Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin is a biguanide. Due to its effects in decreasing the hepatic production of glucose and in increasing insulin sensitivity in peripheral tissues, such as adipose tissue and skeletal muscle, the agent is used in metabolic syndrome and type 2 diabetes mellitus and, in which insulin resistance is especially pronounced. Eighty-one-year old male patient was admitted to the emergency unit with sudden vertigo, tiredness, dyspnea, cyanosis, and lethargy. He had had type 2 diabetes mellitus for 10 years and was taking glargin 12 U/kg once daily and metformin (glucophage) 850 mg thrice daily. The patient showed no cooperation and orientation. Metabolic acidosis, hypoxemia, and hypercapnea were detected in arterial blood gases (ABG). The patient was transferred to an intensive care unit of the hospital; endotracheal intubation was applied and mechanic ventilation was started. On the following day, his ABG got better; he was disconnected and weaning was applied. Lung X-ray study revealed no signs of pneumonia or pulmonary edema. On the same day, extubation was ended and O2 was given by mask at a rate of 4 L/min. After the patient's vital signs, blood sugar, and lactate levels were stabilized; his treatment regimen was arranged again and the patient was discharged on day 4 of his admission. Dyspnea, acidosis, and hypoxia seen in the patient were thought to be due to lactic acidosis which may rarely occur when metformin is used.
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PMID:[A clinical case of lactic acidosis development in a diabetic patient taking metformin]. 1951 47

Metformin has now been established as the drug of choice for the first-line management of type 2 diabetes mellitus. It reduces insulin resistance, improves glycaemic control, and can be safely combined with other classes of oral hypoglycaemic agents. Equally important, metformin has been shown to have a significant beneficial effect on cardiovascular morbidity. Moreover, this agent acts favourably on blood pressure, lipids, haemostasis and other features of the metabolic syndrome. Metformin also contributes to weight reduction and diabetes prevention.
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PMID:Metformin: diamonds are forever. 1967 95

Hyperglycaemia is a typical feature of metabolic syndrome (MeTS) and one of its independent diagnostic criteria. The term includes impaired glucose homeostasis (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus. Although glycaemic control has been shown to lower the risk of microvascular events, the effect of intensive glycaemic control on macrovascular outcomes is less clear. Epidemiological studies show hyperglycaemia, particularly the postprandial one, to be a clear risk factor for cardiovascular (CV) mortality and morbidity. However, the intervention studies are less conclusive. The large interventional studies published in 2008 and 2009 (UKPDS, VADT, ACCORD, ADVANCE, RECORD) advocate the controlling of nonglycemic risk factors (through blood pressure control, lipid lowering with statin therapy, aspirin therapy, and lifestyle modifications) as the primary strategies for reducing the burden of CV disease in people with diabetes, and demonstrated the need for individualized approach to the patients' care in terms of blood glucose control. The patients with shorter duration of type 2 diabetes and without established atherosclerosis might reap CV benefit from intensive glycemic control. Conversely, it is possible that potential risks of intensive glycaemic control (hypoglycaemia) may outweigh its benefits in other patients, such as those with a very long duration ofdiabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty. According to the latest recommendations of the Czech Diabetes Society that are in line with the European and US standards the best way to protect type 2 diabetic patients against coronary and cerebrovascular disease is to target all cardiovascular risk factors (blood pressure treatment, including lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors hypertension, dyslipidemia, obesity and other symptoms of metabolic syndrome. The target HbA1c levels in patients with the low CV risk shoul be below 4.5%. Less strict goals (HbA1c below 6%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with long-standing diabetes. The individual targets should be achieved safely (without hypoglycaemias). Slow advancing in diabetes compensation is preferred. Lifestyle changes are the cornerstone of therapy. Metformin is the drug of choice; its administration, together with lifestyle changes, should be initiated immediately after the diagnoses of diabetes. If monotherapy does not provide satisfactory glucose control, other oral antidiabetic agents or insulin are added to the combination. Since it is not known which hypoglycaemic agents are beneficial from the perspective of long-term patient prognosis, the selection is liberal. Contraindication of the various farmaceuticals must be respected. It is possible to use a range of different combinations, metformin is administered with a glitazone (zero risk of hypoglycaemias is the advantage) with sulphonylurea derivatives (low price is the advantage) with glinides, with incretins, acarbose, antiobesity agents or insulin. The next step is a triple combination of hypoglycaemic agents with different mechanisms of action. Therapy also includes education focusing on changes to dietary and lifestyle habits, including smoking cessation, and education related to the prevention of complications, with particular regard to prevention of diabetic foot and atherosclerosis.
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PMID:[Treatment of diabetes in metabolic syndrome]. 1973 68

Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events.
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PMID:Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. 2020 98

Insulin resistance is a central feature of the PCOS and may increase cardiovascular risk. Owing to insulin resistance, the metabolic syndrome is more prevalent in women with PCOS compared with unaffected women. Metformin improves the metabolic profile in PCOS in short-term studies. In this study, we evaluated the long-term effect of metformin on metabolic parameters in women with PCOS during routine care without a controlled diet.We performed a retrospective medical chart review of 70 women with PCOS receiving metformin from an academic endocrine clinic. Metabolic risk factors were compared before and after metformin treatment. Time trends of these metabolic parameters were also analysed. After a mean follow-up of 36.1 months with metformin treatment, improvements were observed for BMI (-1.09 +/- 3.48 kg/m2, p = 0.0117), diastolic blood pressure (-2.69 +/- 10.35 mmHg, p = 0.0378), and HDL cholesterol (+5.82 +/- 11.02 mg/dL, p <0.0001).The prevalence of metabolic syndrome decreased from 34.3% at baseline to 21.4% (p = 0.0495). The course of BMI reduction during metformin treatment was significantly more pronounced in women with PCOS with metabolic syndrome at baseline, compared with those without the metabolic syndrome (p = 0.0369 for interaction). In conclusion, metformin improved the metabolic profile of women with PCOS over 36.1 months, particularly in HDL cholesterol, diastolic blood pressure and BMI.
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PMID:Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome. 2036 1

Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.
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PMID:Metabolic syndrome and chronic kidney disease. 2036 11

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become a common entity in clinical practice. In most of the patients it presents as simple steatosis with nonprogressive clinical course. However, some patients have progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), and are at increased risk of developing cirrhosis and hepatocellular carcinoma. NAFLD treatment includes lifestyle modifications and pharmacotherapy aiming at increasing insulin sensitivity, and attenuating inflammation and hepatic fibrosis. Weight reduction has consistently been shown to reduce levels of liver enzymes and insulin resistance. Although dietary intervention and exercise remain the first-line therapy, due to low patients compliance to these measures pharmacotherapy or surgical approaches are often required. Metformin and thiazolidinediones may improve insulin sensitivity, serum aminotransferase level and liver histology. However, little evidence exists regarding their sustained effects after drug discontinuation which, together with their side effects, limits their widespread use in clinical practice. Statins appear to be safe agents for the treatment of hyperlipidemia, although trials documenting their efficacy in NAFLD are scarce. Based on the recent clinical trials, weight loss medication orlistat, ursodeoxycholic acid and antioxidant agents could potentially be used as adjunctive therapy. Considering still largely controversial clinical data regarding pharmacological agents, their high cost and known side-effects, lifestyle modifications at present remain the only essential considerations in the NAFLD treatment.
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PMID:Therapy of nonalcoholic fatty liver disease: current status. 2038 46

The relationship between obesity, metabolic syndrome, diabetes and cancer has been recognized for many years. Multiple studies conducted in the last 20 years have identified molecular mechanisms responsible for this phenomenon. Elucidation of the important role of insulin, IGF receptor, mTOR and AMP-activated protein kinase in breast cancer biology has led to the development and subsequent clinical evaluation of novel targeted therapies, including IGF-1 receptor-specific antibodies or tyrosine kinase inhibitors and inhibitors of mTOR. There is also a growing interest in the use of metformin, which has been shown to possess antitumor activity resulting from activation of AMP-activated protein kinase and subsequent inhibiton of mTOR, as well as from decreased circulating insulin levels. Metformin has been shown to inhibit proliferation, invasion and angiogenesis of neoplastic cells and to overcome resistance of breast cancer to chemotherapy, hormonal therapy and HER2 inhibition. Recently, metformin has been demonstrated to inhibit breast cancer stem cell growth and to synergize with chemotherapy in suppression of tumor growth and prolongation of survival of breast tumor-bearing animals. Several currently ongoing Phase II and III clinical studies are evaluating the therapeutic efficacy of metformin in the treatment of early and advanced breast cancer patients.
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PMID:Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin. 2046 5

Metformin is quite an old drug, but it is optimal for the control of glycemia in Type 2 diabetes. It was reported, 15 years ago, that insulin resistance was abnormally high in most polycystic ovary syndrome (PCOS) patients. Starting from that moment, increasing numbers of studies were performed to demonstrate the efficacy of metformin in controlling and/or modulating several aspects of PCOS, which is the most common cause of menstrual irregularity, inesthetisms and infertility. Metformin induces higher glucose uptake, thus inducing a lower synthesis/secretion of insulin. Such an effect permits the possible restoration of the normal biological functions that are severely affected by the compensatory hyperinsulinemia reactive to the increased peripheral insulin resistance. These are the basis of the many positive effects of this drug, such as the restoration of menstrual cyclicity, ovulatory cycles and fertility, because abnormal insulin levels affect the hypothalamus-pituitary-ovarian function, as well as the use of glucose in peripheral tissues. Metformin improves the impairments typically observed in hyperinsulinemic PCOS patients, reducing the possible evolution towards metabolic syndrome and Type 2 diabetes; and when pregnancy occurs, it consistently reduces the risk of gestational diabetes, eclampsia and hypertension. PCOS seems to be the perfect physiopathological condition that might have higher benefits from metformin administration, obviously after Type 2 diabetes. This review focuses on the many aspects of PCOS and on the possible issues of this disease for which metformin might be a putative optimal treatment.
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PMID:Use of metformin in the treatment of polycystic ovary syndrome. 2059 21

We shall open our overview of issues related to obesity and hyperlipoproteinemia (HLP) or dyslipidemia with a notoriously known truth (that some are still reluctant to accept): HLP/DLP is not obesity. It is certainly not possible to put an equal sign between subcutaneous fat and the level of plasma lipids and lipoproteins. On the other hand, it is obvious that there is a number of connecting links between HLP/DLP and obesity. These associations on one side and differences on the other are the focus of this review paper. (1) HLP/DLP as well as obesity represent a group of high incidence metabolic diseases (gradually evolving from epidemic to pandemic) that affect several tens of percent of inhabitants. (2) Both HLP/DLP and obesity often occur concurrently, often as a result of unhealthy lifestyle. However, genetic factors are also been studies and it is possible that mutual predispositions for the development of both diseases will be identified. At present, it is only possible to conclude that obesity worsens lipid metabolism in genetically-determined HLP. (3) Both these metabolic diseases represent a risk factor for other pathologies, cardiovascular diseases are the most important common complication of both conditions (central type of obesity only). Concurrent presence of HDL/DLP and obesity is often linked to other diagnoses, such as type 2 diabetes mellitus (DM2T), hypertension, pro-coagulation or pro-inflammatory states; all as part of so called metabolic syndrome. (4) Patients with metabolic syndrome and, mainly, central obesity usually have typical dyslipidemia with reduced HDL-cholesterol (HDL-C) and sometimes hypertriglyceridaemia. Current treatment of HDL/DLP aims to first impact on the primary aim, i.e. LDL-cholesterol (LDL-C), and than influence HDL-C. (5) It seems that the therapeutic efforts in HLP/DLP and obesity will go in the same direction. I will skip the trivial (and difficult to accept by patients) dietary changes. Pharmacotherapy, however, (very scarce with respect to obesity) may bring positive effects on lipids and BMI. Metformin used to be considered as a drug that could improve lipid profile and lead to body weight reduction. Even though larger studies did not provide an unambiguous evidence for this, metformin keeps its position as a first line oral antidiabetic (not only) in patients with T2DM, HLP and obesity. Positive effect on lipids, mainly HDL-C is reported with pioglitazone. This drug, unlike other glitazones, does not bring body weight reduction but at least does not have a negative effect. Other antidiabetics with a positive effect on lipids and body weight include incretins, liraglutid in particular. Liraglutid importantly decreases triglyceride levels and has anorectic effect. Furthermore, metabolic effects of bariatric surgery should not be overlooked. Bariatric surgery brings weight reduction as well as it improves lipid profile and compensation of diabetes mellitus (DM). It should be mentioned here that bariatric surgery has been used for the treatment of HLP as early as 1980s. The results of the 25-year follow up within the POSCH study (ideal bypass indicated for HLP), presented in 2010, confirm a decrease in overall as well as cardiovascular mortality in an operated group, even though patients who did not undergo surgery were significantly more frequently treated with statins.
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PMID:[Dyslipidemia and obesity 2011. Similarities and differences]. 2149 5


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