title: Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency.
abstract: GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children.
  
  
  
  In 48 GHD children, at baseline and after 12 and 24months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUCCpep) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUCINS), Homa-β, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters.
  
  
  
  At baseline GHD children showed a significant lower AUCCpep (p=0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0.307, p=0.016) and AUCCpep (beta 0.379, p=0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12months an increase in Homa-β (p<0.001), fasting C-peptide (p=0.002) and AUCCpep (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p=0.001) and AUCCpep (beta 0.880, p<0.001) were independently correlated with IGF-I SDS.
  
  
  
  C-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children.
authors.affiliation: Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ciresi
authors.affiliation: Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Cicciò
authors.affiliation: Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Radellini
authors.affiliation: Section of Cardio-Respiratory and Endocrine-Metabolic Diseases, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. Electronic address: carla.giordano@unipa.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
mesh_terms: D019540:Area Under Curve; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005215:Fasting; D005260:Female; D005934:Glucagon; D005951:Glucose Tolerance Test; D006728:Hormones; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D011446:Prospective Studies
chemical_list: D002096:C-Peptide; D006728:Hormones; C583557:IGF1 protein, human; D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005934:Glucagon
keywords: C-peptide; Glucose metabolism; Growth hormone treatment; Insulin secretion