
doi: 10.1530/eje-12-0844
pmid: 23333902
ObjectiveIGF 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.Design and methodsWe 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).ResultsAtorvastatin 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).ConclusionIGF1, 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.
Male, Diabetes Mellitus, Type 2/ blood/drug therapy, Type 2/ blood/drug therapy, Biological Availability, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Insulin-Like Growth Factor I/ metabolism, Dose-Response Relationship, Double-Blind Method, Heptanoic Acids/ administration & dosage, Insulin-Like Growth Factor II, Diabetes Mellitus, Atorvastatin, Humans, Pyrroles, Insulin-Like Growth Factor I, Aged, Dose-Response Relationship, Drug, Middle Aged, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 1/ blood, Insulin-Like Growth Factor Binding Protein 3, Diabetes Mellitus, Type 2, Insulin-Like Growth Factor Binding Protein 3/ blood, Insulin-Like Growth Factor II/ metabolism, Heptanoic Acids, Female, Drug, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrroles/ administration & dosage
Male, Diabetes Mellitus, Type 2/ blood/drug therapy, Type 2/ blood/drug therapy, Biological Availability, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Insulin-Like Growth Factor I/ metabolism, Dose-Response Relationship, Double-Blind Method, Heptanoic Acids/ administration & dosage, Insulin-Like Growth Factor II, Diabetes Mellitus, Atorvastatin, Humans, Pyrroles, Insulin-Like Growth Factor I, Aged, Dose-Response Relationship, Drug, Middle Aged, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 1/ blood, Insulin-Like Growth Factor Binding Protein 3, Diabetes Mellitus, Type 2, Insulin-Like Growth Factor Binding Protein 3/ blood, Insulin-Like Growth Factor II/ metabolism, Heptanoic Acids, Female, Drug, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrroles/ administration & dosage
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