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Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus.

ABSTRACT: BACKGROUND:This uncontrolled open label study evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i): sitagliptin and vildagliptin on augmentation index standardized for 75 beats per minute (cAiX@75), blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) in patients with type 2 diabetes mellitus (T2DM). METHODS:Fifty-one well-regulated T2DM patients were randomly assigned to either sitagliptin or vildagliptin (100 mg/day) for 3 months continuing their previous treatment. Lipid profile, cAiX@75, hsCRP, glycated hemoglobin (HbA1c) were measured at baseline at 4, 8 and 12th week were accessed. cAiX@75 and pulse wave velocity (PWV) were determined by SphygmoCor device. RESULTS:Following DPP-4 treatment there was a significant reduction in total serum cholesterol (5.18 vs 4.62 mmol/L), low-density lipoprotein (2.89 vs 2.54 mmol/L), hsCRP (3.21 vs 1.95 mg/L), cAiX@75 (24.5 vs 22.3) and central systolic BP (131.8 vs 119.5 mmHg). The sitagliptin treated group reached cAiX@75 reduction earlier in the study period while neither sitagliptin or vildagliptin use resulted in the significant HbA1c reduction. CONCLUSION:The treatment with DPP-4i: sitagliptin and vildagliptin provides favorable metabolic and vascular effects beyond glucose-control. Further studies are required to elucidate their implication in metabolic pathways.

SUBMITTER: Duvnjak L

PROVIDER: S-EPMC4802883 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus.

Duvnjak Lea L Blaslov Kristina K

Diabetology & metabolic syndrome 20160322

<h4>Background</h4>This uncontrolled open label study evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i): sitagliptin and vildagliptin on augmentation index standardized for 75 beats per minute (cAiX@75), blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) in patients with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>Fifty-one well-regulated T2DM patients were randomly assigned to either sitagliptin or vildagliptin (100 mg/day) for 3 months conti ...[more]

PMID: 27006706

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Project description:UnlabelledBecause the effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure are controversial, we examined the long-term effects of sitagliptin (80 mg/kg per day) on blood pressure (radiotelemetry) in spontaneously hypertensive rats (SHR), Wistar-Kyoto rats, and Zucker Diabetic-Sprague Dawley rats (metabolic syndrome model). In SHR, chronic (3 weeks) sitagliptin significantly increased systolic, mean, and diastolic blood pressures by 10.3, 9.2, and 7.9 mm Hg, respectively, a response abolished by coadministration of BIBP3226 (2 mg/kg per day; selective Y1-receptor antagonist). Sitagliptin also significantly increased blood pressure in SHR treated with hydralazine (vasodilator; 25 mg/kg per day) or enalapril (angiotensin-converting enzyme inhibitor; 10 mg/kg per day). In Wistar-Kyoto rats, chronic sitagliptin slightly decreased systolic, mean, and diastolic blood pressures (-1.8, -1.1, and -0.4 mm Hg, respectively). In Zucker Diabetic-Sprague Dawley rats, chronic sitagliptin decreased systolic, mean, and diastolic blood pressures by -7.7, -5.8, and -4.3 mm Hg, respectively, and did not alter the antihypertensive effects of chronic enalapril. Because DPP4 inhibitors impair the metabolism of neuropeptide Y1-36 (NPY1-36; Y1-receptor agonist) and glucagon-like peptide (GLP)-1(7-36)NH2 (GLP-1 receptor agonist), we examined renovascular responses to NPY1-36 and GLP-1(7-36)NH2 in isolated perfused SHR and Zucker Diabetic-Sprague Dawley kidneys pretreated with norepinephrine (to induce basal tone). In Zucker Diabetic-Sprague Dawley kidneys, NPY1-36 and GLP-1(7-36)NH2 exerted little, if any, effect on renovascular tone. In contrast, in SHR kidneys, both NPY1-36 and GLP-1(7-36)NH2 elicited potent and efficacious vasoconstriction.In conclusion(1) The effects of DPP4 inhibitors on blood pressure are context dependent; (2) The context-dependent effects of DPP4 inhibitors are due in part to differential renovascular responses to DPP4’s most important substrates (NPY1–36 and GLP-1(7–36)NH2) [corrected]; (3) Y1 receptor antagonists may prevent the prohypertensive and possibly augment the antihypertensive effects of DPP4 inhibitors.

Project description:BackgroundEmpagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness.MethodsOur analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial ( http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis.ResultsAs previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = - 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found.ConclusionBesides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms. Trial registration http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered.

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Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus.

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Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus.

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