title: Glucose turnover after replacement of usual therapy by insulin in insulin-naive type 2 diabetes subjects.
abstract: BACKGROUND
  Discontinuation of anti-hyperglycemic oral agents and initiation of insulin is recommended in certain clinical situations for inpatients with type 2 diabetes (T2D). The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated.
  
  
  OBJECTIVE
  Our objective was to investigate alterations in glucose turnover after acute withdrawal of noninsulin therapy.
  
  
  METHODS
  This was a randomized crossover study at a clinical research facility.
  
  
  METHODS
  Participants included 12 insulin-naive subjects with T2D.
  
  
  METHODS
  Subjects attended two 24-hour visits. Standard therapy was discontinued and replaced by closed-loop insulin delivery during the intervention visit. Usual anti-hyperglycemic therapy was continued during the control visit. Systemic glucose appearance (Ra) and glucose disposal (Rd) were measured using a tracer dilution technique with iv [6,6-(2)H2]glucose.
  
  
  RESULTS
  Plasma glucose profiles during both visits were comparable (P = .48). Glucose Ra increased during the day (21.4 [19.5, 23.5] vs 18.6 [17.0, 21.6) μmol/kg/min, P = .019) and decreased overnight (9.7 [8.5, 11.4] vs 11.6 [10.3, 12.9] μmol/kg/min, P = .004) when the usual therapy was discontinued and replaced with insulin. Increased daytime glucose Rd (21.2 [19.4, 23.9] vs 18.8 [18.3, 21.7] μmol/kg/min, P = .002) and decreased overnight Rd (10.4 [9.1, 12.0] vs 11.8 [10.7, 13.7] μmol/kg/min, P = .005) were observed when the usual therapy was discontinued, whereas daytime peripheral insulin sensitivity was reduced (47.8 [24.8, 66.1] vs 62.5 [34.8, 75.8] nmol/kg/min per pmol/L, P = .034).
  
  
  CONCLUSIONS
  In T2D, acute discontinuation of anti-hyperglycemic therapy and replacement with insulin increases postprandial Ra and reduces peripheral insulin sensitivity. Insulin dose initiation may need to compensate for these alterations.
authors.affiliation: Metabolic Research Laboratories (H.T., K.K., L.L., K.C., D.E., J.M.A., M.N., M.E.W., M.L.E., R.H.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, and Department of Paediatrics (D.E., J.M.A., M.E.W., R.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Centre for Intelligent Machines (A.H.), McGill University, Montreal, Quebec H3A 0E9, Canada; and Postgraduate Medical School (N.C.J., A.M.U.), University of Surrey, Guildford GU2 7TE, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Thabit
authors.forename: K
authors.initials: K
authors.lastname: Kumareswaran
authors.forename: A
authors.initials: A
authors.lastname: Haidar
authors.forename: L
authors.initials: L
authors.lastname: Leelarathna
authors.forename: K
authors.initials: K
authors.lastname: Caldwell
authors.forename: D
authors.initials: D
authors.lastname: Elleri
authors.forename: J M
authors.initials: JM
authors.lastname: Allen
authors.forename: M
authors.initials: M
authors.lastname: Nodale
authors.forename: M E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: N C
authors.initials: NC
authors.lastname: Jackson
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007332:Insulin Infusion Systems; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin