Gluconeogenesis Health Dictionary

Biguanides are a group of oral drugs, of which METFORMIN is the only one available for treatment, used to treat non-insulin-dependent diabetics when strict dieting and treatment with SULPHONYLUREAS have failed. Metformin acts mainly by reducing GLUCONEOGENESIS and by increasing the rate at which the body uses up glucose. Hypoglycaemia is unusual, unless taken in overdose. Gastrointestinal side-effects such as anorexia, nausea, vomiting and transient diarrhoea are common initially and may persist, particularly if large doses are taken. Metformin should not be given to patients with renal failure, in whom there is a danger of inducing lactic acidosis. (See also DIABETES MELLITUS.)... biguanides

These oral agents reduce the excessive amounts of GLUCOSE in the blood (HYPERGLYCAEMIA) in people with type 2 (INSULIN-resistant) diabetes (see DIABETES MELLITUS). Although the various drugs act di?erently, most depend on a supply of endogenous (secreted by the PANCREAS) insulin. Thus they are of no value in treating patients with type 1 diabetes (insulin-dependent diabetes mellitus (IDDM), in which the pancreas produces little or no insulin and the patient’s condition is stabilised using insulin injections). The traditional oral hypoglycaemic drugs have been the sulphonylureas and biguanides; new agents are now available – for example, thiazolidine-diones (insulin-enhancing agents) and alpha-glucosidase inhibitors, which delay the digestion of CARBOHYDRATE and the absorption of glucose. Hypoglycaemic agents should not be prescribed until diabetic patients have been shown not to respond adequately to at least three months’ restriction of energy and carbohydrate intake.

Sulphonylureas The main group of hypoglycaemic agents, these act on the beta cells to stimulate insulin release; consequently they are e?ective only when there is some residual pancreatic beta-cell activity (see INSULIN). They also act on peripheral tissues to increase sensitivity, although this is less important. All sulphonylureas may lead to HYPOGLYCAEMIA four hours or more after food, but this is relatively uncommon, and usually an indication of overdose.

There are several di?erent sulphonylureas; apart from some di?erences in their duration or action (and hence in their suitability for individual patients) there is little di?erence in their e?ectiveness. Only chlorpropamide has appreciably more side-effects – mainly because of its prolonged duration of action and consequent risk of hypoglycaemia. There is also the common and unpleasant chlorpropamide/ alcohol-?ush phenomenon when the patient takes alcohol. Selection of an individual sulphonylurea depends on the patient’s age and renal function, and often just on personal preference. Elderly patients are particularly prone to the risks of hypoglycaemia when long-acting drugs are used. In these patients chlorpropamide, and preferably glibenclamide, should be avoided and replaced by others such as gliclazide or tolbutamide.

These drugs may cause weight gain and are indicated only if poor control persists despite adequate attempts at dieting. They should not be used during breast feeding, and caution is necessary in the elderly and in those with renal or hepatic insu?ciency. They should also be avoided in porphyria (see PORPHYRIAS). During surgery and intercurrent illness (such as myocardial infarction, COMA, infection and trauma), insulin therapy should be temporarily substituted. Insulin is generally used during pregnancy and should be used in the presence of ketoacidosis.

Side-effects Chie?y gastrointestinal disturbances and headache; these are generally mild and infrequent. After drinking alcohol, chlorpropamide may cause facial ?ushing. It also may enhance the action of antidiuretic hormone (see VASOPRESSIN), very rarely causing HYPONATRAEMIA.

Sensitivity reactions are very rare, usually occurring in the ?rst six to eight weeks of therapy. They include transient rashes which rarely progress to erythema multiforme (see under ERYTHEMA) and exfoliate DERMATITIS, fever and jaundice; chlorpropamide may also occasionally result in photosensitivity. Rare blood disorders include THROMBOCYTOPENIA, AGRANULOCYTOSIS and aplastic ANAEMIA.

Biguanides Metformin, the only available member of this group, acts by reducing GLUCONEOGENESIS and by increasing peripheral utilisation of glucose. It can act only if there is some residual insulin activity, hence it is only of value in the treatment of non-insulin dependent (type 2) diabetics. It may be used alone or with a sulphonylurea, and is indicated when strict dieting and sulphonylurea treatment have failed to control the diabetes. It is particularly valuable in overweight patients, in whom it may be used ?rst. Metformin has several advantages: hypoglycaemia is not usually a problem; weight gain is uncommon; and plasma insulin levels are lowered. Gastrointestinal side-effects are initially common and persistent in some patients, especially when high doses are being taken. Lactic acidosis is a rarely seen hazard occurring in patients with renal impairment, in whom metformin should not be used.

Other antidiabetics Acarbose is an inhibitor of intestinal alpha glucosidases (enzymes that process GLUCOSIDES), delaying the digestion of starch and sucrose, and hence the increase in blood glucose concentrations after a meal containing carbohydrate. It has been introduced for the treatment of type 2 patients inadequately controlled by diet or diet with oral hypoglycaemics.

Guar gum, if taken in adequate doses, acts by delaying carbohydrate absorption, and therefore reducing the postprandial blood glucose levels. It is also used to relieve symptoms of the DUMPING SYNDROME.... hypoglycaemic agents

n. a vitamin of the B complex that is an essential coenzyme for several carboxylase enzymes involved in fatty acid synthesis, *gluconeogenesis, and the metabolism of branched-chain amino acids. A biotin deficiency is extremely rare in humans; it can be induced by eating large quantities of raw egg white, which contains a protein – avidin – that combines with biotin, making it unavailable to the body. Rich sources of the vitamin are egg yolk and liver. There are no known reports of biotin toxicity.... biotin

n. one of a group of organic compounds of carbon, hydrogen, oxygen, and nitrogen (sulphur and phosphorus may also be present). The protein molecule is a complex structure made up of one or more chains of *amino acids, which are linked by peptide bonds. Proteins are essential constituents of the body; they form the structural material of muscles, tissues, organs, etc., and are equally important as regulators of function, as enzymes and hormones. Proteins are synthesized in the body from their constituent amino acids, which are obtained from the digestion of protein in the diet. Excess protein, not required by the body, can be converted into glucose and used as an energy source (*gluconeogenesis).... protein