Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

Lund, Søren S; Tarnow, Lise; Stehouwer, Coen D. A.; Schalkwijk, Casper G.; Teerlink, Tom; Gram, Jørgen Brodersen; Winther, Kaj; Frandsen, M.; Smidt, Ulla M; Pedersen, Oluf; Parving, Hans‐Henrik; Vaag, Allan

doi:10.1530/eje-07-0815

Cited by 87 publications

(64 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has previously been reported that metformin treatment improves endothelial function (13), and our findings are in agreement with one other human study, where metformin, in contrast to treatment with repaglinide, improved markers of endothelial function, such as von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor-1, and intercellular adhesion molecule despite similar effects on the glycemic levels (16). Metformin has also been reported to improve endothelial function in normoinsulinemic, normalweight polycystic ovary syndrome patients (35), suggesting a possible direct effect of the drug on arterial cells beside putative secondary effects due to the glucose-lowering properties.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

et al. 2014

View full text Add to dashboard Cite

OBJECTIVEThe extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes. We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODSAfter a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metfor-min, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTSPlasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin-and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA 1c levels to comparable levels and in combination even further. CONCLUSIONSMetformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin. Increased mortality and morbidity owing to a higher incidence of cardiovascular diseases (CVDs) is a major clinical challenge in type 2 diabetes (T2D) (1,2). Several studies have demonstrated that management of hypertension, LDL cholesterol, and other major CVD risk factors have reduced micro-and macrovascular complications in patients with T2D; however, optimal risk reduction is still not achieved when these important risk factors are controlled, indicating that further attempts are needed to control the CVD risk burden (3-5). One assumption is that improvement

show abstract

Section: Discussionsupporting

confidence: 93%

“…These explanations are mainly based on data from experimental animal and in vitro studies. A few results from human studies have, however, indicated that there is an effect of metformin treatment on endothelial markers and this effect may be independent of the effects on the glycemic status (16).…”

mentioning

confidence: 99%

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…15,27 Furthermore, PAI-1 levels repeatedly have been reported to be markedly lower in patients with diabetes that are treated with metformin. 28,29 In addition, results of in-vitro studies and studies in TNF receptor 1 (TNFR1)À/À mice suggest that PAI-1 is induced through TNFa receptor 1-dependent signalling cascades in the liver. 15,30 It further has been shown in in-vitro studies that metformin can block the TNFadependent induction of PAI-1 through yet not fully understood mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function

Spruss

Kanuri

Stahl

et al. 2012

Laboratory Investigation

144

151

View full text Add to dashboard Cite

To test the hypothesis that metformin protects against fructose-induced steatosis, and if so, to elucidate underlying mechanisms, C57BL/6J mice were either fed 30% fructose solution or plain water for 8 weeks. Some of the animals were concomitantly treated with metformin (300 mg/kg body weight/day) in the drinking solution. While chronic consumption of 30% fructose solution caused a significant increase in hepatic triglyceride accumulation and plasma alanineaminotransferase levels, this effect of fructose was markedly attenuated in fructose-fed mice concomitantly treatment with metformin. The protective effects of the metformin treatment on the onset of fructose-induced non-alcoholic fatty liver disease (NAFLD) were associated with a protection against the loss of the tight junction proteins occludin and zonula occludens 1 in the duodenum of fructose-fed mice and the increased translocation of bacterial endotoxin found in mice only fed with fructose. In line with these findings, in metformin-treated fructose-fed animals, hepatic expression of genes of the toll-like receptor-4-dependent signalling cascade as well as the plasminogen-activator inhibitor/cMet-regulated lipid export were almost at the level of controls. Taken together, these data suggest that metformin not only protects the liver from the onset of fructose-induced NAFLD through mechanisms involving its direct effects on hepatic insulin signalling but rather through altering intestinal permeability and subsequently the endotoxin-dependent activation of hepatic Kupffer cells.

show abstract

“…In patients with a high risk of developing CD, such as diabetic patients, it is important to improve endothelial function since vascular damage may continue even when good glycemic control has been achieved (Volpe et al, 2007). Accordingly, some therapeutic strategies have been directed towards the stimulation of distinct processes that may reestablish the function of the endothelium, including the use of 3-hydroxy-3-methylglutaryl www.intechopen.com coenzyme A reductase inhibitors (Endemann & Schiffrin, 2004), the angiotensin converting enzyme (ACE) inhibitors , selective blockade of the AT1 receptor of angiotensin-II (ARBs) (Behrendt & Ganz, 2002) and folic acid supplementation , antioxidants , antidiabetics (Lund et al, 2008), insulin and others (Grover-Páez et al, 2007). All these strategies are aimed at decreasing the progress of atherosclerotic disease Herein, we review the literature about endothelial dysfunction in diabetes mellitus with regards to its pathogenesis at molecular and clinical level, and possible available mode of therapy.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction and Therapeutic Intervention in Type 2 Diabetes

Páez¹

2011

Medical Complications of Type 2 Diabetes

View full text Add to dashboard Cite

Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

Cited by 87 publications

References 74 publications

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes

Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function

Endothelial Dysfunction and Therapeutic Intervention in Type 2 Diabetes

Contact Info

Product

Resources

About