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Monitoring for diabetes warranted before, after childhood GH treatment
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Children and adolescents who are treated with growth hormone have a higher incidence of type 2 diabetes compared with the general population. This finding prompted researchers for a recent study to recommend careful glucose monitoring before and after growth hormone treatment in patients with risk factors for diabetes.
“Although the incidence of type 2 diabetes is generally low in childhood and has not been well defined in children with growth disorders, incident cases of type 2 diabetes have been reported in observational studies of GH-treated children,” members of the GeNeSIS International Advisory Board wrote in The Journal of Clinical Endocrinology & Metabolism.
Comparing prevalence of diabetes
In a new study, researchers analyzed the prevalence and incidence of diabetes in more than 11,000 GH-treated patients in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS), a multinational, observational study of children with growth orders. For this analysis, researchers focused on data from children in the US. They compared those data with those from a contemporary population of people aged younger than 20 years in the US SEARCH for Diabetes in Youth study.
According to the results, the prevalence of type 1 diabetes at baseline was higher among GH-treated children compared with the general population. Prevalence of diabetes was 4.92 per 1,000 people aged 0 to 9 years in the GeNeSIS cohort vs. 1.03 per 1,000 people in the general population cohort. The prevalence was also higher for children aged 10 to 19 years: 7.33 per 1,000 people in GeNeSIS vs. 2.99 per 1,000 people in the general population. Type 2 diabetes was not reported in any children before initiation of GH treatment, the researchers said.
During a median follow-up of 1.8 years, the researchers calculated a standardized incidence ratio of 1.4 for type 1 diabetes and 8.5 for type 2 diabetes in the US GeNeSIS cohort. For the entire cohort, including patients living outside of the US, the standardized incidence ratio was also 1.4 for type 1 diabetes and 6.5 for type 2 diabetes.
Eleven patients developed type 2 diabetes, 10 of whom had risk factors for the disease, including pre-existing insulin resistance, pre-existing impaired glucose tolerance, baseline diagnoses associated with increased risk for insulin resistance and cancer. Of these patients, four experienced resolution of hyperglycemia after discontinuation of GH treatment and three experienced resolution despite continuation of treatment.
Future directions
Although higher than the general population, the researchers concluded that the “incidence of type 2 diabetes during GH treatment remains low, with approximately one case for every 3,000 person-years of treatment.”
Periodic monitoring of glucose metabolism is recommended on most GH product labeling, according to the researchers. However, these data indicate that most patients who develop type 2 diabetes while taking GH also have pre-existing risk factors for impairment of glucose homeostasis.
“Therefore, particular attention to glucose metabolism, both before initiation of and during GH treatment, appears warranted in such patients, including advice regarding preventive lifestyle measures,” the researchers wrote.
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Disclosure: The study was sponsored by Eli Lilly.
This study doesn’t add anything to what’s already known in the general literature about growth hormone and diabetes. The researchers’ results, for example, do not indicate that GH is the cause of type 2 diabetes. If you look at the patients, 11 of whom developed diabetes, 10 had risk factors and, therefore, could likely have developed the disease anyway. Certainly, one could argue that GH is a trigger; yet, the same can be said for many factors, such as inactivity, diet, genetics, vitamin D deficiency, mother’s diet during pregnancy, cigarette smoke, inhaled steroids and more. However, the main message that the researchers put forth in their conclusion is not that GH causes diabetes, but that one should monitor for diabetes in patients using GH, which endocrinologists have been doing for the last 30 to 40 years anyway.
They also reported that they compared their group to a random population as opposed to a comparable group who had risk factors [for diabetes]. They should have compared their group to those who are prone to diabetes, such as those with SGA or Prader-Willi syndrome — a factor that further skewed the data.
In addition, the researchers discussed using a glucose tolerance test as a diagnostic measure for diabetes. Two patients in the study had abnormal oral glucose tolerance tests, with results of 207 mg/dL and 219 mg/dL. These numbers, however, are very close to the diagnostic cutoff of 200 mg/dL. Therefore, had they done the test on a different day, the results may have been lower, indicating that the patients may not have actually had diabetes.
Further, among the 11 patients allegedly with type 2 diabetes, one had insulin resistance and one had pre-existing impaired glucose tolerance before initiation of GH treatment. Five patients were also at increased risk for diabetes. This raises the question: Should you give the patient GH in the first place if they’re at higher risk? One could argue that the results would have been different had they not initiated GH treatment in these children.
The researchers also reported that the hyperglycemia observed in seven of the 11 patients eventually resolved. Four of these patients were treated and three were untreated. These results raise several questions: Did they actually have diabetes? Were they in a prediabetic state? None experienced any permanency, but they were also not followed for very long, so one cannot draw firm conclusions from these results.
Moreover, the statistics regarding the incidence of diabetes cited in the study require closer inspection. Current statistics indicate that around 1 in 10 to 1 in 12 US people have diabetes. The researchers, however, suggest that 1 in 1,000 people have diabetes. The numbers they have are actually lower than the general population to whom they compared their patients.
Finally, in my experience, of the thousands of patients whom I’ve seen on GH, none have had type 2 diabetes. When I informally polled my colleagues at at a major medical school as well as endocrinologists at a large HMO, they also reported not seeing any cases of type 2 diabetes among their patients treated with GH. Although this information isn’t evidence-based medicine, it is the personal experience of our community.
– Norman Lavin, MD, PhD
Professor of
Pediatric Endocrinology and Metabolism, UCLA
Director of Education in
Endocrinology, UCLA
Director, Diabetes Care Center Encino-Tarzana
Disclosure: Dr. Lavin reports no relevant financial disclosures.
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