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A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [second cohort, untargeted]

ABSTRACT: Circulating microRNAs are linked to the onset and progression of type 1 diabetes mellitus (T1DM), making them potential biomarkers for the disease. In this study, we employ a multiplatform sequencing approach to analyze circulating microRNAs in an extended cohort of individuals with T1DM from the INNODIA consortium. Our findings reveal that a set of microRNAs located within the T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conduct additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named Cluster A and Cluster B. Remarkably, Cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycaemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating microRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265981 | GEO | 2024/05/03

REPOSITORIES: GEO

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Project description:Type 1 diabetes mellitus (T1DM) results from immune mediated destruction of pancreatic beta cells. However, clinical and immunologic phenotypes of T1DM are variable. Several auto-antibodies including GADA, IA-2A, and ZnT8A, were identified in T1DM, but the prevalence of these auto-antibodies varied for a broad spectrum of T1DM. Here, we systemically profiled auto-antibodies from serum samples of 16 T1DM, 16 type 2 diabetes (T2DM) patients, and 27 healthy controls with normal glucose tolerance (NGT) using protein microarrays containing 9,480 proteins. Among 9,480 different proteins on the array, we identified novel auto-antibody candidates (EEF1A1-AAb and UBE2L3-AAb) by M-test coupled with PLS-DA. These auto-antibodies were highly present in T1DM than controls and detected in 40% of T1DM without GADA. Furthermore, these auto-antibodies might help to differentiate subtype of T1DM when combined with GADA. These novel auto-antibodies provide new diagnostic information of T1DM, as well as new insights into the pathogenesis of T1DM. Auto-antibodies from serum samples were profiled using a high-density, fluorescence-based protein microarray containing duplicate spots of 9,480 human proteins derived from the Ultimate ORF collection The cohort of patients and controls consisted of 16 T1DM, 16 T2DM patients, and 27 healthy controls with NGT. This cohort was used to screen candidate auto-antibodies using protein microarrays (ProtoArray platform version 5.0, Invitrogen Corp., Carlsbad, CA). Serum samples were drawn from T1DM patients who have 1) fasting C-peptide level <0.3 nmol/L or serum C-peptide <0.6 nmol/L after glucagon loading, 2) initiation of insulin treatment within six months after diagnosis, and 3) duration of diabetes M-bM-^IM-$12 months. Mean age of T1DM in the first cohort was 42 M-BM-1 16 years. The control serum samples were obtained from T2DM patients who were treated only with oral anti-diabetic drug at least 5 years and from NGTs who had no history of diabetes, no first-degree relatives with diabetes, a fasting plasma glucose concentration of <6.1 mmol/l, and a HbA1c value of <5.8%.

Dataset Information

A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two different subgroups of individuals with recent onset Stage 3 type 1 diabetes [second cohort, untargeted]

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