LADA beta-cell function shows ‘biphasic’ decline
medwireNews: Reductions in the function of islet beta cells within the pancreas occur in two distinct phases among individuals with latent autoimmune diabetes of adulthood (LADA), Chinese researchers report.
Their study of 101 LADA patients who were assessed annually for up to 8 years showed that fasting C-peptide levels – measured to reflect islet beta-cell function – initially dropped rapidly and linearly by 55.19 pmol/L per year for the first 5 years, before stabilizing to a decline of just 4.62 pmol/L per year.
This “fast followed by slow” biphasic mode resulted in beta-cell function failure – defined as a fasting C-peptide level below 75 pmol/L – rising dramatically from a rate of just 4.0% in the first year to 24.8% in the fifth year, before increasing slowly to 28.7% in the eighth year.
Being positive for autoantibodies against glutamic acid decarboxylase (GADA) was the most potent baseline characteristic predicting the progression of beta-cell function failure, with an accuracy of 82%. A GADA diagnostic threshold of 173.5 WHO units/mL conferred a sensitivity of 86% and a specificity of 85%.
When participants were divided into two groups based on GADA titer, 93.8% of the 65 patients in the low-titer group preserved their beta-cell function during follow-up, maintaining a fasting C-peptide level of at least 200 pmol/L. This compared with just 30.5% of the 36 patients in the high-titer group.
“Our results confirmed the discriminatory role of GADA titer in identifying two distinct subgroups of patients with LADA,” Zhiguang Zhou (Central South University, Changsha) and colleagues report in the Journal of Clinical Endocrinology & Metabolism.
“About 95% of our low titer patients preserved beta-cell function and most of them did not need insulin treatment during the entire follow-up.”
The study participants had diabetes for less than 2 years and were at least 30 years old at its onset. All had fasting C-peptide levels of at least 200 pmol/L or postprandial C-peptide levels of at least 400 pmol/L.
Among the 101 patients who completed follow-up, consisting of annual measurements of fasting C-peptide and post-prandial C-peptide levels, 29 “progressors” developed beta-cell function failure.
Progressors were significantly younger at LADA diagnosis, had lower baseline BMI and lower initial fasting and post-prandial C-peptide levels, as well as a higher GADA titer and greater use of insulin than patients whose beta-cell function did not fail.
Baseline GADA titer was 775.65 WHO units/mL among the participants who progressed to beta-cell function failure versus just 52.76 WHO units/mL among those who did not.
The researchers conclude: “Our findings deemed that attention should be paid to the individuals with high GADA titer, especially during the first 5 years’ duration.”
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