title: Both insulin sensitivity and insulin clearance in children and young adults with type I (insulin-dependent) diabetes vary with growth hormone concentrations and with age.
abstract: OBJECTIVE
  We measured insulin clearance rates in children and young adults with Type I (insulin-dependent) diabetes mellitus to establish their relation with insulin sensitivity and with factors such as growth hormone secretion and body mass index.
  
  
  METHODS
  We studied 46 subjects mean (range) age 14.4 (9.8-24.6) years), body mass index 21.1 (15.8-29.6) Kgm2[ using an overnight (1800-0800 hours) variable rate insulin infusion euglycaemic clamp protocol (5 mmol/l). Plasma free insulin concentrations during steady-state euglycaemia were used as an index of insulin sensitivity and insulin clearance determined as a ratio of insulin infusion rate to plasma free insulin.
  
  
  RESULTS
  During steady-state euglycaemia (0500-0730 hours), insulin sensitivity mean (SEM) plasma insulin 0.020 (0.002) mU/l[ and insulin clearance rates 19.1 (1.8) ml.kg-1.min[ varied with age non-linearly and in a reciprocal fashion to each other (cubic regression F = 4.09, p = 0.01; F = 3.55, p = 0.02, respectively). Insulin sensitivity was negatively related to BMI (r = -0.37, p = 0.011) and mean overnight growth hormone concentrations (r = -0.40, p = 0.007). Insulin clearance was only related to growth hormone concentrations (r = -0.37, p = 0.014). These relations were still evident after stepwise multiple regression analysis (potential determinants: C peptide, sex, age, puberty stage, HbA1c, duration of diabetes): insulin sensitivity r = 0.55, p < 0.001; insulin clearance r = 0.37, p < 0.02.
  
  
  CONCLUSIONS
  Insulin clearance rates vary with age in young subjects with Type I diabetes and are highest during mid-adolescence when insulin sensitivity is at its lowest. Both insulin sensitivity and insulin clearance are related to circulating growth hormone concentrations.
authors.affiliation: Department of Paediatrics, University of Oxford, John Radcliffe Hospital.
authors.forename: C L
authors.initials: CL
authors.lastname: Acerini
authors.forename: T D
authors.initials: TD
authors.lastname: Cheetham
authors.forename: J A
authors.initials: JA
authors.lastname: Edge
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use; D007328:Insulin / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D012044:Regression Analysis; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D019382:Human Growth Hormone