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Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes
OBJECTIVE: Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836121/ https://www.ncbi.nlm.nih.gov/pubmed/24130366 http://dx.doi.org/10.2337/dc12-2328 |
Sumario: | OBJECTIVE: Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A−β+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (“provoked,” with progressive β-cell function loss over time) or no precipitant (“unprovoked,” with sustained β-cell functional reserve). These three A− KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown. RESEARCH DESIGN AND METHODS: Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A−β− (n = 7), provoked A−β+ (n = 15), and unprovoked A−β+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes–associated HLA class II alleles. RESULTS: Provoked A−β+ and A−β− KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A−β+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed. CONCLUSIONS: Provoked A−β+ KPD and A−β− KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A−β+ KPD lacks both humoral and cellular islet autoimmunity. |
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