title: Atorvastatin administration is associated with dose-related changes in IGF bioavailability.
abstract: OBJECTIVE
  IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.
  
  
  METHODS
  We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (S.D.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).
  
  
  RESULTS
  Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: -3 (-21 to 14) ng/ml; IGF2: -23 (-65 to 18) ng/ml and IGFBP3: -0.34 (-0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant -0.41 (-0.69 to 0.13, P=0.004).
  
  
  CONCLUSIONS
  IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.
authors: Salford Royal Hospital NHS Foundation Trust, The University of Manchester, Salford, UK. ram.narayanan@manchester.ac.uk
authors: Ram P
authors: RP
authors: Narayanan
authors: Matthew
authors: M
authors: Gittins
authors: Kirk W
authors: KW
authors: Siddals
authors: Robert L
authors: RL
authors: Oliver
authors: Julie E
authors: JE
authors: Hudson
authors: Anne
authors: A
authors: White
authors: Paul
authors: P
authors: Durrington
authors: Robert R
authors: RR
authors: Davies
authors: Martin K
authors: MK
authors: Rutter
authors: J Martin
authors: JM
authors: Gibson
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001682:Biological Availability; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D011758:Pyrroles; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000069059:Atorvastatin