Islet cell antibodies and antibodies against glutamic acid decarboxylase in newly diagnosed adult-onset diabetes mellitus

Jinny A. Willis, Russell S. Scott, Laurie J. Brown, Louisa V. Forbes, Robert S. Schmidli, Paul Z. Zimmet, Ian R. MacKay, Merrill J. Rowley

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Abstract

This study aimed to determine the prevalence of antibodies against glutamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to β-cell function in adults newly-diagnosed with diabetes mellitus. β-cell function was assessed in adults aged 25-70 years newly-diagnosed with diabetes mellitus (n = 84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. β-cell function was evaluated by the true insulin (defined as immunoreactive insulin minus proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true insulin curve (normal 16 830-107 700 pmol min/l) and the sum of the 30 and 60 min incremental response (normal 285-3295 pmol/l). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were insulin deficient showing little or no true insulin release. Of the insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without insulin deficiency (P < 0.001). Seven (58%) insulin deficient subjects were ICA positive, whereas only two (3%) non-insulin deficient subjects were ICA positive (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not insulin deficient (P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both antibodies for detecting insulin deficiency was 50%. The specificity for detecting insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with diabetes mellitus as a new diagnosis are insulin deficient using our criteria. Loss of β-cell function in two thirds of individuals who are insulin deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of β-cell damage creates the potential for immune modulation to limit such damage.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalDiabetes Research and Clinical Practice
Volume33
Issue number2
DOIs
Publication statusPublished - Jul 1996

Keywords

  • Adult-onset diabetes mellitus
  • Anti-GAD
  • Insulin-treated diabetes mellitus
  • Islet cell antibodies

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