Elsevier

The Lancet

Volume 355, Issue 9204, 19 February 2000, Pages 610-613
The Lancet

Articles
Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment

https://doi.org/10.1016/S0140-6736(99)04055-6Get rights and content

Summary

Background

Growth hormone (GH) contributes to insulin resistance, but whether children treated with GH are at increased risk of diabetes has not been established. We undertook a retrospective analysis of data from an international pharmacoepidemiological survey of children treated with GH to find out the incidence of impaired glucose tolerance and types 1 and 2 diabetes mellitus.

Methods

Reports to the survey of abnormal glucose metabolism were investigated and classified. The incidence and age-distribution of type 1 diabetes were compared with values from a model of reference data. The incidence of type 2 diabetes was compared with data from two reports of children not treated with GH.

Findings

85 (0·36%) of 23 333 children were reported with abnormal glucose metabolism. After investigation, 43 had confirmed glucose disorders (11 with type 1 diabetes, 18 with type 2 diabetes, and 14 with impaired glucose tolerance). The incidence and age at diagnosis of type 1 diabetes in children treated with GH did not differ from expected values. The incidence of type 2 diabetes was 34·4 cases per 100 000 years of GH treatment which was six-fold higher than reported in children not treated with GH. Type 2 diabetes did not resolve after GH therapy was stopped.

Interpretation

GH treatment did not affect the incidence of type 1 diabetes mellitus in any age group. We postulate that the higher than expected incidence of type 2 diabetes mellitus with GH treatment may be an acceleration of the disorder in predisposed individuals.

Introduction

Growth hormone (GH) contributes to insulin resistance but few studies have examined whether there is a relation in children between GH therapy and diabetes mellitus. In a retrospective study of nearly 2000 Japanese children who had received GH treatment for at least 6 months, only three were found to have glucose intolerance.1 Based on the limited information available in 1993, the European Society of Paediatric Endocrinology issued a statement that diabetes mellitus is rare among GH-treated children, with a prevalence that did not seem to differ from that of the population.2

Pharmacia and Upjohn International Growth Study (KIGS) is a large international pharmacoepidemiological survey principally designed to monitor efficacy and safety of GH therapy in children and adolescents. We analysed the database to determine the incidence of type 1 and 2 diabetes and impaired glucose tolerance (IGT) in this population.

Section snippets

Methods

We investigated 85 reports to the KIGS database between 1987 and 1997 of diabetes mellitus, abnormal glucose tolerance, and hyperglycaemia. The clinician responsible for the patient was sent a detailed questionnaire to define the diagnosis. We recorded details of the date of diagnosis, presenting symptoms, family history of diabetes (at least one first-degree relative with the same type of diabetes), blood tests (measurements of antibodies, oral glucose-tolerance test) and risk factors for

Results

The age, sex, and diagnoses of the patients are shown in table 1. The total number of years of GH treatment was 52 375. 11 433 (49%) children had received more than 3 years of GH therapy.

Of the 85 reports of abnormal glucose tolerance, 42 were excluded because they did not meet the criteria for diagnosis of type 1 or type 2 diabetes, or IGT. The clinical and demographic details of the 43 (0·18%) children who developed type 1 or type 2 diabetes mellitus, or IGT during GH therapy are shown in

Discussion

We found that the incidence of type 1 diabetes mellitus in children and adolescents treated with GH therapy was not higher than the expected incidence in the population. It is difficult to compare our data with that from the National Cooperative Growth Study14 of GH treated children in the USA since this study did not distinguish between the different types of diabetes mellitus and only assessed patients during the period that recombinant GH was given, which excludes potential effects on

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