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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose.
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PMID:Management of non-insulin-dependent diabetes mellitus. 128 May 75

Glycosidases are lysosomal enzymes that participate in the catabolism of glycoproteins and other glycoconjugates, and in some way may modify their activity in situations in which carbohydrate metabolism could be altered, such as the case of obesity. Using a fluorometric assay, a study was made of four glycosidase activities: N-acetyl-beta-D-hexosaminidase (NAG), alpha-mannosidase and alpha- and beta-glucosidase in the serum, pancreas, liver and kidney of 22 Zucker fa/fa genetically obese rats and of 23 fa/? controls, both with ages ranging between 13 and 15 weeks. After 12-14 hours fast and prior anaesthesia with sodium pentobarbital intraperitoneally, blood and the afore-mentioned organs were removed for enzymatic study of the serum and the organs after homogenization and centrifugation. In the serum a statistically significant increase in alpha-mannosidase (p < 0.0001) and alpha-glucosidase (p < 0.02) activities was found in the fa/fa obese rats as compared with the controls. No statistically significant differences were found in serum hexosaminidase activity between the two groups, and no serum beta-glucosidase enzymatic activity was detected. In liver, a decrease was observed in hexosaminidase (p < 0.002) and alpha-glucosidase (p < 0.01) activities in the obese rats as compared with the controls. In whole pancreas an increase was found in alpha-glucosidase activity in the obese rats with respect to the controls (p < 0.001), with no statistically significant differences in the hexosaminidase, alpha-mannosidase and beta-glucosidase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic glycosidase activities in experimental obesity. 142 11

1. Groups of lean and obese LA/N-cp and obese Type II diabetic SHR/N-cp rats were fed semisynthetic diets with or without the alpha-glucosidase inhibitor acarbose (ACB, 100 mg/kg diet, p.o.) from 8 until 15 weeks of age, and measures of fasting serum total cholesterol (TC), insulin (INS), and hepatic HMG-CoA synthase activity determined at the end of the study. 2. ACB was without marked effect on mean food intake in either strain or either phenotype, and resulted in less weight gain and decreased adipose mass in obese LA/N-cp rats. INS was greater in the obese than the lean phenotype of both strains, and ACB resulted in greater reductions in INS in obese LA/N-cp than in obese LA/N-cp rats. 3. Serum TC concentrations were greater in the obese than in the lean phenotype of both strains, and ACB resulted in decreases in TC in both strains and in lower beta:alpha lipoprotein cholesterol ratios in obese LA/N-cp rats. Liver HMG Co-A synthase activity was greater in lean than obese rats and ACB resulted in normalization of enzyme activity in obese LA/N-cp but not SHR/N-cp rats. 4. These results confirm the hypercholesterolemia which occurs in the obese phenotype of the corpulent rat strains, and indicates that ACB may bring about significant reductions in body weight and fatness, TC, and in improved beta:alpha lipoprotein ratios and HMG-CoA synthase activity in obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of the intestinal glucosidase inhibitor acarbose on cholesterogenesis in corpulent rats. 168 84

Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis (Ro 22-0654). All drugs were presented as diet admixtures over 3 or 4 consecutive days. Total food and water intakes, the temporal pattern of feeding, and the average meal frequency and meal size were measured using computerized data collection procedures. Inhibitors of carbohydrate absorption failed to suppress food intake in either obese or lean Zucker rats and had no effect on the parameters of feeding. In contrast, inhibitors of lipid metabolism reduced food intake by 56-77% by reducing both meal frequency and meal size. Direct inhibition of lipid metabolism may be a viable mechanism for anti-obesity agents.
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PMID:Effects of inhibitors of carbohydrate absorption or lipid metabolism on meal patterns of Zucker rats. 384 Dec 13

Acarbose is an alpha-glucosidase inhibitor which reversibly and competitively inhibits the digestion of oligo- and disaccharides at the brush border of the small intestine. This study evaluates the preventive and therapeutic properties of acarbose in the treatment of obesity. Dose-response experiments were performed during repeated sucrose loads in man in order to investigate the effects of acarbose on plasma insulin and blood glucose levels. After titration of efficient doses, a long-term tolerance test of acarbose was undertaken in a small pilot study. Finally, the relapse preventing effect of acarbose was tested during double-blind cross-over conditions in 24 weight reduced obese women. In growing Sprague-Dawley rats, the effects of acarbose on body weight, lipid depots and adipose tissue cellularity were tested during pair-feeding and ad libitum conditions. Such effects were also studied in adult ad libitum-fed rats. Blood glucose, plasma insulin, body fat, depot lipids as well as fat cell weight and number were determined with established techniques. During a sucrose load, acarbose reduced insulin in a dose-dependent fashion. Glucose was also reduced, but not dose-dependently and only to a moderate extent. During a 200 g sucrose load, 400 mg of acarbose did not necessarily result in a maximal reduction of the insulin response while the glucose response was maximally inhibited after 100 mg. Acarbose reduced the relapse rate after weight reduction. No serious side effects were observed. Flatulence and meteorism occurred frequently. In growing rats, acarbose retarded the development of body weight and of lipid depots not only during pair-feeding conditions but also in ad libitum-fed animals eating considerably more than their controls. The spontaneous food consumption was increased by acarbose also in adult rats but in these animals neither body weight nor lipid depots were significantly reduced by acarbose. It is concluded that acarbose induces a carbohydrate malabsorption. Insulin levels are reduced not only via a decreased glycemic stimulus but also by interference with other insulin releasing mechanism(s). Acarbose is the first drug ever tested with long-term relapse reducing effects after weight reduction. Animal experiments suggest that acarbose may be of value in the prevention of obesity, particularly since the drug retards lipid accumulation also during ad libitum-feeding.
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PMID:alpha-Glucosidase inhibition in obesity. 391 27

The only new pharmaceutical therapy for Type 2 (non-insulin-dependent) diabetes that has become available for clinical use in the last 40 years is the alpha-glucosidase inhibitor, acarbose, which reduces postprandial glucose levels by retarding digestion of complex carbohydrates in the gut. It has proved difficult to find other new metabolically active drugs that lack toxicity. Agents that reduce insulin resistance include the thiazolidinediones, which are very effective in animals. Of these, the only one that has been maintained in clinical evaluation appears from preliminary data to have an effect that although still useful, is not greater than that reported for current oral agents. Agents that reduce non-esterified fatty acid levels by inhibiting lipolysis, thereby allowing increased peripheral uptake of glucose, have so far given minimal reduction in glycaemia. The development of fatty acid oxidation inhibitors to reduce gluconeogenesis in the liver has been hampered by toxicity, but additional new agents are being studied. The most promising new approach for enhancing insulin secretion has been suggested by the demonstration that pharmacological doses of GLP-1 (7-36 amide), a natural enteric incretin hormone, improves pancreatic beta-cell and alpha-cell sensitivity to glucose and can induce normal basal glucose levels in diabetic man. The future development of GLP-1 agonists will be of great interest. This is timely as other insulin secretogogues, such as alpha 2 adrenergic blockers have proved relatively ineffective. Anti-obesity agents would in theory be beneficial, but have either had limited efficacy or have been avoided because of concern about long-term safety. Until new pharmaceutical agents become available, if near-normal glycaemia is to be achieved, many more Type 2 diabetic patients will need insulin therapy. When full insulin replacement therapy is not feasible, reducing the fasting blood glucose level towards normal with a single daily basal insulin supplement, either alone or in combination with oral agents, could become a more widely used therapy.
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PMID:Drugs on the horizon for treatment of type 2 diabetes. 764 18

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) affects middle-aged or elderly people who frequently have several other concomitant diseases, especially obesity, hypertension, dyslipidaemias, coronary insufficiency, heart failure and arthropathies. Thus, polymedication is the rule in this population, and the risk of drug interactions is important, particularly in elderly patients. The present review is restricted to the interactions of other drugs with antihyperglycaemic compounds, and will not consider the mirror image, i.e. the interactions of antihyperglycaemic agents with other drugs. Oral antihyperglycaemic agents include sulphonylureas, biguanides--essentially metformin since the withdrawn of phenformin and buformin--and alpha-glucosidase inhibitors, acarbose being the only representative on the market. These drugs can be used alone or in combination to obtain better metabolic control, sometimes with insulin. Drug interactions with antihyperglycaemic agents can be divided into pharmacokinetic and pharmacodynamic interactions. Most pharmacokinetic studies concern sulphonylureas, whose action may be enhanced by numerous other drugs, thus increasing the risk of hypoglycaemia. Such an effect may result essentially from protein binding displacement, inhibition of hepatic metabolism and reduction of renal clearance. Reduction of the hypoglycaemic activity of sulphonylureas due to pharmacokinetic interactions with other drugs appears to be much less frequent. Drug interactions leading to an increase in plasma metformin concentrations, mainly by reducing the renal excretion or the hepatic metabolism of the biguanide, should be avoided to limit the risk of hyperlactaemia. Owing to its mode of action, pharmacokinetic interferences with acarbose are limited to the gastrointestinal tract, but have not been extensively studied yet. Pharmacodynamic interactions are quite numerous and may result in a potentiation of the hypoglycaemic action or, conversely, in a deterioration of blood glucose control. Such interactions may be observed whatever the type of antidiabetic treatment. They result from the intrinsic properties of the coprescribed drug on insulin secretion and action, or on a key step of carbohydrate metabolism. Finally, a combination of 2 to 3 antihyperglycaemic agents is common for treating patients with NIDDM to benefit from the synergistic effect of compounds acting on different sites of carbohydrate metabolism. Possible pharmacokinetic interactions between alpha-glucosidase inhibitors and classical antidiabetic oral agents should be better studied in the diabetic population.
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PMID:Antihyperglycaemic agents. Drug interactions of clinical importance. 774 82

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually. The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies. Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight. Sulphonylurea drugs stimulate insulin secretion from beta-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. alpha-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate. Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.
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PMID:Treatment of non-insulin-dependent diabetes mellitus and its complications. A state of the art review. 807 74

Non-insulin-dependent diabetes mellitus (NIDDM) appears to be an heterogeneous disorder characterized by both relative insulin deficiency and impaired insulin action. The initial management of NIDDM should include patient education, dietary counselling and individualized programs of physical activity. It is only when such measures fail that drug therapy should be considered. Oral drug therapies include sulphonylurea derivatives, biguanides, among which metformin remains the only one commercialized in our country, and alpha-glucosidase inhibitors such as acarbose. However, insulin therapy may be required to achieve adequate glycaemic control in some patients, the so-called secondary failures to oral treatment. The rationale for combining insulin and oral drug therapy derives from a better understanding of the pathophysiology of NIDDM and of the mechanisms of action of the oral drugs available: 1) type 2 diabetic patients are both insulin-deficient and insulin-resistant, thus requiring quite high doses of exogenous insulin; 2) peripheral insulin delivery leads to hyperinsulinaemia which could play a role in the pathogenesis of late diabetic complications; 3) sulphonylureas stimulate insulin release directly into the portal vein and could also potentiate peripheral insulin action; and 4) metformin (by improving glucose metabolism and insulin sensitivity) and alpha-glucosidase inhibitors (by slowing down the digestion of complex carbohydrates and sucrose) are able to reduce the amounts of insulin needed to control postprandial hyperglycaemia. Numerous studies have shown that a combination of insulin and sulphonylurea is more effective than insulin alone in the treatment of patients with NIDDM after secondary failure to oral drugs, leading to better glucose profiles and/or decreased insulin needs. The available data suggest that combination therapy is most beneficial in the diabetic patient who still has residual insulin secretory capacity and that the best scheme comprises an evening injection of lente insulin and the administration of sulphonylureas before meals. Preliminary results suggested that insulin-metformin (when obesity is present) or insulin-acarbose (when post-prandial hyperglycaemia occurs) combinations might offer some favourable features for the treatment of NIDDM patients although these therapeutical approaches still require adequate evaluation in further controlled studies. The additional cost of such combined therapy should be weighed against the potential advantages of better metabolic control.
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PMID:Combination of oral antidiabetic drugs and insulin in the treatment of non-insulin-dependent diabetes. 821 78

1. Groups of lean and obese-diabetic (NIDDM) congenic male SHR/Nutl parallel-cp rats were fed a nutritionally adequate, high carbohydrate diet ad libitum with or without the alpha-glucosidase inhibitor miglitol (150 mg/kg diet) from 8 until 15 weeks of age, and key glycemic parameters were monitored throughout the study. 2. Miglitol treatment resulted in clinical improvement toward normal in percent glycosylated hemoglobin, glycemic and insulinogenic responses to an oral glucose tolerance, and in liver glucokinase activity, in concert with modest decreases in weight gain in obese rats. 3. These observations are consistent with improved insulin sensitivity in peripheral tissues following miglitol treatment, and indicate that this drug may be a useful adjunct to diet in the treatment of obesity, NIDDM, and possibly other disorders of carbohydrate metabolism.
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PMID:The effects of the intestinal glucosidase inhibitory BAY M 1099 (miglitol) on glycemic status of obese-diabetic rats. 848 29


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