Metformin use in patients with type 2 diabetes mellitus is associated with reduced risk of deep vein thrombosis: a non-randomized, pair-matched cohort study

Lu, Dai Yin; Huang, Chin Chou; Huang, Po Hsun; Chung, Chia Min; Lin, Shing Jong; Chen, Jaw Wen; Chan, Wan Leong; Leu, Hsin Bang

doi:10.1186/1471-2261-14-187

Cited by 26 publications

(24 citation statements)

References 44 publications

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“…The studied comorbidities, diabetes, ischemic heart diseases and cancer, were not significantly associated with the occurrence of DVT among the participants in the current study. These findings are in line with what was reported by ( 16 , 18 , 23 , 24 ) where these comorbidities had no significant effect on DVT development in the studied population. Furthermore, another study conducted by ( 17 , 26 ) found that diabetes and ischemic heart diseases were not significantly associated with the occurrence of DVT.…”

Section: Discussionsupporting

confidence: 93%

Deep Venous Thrombosis among hypertensive patients in King Abdulaziz University (KAU) Hospital, Jeddah, Kingdom of Saudi Arabia

et al. 2017

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BackgroundDeep venous thrombosis (DVT) is a frequent cardiovascular disorder. It is among the main causes of morbidity and mortality among hospitalized patients and, at the same time, can be easily avoided. Studies clarified that there are a variety of factors which can be significantly associated with the development of DVT in hospitalized patients.Objectiveto identify frequency and factors associated with occurrence of DVT among hypertensive patients referred to KAU hospital, Jeddah, Kingdom of Saudi Arabia.MethodsA cross-sectional hospital-based study was conducted from October 2016 to March, 2017. All hypertensive patients referred to or admitted to the hospital departments and who were suspected to have DVT and subjected to Doppler examination were included in the study. A questionnaire was designed to obtain data about DVT frequency among participants and factors associated with the development of DVT among them. Data was collected through face to face interviews of patients included in the study.ResultsDVT was detected in 13.5 % of the studied hypertensive patients. Increased age and gender had no significant association with the development of DVT among the studied patients. In addition, other studied factors and comorbidities had no significant role in DVT development among the study participants.ConclusionKnowing the most common risk factors and their significance in developing DVT is essential for early detection of DVT to prevent it, especially for hypertensive patients. Awareness campaigns should be held more often in different neighborhoods of the city.

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Section: Discussionsupporting

confidence: 93%

Deep Venous Thrombosis among hypertensive patients in King Abdulaziz University (KAU) Hospital, Jeddah, Kingdom of Saudi Arabia

et al. 2017

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“…Literature reports have connected metformin with reduced mortality and diabetes-associated cardiovascular and cerebrovascular events in diabetic patients891011. However, it is not known whether metformin is effective against thrombosis in both diabetic and normal individuals, and further investigation is merited to determine its precise mechanism of action with respect to thrombosis prevention.…”

Section: Discussionmentioning

confidence: 99%

“…Metformin is widely used as the first-line therapy for type-2 diabetic patients. It has been reported that metformin reduced mortality and diabetes-associated thrombotic complications89101112. However, its mechanism of action is largely unknown with respect to thrombosis prevention, and further investigation is merited.…”

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confidence: 99%

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

Xin

Wei

et al. 2016

Sci Rep

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Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

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“…18 Metformin treatment is protective in experimental models of heart failure 19, 20 and is safe when used in diabetic patients with congestive heart. 20, 21 The mechanism of metformin protection is involved in activation of AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor that regulates mitochondrial metabolism and the redox state of the cell.…”

mentioning

confidence: 99%

Metformin attenuates ER stress–induced mitochondrial dysfunction

Chen

Thompson

et al. 2017

Translational Research

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Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. Metformin, a traditional anti-diabetic drug, decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER stress in cultured cells. We hypothesized that metformin can attenuate the ER stress-induced mitochondrial dysfunction and subsequent cardiac injury. Thapsigargin (THAP, 3 mg/kg) was used to induce ER stress in C57BL/6 mice. Cell injury and mitochondrial function were evaluated in the mouse heart 48 hours after one-time THAP treatment. Metformin was dissolved in drinking water (0.5g/250 ml) and fed to mice for 7 days before THAP injection. Metformin feeding continued after THAP treatment. THAP treatment increased apoptosis in mouse myocardium compared to control. THAP also led to decreased oxidative phosphorylation in heart mitochondria oxidizing complex I substrates. THAP decreased the calcium retention capacity (CRC), indicating that ER stress sensitizes mitochondria to mitochondrial permeability transition pore opening. The cytosolic CHOP content was markedly increased in THAP-treated hearts compared to control, particularly in the nucleus. Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus. Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.

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Metformin use in patients with type 2 diabetes mellitus is associated with reduced risk of deep vein thrombosis: a non-randomized, pair-matched cohort study

Cited by 26 publications

References 44 publications

Deep Venous Thrombosis among hypertensive patients in King Abdulaziz University (KAU) Hospital, Jeddah, Kingdom of Saudi Arabia

Deep Venous Thrombosis among hypertensive patients in King Abdulaziz University (KAU) Hospital, Jeddah, Kingdom of Saudi Arabia

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

Metformin attenuates ER stress–induced mitochondrial dysfunction

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