Abstract
Numerous rheological and microvascular alterations characterize the vascular pathology in patients with type 2 diabetes mellitus (T2DM). This study investigated effects of vildagliptin in comparison to glimepiride on retinal microvascular blood flow and erythrocyte deformability in T2DM.Fourty-four patients with T2DM on metformin monotherapy were included in this randomized, exploratory study over 24 weeks. Patients were randomized to receive either vildagliptin (50 mg twice daily) or glimepiride individually titrated up to 4 mg in addition to ongoing metformin treatment. Retinal microvascular blood flow (RBF) and the arteriolar wall to lumen ratio (WLR) were assessed using a laser doppler scanner. In addition, the erythrocyte elongation index (EI) was measured at different shear stresses using laserdiffractoscopy.Both treatments improved glycaemic control (p < 0.05 vs. baseline; respectively). While only slight changes in RBF and the WLR could be observed during treatment with glimepiride, vildagliptin significantly increased retinal blood flow and decreased the arterial WLR (p < 0.05 vs. baseline respectively). The EI increased during both treatments over a wide range of applied shear stresses (p < 0.05 vs. baseline). An inverse correlation could be observed between improved glycaemic control (HbA1c) and EI (r = −0.524; p < 0.0001) but not with the changes in retinal microvascular measurements.Our results suggest that vildagliptin might exert beneficial effects on retinal microvascular blood flow beyond glucose control. In contrast, the improvement in erythrocyte deformability observed in both treatment groups, seems to be a correlate of improved glycaemic control.
Highlights
Type 2 diabetes mellitus (T2DM) is associated with numerous vascular and hemorheological abnormalities which merge together in an unproportional high risk for the development of micro- and macrovascular complications like retinopathy, nephropathy, neuropathy, or cardiovascular disease
Patients in the vildagliptin group were found to have a slightly longer duration of T2DM compared to the patients in the glimepiride group
In patients treated with vildagliptin a reduction in body weight and an increase in adiponectin levels could be observed, while patients treated with glimepiride increased body weight with no change in adiponectin levels
Summary
Type 2 diabetes mellitus (T2DM) is associated with numerous vascular and hemorheological abnormalities which merge together in an unproportional high risk for the development of micro- and macrovascular complications like retinopathy, nephropathy, neuropathy, or cardiovascular disease. The assessment of retinal microvascular architecture and the investigation of retinal arterial blood flow allows to detect early vascular abnormalities in Recently, dipeptidyl-peptidase IV (DPP-IV) inhibitors have been introduced in the treatment of T2DM. Treatment with DPP-IV inhibitors was found to improve myocardial and endothelial function, to improve blood lipids, to lower blood pressure and to improve markers of renal function [9,10,11,12,13,14,15,16]. In vitro studies demonstrated that DPP-IV is expressed in endothelial cells, and the inhibition of DPP-IV reduced the microvascular tone through direct mediation of the nitric oxide system [17]. It seems conceivable that glucoseindependent effects of DPP-IV inhibition might be mediated through GLP-1 receptor signalling and /or direct inhibition of the enzyme DPP-IV in vascular, renal, or retinal cells. Based on the different mode of action, these effects might not be applicable to other antidiabetic treatments like K-ATP-channel blocker such as sulfonylureas
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