Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on glucose-induced changes of endothelial function in adults with newly diagnosed type 2 diabetes mellitus: A single-blind study

Tousoulis, Dimitris; Koniari, Katerina; Antoniades, Charalambos; Miliou, Antigoni; Noutsou, Marina; Nikolopoulou, Aggeliki; Papageorgiou, Nikolaos S.; Marinou, Kyriakoula; Stefanadi, Elli; Stefanadis, Christodoulos

doi:10.1016/j.clinthera.2010.09.007

Cited by 22 publications

(12 citation statements)

References 37 publications

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“…Vitamin D replenishment may, therefore, be considered as an effective preventive measure against development of both macro- and micro-angiopathy by improving lipid profile, BMI and HbA1c. This effect may be comparable with that of the combination of metformin and atrovastatin [45]. …”

Section: Discussionmentioning

confidence: 83%

Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

Shab-Bidar

Neyestani

Djazayery

et al. 2011

BMC Med

129

136

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BackgroundEndothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D). In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated.MethodsSubjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50) or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50) twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM) and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period.ResultsThe intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI), glycated hemoglobin (HbA1c), triacylglycerols, high-density lipoprotein cholesterol (HDL-C), endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P < 0.05, for all). Interestingly, difference in changes of endothelin-1, E-selectin and MMP-9 concentrations in FYD compared to PYD (-0.35 ± 0.63 versus -0.03 ± 0.55, P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P < 0.05 for all), even after controlling for changes of QUICKI, FM and waist circumference, remained significant for endothelin-1 and MMP-9 (P = 0.009 and P = 0.005, respectively) but disappeared for E-selectin (P = 0.092). On the contrary, after controlling for serum 25(OH)D, the differences disappeared for endothelin-1(P = 0.066) and MMP-9 (P = 0.277) but still remained significant for E-selectin (P = 0.011).ConclusionsAmeliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers.Trial registrationClinicalTrials.gov: NCT01236846

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Section: Discussionmentioning

confidence: 83%

Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

Shab-Bidar

Neyestani

Djazayery

et al. 2011

BMC Med

129

136

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“…A study investigating the effect of statins on glucose-induced endothelial dysfunction indicated that in patients with type 2 diabetes, glucose loading blunted endothelial function and deteriorated endothelium-dependent dilation (EDD). The co-administration of metformin and atorvastatin for 6 weeks partially prevented the glucose-induced impairment of EDD in these patients 31. More interestingly, metformin inhibited both glucose and lipid biosynthesis by downregulating sterol regulatory element −2 gene expression 32.…”

Section: Discussionmentioning

confidence: 90%

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

Ghim

Phương

Kim

et al. 2019

DDDT

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Purpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR). Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet. Results: After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (C max,ss ) and area under the plasma concentration–time curve during the dosing interval at steady state (AUC τ,ss ) were 1.07 (0.94–1.22) and 1.05 (0.99–1.10) for atorvastatin, 1.06 (0.96–1.16) and 1.16 (1.10–1.21) for 2-OH-atorvastatin, and 1.00 (0.86–1.18) and 0.99 (0.87–1.13) for metformin, respectively. Food delayed time to reach maximum concentration (t max ), decreased atorvastatin C max by 32% with a GMR (90% CI) of 0.68 (0.59–0.78), and increased metformin AUC t by 56% with a GMR (90% CI) of 1.56 (1.43–1.69). Conclusion: No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.

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“…Felig et al (1974) also indicates that glucose precursors are increased in obese population [ 76 ], although the clear role of this gene set in obesity is still controversial [ 77 ]. A few studies have already investigated the possibility of glycolysis and gluconeogenesis gene set as targets for diabetes therapies [ 78 – 80 ].…”

Section: Resultsmentioning

confidence: 99%

Changes in selective pressures associated with human population expansion may explain metabolic and immune related pathways enriched for signatures of positive selection

Vatsiou

Gaggiotti

2016

BMC Genomics

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BackgroundThe study of local adaptation processes is a very important research topic in the field of population genomics. There is a particular interest in the study of human populations because they underwent a process of rapid spatial expansion and faced important environmental changes that translated into changes in selective pressures. New mutations may have been selected for in the new environment and previously existing genetic variants may have become detrimental. Immune related genes may have been released from the selective pressure exerted by pathogens in the ancestral environment and new variants may have been positively selected due to pathogens present in the newly colonized habitat. Also, variants that had a selective advantage in past environments may have become deleterious in the modern world due to external stimuli including climatic, dietary and behavioral changes, which could explain the high prevalence of some polygenic diseases such as diabetes and obesity.ResultsWe performed an enrichment analysis to identify gene sets enriched for signals of positive selection in humans. We used two genome scan methods, XPCLR and iHS to detect selection using a dense coverage of SNP markers combined with two gene set enrichment approaches. We identified immune related gene sets that could be involved in the protection against pathogens especially in the African population. We also identified the glycolysis & gluconeogenesis gene set, related to metabolism, which supports the thrifty genotype hypothesis invoked to explain the current high prevalence of diseases such as diabetes and obesity. Extending our analysis to the gene level, we found signals for 23 candidate genes linked to metabolic syndrome, 13 of which are new candidates for positive selection.ConclusionsOur study provides a list of genes and gene sets associated with immunity and metabolic syndrome that are enriched for signals of positive selection in three human populations (Europeans, Africans and Asians). Our results highlight differences in the relative importance of pathogens as drivers of local adaptation in different continents and provide new insights into the evolution and high incidence of metabolic syndrome in modern human populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2783-2) contains supplementary material, which is available to authorized users.

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Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on glucose-induced changes of endothelial function in adults with newly diagnosed type 2 diabetes mellitus: A single-blind study

Cited by 22 publications

References 37 publications

Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

Changes in selective pressures associated with human population expansion may explain metabolic and immune related pathways enriched for signatures of positive selection

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