title: Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients.
abstract: OBJECTIVE
  Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated. The aim of this study was to investigate the effect of loss of 50% of excess weight [50% excess weight reduction (EWR)] on EGP, whole-body insulin sensitivity and the disturbed myocellular insulin-signalling pathway in ten obese insulin-treated type 2 diabetic patients.
  
  
  METHODS
  A euglycaemic-hyperinsulinaemic clamp with stable isotopes ([6,6-(2)H2]glucose and [2H5]glycerol) combined with skeletal muscle biopsies was performed during a very low energy diet (VLED; 1,883 kJ/day) on day 2 and again after 50% EWR. Oral blood glucose-lowering agents and insulin were discontinued 3 weeks prior to the VLED and at the start of the VLED, respectively.
  
  
  RESULTS
  Loss of 50% EWR (20.3+/-2.2 kg from day 2 to day of 50% EWR) normalised basal EGP and improved insulin sensitivity, especially insulin-stimulated glucose disposal (18.8+/-2.0 to 39.1+/-2.8 micromol kg fat-free mass(-1) min(-1), p=0.001). The latter was accompanied by improved insulin signalling at the level of the recently discovered protein kinase B/Akt substrates AS160 and PRAS40 along with a decrease in intramyocellular lipid (IMCL) content.
  
  
  CONCLUSIONS
  Considerable weight loss in obese, insulin-treated type 2 diabetic patients normalises basal EGP and improves insulin sensitivity resulting from an improvement in insulin signal transduction in skeletal muscle. The decrease in IMCL might contribute to this effect.
authors: Department of General Internal Medicine, C4-r-73, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands. i.m.jazet@lumc.nl
authors: I M
authors: IM
authors: Jazet
authors: G
authors: G
authors: Schaart
authors: A
authors: A
authors: Gastaldelli
authors: E
authors: E
authors: Ferrannini
authors: M K
authors: MK
authors: Hesselink
authors: P
authors: P
authors: Schrauwen
authors: J A
authors: JA
authors: Romijn
authors: J A
authors: JA
authors: Maassen
authors: H
authors: H
authors: Pijl
authors: D M
authors: DM
authors: Ouwens
authors: A E
authors: AE
authors: Meinders
mesh_terms: D001786:Blood Glucose / Q000032:analysis*; D001823:Body Composition; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy; D004038:Diet, Reducing; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000503:physiopathology; D050177:Overweight; D015398:Signal Transduction; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin