ADA: HbA1c May Predict Treatment Failure in Diabetic Kids

Kenneth Copeland, MD, of the University of Oklahoma Health Sciences Center, and colleagues reported that in a subanalyses of the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study, both factors remained significant predictors of treatment failure in multivariate analyses (P<0.0001 and P=0.05). "Baseline A1c is the best predictor of treatment failure, even if it's within the non-diabetic range," Copeland said.

In the TODAY trial, published in April in the New England Journal of Medicine, almost half of 699 youth, ages 10 to 17, with type 2 diabetes eventually failed treatment. They'd been randomized to one of three interventions: metformin alone, metformin plus lifestyle intervention, or metformin plus rosiglitazone (Avandia).

In TODAY, treatment failure was defined as a "persistently elevated HbA1c level (≥8%) over a period of 6 months, or persistent metabolic decompensation." The latter was further defined as either the "inability to wean the participant from insulin within 3 months after its initiation for decompensation or the occurrence of a second episode of decompensation within 3 months after discontinuation of insulin."

Over a mean follow-up of 4 years, treatment failure rates were 52%, 47%, and 39%, respectively.

To assess factors that may predict treatment failure, Copeland and colleagues evaluated 172 patients who maintained glycemic control for 48 months and compared them with 305 patients who failed to maintain control during that time.

At baseline, they saw that blacks and patients who were depressed were more likely to fail therapy (P=0.03 and P=0.02, respectively), and HbA1c levels and insulin sensitivity were significant predictors of treatment failure (P<0.0001 for both). But in multivariate analyses, only HbA1c levels and insulin secretion were significant predictors of treatment failure.

The researchers also found that the rate of rise in A1c was the only longitudinal factor associated with treatment failure, which "may suggest the need to intensify treatment early," Copeland said. "Even if the A1c is in the non-diabetic range, the higher it was, the more likely they were to fail."

In a second subanalysis of TODAY Study data, Neil White, MD, of Washington University in St. Louis, and colleagues found that children with type 2 diabetes had early signs of cardiovascular and kidney disease.

Just over a third (34%) had hypertension, and 10% to 30% had dyslipidemia, White reported. They also found that 17% of kids had microalbuminuria, an early marker of renal disease, and 14% had retinopathy.

In terms of cardiovascular risks, White and colleagues found that while there were no differences between groups in terms of left atrial diameter or left ventricular mass on echocardiography, a very high percentage of these were above the normal median. "These children have large hearts, and that's suggestive of future risk for cardiovascular disease," White said.

Copeland took it a step further, calling for better efforts aimed at prevention. "The time to intervene with major lifestyle changes is not after diabetes has happened. Our focus needs to be on the kids who are at risk before they develop diabetes," he said.

• Glycated hemoglobin (HbA1c) levels and insulin secretion may forecast how children with type 2 diabetes will respond to therapy.
• Note that children with type 2 diabetes had early signs of cardiovascular and kidney disease: over a third (34%) had hypertension, 10% to 30% had dyslipidemia, and 17% of kids had microalbuminuria.
• These studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Copeland K, et al "Determinants of durable glycemic control in the TODAY trial" ADA 2012. White NH, et al "Burden of comorbidities in youth in the TODAY trial" ADA 2012.