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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral antidiabetic agents continue to play an important role in the treatment of type 2 diabetes. Of decisive importance is the timing of their use, together with a knowledge of their specific properties. Acarbose, which needs to be initiated at a low, slowly increasing dose, is noted for the fact that it has virtually no systemic side effects. Metformin reduces plasma glucose levels without inducing hyperinsulinemia, and carries virtually no risk of lactic acidosis. Glibenclamide can be used either alone to treat type 2 diabetes or in combination with other oral antidiabetics or insulin. Today, intensified insulin therapy represents the optimal standard of insulin replacement. It permits meal-oriented injection of normal insulin and the use of longer-acting insulin overnight. This form of treatment is now facilitated by the possibilities of plasma glucose selfmonitoring and the use of injection aids (pen). Intensified treatment should be initiated at the time type I diabetes is diagnosed. In the case of a particularly instable metabolic situation or neuropathy, it may become necessary to use insulin pumps.
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PMID:[Management of diabetes in general practice--current requirements. 2: Oral antidiabetics and insulin therapy]. 820 Jun 2

NIDDM is the result of concomitant defects in both insulin secretion and insulin action. Although plasma insulin concentration in NIDDM patients may be normal or even increased as compared to normal individuals, insulin secretion is always impaired when related to ambient hyperglycemia. Moreover, the loss of first-phase insulin secretion is always present and it occurs at the very early stage of the disease. The defect in the early release of insulin may have quite an impact in post-prandial glucose homeostasis, due to inadequate suppression of hepatic glucose production. Therefore, insulin releasers should be able; 1. to increase total insulin secretory capacity, and 2. to restore physiologic profile of insulin secretion. However, this is rarely achieved with the current therapeutical tools. Sulfonylureas may exert some suppressive action on the liver and may maintain a portal-peripheral venous insulin gradient. Metformin may improve insulin sensitivity but has no effect on the beta-cell. Exogenous insulin exerts an inhibitory effect on hepatic glucose production but it does not maintain the physiologic gradient, neither can it mimic first-phase insulin secretion. Therefore, more appropriate tools must be sought. Prompt stimulation of insulin secretion can be elicited by alpha 2-adrenoreceptor antagonists, but their clinical use is still under evaluation. New sulfonylureas are under development, though some of them may exert a better peripheral action than more potent stimulation of the beta-cell. Special interest has been focused on incretin peptides. Infusion of glucagon-like peptide 1 (GLP-1) in NIDDM patients improves glucose tolerance through enhancement of acute release of insulin, suppression of glucagon secretion, and improvement of peripheral glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:What therapy do our NIDDM patients need? Insulin releasers. 852 9

Non-insulin-dependent diabetes (NIDDM) is a common problem in the elderly. The discovery of several classes of oral antidiabetic agents has increased the prospects of achieving better control of hyperglycaemia with reduced risk of severe adverse events. Some of these agents, such as acarbose or miglitol, do not cause hypoglycaemia and act locally in the gut. As such they are safer agents. On the other hand, the low cost of some sulphonylurea agents and a once or twice daily administration schedule make them an attractive option. Metformin appears to be especially useful in obese insulin-resistant patients with NIDDM. However, obesity is not as much of a problem in the elderly as it is in middle-aged patients, and contraindications to the use of metformin are common in the elderly. The use of a combination of 2 or 3 oral antidiabetic agents to delay the need for insulin therapy is now possible. The long term effects of this approach are not known and the cost of polypharmacy is of concern.
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PMID:Drug therapy of non-insulin-dependent diabetes mellitus in the elderly. 873 15

We have investigated the effects of metformin treatment on concentrations of proinsulin-like molecules in subjects with Type 2 (non-insulin-dependent) diabetes mellitus. Metformin was given for 12 weeks in an increasing dose up to 850 mg three times daily in a double-blind placebo-controlled cross-over design to 27 subjects (age 53.0 +/- 9.9 years; 19 male, 8 female). Concentrations of insulin and proinsulin-like molecules were measured by highly specific enzymoimmunometric assays. The end of metformin treatment was compared with end of placebo treatment. Metformin lowered fasting plasma glucose concentrations (at 12 weeks, metformin: 8.0 +/- 2.5 vs placebo: 12.0 +/- 2.3 mmol l-1, p r2 0.001;). Concentrations of intact (median change -2.9 (range -28.4 to +2.5 pmol l-1), p = 0.02) and des 31,32 proinsulin (median change -1.6 (range -14.1 to +5.4 pmol l-1), p = 0.07) and percentage of proinsulin-like molecules were reduced by metformin treatment (median change -6% (range -16% to +6%), p = 0.02). Changes in the ratio of proinsulin-like molecules were significantly related with those in fasting plasma glucose (r1 = 0.69, p < 0.001). Changes in concentrations of intact and des 31,32 proinsulin on metformin were not related to changes in body mass index or fasting glucose concentration or changes in concentrations of total triglyceride, cholesterol, and plasminogen activator inhibitor-1. Therefore, metformin treatment in subjects with Type 2 diabetes mellitus significantly reduced concentrations of proinsulin-like molecules over a 12-week period. However, these changes were not related to changes in cardiovascular risk factors seen during metformin treatment. We conclude that short-term effects of metformin treatment on proinsulin-like molecules are similar to those previously observed with dietary treatment in subjects with Type 2 diabetes but opposite to those of sulphonylurea treatment. The effect of long-term treatment with metformin on proinsulin-like molecules needs to be assessed.
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PMID:Effect of metformin on intact proinsulin and des 31,32 proinsulin concentrations in subjects with non-insulin-dependent (type 2) diabetes mellitus. 886 52

Chronic hyperglycaemia, i.e. impaired glucose tolerance (IGT) and NIDDM, conveys a great risk of macrovascular disease. Both insulin resistance and impaired insulin secretion seem necessary to establish chronic hyperglycaemia, and untreated it appears to promote and worsen both insulin resistance and impaired insulin secretion. The prevention and treatment of chronic hyperglycaemia should include measures directed at both derangements, and the therapeutic goal should be normoglycaemia. As this is rarely achieved by non-pharmacologic treatment alone, addition of oral antidiabetic drugs are often indicated. Their ability to attain euglycaemia is greater the earlier they are employed, but they should never be introduced until after optimization of non-pharmacologic measures. Delayed early insulin response to glucose or a meal always accompanies chronic hyperglycaemia and is not normalized by non-pharmacologic treatment. This justifies the use of insulin-releasing drugs with a rapid onset of action, e.g. the sulphonylurea glipizide. The non-sulphonylureas, repaglinide and A-4166, are even more rapid- and also short-acting, representing a reduced risk of long-lasting, and hence dangerous, hypoglycaemia. Continuous exposure to high concentrations of sulphonylureas may downregulate beta-cell sensitivity. Maximum doses are much lower than previously assumed. The most effective improvers of insulin action seem to be the thiazolidinediones, but they are not yet marketed. Metformin is the only globally available drug for improving insulin action. It is as antihyperglycaemic as sulphonylureas but does not cause hyperinsulinaemia, weight increase or hypoglycaemia. The risk of lactic acidosis can be minimized by avoiding metformin in subjects with renal impairment. Combined treatment with sulphonylurea and metformin can be highly effective even in advanced NIDDM.
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PMID:Oral antidiabetic drugs: an overview. 889 98

Non-insulin-dependent diabetes mellitus (NIDDM) is a metabolic disease that is common in the elderly, and is characterised by insulin insufficiency and resistance. Measures such as bodyweight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase glucose disposal and decrease hepatic glucose output without causing hypoglycaemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, should improve blood glucose regulation in patients with NIDDM.
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PMID:Oral antidiabetic drug use in the elderly. 897 42

Noninsulin-dependent diabetes mellitus has historically been treated with diet therapy alone or the addition of an oral hypoglycemic agent such as a sulfonylurea, or the two in combination with insulin. Although these medical interventions lower blood glucose concentrations, they may also potentiate hyperinsulinism through increased serum insulin concentrations. Insulin resistance and hyperinsulinism are associated with cardiovascular risk factors such as hypertriglyceridemia, decreased high-density lipoprotein cholesterol levels, hypertension, and hyperglycemia, among others. Therefore, a desirable therapeutic alternative would lower blood glucose, not result in hyperinsulinism, and have beneficial effects on lipid profiles. Metformin is a biguanide antihyperglycemic agent that provides these effects. When administered to carefully selected patients and monitored appropriately metformin may prove to be valuable in the treatment of diabetes mellitus and in altering its cardiovascular sequelae.
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PMID:Metformin, a promising oral antihyperglycemic for the treatment of noninsulin-dependent diabetes mellitus. 901 66

The oral antihyperglycemic drug metformin has a unique mechanism of action and controls glycemia in both obese and normal-weight NIDDM patients without inducing hypoglycemia, insulin stimulation or hyperinsulinemia. Metformin used in combination with sulfonylureas has a synergistic effect in lowering fasting and postprandial glucose and hemoglobin A1c levels, and improving the lipid profile. Metformin does not increase lactate production from skeletal muscle and has little clinically significant effect on vitamin B12 and folic acid absorption. Lactic acidosis associated with metformin use is extremely rare (reported incidence of 0.03/1,000 patient-years exposure) and has occurred predominantly in patients for whom the drug was contraindicated. Observance of prescribing guidelines will greatly minimize risk, since risk factors have been identified. Metformin can be safely used in the elderly, provided prescribing precautions are followed. Dosing in the elderly should be conservative, with dose adjustment designed to achieve normal blood sugar levels.
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PMID:Metformin: a safe and effective treatment in the management of NIDDM. 907 66

Non-insulin-dependent diabetes mellitus is a metabolic disease that is common and is characterized by insulin insufficiency and resistance. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is the most frequently used and successful therapy. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase disposal and decrease hepatic glucose output without causing hypoglycemia. Acarbose is a dietary aid that spreads the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological agents, either alone or in combination, can improve blood glucose regulation in patients with non-insulin-dependent diabetes mellitus.
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PMID:Pharmacological regulation of blood glucose levels in non-insulin-dependent diabetes mellitus. 912 43

Type 2 diabetes mellitus results from impaired insulin secretion and reduced peripheral insulin sensitivity. Treatment options include diet, oral antihyperglycemic agents, and insulin. Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production. Unlike sulfonylureas, it does not stimulate insulin secretion, aggravate hyperinsulinemia, or cause hypoglycemia or weight gain (weight stabilizes or decreases). It also has beneficial effects on serum lipid profiles. In lean or overweight type 2 diabetic patients uncontrolled by diet, metformin monotherapy significantly improves glycemic control, compared with placebo, and to similar extents as sulfonylurea monotherapy. In secondary sulfonylurea failure, combination metformin-sulfonylurea treatment significantly improves glycemic control beyond that achieved with either agent along. Metformin-sulfonylurea also appears to be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy. Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure. Gastrointestinal side effects are common, but usually tolerated. Lactic acidosis risk is minimal, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected. Aside from elevated plasma metformin levels with cimetidine and synergistic hypoglycemia with sulfonylureas, few interactions occur. Thus, metformin is safe and effective both as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control and may be advantageous when weight control is desirable and/or hyperlipidemia exists.
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PMID:An overview of metformin in the treatment of type 2 diabetes mellitus. 920 6


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