Dataset Information

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes.

ABSTRACT:

Objective

Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), >60% of adults lack three classic islet autoantibodies-IA-2, GAD65, and ZnT8 Abs-associated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative ("A-") KPD patients possess occult IA-2 Ab directed against full-length IA-2 (IA-2FL) or its extracellular domain (IA-2EC).

Research design and methods

We developed an assay that targets IA-2FL and IA-2EC and used it to analyze 288 subjects with A- KPD.

Results

Ten A- KPD patients were positive for IA-2EC Ab (3.5%), and three were also positive for IA-2FL Ab (1.0%), similar to frequencies in type 1 and type 2 diabetes.

Conclusions

Measurement of IA-2FL Ab and IA-2EC Ab improves the accuracy of the A? classification of KPD patients.

SUBMITTER: Mulukutla SN

PROVIDER: S-EPMC6245211 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes.

Mulukutla Surya N SN Acevedo-Calado Maria M Hampe Christiane S CS Pietropaolo Massimo M Balasubramanyam Ashok A

Diabetes care 20181016 12

<h4>Objective</h4>Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), >60% of adults lack three classic islet autoantibodies-IA-2, GAD65, and ZnT8 Abs-associated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative ("A-") ...[more]

PMID: 30327357

Similar Datasets

Project description:Background:A-? + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible ? cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. Objective:The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and ? cell function in KPD patients compared with control participants. Methods:Kinetics of arginine and related metabolites were measured with stable isotope tracers, and insulin secretory responses to arginine and glucose were determined under euglycemic and hyperglycemic conditions in 6 KPD patients and 6 age-, gender-, and body mass index-matched control participants. Glucose potentiation of arginine-induced insulin secretion was performed in a different set of 6 KPD and 3 control participants. Results:Arginine availability was higher in KPD patients during euglycemia [53.5 ± 4.3 (mean ± SEM) compared with 40.3 ± 2.4 ?mol · kg lean body mass (LBM)-1 · h-1, P = 0.03] but declined more in response to hyperglycemia (? 10.15 ± 2.6 compared with ? 3.20 ± 1.3 ?mol · kg LBM-1 · h-1, P = 0.041). During hyperglycemia, ornithine flux was not different between groups but after an arginine bolus, plasma ornithine AUC trended higher in KPD patients (3360 ± 294 compared with 2584 ± 259 min · ?mol · L-1, P = 0.08). In both euglycemia and hyperglycemia, the first-phase insulin responses to glucose stimulation were lower in KPD patients (euglycemic insulin AUC 282 ± 108 compared with 926 ± 257 min · ?U · mL-1, P = 0.02; hyperglycemic insulin AUC 358 ± 79 compared with 866 ± 292 min · ?U · mL-1, P = 0.05), but exogenous arginine restored first-phase insulin secretion in KPD patients to the level of control participants. Conclusion:Compared with control participants, KPD patients have increased arginine availability in the euglycemic state, indicating a higher requirement. This is compromised during hyperglycemia, with an inadequate supply of arginine to sustain metabolic functions such as insulin secretion. Exogenous arginine administration restores a normal insulin secretory response.

Dataset Information

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes.

Objective

Research design and methods

Results

Conclusions

Publications

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes.

Similar Datasets

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