Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

Abstract

In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 ± 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 ± 1.3 years GHT (0.22 ± 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children.

Effects on Growth and Metabolism of Growth Hormone Treatment for 3 Years in 36 Children with Prader-Willi Syndrome

“…At baseline, 23.8% of our children had impaired glucose tolerance and we found 0% after 3 years of hGH therapy. In this study, fasting glucose, 2-hour glucose and HbA1c levels remained within the normal range in accordance with earlier results [13,14,17,25]. …”

“…The homeostasis model assessment index of insulin resistance (HOMA-IR) was computed as glycemia (mmol/l)·insulinemia (ìIU/ml)/22.5 [24]. Fasting hyperinsulinemia was defined as levels >15 µU/ml [25]. Insulin resistance was defined as HOMA-IR greater than 3.16 [26].…”

Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome

“…Previous investigations suggested a lower degree of insulin resistance in PWS when compared to nonsyndromic obesity [24, 25]. However, in our study, either GH therapy [26] or obesity [27] could account for comparable insulin concentrations in those with PWS and obese controls. Considering the lack of hypoglycemia experienced by the children in the present study and the increase in glucose IP (see below), the lack of an increase in glucagon is normal [28].…”

The Italian National Survey for Prader–Willi syndrome: An epidemiologic study

“…Therefore, we would recommend GH therapy for a greater percentage of Italian PWS patients and at an earlier age, taking into consideration both growth pattern and body composition abnormalities. Nevertheless, considering the limited evidence on GH treatment in younger children with PWS, the effects of GH administration should be closely monitored to avoid significant adverse effects [Crinò et al, 2007] and sudden deaths. In our study, 12% of patients under 18 years of age discontinued GH administration.…”