Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAl-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women: ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean t-PA antigen (5.15 +/- 3.02 vs 3.20 +/- 2.30 ng/ml) and PAl-1 antigen (35.89 +/- 18.59 vs 17.60 +/- 15.36 ng/ml) levels (p < 0.05). Plasma t-PA antigen level was not influenced by each treatment modality. There was a significant decrease of plasma PAl-1 antigen level after Metformin administration compared to that of before Metformin administration (39.74 +/- 19.39 vs 25.14 +/- 16.18 ng/ml) (p < 0.05), and the insulin-treated group showed a tendency for a decrease of plasma PAl-1 antigen levels after insulin administration but this did not reach statistical significance (29.93 +/- 15.37 vs 17.32 +/- 10.60 ng/ml). Sulfonylurea did not change both plasma t-PA and PAl-1 antigen levels. In conclusion, diabetic patients have high t-PA and PAl-1 antigen levels. Biguanide reduced plasma PAl-1 antigen levels, which might play some helpful role in the improvement of chronic complications in NIDDM.
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PMID:Plasma t-PA and PAl-1 antigen concentrations in non-insulin dependent diabetic patients: effects of treatment modality on fibrinolysis. 130 76

Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year. The drugs had an equivalent effect on glycaemic control, but, in contrast to glibenclamide, metformin reduced body weight. Neither drug affected triglycerides, total- and LDL-cholesterol or C-peptide. Metformin caused a slight elevation of HDL-cholesterol (P less than 0.05). No serious adverse effects were observed. The results show that oral hypoglycaemic agents are not associated with undesirable effects on lipids and lipoproteins.
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PMID:Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles. 174 45

As monotherapy, metformin is similar to the sulphonylureas, in improving both fasting and post-prandial plasma glucose levels by approx. 25-30%. Metformin, unlike the sulphonylureas, does not promote insulin secretion and does not cause weight gain and is therefore preferable in obese NIDDM. Metformin is also of benefit as combined therapy with a sulphonylurea, and in older subjects the two drugs may give as good glycaemic control as insulin. Lactic acidosis with metformin is less common than sulphonylurea-induced hypoglycaemia although the mortality risk is similar. However, where both groups of drugs are properly used clinically, serious side-effects are unusual. Metformin may have a potential advantage in the management of NIDDM with hyperinsulinaemia in that it does not increase insulin levels. Where insulin levels have been compared in the same type II patients, metformin can achieve similar glycaemic control as a sulphonylurea (gliclazide) but with significantly lower plasma insulin levels.
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PMID:Management of type 2 diabetes mellitus with special reference to metformin therapy. 193 75

Coronary heart disease is a major cause of morbidity in NIDDM and is likely to be related to the abnormalities in serum lipids and lipoproteins commonly associated with it. The effects of treatment in general, and of oral hypoglycaemic drugs in particular, on serum lipids in NIDDM are not clear. In a cross-over study, the effects of 3 months treatment with metformin glibenclamide on body weight, blood glucose control, and serum lipoproteins were compared in 35 patients with NIDDM, inadequately controlled by diet alone. Glibenclamide alone increased body weight. Glibenclamide and metformin achieved equivalent blood glucose control, independent of initial body mass index. Neither drug affected serum triglyceride. Metformin significantly reduced low density lipoprotein cholesterol (mean change -0.34 mmol/1.95% confidence intervals -0.12 to -0.57 mmol/l, p less than 0.01). Neither drug altered high density lipoprotein or subfraction cholesterol. Changes in serum lipoproteins were also studied in 14 patients with NIDDM on long term metformin therapy, after 6 weeks placebo and again 6 weeks after restarting active drug therapy. Withdrawal of metformin resulted in a rise in fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol. Restarting the drug reversed these changes. Multivariate analysis showed that serum total and LDL cholesterol varied with treatment, but not with glycaemic control. Metformin can therefore lower total and LDL cholesterol in NIDDM and this effect appears to be maintained long term.
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PMID:The effects of oral hypoglycaemic drugs on serum lipids and lipoproteins in non-insulin-dependent diabetes (NIDDM). 193 76

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double-blind, double-placebo, cross-over study. Both active agents decreased fasting blood glucose from 11.4 +/- 3.7 mmol l-1 (mean +/- SD) to 8.6 +/- 2.8 mmol l-1 on metformin (p less than 0.001) and to 9.5 +/- 3.9 mmol l-1 on guar gum (p less than 0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+0.73, -0.34) mmol l-1 (geometric mean (+SD, -SD)) to 0.43 (+0.58, -0.25) mmol l-1, (p less than 0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 (+3.27, -1.64) to 2.46 (+2.55, -1.25) mmol l-1 (p less than 0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 +/- 0.90 to 6.41 +/- 1.11 mmol l-1, p less than 0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.
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PMID:Placebo-controlled trial of the effects of guar gum and metformin on fasting blood glucose and serum lipids in obese, type 2 diabetic patients. 215 10

Metformin efficacy and safety in type 2 diabetes has not been studied in the elderly patient under conditions pertaining to clinical practice. We have therefore, studied prospectively over two months 24 patients aged between 70-88 years with 115% mean ideal body wt and glycemic control greater than 10 mol.l-1 fasting and/or greater than 14 mol.l-1 postprandial, and/or an HbA1 value greater than 10%. At entry into the study, patients were on metformin + sulfonylurea (n = 15), sulfonylurea (n = 3), metformin (n = 2), insulin (n = 1) or diet alone (n = 3). They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively. Compared to pretreatment values, glycemic control at 1 and 2 months were unchanged, with metformin blood levels remaining within expected values for both dosage groups. Blood lactate levels remained unchanged in the high dosage group but were reduced (p less than 0.05) on 850 mg/day probably because of the reduction of metformin dosage in patients already treated prior to the study. It is concluded that provided the dosage is adjusted to renal function, the metabolic tolerance of metformin therapy is satisfactory in the elderly type 2 diabetic patient. With regard to efficacy, longer observations are needed to know whether this therapy may offer on a long-term basis equivalent glycemic control compared to other treatment modalities.
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PMID:Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly). 227 14

The hyperglycaemia of NIDDM is associated with insulin resistance due, in part, to reduced insulin receptor binding and more especially postreceptor defects. Metformin is an antihyperglycaemic agent which can be used to ameliorate insulin resistance. It appears to act directly on insulin target cells to enhance insulin action. Although metformin may increase insulin-receptor binding, its main effect appears to be directed at the postreceptor level of insulin action. Accordingly the drug potentiates insulin-suppression of hepatic gluconeogenesis and increases insulin-mediated peripheral glucose uptake and metabolism. It does not stimulate insulin release, does not cause weight gain and does not cause clinical hypoglycaemia. The risk of lactate accumulation should be appreciated in patients with renal insufficiency, liver dysfunction and following acute illness with hypoxia, when therapy should be stopped. Although metformin is often bracketed with phenformin in the context of lactic acidosis, different pharmacodynamics and adherence to prescribing guidelines render such a comparison unwarranted.
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PMID:Treatment--metformin. 307 2

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

The incidence of birth defects among offspring of mothers with non-insulin dependent diabetes mellitus (NIDDM) is 2-3-fold higher than among infants of non diabetics. Since mothers with NIDDM are frequently given oral hypoglycemic agents, including sulphonylureas and biguanides, to control their disease and since these agents have been associated with the occurrence of congenital malformations in humans and animals, the embryotoxic effects of the most commonly employed biguanides, metformin and phenformin, were evaluated in whole embryo culture. Neurulating mouse embryos were exposed to therapeutic concentrations (metformin 500-2,550 mg per day; phenformin 50-400 mg per day, respectively) of the compounds for 24-48 h. Concentrations of metformin in culture ranged from 0.15 to 1.8 mg/ml and phenformin from 2.5 x 10(-5) to 0.4 mg/ml. Cultures were terminated and scored for gross morphological alterations and total protein content. Metformin produced no alterations in embryonic growth and no major malformations. Approximately 10% of all embryos exposed to metformin regardless of dose, exhibited open cranial neuropores after 24 h of culture. However, this anomaly appeared to represent a delay in closure as opposed to an overt defect, since no embryos exposed to the highest concentration of the drug and cultured for 48 h showed open neural tubes. In contrast, phenformin produced dose dependent changes in incidence of malformations, protein content, and embryolethality. Malformations included neural tube closure defects, craniofacial hypoplasia, and reduction in size of the first and second visceral arches. Doses above 0.1 mg/ml produced embryolethality and all embryos were killed at the 0.4 mg/ml concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the biguanide class of oral hypoglycemic agents on mouse embryogenesis. 807 64

Metformin (dimethylbiguanide) is an antihyperglycaemic drug used to treat non-insulin dependent diabetes mellitus. It acts in the presence of insulin to increase glucose utilization and reduce glucose production, thereby countering insulin resistance. The effects of metformin include increased glucose uptake, oxidation and glycogenesis by muscle, increased glucose metabolism to lactate by the intestine, reduced hepatic gluconeogenesis and possibly a reduced rate of intestinal glucose absorption. Metformin appears to facilitate steps in the postreceptor pathways of insulin action, and may exert effects that are independent of insulin. In muscle, metformin increases translocation into the plasma membrane of certain isoforms of the glucose transporter. The effects of metformin are generally moderate, and do not cause clinical hypoglycaemia or increased weight gain. Metformin has an antihypertriglyceridaemic effect and exerts various potentially useful effects on haemostasis. A risk of lactic acidosis is negligible provided that the contraindications, particularly renal incompetence are respected.
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PMID:Metformin--an update. 811 99


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