title: Features of hepatic and skeletal muscle insulin resistance unique to type 1 diabetes.
abstract: BACKGROUND
  Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control.
  
  
  OBJECTIVE
  We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration.
  
  
  METHODS
  Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose.
  
  
  RESULTS
  Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages.
  
  
  CONCLUSIONS
  Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, P.O. Box 6511, MS 8106, Aurora, Colorado 80045, USA. bryan.bergman@ucdenver.edu
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
authors.forename: David
authors.initials: D
authors.lastname: Howard
authors.forename: Irene E
authors.initials: IE
authors.lastname: Schauer
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D050154:Adiposity; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004032:Diet; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin