Dataset Information

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

ABSTRACT: Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset 'classic' T1DM (n = 156), LADA (n = 174), T2DM (n = 195) and healthy cohorts (n = 166). Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ) together with liquid chromatography tandem mass spectrometry (LC-MS) to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0%) proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1), which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM.

SUBMITTER: Qin W

PROVIDER: S-EPMC4925120 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

Qin Wen W Liang Yu-Zhen YZ Qin Bao-Yu BY Zhang Jia-Li JL Xia Ning N

PloS one 20160628 6

Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset ' ...[more]

PMID: 27351175

Similar Datasets

Project description:AIMS/HYPOTHESIS:Pathophysiological similarities between latent autoimmune diabetes in adults (LADA) and type 1 diabetes indicate an overlap in genetic susceptibility. HLA-DRB1 and HLA-DQB1 are major susceptibility genes for type 1 diabetes but studies of these genes in LADA have been limited. Our aim was to define patterns of HLA-encoded susceptibility/protection in a large, well characterised LADA cohort, and to establish association with disease and age at diagnosis. MATERIALS AND METHODS:Patients with LADA (n = 387, including 211 patients from the UK Prospective Diabetes Study) and non-diabetic control subjects (n = 327) were of British/Irish European origin. The HLA-DRB1 and -DQB1 genes were genotyped by sequence-specific PCR. RESULTS:As in type 1 diabetes mellitus, DRB1 0301_DQB1 0201 (odds ratio [OR] = 3.08, 95% CI 2.32-4.12, p = 1.2 x 10(-16)) and DRB1 0401_DQB1 0302 (OR = 2.57, 95% CI 1.80-3.73, p = 4.5 x 10(-8)) were the main susceptibility haplotypes in LADA, and DRB1 1501_DQB1 0602 was protective (OR = 0.21, 95% CI 0.13-0.34, p = 4.2 x 10(-13)). Differential susceptibility was conferred by DR4 subtypes: DRB1 0401 was predisposing (OR = 1.79, 95% CI 1.35-2.38, p = 2.7 x 10(-5)) whereas DRB1 0403 was protective (OR = 0.37, 95% CI 0.13-0.97, p = 0.033). The highest-risk genotypes were DRB1 0301/DRB1 0401 and DQB1 0201/DQB1 0302 (OR = 5.14, 95% CI 2.68-10.69, p = 1.3 x 10(-8); and OR = 6.88, 95% CI 3.54-14.68, p = 1.2 x 10(-11), respectively). These genotypes and those containing DRB1 0401 and DQB1 0302 associated with a younger age at diagnosis in LADA, whereas genotypes containing DRB1 1501 and DQB1 0602 associated with an older age at diagnosis. CONCLUSIONS/INTERPRETATION:Patterns of susceptibility at the HLA-DRB1 and HLA-DQB1 loci in LADA are similar to those reported for type 1 diabetes, supporting the hypothesis that autoimmune diabetes occurring in adults is an age-related extension of the pathophysiological process presenting as childhood-onset type 1 diabetes.

Project description:BackgroundThe Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA.MethodologyWe enrolled 186 phenotypically T2D patients in this cross-sectional study, through a standardized data collection tool we obtained participants' demographic and clinical information. For testing GAD levels, we used a double-antibody Enzyme-Linked Immunosorbent Assay (ELISA). The Fisher's Exact and student t-tests were used to test the significance of the statistical associations of the glycaemic control and diabetes complications between T2D and LADA.ResultsOut of 186 patients, 156 gave conclusive GAD Ab ELISA reading with LADA accounting for 5.1% (95% CI: 2.5 - 10.0). The mean age of subjects was 54.3 years (Range: 33-85 years). The parameters such as mean age, family history of diabetes mellitus status, Fasting Blood Glucose, clinical characteristics, and complications did not show significant statistical differences between patients with LADA and Type 2 diabetes. However, all LADA- Human Immunodeficiency Virus (HIV) comorbid patients had retinopathy, which was statistically insignificant in 20 (87%) T2D-HIV comorbid patients (p = 0.669). Neither neuropathy, nephropathy, nor Diabetic Mellitus (D.M.) foot syndrome was observed among LADA-HIV comorbid patients. Nevertheless, 22 (95.7%), 3 (13%), and 2 (8.7%) of T2D-HIV comorbidity had neuropathy, nephropathy, or D.M. foot syndrome, respectively.ConclusionsThe study established a LADA prevalence of 5.1% among T2D patients and has shown the role of GAD autoantibody in the screening for LADA. The study calls for a well- designed larger longitudinal study to generate strong evidence on the association of risk factors and complications associated with the LADA. This will develop robust evidence on the association of risk factors and complications associated with the LADA and T2D.

Dataset Information

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

Publications

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets