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- Mishra, Rajashree, et al.
(författare)
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Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:2, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.
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| 2. |
- Leslie, R David, et al.
(författare)
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Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment.
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 59:1, s. 13-20
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Forskningsöversikt (refereegranskat)abstract
- Diabetes is not a single homogeneous disease but composed of many diseases with hyperglycaemia as a common feature. Four factors have, historically, been used to identify this diversity: the age at onset; the severity of the disease, i.e. degree of loss of beta cell function; the degree of insulin resistance and the presence of diabetes-associated autoantibodies. Our broad understanding of the distinction between the two major types, type 1 diabetes mellitus and type 2 diabetes mellitus, are based on these factors, but it has become apparent that they do not precisely capture the different disease forms. Indeed, both major types of diabetes have common features, encapsulated by adult-onset autoimmune diabetes and maturity-onset diabetes of the young. As a result, there has been a repositioning of our understanding of diabetes. In this review, drawing on recent literature, we discuss the evidence that autoimmune type 1 diabetes has a broad clinical phenotype with diverse therapeutic options, while the term non-autoimmune type 2 diabetes obscures the optimal management strategy because it encompasses substantial heterogeneity. Underlying these developments is a general progression towards precision medicine with the need for precise patient characterisation, currently based on clinical phenotypes but in future augmented by laboratory-based tests. Key points • The need to clarify diabetes classification, which is currently imprecise in distinguishing major disease types, using laboratory tests • The importance of predictors of disease progression, including genetic, immune and metabolic features • The potential for predicting therapeutic responses to provide a more personalised approach to therapy.
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| 3. |
- Nguyet Pham, Minh, et al.
(författare)
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Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes: positive association with leptin and resistin and negative association with adiponectin
- 2013
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Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley and Sons. - 1520-7552 .- 1520-7560. ; 29:2, s. 166-170
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Tidskriftsartikel (refereegranskat)abstract
- Background We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes. Methods One hundred and eighteen patients with type 1 diabetes (20.3 +/- 7.5years) diagnosed andlt;5years underwent standardized mixed meal test (MMTT) for 2h. Systemic concentrations of C-peptide, adiponectin, leptin and resistin obtained during MMTT were measured and compared between patient groups by multiple regression analysis. Results Patients were divided by their adipokine levels in subgroups above or below the median level (high versus low). High adiponectin levels (andgt;10.6 mu g/mL) were associated with lower C-peptide compared to the low adiponectin subgroup (pandlt;0.03). Increased leptin or resistin concentrations associated positively with beta-cell function even after adjustment for metabolic confounders (pandlt;0.04). The described associations between adipokines and C-peptide concentrations persisted in Spearman correlation tests (pandlt;0.05). Serum adipokines fell during MMTT (pandlt;0.05). Conclusions Serum adipokine levels differentially correlate with beta-cell function in type 1 diabetes independent of BMI or metabolic control. Serum adipokines should be investigated as biomarkers of beta-cell function in prospective studies and intervention trials in type 1 diabetes.
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