title: 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.
authors.affiliation: Paediatric and Autoimmune Endocrine Diseases Unit, Bambino Gesù Children's Hospital, Research Institute, Roma, Italy. crino@opbg.net
authors.forename: A
authors.initials: A
authors.lastname: Crinò
authors.forename: G
authors.initials: G
authors.lastname: Di Giorgio
authors.forename: M
authors.initials: M
authors.lastname: Manco
authors.forename: G
authors.initials: G
authors.lastname: Grugni
authors.forename: A
authors.initials: A
authors.lastname: Maggioni
mesh_terms: D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006305:Health Status Indicators; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011627:Puberty / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D001786:Blood Glucose; D019382:Human Growth Hormone; D005947:Glucose