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- Is there any difference in antibody profile of patients with LADA and T1DM?
The presence of multiple (≥2) islet autoantibodies (ICA, GAD65, IA-2,
IAA, and ZnT8) at diagnosis is usually a feature of T1DM, while patients
with LADA commonly have single autoantibody (ICA or GAD65) at diag-
nosis. Approximately 90 % of individuals with T1DM who are ICA positive,
are also positive for anti-GAD 65 antibody, whereas only <20 % of individu-
als with LADA who have ICA positivity have anti-GAD 65 antibody. In
addition, IA-2 and IAA are more commonly present in patients with T1DM
than in LADA.- Why is β-cell destruction tardy in LADA?
The immunological mechanisms implicated in β-cell destruction in patients
with LADA and T1DM are not well understood. However, certain differences
in islet antigenicity and T-cell response to islet proteins (of molecular weight
65–90 and 21–38 kDa) may explain the slow destruction of β-cells in patients
with LADA as compared to T1DM.- What are the predictors of β-cell failure in LADA?
The presence of multiple islet autoantibodies and higher antibody titer predict
the progression of β-cell failure in patients with LADA. Patients with the pres-
ence of ≥2 antibodies (ICAs, GADAs, IA-2As, or IAA) at diagnosis have
severe impairment in β-cell function over 5 years, whereas those who are only
ICA or GAD65 positive at diagnosis have decline in β-cell function by 12 years.
However, those who have only IA-2A positivity at diagnosis do not have decline
in β-cell function over 12 years. Further, patients who are ICA negative at diag-
nosis and develop ICA later have a progressive decline in fasting plasma
C-peptide, thereafter. ICA positivity has a positive predictive value (PPV) of
74 %, whereas GAD65 and/or IA-2As positivity have PPV of 47 % to predict
β-cell failure. Further, high GAD65 titers (41.4 U/ml) and/or IA-2As index
(>2.7) predict a complete β-cell failure, whereas low GAD65 titer predicts
slowly progressive β-cell failure.- How to differentiate LADA from type 2 DM?
Age of onset of diabetes >30 years, lean body habitus (BMI<25 Kg/m^2 ), acute
onset of osmotic symptoms (e.g., polydypsia/polyuria/weight loss), the pres-
ence of autoimmune disorders in the patient or family, the absence of family
history of T2DM, high fasting plasma glucose, and early failure to oral antidia-
betic drugs should raise a suspicion of LADA. On the contrary, patients with12 Diabetes in the Young