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Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.

ABSTRACT: OBJECTIVE:We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS:Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes. RESULTS:Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D(>35y) patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS:LADA patients differed genetically and phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner dependent on GADA levels.

SUBMITTER: Andersen MK

PROVIDER: S-EPMC2928363 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.

Andersen Mette K MK Lundgren Virve V Turunen Joni A JA Forsblom Carol C Isomaa Bo B Groop Per-Henrik PH Groop Leif L Tuomi Tiinamaija T

Diabetes care 20100901 9

<h4>Objective</h4>We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years.<h4>Research design and methods</h4>Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes.<h4>Results</h4>Although patients with LADA had an in ...[more]

PMID: 20805278

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Project description:ObjectiveLatent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA.MethodsPeripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples.ResultsCompared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, SELL, ITGA4, ITGAM, NCF4, ARHGAP3, and CLDN15 are upregulated in neutrophils by qPCR.ConclusionThe present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA's pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease.

Project description:PurposeBreast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.Methods and materialsFemale patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology.ResultsA total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P <.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P <.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P < .001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P <.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer.ConclusionSurvival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.

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Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.

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Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.

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