{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:04:09Z","timestamp":1776261849246,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","award":["CLAF237ABR04T"],"award-info":[{"award-number":["CLAF237ABR04T"]}],"id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["225014"],"award-info":[{"award-number":["225014"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["405788"],"award-info":[{"award-number":["405788"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides. Subjects\/Methods: We included 38 drug-na\u00efve patients, all women aged between 19 and 50 years, with BMI \u2265 30 kg\/m2. We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points. Results: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged. Conclusions: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation.<\/jats:p>","DOI":"10.3390\/jcm9103228","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T05:45:51Z","timestamp":1602913551000},"page":"3228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acute Effects of Metformin and Vildagliptin after a Lipid-Rich Meal on Postprandial Microvascular Reactivity in Patients with Type 2 Diabetes and Obesity: A Randomized Trial"],"prefix":"10.3390","volume":"9","author":[{"given":"Alessandra","family":"Schiappacassa","sequence":"first","affiliation":[{"name":"Post-Graduate Program in Clinical and Experimental Physiopathology (FISCLINEX), Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-4999","authenticated-orcid":false,"given":"Priscila A.","family":"Maranh\u00e3o","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Clinical and Experimental Physiopathology (FISCLINEX), Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-2871","authenticated-orcid":false,"given":"Maria das Gra\u00e7as Coelho de","family":"Souza","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Clinical and Experimental Physiopathology (FISCLINEX), Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"},{"name":"Laboratory of Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9066-0728","authenticated-orcid":false,"given":"Diogo G.","family":"Panazzolo","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Clinical and Experimental Physiopathology (FISCLINEX), Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"}]},{"given":"Jos\u00e9 Firmino","family":"Nogueira Neto","sequence":"additional","affiliation":[{"name":"Lipids Laboratory (Lablip), Policl\u00ednica Piquet Carneiro, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-003, Brazil"}]},{"given":"Eliete","family":"Bouskela","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3528-5881","authenticated-orcid":false,"given":"Luiz Guilherme","family":"Kraemer-Aguiar","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Research on Vascular Biology (BioVasc), Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-013, Brazil"},{"name":"Obesity Unit, Policl\u00ednica Piquet Carneiro, Department of Internal Medicine, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ 20550-030, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCULATIONAHA.106.171016","article-title":"Obesity and cardiovascular disease: Pathophysiology, evaluation, and effect of weight loss: An update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism","volume":"113","author":"Poirier","year":"2006","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1161\/01.CIR.67.5.968","article-title":"Obesity as an independent risk factor for cardiovascular disease: A 26-year follow-up of participants in the Framingham Heart Study","volume":"67","author":"Hubert","year":"1983","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.beem.2005.07.010","article-title":"Link between obesity and type 2 diabetes","volume":"19","author":"Golay","year":"2005","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1161\/hc0502.104540","article-title":"Fundamentals of endothelial function for the clinical cardiologist","volume":"105","author":"Verma","year":"2002","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1464-5491.2003.00869.x","article-title":"Pathophysiological implications of insulin resistance on vascular endothelial function","volume":"20","author":"Wheatcroft","year":"2003","journal-title":"Diabet. Med."},{"key":"ref_6","first-page":"5046508","article-title":"Metabolic Changes Induced by High-Fat Meal Evoke Different Microvascular Responses in Accordance with Adiposity Status","volume":"2018","author":"Panazzolo","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2337\/diabetes.55.02.06.db05-1064","article-title":"Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase","volume":"55","author":"Davis","year":"2006","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2337\/db07-0136","article-title":"Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes","volume":"56","author":"Vella","year":"2007","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.2337\/dc17-S005","article-title":"Classification and diagnosis of diabetes","volume":"40","author":"Association","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1743-7075-8-32","article-title":"Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: A randomized controlled trial","volume":"8","author":"Kuschnir","year":"2011","journal-title":"Nutr. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.physbeh.2011.12.004","article-title":"Novel findings in the cephalic phase of digestion: A role for microcirculation?","volume":"105","author":"Buss","year":"2012","journal-title":"Physiol. Behav."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1109\/10.790500","article-title":"Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique","volume":"46","author":"Stefanovska","year":"1999","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1097\/GME.0000000000000686","article-title":"Short-term effects of low-dose estradiol on endothelial function and blood viscosity in nondiabetic postmenopausal overweight women: A double-blind, placebo-controlled study","volume":"23","author":"Panazzolo","year":"2016","journal-title":"Menopause"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.2337\/dc05-2146","article-title":"metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance","volume":"29","author":"Bahia","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e003277","DOI":"10.1161\/JAHA.112.003277","article-title":"Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients","volume":"2","author":"Ayaori","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1210\/jcem-73-4-758","article-title":"Contribution of postprandial insulin and glucose to glucose disposal in normal and insulin-resistant obese subjects","volume":"73","author":"Klauser","year":"1991","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11892-009-0088-4","article-title":"Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus","volume":"10","author":"Enkhmaa","year":"2010","journal-title":"Curr. Diabetes Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1161\/01.CIR.100.7.723","article-title":"Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men","volume":"100","author":"Boquist","year":"1999","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1515\/bc.2011.002","article-title":"Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries","volume":"392","author":"Matheeussen","year":"2011","journal-title":"Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00592-010-0195-3","article-title":"Different modulation of dipeptidyl peptidase-4 activity between microvascular and macrovascular human endothelial cells","volume":"49","author":"Pala","year":"2012","journal-title":"Acta Diabetol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.mvr.2018.07.005","article-title":"Constitutive DPP4 activity, inflammation, and microvascular reactivity in subjects with excess body weight and without diabetes","volume":"120","author":"Neto","year":"2018","journal-title":"Microvasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/bcpt.12402","article-title":"Antidiabetic agents and endothelial dysfunction\u2013beyond glucose control","volume":"117","author":"Eriksson","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4330\/wjc.v3.i1.25","article-title":"Endothelium-derived hyperpolarizing factor and diabetes","volume":"3","author":"Gao","year":"2011","journal-title":"World J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/157339908786241133","article-title":"The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism","volume":"4","author":"Eleftheriadou","year":"2008","journal-title":"Curr. Diabetes Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.2337\/diacare.19.11.1200","article-title":"The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients","volume":"19","author":"Pigon","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2796.2004.01328.x","article-title":"The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: A systematic review","volume":"256","author":"Kooy","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12325-011-0088-z","article-title":"DPP-4 inhibitors and lipids: Systematic review and meta-analysis","volume":"29","author":"Monami","year":"2012","journal-title":"Adv. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"G943","DOI":"10.1152\/ajpgi.00303.2004","article-title":"GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats","volume":"288","author":"Qin","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1475-2840-10-61","article-title":"Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: Focus on incretins","volume":"10","author":"Ansar","year":"2011","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Expert Panel on Detection, Evaluation (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 285, 2486.","DOI":"10.1001\/jama.285.19.2486"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/00041433-199510000-00008","article-title":"Postprandial state and atherosclerosis","volume":"6","author":"Ebenbichler","year":"1995","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/ijo.2009.209","article-title":"Microvascular dysfunction: A direct link among BMI, waist circumference and glucose homeostasis in young overweight\/obese normoglycemic women?","volume":"34","author":"Sicuro","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00125-012-2783-y","article-title":"Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes","volume":"56","author":"Heymans","year":"2013","journal-title":"Diabetologia"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/10\/3228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:17:48Z","timestamp":1760177868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/10\/3228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,9]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["jcm9103228"],"URL":"https:\/\/doi.org\/10.3390\/jcm9103228","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,9]]}}}