medwireNews: Research shows that insulin sensitivity improves during the first 5 years after stopping long-term recombinant human growth hormone (rhGH), despite an increase in fat mass, in young adults born small for gestational age (SGA).

In a commentary accompanying the study in The Lancet Diabetes & Endocrinology, Nicholas Tritos (Massachusetts General Hospital, Boston, USA) describes the data as “reassuring”.

He notes that being born SGA is itself a risk factor for later metabolic complications. “As a corollary, establishing long-term metabolic outcomes in adults who were born small for gestational age and received growth hormone therapy in childhood is important”, he says.

The study involved 199 patients who had an average birthweight standard deviation score (SDS) of –2.3 and birth length SDS of –3.2. They received rhGH for persistent short stature from an average age of 6.4 years (height SDS of –3.0), taking it for an average duration of 10.0 years and achieving an adult height SDS of –1.6.

Manouk van der Steen (Erasmus University Medical Center, Rotterdam, Netherlands) and study co-authors monitored the patients for 5 years after they stopped taking rhGH, during which period overall fat mass, trunk fat and limb fat steadily and significantly increased. For example, total fat mass rose from an average of 10.73 to 16.12 kg. Conversely, age-adjusted lean body mass declined from 46.81 to 30.42 kg.

The researchers say that these changes are consistent with the expected effects of withdrawing rhGH treatment, reflecting “the loss of the lipolytic characteristics of growth hormone”.

Indeed, at 5 years after stopping treatment, the patients’ fat mass measures were in line with those of age-matched controls who had never received rhGH, including 51 born SGA with persistent short stature, 92 SGA patients with spontaneous catch-up growth and 142 individuals with an age-appropriate birth length.

The 5-year lean body mass of rhGH-treated SGA patients was similar to that of untreated SGA patients with persistent short stature, but significantly lower than that of the other two control groups.

Despite the increases in fat mass, patients’ metabolic indices improved significantly, until they were similar to or better than those of the control groups, with all changes occurring during the first 6 months after stopping treatment.

Insulin sensitivity improved from 4.14 to 6.30 mU/L, glucose effectiveness from 0.017 to 0.019 mg/dL and acute insulin response from 597.63 to 480.12 mU/L. Also, the disposition index (a measure of β-cell function) improved from 2483.94 to 3090.30.

In his commentary, Tritos concludes that the study findings “not only support the metabolic safety of growth hormone in patients born small for gestational age but also affirm the importance of careful monitoring of patients treated with growth hormone.”

By Eleanor McDermid

Lancet Diabetes Endocrinol 2017; Advance online publication

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