11.9-4.91, all P<0.01). Conclusions The four types of IA-2843-855 peptides we designed and synthesized can specifically make the T lymphocyte proliferate, the further β-fold structure IA-2843-855 peptide is different from the parental peptide in effect on proliferation and cytokines secretion. The level of amino acid sequence plays an important role between T and B lymphocyte cross talk. [ABSTRACT FROM AUTHOR]