Plasma levels of three proteins involved in growth hormone activity showed significant links to the controllability of type 2 diabetes in adolescents, a finding that suggests these proteins may serve as risk markers for incident type 2 diabetes and help identify kids who could benefit from aggressive preventive care.
Dr Chang Lu
“Plasma growth hormone mediators are associated with glycemic failure in youth with type 2 diabetes,” Chang Lu, MD, said at the at the recent American Diabetes Association 83rd Scientific Sessions. “Our hope is that these mediators could be biomarkers for predicting type 2 diabetes onset,” she added in an interview.
Another potential application is to “leverage these data to find predictive markers” that could identify adolescents with type 2 diabetes “at risk for particularly aggressive disease and target them for more intervention,” added Elvira M. Isganaitis, MD, senior author of the report and a pediatric endocrinologist at the Joslin Diabetes Center in Boston, Massachusetts.
Does Growth Hormone Cause Incident T2D at Puberty?
Changes in levels of growth hormone-associated peptides during puberty “could potentially explain why children with type 2 diabetes have a more aggressive course” of the disorder, added Lu, also a pediatric endocrinologist at Joslin and at Boston’s Children’s Hospital.
Puberty-associated changes in growth hormone and related peptides “could be why type 2 diabetes starts during puberty. Type 2 diabetes is almost unheard of before children reach about age 10,” said Isganaitis in an interview.
A current hypothesis is that “high levels of growth hormone is a cause of insulin resistance during puberty, but in healthy children their beta cells overcome this by making more insulin and so they do not develop diabetes,” commented Kristen J. Nadeau, MD, a pediatric endocrinologist and professor at Children’s Hospital Colorado in Denver.
“But this is a stress situation, and if someone has poor beta-cell function they may develop diabetes. The increase in growth hormone [during puberty] can unmask a physiologic and genetic predisposition” to developing type 2 diabetes, Nadeau said in an interview.
The analyses run by Lu, Isganaitis, and their co-authors used data collected in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which randomized 699 kids aged 10-17 years with type 2 diabetes to one of three antidiabetes treatment regimens and tallied the subsequent incidence of glycemic failure. The study defined the latter as either 6 months with a hemoglobin A1c level of at least 8% or need for insulin treatment.
The primary outcome showed a 39%-52% incidence of failure during 5 years of follow-up depending on the specific treatments the study participants received.
Growth Hormone Correlates of Glycemic Failure
The new analyses focused on 310 study participants from TODAY who had plasma specimens available from baseline and a second specimen obtained after 3 years of follow-up. The researchers compared the levels of three peptides that mediate growth hormone signaling at baseline and after 3 years, and assessed these changes relative to the endpoint of glycemic failure.
The results showed that an increase in insulin-like growth factor-1 significantly linked with a reduced incidence of glycemic failure and improved glycemia and beta-cell function.
In contrast, increasing plasma levels of growth hormone receptor significantly linked with an increased rate of glycemic failure, hyperglycemia, insulin resistance, and diminished beta-cell function. Also, an increase in insulin-like growth factor binding protein-1 significantly linked with glycemic failure and hyperglycemia at 36 months, and with higher insulin sensitivity at baseline. All these analyses adjusted for baseline differences in several demographic and clinical variables.
But these post-hoc analyses could not determine whether these associations resulted from, or had a causal role in, treatment failure, cautioned Lu.
Future studies should examine the relationship of growth hormone signaling and the course of glycemic control in children and adolescents with prediabetes and obesity, Lu said.
Confirming that these growth hormone-related proteins are reliable predictors of future glycemic dysfunction would open the door to studies of interventions to slow or prevent progression to type 2 diabetes in kids identified as high risk.
Potential interventions include early initiation of insulin treatment, which could help preserve beta-cell function, or treatment with a glucagon-like peptide-1 (GLP-1) agonist, a class of agents that may interact with the insulin-like growth factor-1 receptors on beta cells, Lu said.
The study received no commercial funding. Lu, Isganaitis, and Nadeau report no relevant financial relationships.
American Diabetes Association 83rd Scientific Sessions. Abstract 134-OR. Presented June 23, 2023.
Mitchel L. Zoler is a reporter with Medscape and MDedge based in the Philadelphia region. @mitchelzoler.
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