‘Early therapeutic window’ highlighted for LADA
medwireNews: Optimal glycemic control during the first years after a latent autoimmune diabetes of adulthood (LADA) diagnosis could prevent people’s microvascular complication risk from equaling that seen in those with type 2 diabetes, shows an analysis of the UKPDS.
The investigators found that, during the first 9 years after diagnosis, people with LADA had a 48% lower risk for developing any microvascular complication than those with type 2 diabetes.
Ernesto Maddaloni (Sapienza University of Rome, Italy) and co-researchers suggest that people with LADA could have a faster progression to overt disease, resulting in a shorter period of undetected detrimental hyperglycemia prior to diagnosis.
In line with this, people with two autoantibodies had the largest reduction in risk for microvascular complications, by 77% relative to people with type 2 diabetes, whereas those with just one autoantibody, suggesting a more gradual onset, had a 39% reduced risk.
However, from 9 years after diagnosis, the situation reversed and people with LADA were 47% more likely than those with type 2 diabetes to be diagnosed with microvascular complications, and their total rates for the median 17.3-year follow-up were slightly higher, at 15.8 versus 14.2 per 1000 person–years.
This “probably reflects their 0.5% absolute higher baseline HbA1c [glycated hemoglobin] values and approximately 10% absolute lower median baseline [steady-state beta-cell function], which could have affected the effectiveness of their glucose-lowering therapies,” write Maddaloni and team in The Lancet Diabetes & Endocrinology.
Indeed, average HbA1c during the first 9 years after diagnosis accounted for the entirety of the increased microvascular risk in people with LADA beyond this point; adjusting for this variable reduced the hazard ratio from 1.47 to 0.99.
In total, the UKPDS enrolled 5102 people with newly diagnosed type 2 diabetes, but autoantibody tests in 5028 of these participants identified 564 (11%) who actually had LADA. These people were younger, leaner, and had fewer cardiovascular risk factors than those with type 2 diabetes, and the investigators previously reported that they progressed to insulin dependence significantly faster.
Writing in a linked commentary, Didac Mauricio (Autonomous University of Barcelona, Spain) argues for routine screening for autoantibodies at the point of diabetes diagnosis in adults, so that insulin can be started promptly.
Delayed diagnosis in people with LADA leads to delayed initiation of insulin, he points out, and as shown in the current analysis, the resulting prolonged period of poor glycemic control results in an increased risk for microvascular complications.
He believes that routine autoantibody screening “is probably cost-effective, and maybe even cost-saving, if this strategy contributes to more informed and timely decisions taken early in the course of the disease.”
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