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

Hyperglycemic obese and hyperinsulinemic mice of DBM strain develop a diabetic syndrome which can be compared to human maturity onset diabetes. In this study 6 to 49 weeks old female mice were used. Hyperglycemia and concomitant obesity were observed at 9 weeks. Plasma immunoreactive insulin (IRI) was maximum at 15--20 weeks, then decreased progressively with broad individual variations. Metformin, administered at 200 mg/kg per os, ineffective dosage in normal mice, showed a strong hypoglycemic effect in younger mice (11--18 weeks) with a plasma IRI decrease and no blood lactate and liver glycogen alteration. Plasma metformin concentration curve showed an exponential elimination fitted to a one compartment model with a plasma half-life of 2.7 hours. Metformin-induced hypoglycemia was lower in older mice (23--29 weeks) and corroborated their lower initial plasma IRI. All these results are in accordance with those reported in man and show that DBM mice provide a suitable model for a better understanding of antidiabetic drugs effects.
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PMID:DBM mice as a pharmacological model of maturity onset diabetes. Studies with metformin. 52 68

Hypertension appears to predispose to both atheroma and thrombus formation and is a risk factor for stroke and coronary artery disease. Insulin resistance and hyperinsulinaemia are also associated with hypertension, whether treated or untreated and irrespective of obesity. In an attempt to treat the possible insulin resistance in hypertension, an antidiabetic agent, metformin, which enhances glucose uptake, was given to non-obese, non-diabetic, untreated hypertensives in a pilot study. Metformin improved insulin sensitivity, decreased plasma insulin, serum cholesterol and triglycerides, increased fibrinolytic activity and markedly decreased blood pressure. These findings support the concept that insulin resistance may be important in cases of primary hypertension, i.e. those with concomitant metabolic and possibly also fibrinolytic abnormalities. Furthermore, the results indicate that insulin resistance may precede hypertension in these cases.
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PMID:Metformin and blood pressure. 158 82

Two main classes of oral hypoglycaemic drugs, the sulphonylureas and the biguanides, are currently used in the therapy of type II, non-insulin-dependent diabetes mellitus (NIDDM). The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment. Both first- and second-generation sulphonylureas are rapidly absorbed from the gastrointestinal tract. In the plasma compartment, these drugs are strongly bound to serum proteins. All sulphonylureas are metabolised in the liver, and the metabolites and the parent drugs are eliminated mainly in the urine, but also (second-generation derivatives) in the faces. Rapid- and short-acting sulphonylureas may improve early insulin release and promote better postprandial glucose control. Long-acting derivatives may ensure better control of overnight glycaemia. The elderly are at risk of developing severe sulphonylurea-induced hypoglycaemia, and in this population the agent chosen should have a short or intermediate duration of action and no active metabolites. Caution is needed when prescribing any sulphonylurea in patients receiving drugs known to affect sulphonylurea action, and in those with impaired liver and/or kidney function. The bioavailability of the biguanides ranges from 40 to 60%. Binding to plasma proteins is absent or very low. Metformin and buformin are not metabolised and are excreted in the urine; phenformin undergoes hepatic hydroxylation and is excreted in both urine and faeces. Metformin is the only agent of this class currently recommended for clinical use. The main indications of metformin treatment are NIDDM associated with obesity and/or hyperlipidaemia, and in combination with sulphonylurea both as primary treatment and when secondary failure occurs with sulphonylurea alone. Lactic acidosis may develop in patients receiving therapy with biguanides, especially in the presence of a preexisting contraindication to their use.
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PMID:Pharmacokinetic optimisation of oral hypoglycaemic therapy. 176 Sep 2

Metformin, glibenclamide and their combination were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the purpose was to assess possible synergistic effects of combination therapy with the two drugs as primary treatment versus conventional oral therapy, starting with one drug and adding the other, if necessary. Lipids and lipoproteins were measured in the study, and preliminary results are reported for one hundred sixteen patients concluding 6 months maintenance therapy. Comparison of mean differences showed that patients randomized to combination therapy (n = 60) demonstrated a greater decrease in total- and LDL-cholesterol levels after 4 and 6 months treatment than patients randomized to conventional therapy starting with either metformin (n = 28) or glibenclamide (n = 28). For LDL-cholesterol a significant difference was also found between patients solely on monotherapy with lower values after treatment with metformin. Triglycerides did not change significantly, and only minor fluctuations were seen in HDL-cholesterol, independent of treatment. Obese patients had significantly higher triglyceride concentrations than the non-obese group, both at baseline and after treatment, as well as significantly lower HDL-cholesterol levels. The mean triglyceride concentration (+/- SD) after 6 months treatment was 2.32 +/- 1.38 mmol/l in the obese group (n = 69) and 1.54 +/- 0.84 mmol/l in non-obese (n = 47). For HDL-cholesterol the corresponding values were 0.83 +/- 0.23 mmol/l in obese and 0.93 +/- 0.29 mmol/l in non-obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of metformin and glibenclamide alone and in combination on serum lipids and lipoproteins in patients with non-insulin-dependent diabetes mellitus. 193 72

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients. 219 88

Obese type II diabetic patients are often treated with metformin after full doses of sulfonylureas or insulin fail to achieve a satisfactory metabolic control. Clinical practice has often indicated that metformin has little effect on normal weight type II diabetics. The effectiveness of metformin vs placebo was evaluated in a double blind cross-over study on 53 type II diabetic patients with unsatisfactory glycaemic control. The patients were divided into two groups-the sulfonylurea-treated (S) and the insulin treated (I). Each group was then subdivided into three classes: 1) normal weight [BMI less than 25], 2) overweight [BMI 25-30] and 3) obese [BMI greater than 30]. Metformin did not modify body weight, plasma lipids or insulin profiles. Blood lactate increased slightly but only occasionally reached statistical significance. Metformin's antidiabetic activity was not influenced by the basal treatment (S or I) of the diabetics but was strongly linked to the degree of adiposity. Indeed both plasma glucose and HbA1 remained almost unchanged in normal weight patients. In the overweight and in the obese metformin significantly improved glycaemic profiles and reduced HbA1 levels. These results confirm clinical experience indicating that some degree of adiposity is a necessary prerequisite for metformin efficacy in diabetics.
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PMID:[Body mass index, blood lactate and therapeutic effectiveness of metformin in type II diabetes mellitus]. 268 23

Plasminogen Activator Inhibitors (PA Inhibitor) have recently been identified in plasma. They are directed against t-PA and Urokinase. Two PA Inhibitors have been described: PA Inhibitor 1 from endothelial cells, hepatocytes and platelets and PA Inhibitor 2 from placenta. Enzymatic assays have been developed. They show that plasma levels of PA Inhibitor are very low under normal conditions, but a considerable increase (X10 or 20) is found in several pathological conditions (thrombo embolic disease, atherosclerosis, thrombotic risk factors (obesity, hypertriglyceridemia, diabetes) inflammatory syndrome, post operative period for PA Inhibitor 1, and in some physiological conditions (pregnancy for PA Inhibitor 2). These results plead for a pathogenic role of PA Inhibitor 1 in the development of thrombosis. Pharmacological products able to decrease the plasma level of PA Inhibitor are as yet scarce. Stanozolol, an anabolic steroid, some biguanides such as Metformin possess this property.
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PMID:[Anti-activator inhibitors of plasminogen]. 311 99

The patient with type II, or non-insulin-dependent, diabetes mellitus (NIDDM) is characterized by obesity and insulin resistance, with resultant hyperinsulinemia and hyperglycemia. Sulfonylureas are the chief therapy for patients with NIDDM; for a limited time, these agents stimulate increased insulin secretion. With chronic administration, sulfonylureas improve the diabetic patient's insulin activity by increasing cellular insulin receptors and reducing insulin postreceptor defects. Metformin, a drug in the biguanide class, is now approved for use in the United States. This drug does not stimulate insulin release but works by lowering glucose in peripheral tissues. It can be used alone or in combination with a sulfonylurea. With sulfonylureas and metformin, therapy for the patient with NIDDM can be more effectively tailored.
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PMID:Oral hypoglycemic agents in type II diabetes mellitus. 748 7

Patients with diabetes mellitus are at a higher risk to undergo surgical intervention compared with the non-diabetic population, and additionally, they have an increased perioperative morbidity and mortality. Insulin deficiency and insulin resistance are aggravated by surgery and anaesthesia. The consequences of hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment of wound healing and leucocyte function and exacerbation of ischemic brain damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are enhanced which may result in metabolic acidosis with subsequent electrolyte disturbances. Protein catabolism is increased because of increased breakdown and decreased synthesis. Insulin administration reverts or overcomes most of these disturbances. The preoperative assessment includes the diagnoses of the long-term complications to judge the intraoperative risks. Long-acting insulins, such as ultralente of animal origin should be stopped preoperatively and substituted by protamine and lente insulins. In type-2-diabetic patients, long-acting sulfonylurea drugs such as chlorpropamide should be stopped and substituted by short-acting agents. Metformin must always be stopped. Type-2-diabetic patients with marked hyperglycemia under oral treatment should be switched to insulin before operation. The insulin requirements in diabetic patients during surgery vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8-1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery. Therefore, the appropriate dose has to be determined individually. The regimen nowadays preferred by most authors is based on variable rate insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perioperative management of the diabetic patient. 758 26

Obesity is a well-known risk factor for non-insulin-dependent (or Type 2) diabetes mellitus. Consequently, reduction of weight excess comes to the front line in the prevention and management of NIDDM. It is only when diet and physical exercise fail that drug treatment should be considered. Pharmacological treatment of obesity should favour drugs which not only promote weight loss, by reducing caloric intake and/or increasing thermogenesis and energy expenditure, but also, and especially, improve insulin sensitivity. Serotoninergic anorectic compounds (dexfenfluramine, fluoxetine) appear to possess, to some extent, all these properties. Metformin significantly reduces insulin resistance and improves glycaemic control without inducing weight gain, and even favouring some weight loss. This biguanide is now considered as the first line drug for the obese diabetic patient. Alpha-glucosidase inhibitors may help to reduce post-prandial glucose excursions but do not promote weight loss per se. Sulfonylureas can be prescribed to an obese patient when hyperglycaemia persists despite diet and the above-mentioned oral agents, but their use should be associated with reinforcement of dietary advices in order to prevent further weight increase; it is also the case for insulin therapy. Finally, drugs specifically stimulating thermogenesis and energy expenditure, new agents sensitizing tissues to the action of insulin and various compounds interfering with lipid metabolism are currently under extensive investigation with promising preliminary results in the obese diabetic patient. In conclusion, obesity remains a major problem in the management of Type 2 diabetes mellitus and this justifies the search for new, safe and effective, pharmacological approaches.
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PMID:Pharmacological treatment of the obese diabetic patient. 802 6


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