J Am Chem Soc. How to Treat Elevated Blood Enzymes. For example, a review found tentative evidence that people treated with sulfonylureas had a higher risk of severe low blood sugar events RR 5. The prevalence of abdominal obesity is increasing in western populations, possibly due to a combination of low physical activity and high-calorie diets, and also in developing countries, where it is associated with the urbanization of populations. American Journal of Clinical Nutrition.
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Adjunctive therapies which may be prescribed by a physician are orlistat or sibutramine , although the latter has been associated with increased cardiovascular events and strokes and has been withdrawn from the market in the United States ,  the UK ,  the EU ,  Australia ,  Canada ,  Hong Kong ,  Thailand ,  Egypt and Mexico. A study published in the International Journal of Sport Nutrition and Exercise Metabolism ,  suggests that combining cardiovascular aerobic exercise with resistance training is more effective than cardiovascular training alone in getting rid of abdominal fat.
An additional benefit to exercising is that it reduces stress and insulin levels, which reduce the presence of cortisol , a hormone that leads to more belly fat deposits. Self-motivation by understanding the risks associated with abdominal obesity is widely regarded as being far more important than worries about cosmetics. In addition, understanding the health issues linked with abdominal obesity can help in the self-motivation process of losing the abdominal fat.
As mentioned above, abdominal fat is linked with cardiovascular disease, diabetes, and cancer. Specifically it's the deepest layer of belly fat the fat you cannot see or grab that poses health risks, as these "visceral" fat cells produce hormones that can affect health e.
The risk increases considering the fact that they are located in the proximity or in between organs in the abdominal cavity. For example, fat next to the liver drains into it, causing a fatty liver , which is a risk factor for insulin resistance, setting the stage for Type 2 diabetes.
In the presence of diabetes mellitus type 2 , the physician might instead prescribe metformin and thiazolidinediones rosiglitazone or pioglitazone as antidiabetic drugs rather than sulfonylurea derivatives. Thiazolidinediones may cause slight weight gain but decrease "pathologic" abdominal fat visceral fat , and therefore may be prescribed for diabetics with central obesity. Low-fat diets may not be an effective long-term intervention for obesity: The conclusion was that mean weight decreased significantly in the intervention group from baseline to year 1 by 2.
This difference from baseline between control and intervention groups diminished over time, but a significant difference in weight was maintained through year 9, the end of the study. There is a common misconception that spot exercise that is, exercising a specific muscle or location of the body most effectively burns fat at the desired location, but this is not the case. Spot exercise is beneficial for building specific muscles, but it has little effect, if any, on fat in that area of the body, or on the body's distribution of body fat.
The same logic applies to sit-ups and belly fat. Sit-ups , crunches and other abdominal exercises are useful in building the abdominal muscles , but they have little effect, if any, on the adipose tissue located there. Several colloquial terms used to refer to central obesity, and to people who have it, refer to beer drinking.
However, there is little scientific evidence that beer drinkers are more prone to central obesity, despite its being known colloquially as "beer belly", "beer gut", or "beer pot".
One of the few studies conducted on the subject did not find that beer drinkers are more prone to central obesity than nondrinkers or drinkers of wine or spirits. These symptoms can suggest the appearance of central obesity.
Deposits of excess fat at the sides of one's waistline are commonly referred to as "love handles". Researchers in Copenhagen examined the relationship between waist circumferences and costs among 31, subjects aged 50—64 years of age with different waist circumferences. Their study showed that an increase in just an additional centimetre above normal waistline caused a 1.
From Wikipedia, the free encyclopedia. Central obesity Synonyms beer belly, beer gut, pot belly, spare tyre, bread box A centrally obese male. The body mass index is Specialty Endocrinology Abdominal obesity , also known as central obesity , occurs when excessive abdominal fat around the stomach and abdomen has built up to the extent that it is likely to have a negative impact on health. Current Opinion in Lipidology.
Retrieved on April 9, Dementia and Geriatric Cognitive Disorders. The Metabolic Multi-risk Factor". Definition of metabolic syndrome: European Journal of Epidemiology. Annales de Réadaptation et de Médecine Physique. Probe of the molecular paradigm associating diabetes and obesity". World Journal of Diabetes. Journal of Clinical Endocrinology and Metabolism. Recent results and their potential implications". Annals of the New York Academy of Sciences. American Journal of Clinical Nutrition.
International Journal of Obesity. The American Journal of Clinical Nutrition. Overview and Human Evidence". Mediterranean Journal of Nutrition and Metabolism. Abnormal obesity and your health. European Journal of Nutrition.
National Institutes of Health. Cohort Study in a Large, Multiethnic Population". American Journal of Epidemiology. Guide to Clinical Preventive Services, 3rd Edition: Current Medical Research and Opinion.
International Journal of Hypertension. The H 2 -receptor antagonist cimetidine causes an increase in the plasma concentration of metformin by reducing clearance of metformin by the kidneys;  both metformin and cimetidine are cleared from the body by tubular secretion , and both, particularly the cationic positively charged form of cimetidine, may compete for the same transport mechanism.
Metformin also interacts with anticholinergic medications, due to their effect on gastric motility. Anticholinergic drugs reduce gastric motility, prolonging the time drugs spend in the gastrointestinal tract.
This impairment may lead to more metformin being absorbed than without the presence of an anticholinergic drug, thereby increasing the concentration of metformin in the plasma and increasing the risk for adverse effects. Metformin's main effect is to decrease liver glucose production.
Metformin decreases high blood sugar , primarily by suppressing liver glucose production hepatic gluconeogenesis. Multiple potential mechanisms of action have been proposed, including; inhibition of the mitochondrial respiratory chain complex I , activation of AMP-activated protein kinase AMPK , inhibition of glucagon-induced elevation of cyclic adenosine monophosphate cAMP with reduced activation of protein kinase A PKA , inhibition of mitochondrial glycerophosphate dehydrogenase , and an effect on gut microbiota.
Activation of AMPK was required for metformin's inhibitory effect on liver glucose production. In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake by inducing the phosphorylation of GLUT4 enhancer factor , decreases insulin-induced suppression of fatty acid oxidation ,  and decreases absorption of glucose from the gastrointestinal tract.
Increased peripheral use of glucose may be due to improved insulin binding to insulin receptors. AMPK probably also plays a role in increased peripheral insulin sensitivity, as metformin administration increases AMPK activity in skeletal muscle. The usual synthesis of metformin, originally described in , involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat.
According to the procedure described in the Aron patent,  and the Pharmaceutical Manufacturing Encyclopedia ,  equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added. Steady state is usually reached in one or two days.
Metformin has acid dissociation constant values pKa of 2. The metformin pKa values make metformin a stronger base than most other basic medications with less than 0.
Furthermore, the lipid solubility of the nonionized species is slight as shown by its low logP value log 10 of the distribution coefficient of the nonionized form between octanol and water of These chemical parameters indicate low lipophilicity and, consequently, rapid passive diffusion of metformin through cell membranes is unlikely.
As a result of its low lipid solubility it requires the transporter SLC22A1 in order for it to enter cells. More lipophilic derivatives of metformin are presently under investigation with the aim of producing prodrugs with superior oral absorption than metformin. Metformin is not metabolized. It is cleared from the body by tubular secretion and excreted unchanged in the urine; metformin is undetectable in blood plasma within 24 hours of a single oral dose.
The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin , originates from the French lilac or goat's rue Galega officinalis , a plant used in folk medicine for several centuries.
Metformin was first described in the scientific literature in , by Emil Werner and James Bell, as a product in the synthesis of N , N -dimethylguanidine. Interest in metformin resumed at the end of the s.
In , metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals. Garcia  used metformin he named it Fluamine to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic.
Garcia believed metformin to have bacteriostatic , antiviral , antimalarial , antipyretic and analgesic actions. Instead he observed antiviral effects in humans. French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine , an alkaloid isolated from Galega officinalis , which is related in structure to metformin and had seen brief use as an antidiabetic before the synthalins were developed.
Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" glucose eater for the medication and published his results in Metformin became available in the British National Formulary in It was sold in the UK by a small Aron subsidiary called Rona. Broad interest in metformin was not rekindled until the withdrawal of the other biguanides in the s. Metformin was approved in Canada in ,  but did not receive approval by the U.
Liquid metformin is sold under the name Riomet in India. Metformin IR immediate release is available in , , and mg tablets. All of these are available as generic medications in the U.
Metformin SR slow release or XR extended release was introduced in It is available in , , and mg strengths, mainly to counteract common gastrointestinal side effects, as well as to increase compliance by reducing pill burden. No difference in effectiveness exists between the two preparations.
When used for type 2 diabetes, metformin is often prescribed in combination with other medications. Several are available as fixed-dose combinations , to reduce pill burden and simplify administration. A combination of metformin and rosiglitazone was released in and sold as Avandamet by GlaxoSmithKline. By it had become the most popular metformin combination.
In , the stock of Avandamet was removed from the market, after inspections showed the factory where it was produced was violating good manufacturing practices. However, following a meta-analysis in that linked the medication's use to an increased risk of heart attack ,  concerns were raised over the safety of medicines containing rosiglitazone.
In September the European Medicines Agency EMA recommended that the medication be suspended from the European market because the benefits of rosiglitazone no longer outweighed the risks. In November , the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the RECORD clinical trial a six-year, open label randomized control trial , which failed to show elevated risk of heart attack or death associated with the medication.
Dipeptidyl peptidase-4 inhibitors inhibit dipeptidyl peptidase-4 and thus reduce glucagon and blood glucose levels. In Europe, Canada, and elsewhere metformin combined with linagliptin is marketed under the trade name Jentadueto. Sulfonylureas act by increasing insulin release from the beta cells in the pancreas.
Metformin is available combined with the sulfonylureas glipizide Metaglip and glibenclamide US: Meglitinides are similar to sulfonylureas. The combination of metformin with pioglitazone and glibenclamide  is available in India as Triformin.
From Wikipedia, the free encyclopedia. B No risk in non-human studies. S4 Prescription only CA: Pharmacy and pharmacology portal Medicine portal. Clinical Pharmacology and Therapeutics. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus".
Archived from the original on 24 December Retrieved 2 January A Systematic Review and Meta-analysis". Annals of Internal Medicine. Archived from the original on