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)

On the occasion of the introduction of gliclazide (Diamicron) in Canada, it seems useful to assess the use of oral hypoglycemics in the treatment of NIDDM. Various types of diabetes occur when insufficient insulin is produced or when various factors reduce the receptor efficacy. Most of the factors involved are favorably affected by the action of sulfonylureas. Many NIDDM patients exhibit poor compliance with regard to exercise and diet, and require oral hypoglycemics. Combinations of oral hypoglycemics and insulin are very useful in patients responding poorly to either type of treatment since this gives effective insulin levels with improved receptor activity. Diamicron offers advantages since it reduces blood glucose effectively, has few side effects and no evidence of long-term problems or toxicity. Studies have shown that there is a significant antiplatelet aggregation effect and a beneficial effect on the fibrinolytic system with gliclazide (but not necessarily with other oral hypoglycemics), which may be useful in preventing or attenuating some long-term complications of diabetes, e.g. diabetic retinopathy. In a study at the Joslin Clinic, three groups of patients with NIDDM were examined: dietary failures, secondary failures with first generation oral hypoglycemics, and poorly regulated patients treated with insulin. After three months of treatment with Diamicron, all 10 dietary failure patients improved, as did three of the 10 secondary failure cases and five of the insulin-treated patients. Receptor studies indicated increased sensitivity in some cases, without a consistent change in numbers. Some patients with the poorest response to insulin alone had the best results with combined therapy, although it took almost eight weeks to achieve this.
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PMID:The treatment of NIDDM in the decade of the 90s. 179 61

Gliclazide is a sulphonylurea drug with an intermediate half-life of around 11 hours. It is extensively metabolised, and renal clearance accounts for only 4% of total drug clearance. The molecule contains an azabicyclo-octyl group which confers special properties on the basic sulphonylurea moiety. Gliclazide stimulates insulin secretion through the beta cell sulphonylurea receptor, and possibly through a direct effect on intracellular calcium transport. It specifically improves the abnormal first phase insulin release in type 2 diabetes, and also has an effect on the second phase. This pattern of insulin release is thought to explain the lower incidence of hypoglycaemic episodes and weight gain compared with some other sulphonylureas. There is also a reduction in hepatic glucose production and improvement in glucose clearance, without changes in insulin receptors. This suggests a possible post-receptor effect on insulin action, perhaps by stimulation of hepatic fructose-2,6-bisphosphatase and muscle glycogen synthase. Gliclazide reduces platelet adhesion, aggregation and hyperactivity and increases fibrinolysis. These actions, thought to be independent of its hypoglycaemic activity, may make gliclazide useful in halting the progression of diabetic microangiopathy.
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PMID:The mode of action and clinical pharmacology of gliclazide: a review. 179 62

Three studies were performed to assess the efficacy of various sulphonylureas in the management of diet-failed NIDDM patients. In the first study, 224 patients inadequately controlled by diet alone or with oral hypoglycaemics received gliclazide in addition to diet or in place of existing drugs for three months. The dosage was adjusted to obtain adequate control or up to the maximum recommended dosage. Good glycaemic control was achieved in 65% of patients. Conversion from other oral hypoglycaemics to gliclazide led to an improvement in control except in cases previously treated with glibenclamide. In the second study, diabetic control was compared in 112 NIDDM patients treated concurrently for one year with chlorpropamide, glipizide, gliquidone, glibenclamide or gliclazide. On the basis of HbA1 levels, the best results were obtained with glibenclamide and gliclazide, leading to normal HbA1 levels in 74% and 80% of patients, respectively. In the third study, secondary failure rates were assessed in 248 NIDDM patients treated for five years with gliclazide, glibenclamide or glipizide. Gliclazide had the lowest secondary failure rate (7%) and was significantly better than glipizide (25.6% failures in five years), but the difference relative to glibenclamide (17.9%) just failed to reach the threshold of significance. The results of these studies show that gliclazide is a potent hypoglycaemic agent which compares favourably with others of its type. It has a low incidence of side effects, few problems with hypoglycaemia, and retains its efficacy longer than other sulphonylureas. Gliclazide may therefore be considered a first choice for the therapy of diet-failed NIDDM patients.
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PMID:Efficacy of gliclazide in comparison with other sulphonylureas in the treatment of NIDDM. 179 68

The efficacy and safety of gliclazide (Diamicron) were studied in 29 NIDDM patients (19 men and 10 women aged 25-68 years) who failed to improve with diet or with diet plus a sulfonylurea. All patients were overweight and had fasting blood glucose levels consistently above 150 mg/dl (8.24 mmol/l). After withdrawal of oral hypoglycemics where applicable, they received 40 mg Diamicron three times daily with meals. The dose was increased by 40-80 mg/day until optimum control was obtained or up to a maximum of 320 mg/day. Treatment lasted for 12 months. At the end of this period the mean fasting blood glucose level had fallen by 35% from 238 to 154 mg/dl and the mean 2-h postprandial blood glucose level had fallen by 28% from 237.7 to 195 mg/dl. The mean glycosylated hemoglobin level also fell by 30% from 10.10 to 7.02%, i.e. within the normal range. In addition, there was a 19% fall in triglyceride and a 10% fall in cholesterol levels, with no change in body weight. No changes were observed for serum insulin, C-peptide and glucagon levels, thyroid function tests, blood counts, liver and kidney function tests, uric acid, electrolytes, blood pressure or heart rate. No clinical or ECG abnormalities were observed in patients with or without cardiovascular disease. There were two presumptive hypoglycemic reactions, but these did not require treatment. Adverse effects were reported by 22 patients, including dizziness and light-headedness, diarrhea, nausea, palpitations and pruritus, but none required modification of Diamicron therapy. The results therefore show that Diamicron is safe, effective and well tolerated in suitably selected NIDDM patients.
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PMID:Evaluation of the efficacy and safety of Diamicron in non-insulin-dependent diabetic patients. 179 70

Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of morbidity and mortality worldwide, with a prevalence of 3-7% in most Western countries. Decreased insulin secretion and diminished tissue insulin sensitivity are both implicated in the pathogenesis of the disease; both may be exacerbated by persistent hyperglycemia and improved by normalization of blood sugar levels. Measures to control hyperglycemia, hypertension, and hyperlipidemia are important in the management of NIDDM and prevention of its long-term complications. The effects of dietary modification, exercise, and antihypertensive and antiplatelet therapy, as well as of pharmacologic control of blood sugar, on the vascular and renal complications of NIDDM have been investigated. Gliclazide is a second-generation sulfonylurea drug whose efficacy in the treatment of NIDDM, alone or in combination with insulin, has been widely demonstrated. Studies of the use of gliclazide, reported at recent symposia, are summarized in this review.
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PMID:Current status of non-insulin-dependent diabetes mellitus (type II): management with gliclazide. 187 2

Sulfonylureas act as hypoglycemic agents by stimulating insulin secretion and improving insulin sensibility by a post-receptor mechanism. Their long term results mainly depend on extra-pancreatic mechanisms. Moreover they indirectly decrease triglyceridemia. Glipizide and gliclazide enhance fibrinolysis. Gliclazide also inhibits platelet aggregation and adhesion. The best indication of sulfonylureas is non insulin dependent diabetes with normal weight.
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PMID:[Mode of action of hypoglycemic sulfanilamides]. 194 7

Gliclazide has been reported to possess the properties of preventing the progression of diabetic retinopathy and of controlling blood glucose levels. This report describes a long-term comparative clinical trial of this agent to assess its efficacy against diabetic retinopathy. One hundred and fifty-nine NIDDM patients with no retinopathy or with simple retinopathy entered this trial. One hundred and nineteen patients receiving other sulfonylurea agents were randomly allocated to two groups (G: gliclazide, SU: other sulfonylureas). Forty patients continued to be treated with diet alone (D group). Finally a total of 60 patients, that is, 21 patients in the G group, 19 patients in the SU group, and 20 patients in the D group, were followed with funduscopic examinations for more than 4 years. The results are summarized as follows. (1) Distribution of background factors between the two drug therapy groups was balanced, but in the D group more male patients and relatively milder cases were involved than in the drug therapy groups. (2) Fasting blood glucose control in the three groups was not significantly different. (3) Funduscopic deterioration was observed less frequently, though not significantly, in the G group than in the other groups. (4) Progression to preproliferative retinopathy was significantly less frequent in the G group than in the SU group. Thus, gliclazide seems to have additional properties compared with other sulfonylurea drugs in preventing deterioration of diabetic retinopathy, and particularly in preventing progression to proliferative retinopathy.
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PMID:Long-term comparison of oral hypoglycemic agents in diabetic retinopathy. Gliclazide vs. other sulfonylureas. 341 10

The effect of prolonged gliclazide treatment on diabetic metabolic control was studied in 10 subjects with non-insulin dependent diabetes mellitus. Patients were examined before, after 15 days of treatment with diet alone and, again, after 60 days of treatment with diet plus gliclazide. Gliclazide did not restore the abnormality of blood glucose, free insulin and C-peptide response to an intensive stimulus of glucose load, although fasting and after-load blood glucose, fasting glycosylated haemoglobin, alanine and lactate significantly decreased after prolonged treatment with diet plus gliclazide, but not with diet alone. These findings support the assumption that the efficacy of prolonged treatment with gliclazide might be related to its extrapancreatic effects on glucose homeostasis.
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PMID:Effect of prolonged gliclazide therapy in non-insulin dependent diabetic subjects. 390 80

Sixty-eight cases of non-insulin dependent diabetes mellitus (NIDDM) complicated with nephropathy were randomly divided into two groups: treated group, 35 cases treated with alcohol extraction of Abelmoschus manihot, Gliclazide and Captopril tablets; control group, 33 cases treated with Gliclazide and Captopril tablets, over a period of 8 weeks. The total effective rate in treated and control group were 83.87% and 31.03%(P < 0.01), urinary micro-albumin were 31.7 mg/L and 76.3 mg/L (P < 0.05), proteinuria were 0.41 g/24h and 0.77 g/24h (P < 0.01), blood beta 2-microglobulin were 3317.8 ng/ml and 3473.1 ng/ml (P < 0.05), urinary beta 2-microglobulin were 367.2 ng/ml and 641.5 ng/ml (P < 0.01), urinary N-acetyl-beta-glucosaminidase (NAG) were 26.3 u/L and 66.7 u/L (P < 0.01), plasma lipid peroxide (LPO) were 6.13 nmol/L and 8.78 nmol/L (P < 0.05), and plasma superoxide anion were 8.36 kcpm and 10.42 kcpm respectively (P < 0.05). It was suggested that Abemoschus manihot alcohol extraction could eliminate oxygen free radicals, alleviate renal tubular-interstitial diseases, improve renal function and reduce proteinuria.
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PMID:[Clinical observation on diabetic nephropathy treated with alcohol of Abelmoschus manihot]. 764 Apr 95

A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake in vivo and in vitro. Here we use a longitudinal design to investigate the effects of 8 weeks of therapy with the sulfonylurea gliclazide on glycemic control, glucose tolerance, insulin-stimulated glucose disposal, and GLUT4 expression in muscle of 10 obese NIDDM subjects. Subjects were on a weight-maintaining diet. Gliclazide treatment results in increased serum C-peptide, decreased hemoglobin-A1c, decreased glucose excursion on glucose tolerance test, and 35% increased insulin-stimulated glucose disposal. Gliclazide therapy is not associated with any change in DNA or protein content per g muscle or any alteration in GLUT4 levels expressed either per microgram membrane protein or per DNA. In summary, the improvement in glycemic control and glucose disposal in NIDDM subjects receiving gliclazide therapy cannot be explained by increased expression of GLUT4 in muscle. Thus, therapeutic effects on insulin-stimulated glucose disposal can be achieved in NIDDM subjects without altering GLUT4 expression in muscle.
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PMID:Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects: a longitudinal study. 782 24


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