Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy: a randomized crossover trial comparing detemir versus glargine

Fadini, Gian Paolo; Kreutzenberg, Saula Vigili de; Mariano, V.; Boscaro, Elisa; Bertolini, Francesco; Mancuso, Patrizia; Quarna, Jessica; Marescotti, Maria Cristina; Agostini, Carlo; Tiengo, Antonio; Avogaro, Angelo

doi:10.1111/j.1463-1326.2011.01396.x

Cited by 50 publications

(46 citation statements)

References 29 publications

(45 reference statements)

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“…Insulin dosage was reduced significantly, but it was not correlated with changes in cEPCs number or PACs adhesion. This is interesting, as insulin has been shown to improve cEPCs number [40, 41] and function in type 2 diabetes [42, 43]. However, the improvement in cEPCs number in Fadini et al [41] could be attributed to improvement in HbA1c.…”

Section: Discussionmentioning

confidence: 99%

“…This is interesting, as insulin has been shown to improve cEPCs number [40, 41] and function in type 2 diabetes [42, 43]. However, the improvement in cEPCs number in Fadini et al [41] could be attributed to improvement in HbA1c. This is in contrast with Humpert et al [40], who showed that effect of insulin on the cEPCs number is independent of HbA1c.…”

Section: Discussionmentioning

confidence: 99%

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

Ahmed

Rider

Glanville

et al. 2016

Cardiovasc Diabetol

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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

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“…75 Blood pressure lowering with different classes of drugs has shown ability to counteract EPC reduction in hypertensive patients. 102, 103 Blood glucose lowering with insulin therapy in diabetic patients was able to increase circulating CD133+KDR+ and CD34+CD133+KDR+ EPCs, 104 while other anti-diabetic medications may be active on EPCs. 105 LDL-apheresis in patients with familial hypercholesterolemia increased CD34+KDR+ EPCs (although CD34+CD133+KDR+ cells remained unchanged), 106 while statin therapy is among the best characterized intervention to increase EPCs.…”

Section: Epcs As Biomarkers Of Cardiovascular Diseasementioning

confidence: 99%

Critical Reevaluation of Endothelial Progenitor Cell Phenotypes for Therapeutic and Diagnostic Use

Fadini

Losordo

Dimmeler

2012

Circulation Research

585

576

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Diverse subsets of endothelial progenitor cells (EPCs) are used for the treatment of ischemic diseases in clinical trials and circulating EPCs levels are considered as biomarkers for coronary and peripheral artery disease. However, despite significant steps forward in defining their potential for both therapeutic and diagnostic purposes, further progress has been mined by unresolved questions around the definition and the mechanism of action of EPCs. Diverse culturing methods and detection of various combinations of different surface antigens were used to enrich and identify EPCs. These attempts were particularly challenged by the close relationship and overlapping markers of the endothelial and hematopoietic lineages. This article will critically review the most commonly used protocols to define EPCs by culture assays or by FACS in the context of their therapeutic or diagnostic use. We also delineate new research avenues to move forward our knowledge on EPC biology.

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“…The second set (SET2) was a cohort of diabetic subjects (N = 42) that has been described previously [12]. Patients and controls were recruited at the outpatient clinics of the Division of Metabolic Diseases, University Hospital of Padova, Italy.…”

Section: Patientsmentioning

confidence: 99%

The increased dipeptidyl peptidase‐4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin‐treated patients

Fadini

Albiero

Menegazzo

et al. 2012

Diabetes Obesity Metabolism

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Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy: a randomized crossover trial comparing detemir versus glargine

Cited by 50 publications

References 29 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

Critical Reevaluation of Endothelial Progenitor Cell Phenotypes for Therapeutic and Diagnostic Use

The increased dipeptidyl peptidase‐4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin‐treated patients

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