Action of metformin therapy against advanced glycation, oxidative stress and inflammation in type 2 diabetes patients: 3 months follow-up study

Adeshara, Krishna; Bangar, Nilima; Doshi, Paras R.; Diwan, Arundhati; Tupe, Rashmi S.

doi:10.1016/j.dsx.2020.07.036

Cited by 35 publications

(28 citation statements)

References 30 publications

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“…48 Metformin may block early glycation reaction and alter the AGE-RAGE axis. 49 However, the SAF does not seem to differ in patients treated compared with not treated by metformin. 50 Although the SAFs were higher among the 12 women who developed a cancer, they did not significantly differ from the other 162 women.…”

Section: Pathophysiology/complicationsmentioning

confidence: 92%

Skin autofluorescence predicts cancer in subjects with type 2 diabetes

Foussard

Larroumet

Rigo

et al. 2021

BMJ Open Diab Res Care

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IntroductionSubjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methodsFrom 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.ResultsThe participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).ConclusionsSkin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

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Section: Pathophysiology/complicationsmentioning

confidence: 92%

Skin autofluorescence predicts cancer in subjects with type 2 diabetes

Foussard

Larroumet

Rigo

et al. 2021

BMJ Open Diab Res Care

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“…In master athletes a Mediterranean diet was shown to reduce both sRAGE and malondialdehyde [ 78 ]. Furthermore, in type 2 diabetes it was recently demonstrated that treatment with metformin for three months resulted in a reduction in sRAGE levels and oxidative stress markers, and also in an increase in antioxidant defenses [ 79 ]. Thus, taken together the above examples caution against considering a comparatively high level of sRAGE, a sign of low oxidative burden and/or good health.…”

Section: The Relationship Between Srage and Oxidative Stressmentioning

confidence: 99%

The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes

Erusalimsky

2021

Redox Biology

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The soluble receptor for advanced glycation end-products (sRAGE) has been classically considered a sink for pro-inflammatory RAGE ligands and as such has been associated with protection from inflammatory stress and disease. An alternative, though not mutually exclusive view is that high levels of sRAGE in circulation reflect the overstimulation of cell surface RAGE which if persistent, lead to the amplification of pro-inflammatory processes and the exacerbation of pathological states. With these two scenarios in mind this review focuses on the potential role of sRAGE as a prospective biomarker of disease risk and adverse outcomes.

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“…The immunomodulatory effects of Metformin (as evidenced by the inhibition of monocyte-macrophage differentiation, suppression of the pro-inflammatory capacity of activated macrophages, and the differentiation of T cells into regulatory and memory T cells) is linked to the Metformin treatment-associated activation of AMPK, subsequent mTOR inhibition, and reduction of oxidative stress [92]. Furthermore, Metformin reportedly inhibits RAGEmediated NF-κB activation and subsequent up-regulation of genes that code for several proinflammatory cytokines and cell adhesion molecules in vascular endothelial cells, smooth muscle cells, and macrophages, thus dampening the inflammatory and immune response and thus conferring vascular protection [93][94][95][96][97].…”

Section: Metformin-mediated Immunomodulatory and Anti-inflammatory Effectsmentioning

confidence: 99%

Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing

et al. 2021

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Coronavirus Disease 2019 (COVID-19), caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on March 11, 2020. Soon after its emergence in late December 2019, it was noticed that diabetic individuals were at an increased risk of COVID-19–associated complications, ICU admissions, and mortality. Maintaining proper blood glucose levels using insulin and/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19. Interestingly, in diabetic COVID-19 patients, while insulin administration was associated with adverse outcomes, Metformin treatment was correlated with a significant reduction in disease severity and mortality rates among affected individuals. Metformin was extensively studied for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral capabilities that would explain its ability to confer cardiopulmonary and vascular protection in COVID-19. Here, we describe the various possible molecular mechanisms that contribute to Metformin therapy’s beneficial effects and lay out the scientific basis of repurposing Metformin for use in COVID-19 patients.

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Action of metformin therapy against advanced glycation, oxidative stress and inflammation in type 2 diabetes patients: 3 months follow-up study

Cited by 35 publications

References 30 publications

Skin autofluorescence predicts cancer in subjects with type 2 diabetes

Skin autofluorescence predicts cancer in subjects with type 2 diabetes

The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes

Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing

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