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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gliclazide is an oral hypoglycaemic agent which has been shown in animal models to reduce platelet adhesiveness. In this study, 50 patients with maturity onset diabetes treated with gliclazide (80 mg/day) were followed up for 6 months to 1 year to assess the effect on platelet adhesiveness and control of blood sugar. A significant fall in mean platelet adhesiveness from 29% before treatment to 19.5% after 1 year (p less than 0.001) was achieved without any deleterious effect on normal haemostasis. The drug was well tolerated and achieved a satisfactory control of blood sugar levels at the dosages used.
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PMID:Effect on platelet adhesiveness in diabetics after long-term treatment with a new oral hypoglycaemic agent, gliclazide. 36 47

Exponentially growing rat islet cells (RINr) and hamster islet cells (HIT T-15) were incubated in presence of tolbutamide (10-1000 microM), gliclazide (0.1-10 microM) or glibenclamide (0.01-10 microM) for 15 hrs. Accumulation of insulin in culture medium was estimated by RIA. Effects of sulfonylureas (SU) on cell proliferation were assessed by 3H-thymidine (3H-T) incorporation into cellular DNA. All of SUs used stimulated insulin production in RIN and HIT cell cultures (with an exception of tolbutamide, which markedly suppressed insulin secretion in HIT cells at 1000 microM). 3H-T incorporation into RIN cells was elevated only in presence of gliclazide (10 microM), whereas tolbutamide at 1000 M significantly inhibited RIN cell proliferation. Gliclazide (0.1 microM) and glibenclamide (0.01-10 microM) enhanced 3H-T incorporation into HIT cells. Further detailed investigations of mechanisms of SU effects on islet cell reproduction will be of use for designing optimal strategy of hypoglycemizing therapy of diabetes mellitus.
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PMID:[The insulin-secreting and proliferative activity of established islet cells in the presence of sulfonylurea]. 128 6

In clinical practice of hypoglycemic therapy of diabetes mellitus the problem of the optimal selection of oral hypoglycemic agent, corresponding to the individual patterns of regulatory and metabolic disturbances is of primary importance. The individual, pathophysiological basis should be met as much as possible by the pharmacodynamic properties of the selected, hypoglycemic drug. For this reason group of 23 diabetics type II underwent a prolonged, open trial of controlled pharmacotherapy with 4 sulphonylurea derivatives. Pertinent clinical and metabolic parameters were assessed before, during and after planned periods of therapy with Tolbutamide or Chlorpropamide to Gliclazide and Gliclazide to Glibenclamide. In the same time the levels of serum insulin fasting and after breakfast were determined. Also the comparative efficacy of the exchange of the drug in a subgroup of diabetics with fasting glycemia below and above 160 mg% was assessed. It was shown, that the change of Tolbutamide or Chlorpropamide to Gliclazide or Glibenclamide improved the therapeutical effectiveness in general. The individual responses to such a change were however individually differentiated. The change of Tolbutamide or Chlorpropamide to Gliclazide increased the therapeutical efficacy only in these patients, in whom such a change was associated with an increase of prandial, reactive serum insulin level (IRI). In practice they were patients with the fasting glycemia lower than 160 mg%. In patients with fasting glycemia higher than 160 mg% the change of oral compounds under study was not connected with an increase of prandial serum insulin. The metabolic parameters have not improved either. Perhaps they were patients with diabetes mellitus type II, who should be primarily qualified to insulin.
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PMID:[Relative effectiveness of tolbutamide, chlorpropamide and gliclazide]. 140 40

Gliclazide is a second-generation sulfonylurea that is widely used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been recommended for use on the basis of both its metabolic and nonmetabolic effects. It has a clear beneficial effect on metabolic control in NIDDM. Blood glucose and lipid levels are lowered. The glucose-lowering effects are secondary to both enhanced insulin secretion and a decrease in insulin resistance. The former is due to closure of a K+ adenosine triphosphate (ATP) channel in the beta cell. The mechanism whereby insulin action on the liver and muscle are potentiated remains unknown. It does not appear to involve the insulin receptor, and although glycogen synthase activation is enhanced, this is probably not specific. It has proven difficult to separate the metabolic effects of gliclazide from the effects of improved control. The metabolic actions are probably also shared with other sulfonylureas. Gliclazide also has beneficial effects on platelet behavior and function and on the endothelium, in addition to improving free radical status. These effects should be beneficial for the prevention of diabetic microangiopathy and macroangiopathy. Some evidence has appeared for the prevention of deterioration of diabetic retinopathy, but results are variable and more convincing studies are required. Many of the nonmetabolic effects of gliclazide appear to be unique to this agent. Gliclazide thus appears to be a reasonable choice in the treatment of NIDDM with diet failure, both from the metabolic and nonmetabolic standpoint.
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PMID:Gliclazide: metabolic and vascular effects--a perspective. 157 15

Using measurements of fibrin fibre thickness (microT) derived from turbidity and permeability (tau) of clotted plasma, it has been found that glucose in vitro added to plasma decreases permeability of the network despite unaltered fibrinogen conversion. Fibrin fibre thickness (microT) in uncontrolled diabetes is found significantly reduced. In diabetic plasma the degree of conversion to fibrin is similar to that in age and sex matched plasma from non-diabetics: the effect on fibrin network and fibre thickness probably arises from glycosylation of fibrinogen. Studies with Gliclazide, Metformin, Glibenclamide and insulin have shown that while all other drugs tested have no effect, Gliclazide increases fibrin fibre thickness (microT) significantly, diminishes tensile strength and reduces permeability. In separate experiments lysability of 125I-labelled fibrin networks developed in the presence of all four hypoglycaemic agents by tissue activator was tested. Networks developed in the presence of Metformin were found to lyse more quickly, followed by insulin and Gliclazide. Alterations induced in fibrin networks in diabetes may be nullified by some oral hypoglycaemic agents such as Gliclazide and not by others. Whether nullification of such changes has long-term effects in reducing the incidence of vascular disease in diabetics remains to be established.
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PMID:Studies on fibrin network structure in human plasma. Part II--Clinical application: diabetes and antidiabetic drugs. 178 32

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.
Diabetes Res Clin Pract 1991
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.
Diabetes Res Clin Pract 1991
PMID:The mode of action and clinical pharmacology of gliclazide: a review. 179 62

We studied, in healthy subjects (n = 4) and in non-insulin-dependent diabetics (n = 4), the effect of a new sulfonylurea, Diamicron, on the secretion and action of insulin, using a mathematical model. This model analyzed, during an intravenous glucose tolerance test, the response of the first and second phase of insulin secretion in relation to the variations in blood glucose (insulin secretion) and the rate of decline in the blood glucose curve in relation to the variations in insulin (insulin response). Each subject was studied twice: once after administration of placebo and once after administration of Diamicron 80 mg 90 min after intravenous injection of 300 mg/kg of D-glucose. In healthy subjects, the glucose load after placebo induced an insulin response of 7.4 +/- 1.0 and 11.3 +/- 1.4 microU ml-1 min-1 mg-1 dl-1 for the first and second phases, respectively, and an insulin sensitivity evaluated to be 4.7 +/- 0.3 min microU-1 ml-1. Following the administration of Diamicron, the insulin response to the same glucose load increased two-fold and five-fold for the first and second phases, respectively, and the insulin sensitivity also increased by a factor of 2. In diabetic subjects the insulin response to the glucose load after placebo was markedly decreased (2.2 +/- 0.5 and 2.5 +/- 0.3 microU ml-1 min-1 mg-1 dl-1, respectively) as was the insulin sensitivity (2.5 +/- 0.3 min microU-1 ml-1). The administration of Diamicron increased all these parameters by a factor of 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1991
PMID:The effect of Diamicron on the secretion and action of insulin. 179 65

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.
Diabetes Res Clin Pract 1991
PMID:Efficacy of gliclazide in comparison with other sulphonylureas in the treatment of NIDDM. 179 68

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.
Diabetes Res Clin Pract 1991
PMID:Effect of 6 months' gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial CSII-induced normoglycemia. 179 69


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