ABSTRACT
BACKGROUND: The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. MATERIAL AND METHODS: Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. RESULTS: Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p < 0.01). PRH% was lower than in the reference group after 7-9 years ( p < 0.01), and lower than baseline after 24-29 years of diabetes ( p < 0.05). All but one patient developed retinopathy and the first signs were found after 10 years of diabetes. CONCLUSIONS: Functional disturbances in total skin microcirculation were observed after seven years in patients with type 1 diabetes and preceded diabetic complications such as retinopathy.
Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/etiology , Microcirculation , Microvessels/physiopathology , Skin/blood supply , Adult , Blood Flow Velocity , Case-Control Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/physiopathology , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/etiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/etiology , Disease Progression , Female , Humans , Laser-Doppler Flowmetry , Longitudinal Studies , Male , Middle Aged , Ophthalmoscopy , Prospective Studies , Regional Blood Flow , Risk Factors , Skin Temperature , Time Factors , Young AdultABSTRACT
INTRODUCTION: Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia. MATERIALS AND METHODS: Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured. RESULTS: During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001). CONCLUSIONS: Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.