Diabetes, Vol 35, Issue 8 894-898, Copyright © 1986 by American Diabetes Association
Are insulin autoantibodies markers for insulin-dependent diabetes mellitus?
MA Atkinson, NK Maclaren, WJ Riley, WE Winter, DD Fisk and RP Spillar
Recent studies have shown that insulin autoantibodies occur in patients
with newly diagnosed insulin-dependent diabetes mellitus (IDDM) before
exogenous insulin treatment. Our study was designed to test the hypothesis
that insulin autoantibodies, like cytoplasmic islet cell antibodies (ICAs),
can identify individuals with ongoing autoimmune beta-cell destruction and
increased risk of IDDM development. Insulin autoantibodies detected by use
of a radioligand-binding assay were found in 1.4% of normal controls, 4% of
first-degree relatives of IDDM patients, and in 37% of newly diagnosed IDDM
patients. A strong positive correlation between insulin autoantibodies and
ICAs was observed. HLA typing of insulin-autoantibody-positive first-degree
relatives of IDDM patients, as well as in the general population, revealed
a strong association with HLA-DR3 and/or-DR4, suggesting that insulin
autoantibodies are restricted to persons genetically susceptible to IDDM.
In an ongoing study of beta-cell function in ICA-positive nondiabetic
individuals, the additional presence of insulin autoantibodies
significantly increased the likelihood of beta-cell dysfunction. After
intravenous glucose stimulation, insulinopenia was present in 70% of ICA
and insulin-autoantibody-positive individuals in contrast to only 23% of
ICA-positive, insulin-autoantibody-negative persons. These data document a
significant association between insulin autoantibodies and ICAs and support
the contention that insulin autoantibodies, like ICAs, are markers of
ongoing beta-cell destruction.