Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo‐controlled randomized study

Pitocco, Dario; Zaccardi, Francesco; Tarzia, Pierpaolo; Milo, Maria; Scavone, Giuseppe; Rizzo, Paola; Pagliaccia, Francesca; Nerla, Roberto; Franco, Antonino Di; Manto, Andrea; Rocca, Bianca; Lanza, Gaetano Antonio; Crea, Filippo; Ghirlanda, Giovanni

doi:10.1111/dom.12041

Cited by 62 publications

(77 citation statements)

References 35 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in contrast with a recent study which showed that 6 months of metformin in people with type 1 diabetes resulted in the loss of nearly 2.5 kg weight when compared to placebo [30]. However, we requested that patient would not aim to improve their diabetic control whilst in the study, so it is possible explanation for the lack of weight loss.…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study

Ahmed

Rider

Glanville

et al. 2016

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundType 1 diabetes is associated with increased cardiovascular disease (CVD). Decreased endothelial progenitor cells (EPCs) number plays a pivotal role in reduced endothelial repair and development of CVD. We aimed to determine if cardioprotective effect of metformin is mediated by increasing circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and decreasing circulating endothelial cells (cECs) count whilst maintaining unchanged glycemic control.MethodsThis study was an open label and parallel standard treatment study. Twenty-three type 1 diabetes patients without overt CVD were treated with metformin for 8 weeks (treatment group-TG). They were matched with nine type 1 diabetes patients on standard treatment (SG) and 23 age- and sex-matched healthy volunteers (HC). Insulin dose was adjusted to keep unchanged glycaemic control. cEPCs and cECs counts were determined by flow cytometry using surface markers CD45dimCD34+VEGFR-2+ and CD45dimCD133−CD34+CD144+ respectively. Peripheral blood mononuclear cells were cultured to assess changes in PACs number, function and colony forming units (CFU-Hill’s colonies).ResultsAt baseline TG had lower cEPCs, PACs, CFU-Hills’ colonies and PACs adhesion versus HC (p < 0.001-all variables) and higher cECs versus HC (p = 0.03). Metformin improved cEPCs, PACs, CFU-Hill’s colonies number, cECs and PACs adhesion (p < 0.05-all variables) to levels seen in HC whilst HbA1c (one-way ANOVA p = 0.78) and glucose variability (average glucose, blood glucose standard deviation, mean amplitude of glycaemic excursion, continuous overall net glycaemic action and area under curve) remained unchanged. No changes were seen in any variables in SG. There was an inverse correlation between CFU-Hill’s colonies with cECs.ConclusionsMetformin has potential cardio-protective effect through improving cEPCs, CFU-Hill’s colonies, cECs, PACs count and function independently of hypoglycaemic effect. This finding needs to be confirmed by long term cardiovascular outcome studies in type 1 diabetes.Trial registration ISRCTN26092132Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0413-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 84%

“…In the UKPD trial [27] the incidence of myocardial infarction was reduced after a median follow-up of 10 years. Furthermore, metformin also reduced cardiac infarct size and improved endothelial function in diabetes [29, 30]. It has been shown that metformin under diabetic environment protects ECs regardless of its glycaemic effects [31].…”

Section: Introductionmentioning

confidence: 99%

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study

Ahmed

Rider

Glanville

et al. 2016

Cardiovasc Diabetol

View full text Add to dashboard Cite

show abstract

“…1). 3,[11][12][13][14][15][16][17] Pooled analysis included 300 patients. Overall, included studies were of adequate methodologic quality (mean Jadad score of 3.5 for included studies; all of the eight studies had a score of ‡ 3).…”

Section: Resultsmentioning

confidence: 99%

Efficacy and Safety of Metformin for Patients with Type 1 Diabetes Mellitus: A Meta-Analysis

Liu

Wu²,

Zheng³

et al. 2015

Diabetes Technology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…However, forearm microvascular dilation in response to acetylcholine was either increased despite similar glycemia (Mather et al 2001) or unchanged at better glycemic control (Natali et al 2004) after 12 or 16 weeks of metformin, respectively, with the reference to T2DM subjects randomized to placebo. Interestingly, 6 months of metformin therapy, in addition to a basal-bolus insulin regimen, improved flow-mediated dilation of the brachial artery in individuals with uncomplicated type 1 diabetes mellitus despite no differences in glucose concentrations compared to placebo (Pitocco et al 2013).…”

Section: Discussionmentioning

confidence: 96%

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

et al. 2015

View full text Add to dashboard Cite

Metformin, the drug of first choice in type 2 diabetes mellitus (T2DM), reduces cardiovascular (CV) morbidity and mortality in part independently of improved glycemic control and changes in traditional risk factors. However, there are discordant reports on the effects of metformin on endothelial function in T2DM. Our aim was to compare biochemical endothelial markers in patients with stable coronary artery disease (CAD) and T2DM stratified by metformin use. We studied 70 patients (29 women, age 68 ± 9 years) with established T2DM referred for elective coronary angiography owing to stable angina who were receiving a standard CV medication and metformin or other oral antidiabetic drugs. Exclusion criteria included heart failure and other relevant coexistent disorders. Biochemical indices of endothelial dysfunction and activation at admission were compared according to metformin use for at least 1 year prior to index hospitalization. Clinical characteristics were similar in patients receiving metformin (n = 40) vs. those on other oral antidiabetic agents (n = 30). Plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) was lower (553 ± 148 vs. 668 ± 170 µg/L, P = 0.004) and asymmetric dimethylarginine (ADMA) higher (0.53 ± 0.09 vs. 0.48 ± 0.08 µM, P = 0.01) in subjects on metformin, which was maintained in multivariate analysis. Symmetric dimethylarginine, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and E-selectin did not differ across the groups. The results were substantially unchanged after exclusion of insulin users. Thus, metformin use appears differentially associated with sVCAM-1 and ADMA in patients with T2DM and stable CAD. Whether this observation may reflect different prognostic effects of these endothelial markers in diabetes remains to be studied.

show abstract

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo‐controlled randomized study

Cited by 62 publications

References 35 publications

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study

Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study

Efficacy and Safety of Metformin for Patients with Type 1 Diabetes Mellitus: A Meta-Analysis

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

Contact Info

Product

Resources

About