Identification of autoantibody-negative autoimmune type 2 diabetic patients.
OBJECTIVE
Islet autoimmunity has long been recognized in the pathogenesis of type 1 diabetes and is becoming increasingly acknowledged as a component in the pathogenesis of type 2 diabetes. Islet reactive T cells and autoantibodies have been demonstrated in type 1 diabetes, whereas islet autoimmunity in type 2 diabetes has been limited to islet autoantibodies. In this study, we investigated whether islet reactive T cells might also be present in type 2 diabetic patients and how islet reactive T cells correlate with β-cell function.


METHODS
Adult phenotypic type 2 diabetic patients (n = 36) were screened for islet reactive T-cell responses using cellular immunoblotting and five islet autoantibodies (islet cell antibody, GADA, insulin autoantibody, insulinoma-associated protein-2 autoantibody, and zinc transporter autoantibody).


RESULTS
We identified four subgroups of adult phenotypic type 2 diabetic patients based on their immunological status (Ab(-)T(-), Ab(+)T(-), Ab(-)T(+), and Ab(+)T(+)). The Ab(-)T(+) type 2 diabetic patients demonstrated T-cell responses similar to those of the Ab(+)T(+) type 2 diabetic patients. Data were adjusted for BMI, insulin resistance, and duration of diabetes. Significant differences (P < 0.02) were observed among groups for fasting and glucagon-stimulated C-peptide responses. T-cell responses to islet proteins were also demonstrated to fluctuate less than autoantibody responses.


CONCLUSIONS
We have identified a group of adult autoimmune phenotypic type 2 diabetic patients who are Ab(-)T(+) and thus would not be detected using autoantibody testing alone. We conclude that islet autoimmunity may be more prevalent in adult phenotypic type 2 diabetic patients than previously estimated.
Brooks-Worrell
Barbara M
BM
Department of Medicine, University of Washington, Seattle, Washington, USA. bbrooks@u.washington.edu
Reichow
Jessica L
JL
Goel
Amit
A
Ismail
Heba
H
Palmer
Jerry P
JP
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D002096:C-Peptide; C024211:islet cell antibody