Beata Małachowska1,2, Krystyna Wyka3, Zuzanna Nowicka1, Marcin A Bartłomiejczyk3,4, Wojciech Młynarski3, Wojciech Fendler1,5. 1. Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. 2. Post-Graduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland. 3. Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland. 4. Department of Hypertensiology, Medical University of Lodz, Lodz, Poland. 5. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract
BACKGROUND/ OBJECTIVE: In type 1 diabetes mellitus (T1DM), the introduction of insulin is typically followed by a brief remission period, with subsequent gradual decline in beta-cell function. Several studies described altered profile of circulating miRNAs (microRNAs) in T1DM patients and proposed them as biomarkers of associated pathologic processes. HYPOTHESIS: Serum miRNA expression profile reflects residual beta-cell function and autoimmunity in T1DM. SUBJECTS: The profiling group included patients with: GCK-MODY (N = 13), T1DM (N = 9), and 10 healthy controls. The longitudinal group included 34 patients with samples collected at diagnosis of T1DM and first, third, and fourth to eighth year since diagnosis. METHODS: We reanalyzed data from the profiling group for miRNAs differentially expressed between patients with T1DM, other types of diabetes and controls. Afterward, we shortlisted miRNAs on the basis of this reanalysis and literature review and quantified their expression with quantitative polymerase chain reaction. Additionally, we measured the levels of anti-islet antibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, IA2 antibodies, and ZnT8A) and C-peptide concentrations across the four timepoints in the longitudinal group. RESULTS: miR-24 and let-7g serum expression differed significantly between GCK-MODY, controls, and HbA1c-matched T1DM patients; P < 0.05, false discovery rate < 0.05. Autoantibodies levels showed decreasing linear trend in repeated timepoints (all P < 0.0001). C-peptide concentration peaked during the first year after diagnosis, corresponding to remission phase, and declined in consecutive measurements. This dynamic was evidenced for let-7g expression levels (P = 0.0058). CONCLUSIONS: The pattern of let-7g expression change during the course of diabetes mirrors that of C-peptide levels, hinting at this microRNA's association with the residual mass of the beta cells in patients with T1DM.
BACKGROUND/ OBJECTIVE: In type 1 diabetes mellitus (T1DM), the introduction of insulin is typically followed by a brief remission period, with subsequent gradual decline in beta-cell function. Several studies described altered profile of circulating miRNAs (microRNAs) in T1DM patients and proposed them as biomarkers of associated pathologic processes. HYPOTHESIS: Serum miRNA expression profile reflects residual beta-cell function and autoimmunity in T1DM. SUBJECTS: The profiling group included patients with: GCK-MODY (N = 13), T1DM (N = 9), and 10 healthy controls. The longitudinal group included 34 patients with samples collected at diagnosis of T1DM and first, third, and fourth to eighth year since diagnosis. METHODS: We reanalyzed data from the profiling group for miRNAs differentially expressed between patients with T1DM, other types of diabetes and controls. Afterward, we shortlisted miRNAs on the basis of this reanalysis and literature review and quantified their expression with quantitative polymerase chain reaction. Additionally, we measured the levels of anti-islet antibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, IA2 antibodies, and ZnT8A) and C-peptide concentrations across the four timepoints in the longitudinal group. RESULTS: miR-24 and let-7g serum expression differed significantly between GCK-MODY, controls, and HbA1c-matched T1DM patients; P < 0.05, false discovery rate < 0.05. Autoantibodies levels showed decreasing linear trend in repeated timepoints (all P < 0.0001). C-peptide concentration peaked during the first year after diagnosis, corresponding to remission phase, and declined in consecutive measurements. This dynamic was evidenced for let-7g expression levels (P = 0.0058). CONCLUSIONS: The pattern of let-7g expression change during the course of diabetes mirrors that of C-peptide levels, hinting at this microRNA's association with the residual mass of the beta cells in patients with T1DM.
Authors: Maciej Borowiec; Wojciech Młynarski; Agnieszka Zmyslowska; Marcin Stanczak; Zuzanna Nowicka; Arleta Waszczykowska; Dobromila Baranska; Wojciech Fendler Journal: BMJ Open Diabetes Res Care Date: 2020-11
Authors: Silvia Garavelli; Sara Bruzzaniti; Elena Tagliabue; Francesco Prattichizzo; Dario Di Silvestre; Francesco Perna; Lucia La Sala; Antonio Ceriello; Enza Mozzillo; Valentina Fattorusso; Pierluigi Mauri; Annibale A Puca; Adriana Franzese; Giuseppe Matarese; Mario Galgani; Paola de Candia Journal: Int J Mol Sci Date: 2020-01-11 Impact factor: 5.923
Authors: Caroline Frørup; Aashiq H Mirza; Reza Yarani; Lotte B Nielsen; Elisabeth R Mathiesen; Peter Damm; Jens Svare; Christian Engelbrekt; Joachim Størling; Jesper Johannesen; Henrik B Mortensen; Flemming Pociot; Simranjeet Kaur Journal: Front Immunol Date: 2021-10-08 Impact factor: 7.561