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Differential expression of microRNA profiles from the peripheral blood of type 1 and type 2 diabetic patients

ABSTRACT: Using microarray, we compared the expression of miRNAs from the peripheral blood of male subjects with T1DM and T2DM with healthy controls. Healthy male controls used were age-matched to the T2DM group patients with mean(SD) 37.3 (7.1) years. Subjects with T1DM were younger [23.3(1.6) years]. Expression was compared and validated using quantitative real-time PCR. Statistical testing (ANOVA, P-value <0.05) was performed and fold changes with respect to the control were calculated Systolic BP, fasting glucose, HbA1c, total cholesterol and LDL-cholesterol levels were significantly higher in T2DM subjects compared with controls (P-value <0.05). Compared with controls, we identified 37 differentially regulated miRNAs in DM subjects. Among them, 21 miRNAs were upregulated (2-5 fold change, p-value < 0.05) and 16 miRNAs were downregulated (1.5-2 fold change, p-value < 0.05). These miRNAs had gene putative targets primarily involved in regulating pancreatic development and functions, adipocyte differentiation, insulin signaling and glucose-dependent insulin secretion.

ORGANISM(S): Human gammaherpesvirus 8 Mus musculus Rattus norvegicus JC polyomavirus Betapolyomavirus macacae Homo sapiens Human immunodeficiency virus 1 Murid gammaherpesvirus 4 Human betaherpesvirus 5 Human alphaherpesvirus 1 Betapolyomavirus hominis human gammaherpesvirus 4 Murid betaherpesvirus 1

PROVIDER: GSE27645 | GEO | 2011/03/05

SECONDARY ACCESSION(S): PRJNA138523

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%.

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Differential expression of microRNA profiles from the peripheral blood of type 1 and type 2 diabetic patients

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