Incidence of Diabetes Mellitus and Evolution of Glucose Parameters in Growth Hormone–Deficient Subjects During Growth Hormone Replacement Therapy

Abstract

OBJECTIVEGrowth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA1c in adult patients with GH deficiency.RESEARCH DESIGN AND METHODSA total of 5,143 GH-deficient patients (male 49.9%; mean age ± SD, 49 ± 13 years; BMI 29.1 ± 5.9 kg/m2) were analyzed. Mean observation period was 3.9 years (range 0.01–13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region.RESULTSPatients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient-years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11–5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 ± 0.9 mg/dL to 89.5 ± 0.8 mg/dL (0.70 mg/dL/year) and HbA1c increased from 4.74 ± 0.04% to 5.09 ± 0.13% (0.036%/year) after 6 years of GHRT.CONCLUSIONSDiabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients.

Efficacy and safety of growth hormone replacement therapy in Japanese adults with growth hormone deficiency: a post-marketing observational study

“…These characteristics may have contributed to the development of diabetes mellitus during GH replacement, as previously suggested [44,45]. Half of the patients who developed diabetes mellitus had high IGF-I SD scores in our study.…”

Safety and effectiveness of long-term growth hormone therapy in Japanese patients with adult growth hormone deficiency: a postmarketing, multicenter, observational study

“…This incidence is similar to that of the general Japanese population in studies reported by Waki et al and Noda et al [27,28] and also to the results from overseas studies on GH treatment in AGHD patients [29][30][31]. Furthermore, Hartman et al reported that the incidence of diabetes mellitus in AGHD patients receiving GH treatment was <2%, which was similar to that in AGHD patients not receiving GH treatment [32].…”

Predictors of Insulin-Like Growth Factor-I Responses to Growth Hormone Replacement in Young Adults with Growth Hormone Deficiency

“…Direct effects of short-term GH therapy on insulin sensitivity may explain our findings of small increases in HbA1c during replacement [37]. Long-term improvements in the body composition are reported to reverse the effects on insulin sensitivity; however, these findings are not universal [38,39]. Our findings of consistent improvements in the QoL-AGHDA scores at 1 and 2 years on replacement extend a previous report [16] and support the beneficial effects of GH replacement on QoL in young adults.…”