title: Insulin resistance in multiple tissues in patients with type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion therapy.
abstract: BACKGROUND
  The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls.
  
  
  METHODS
  We studied eight patients (four men and four women) with type 1 diabetes mellitus on continuous subcutaneous insulin infusion and eight healthy controls, matched for age, gender and body mass index. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with infusion of [6,6-(2) H(2)] glucose.
  
  
  RESULTS
  Endogenous glucose production did not differ in the basal state between patients and controls. However, endogenous glucose production was less suppressed during clamp conditions in patients compared with controls (64% vs 79%, p = 0.01), indicating decreased hepatic insulin sensitivity. During the clamp study, glucose disposal rate was ~38% lower in patients compared with controls (24.4 ± 2.5 vs 39.7 ± 5.6 µmol/kgLBM/min, p = 0.04). Accordingly, the rate of infusion of glucose was ~51% lower in patients (17.7 ± 2.8 vs 39.7 ± 5.7 µmol/kgLBM/min, p = 0.02). Finally, non-esterified fatty acids levels were ~2.5 times higher in patients during steady state clamp conditions (150 ± 26 vs 58 ± 4 pmol/L, p = 0.01), reflecting decreased insulin sensitivity of lipolysis.
  
  
  CONCLUSIONS
  Insulin resistance is a prominent feature of lean patients with type 1 diabetes mellitus, despite long term and stable treatment with continuous subcutaneous insulin infusion. Insulin resistance in type 1 diabetes involves both lipolysis, hepatic and peripheral glucose metabolism.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands. e.donga@lumc.nl
authors.forename: Esther
authors.initials: E
authors.lastname: Donga
authors.forename: Marieke
authors.initials: M
authors.lastname: van Dijk
authors.forename: Roel P L M
authors.initials: RP
authors.lastname: Hoogma
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D040521:Subcutaneous Tissue / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin