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

Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.
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PMID:Adverse cardiovascular effects of sulphonylurea drugs. Clinical significance. 329 23

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.
Diabetes Res Clin Pract 1988 Jul 13
PMID:Long-term comparison of oral hypoglycemic agents in diabetic retinopathy. Gliclazide vs. other sulfonylureas. 341 10

Gliclazide has been reported to decrease platelet function and to inhibit the progression of diabetic retinopathy in addition to having a hypoglycemic effect. To confirm these effects we performed a double-blind randomized study using glibenclamide as a reference drug. Thirty-eight hospitals from eight university groups in Japan performed the study on type II diabetic subjects. Evaluation of blood glucose control, platelet adhesiveness, platelet aggregation and blood lipids over 24 weeks were assessed by the central committee. Two hundred and eighty-nine patients were enrolled in the study. Twelve were excluded and 277 were statistically analysed. Homogeneity between the two diabetic groups was demonstrated for background factors. Forty mg of gliclazide was comparable to 2.5 mg of glibenclamide in the potency of hypoglycemic efficacy. Funduscopic aggravations were observed in a statistically smaller number of cases in the gliclazide group than in the glibenclamide group and in evaluation of serum lipids, the gliclazide group was also superior to the glibenclamide group. No significant difference between the two groups was found in platelet adhesiveness and aggregation. Gliclazide is a useful drug in the therapy of diabetes mellitus.
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PMID:Comparison of gliclazide and glibenclamide treatment in non-insulin-dependent diabetes. 644 Mar 13

Gliclazide is a second generation sulphonylurea oral hypoglycaemic agent used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It improves defective insulin secretion and may reverse insulin resistance observed in patients with NIDDM. These actions are reflected in a reduction in blood glucose levels which is maintained during both short and long term administration, and is comparable with that achieved by other sulphonylurea agents. Gradually accumulating evidence suggests that gliclazide may be useful in patients with diabetic retinopathy, due to its haemobiological actions, and that addition of gliclazide to insulin therapy enables insulin dosage to be reduced. Thus, gliclazide is an effective agent for the treatment of the metabolic defects associated with NIDDM and may have the added advantage of potentially slowing the progression of diabetic retinopathy. These actions, together with its good general tolerability and low incidence of hypoglycaemia have allowed gliclazide to be well placed within the array of oral hypoglycaemic agents available for the control of NIDDM.
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PMID:Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. 769 11

The clinical studies have demonstrated that patients showed significant improvements in their oxidative status after 3 months treatment. This improvement in oxidative status which was associated with a reduction in platelet reactivity, remained constant for the rest of the study period. The effect was independent of glycaemic control. The demonstration of a benefit to clinical vascular disease has proved difficult to achieve in all studies of non-insulin dependent diabetes. This is due to the multifactorial nature of complications and the long duration of disease required before microvascular complications such as retinopathy became apparent. The Japanese Diabetic Retinopathy Program24 studied the progression of retinopathy over a 5 year period comparing Gliclazide with other sulphonylureas and with placebo. The study suggested that with equivalent metabolic control there was a trend towards a lower rate of deterioration of retinopathy and a significantly lower incidence of pre-proliferative retinopathy in the group receiving Gliclazide compared with patients receiving other sulphonylureas or placebo. There is little comparative evidence on the effect of specific sulphonylureas on large vessel disease. Although improvement in parameters of hyperglycaemia is associated with an improvement in morbidity from large vessel disease. In Type II diabetes atherosclerosis coexists in the majority of patients and often predates the clinical diagnosis of diabetes. The presence of atherosclerosis which often determines the ultimate fate of the patient, further increases the level of lipid peroxidation of oxidative stress, amplifying the effects of hyperglycaemia and potentiating vascular damage. In diabetes, therefore where increased glycation and oxidation are fundamental in the pathogenesis of diabetic vascular disease agents such as Gliclazide with anti-oxidant activities may have an enhanced therapeutic role.
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PMID:The potential of gliclazide, a sulphonylurea to influence the oxidative processes within the pathogenesis of diabetic vascular disease. 777 Dec 62

We investigated the stimulatory effect of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on insulin secretion using isolated, perfused pancreases of rats. In the pancreases from normal rats, M16209 (100 microM) greatly augmented glucose-stimulated insulin secretion, but showed no effect on unstimulated insulin secretion at 2.8 mM glucose. In contrast, gliclazide (10 microM), a sulfonylurea, strongly enhanced both glucose-stimulated and unstimulated insulin secretion. Sorbinil and epalrestat, potent aldose reductase inhibitors, had no stimulatory effect on insulin secretion. M16209 (100 microM) improved appreciably the decreased insulin response to 22.2 mM glucose and enhanced slightly unstimulated insulin secretion in the pancreases of rats with neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM). Gliclazide (10 microM), however, failed to affect the pancreases of NIDDM rats. Furthermore, M16209 showed no appreciable effect on ATP-sensitive K(+)-channels in pancreatic beta-cells. These results suggest that M16209, unlike sulfonylureas, selectively enhances glucose-stimulated insulin secretion in both normal and NIDDM rats through a direct action on the pancreas. The site of action remains unknown, but the inhibition of aldose reductase or the ATP-sensitive K+ channels is unlikely to be involved.
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PMID:Effects of M16209 on insulin secretion in isolated, perfused pancreases of normal and diabetic rats. 778 99

Gliclazide is a second-generation sulfonylures that is widely used in the treatment of non-insulin-dependent diabetes mellitus (Type 2 diabetes). 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 Type 2 diabetes. 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 specified. It has proven difficult to separate the metabolic effects of gliclazide form the effects of improved control. The metabolic actions are probably also shared with over 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. 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 Type 2 diabetes with diet failure, both from the metabolic and non-metabolic standpoint.
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PMID:[Gliclazide: review of metabolic and vascular action]. 782 78

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

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with an increased risk of macro- and microvascular degenerative complications. Gliclazide is a second generation sulfonylurea that is widely used in the treatment of type II diabetes mellitus. Its hypoglycemic activity is well documented. In addition to its metabolic effects, gliclazide has beneficial effects on the hemobiological abnormalities of NIDDM. These effects are mediated by the azabicyclo-octyl ring grafted on to its aulfonylurea core. Numerous studies have demonstrated that gliclazide reduces platelet hyperadhesion and platelet hyperaggregability. These actions have been extensively confirmed in diabetic patients over periods of up to 3 years. With regard to platelet functions, several groups have demonstrated a significant reduction in serum and intraplatelet beta thromboglobulin and thromboxane B2. In animal models, in-vitro and in-vivo gliclazide stimulates endothelial prostacyclin synthesis. The beneficial effects of the compound on thromboxane/prostacyclin balance have been recently confirmed in type II diabetic patients after a 3-month treatment period. Concerning fibrinolysis, gliclazide restores low plasminogen activity to normal in NIDDM patients previously treated with first-generation sulfonyl-ureas. Gliclazide increases fibrinolytic potential by increasing endothelial cell tissue plasminogen activator and pre-kallikrein activity. More recent studies suggest that gliclazide may have effects on fibrin network structure, rendering the fibrin more amenable to fibrinolysis. Finally, it has been shown that gliclazide has a potent free-radical-scavenging activity in vitro. This property has been recently confirmed in vivo in type II diabetic patients and may suggest that platelet reactivity and oxidative stress are related in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Hemobiological properties of gliclazide. 783

1. A 6-week gliclazide treatment improved left ventricular developed pressure and left ventricular end-diastolic pressure, left ventricular pressure-rate products in isolated working hearts from streptozotocin-induced diabetic rats. 2. Post-ischemic recovery in heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, left ventricular pressure-rate products and cardiac work were also shown in gliclazide-treated diabetic rats. 3. Gliclazide treatment did not modify the degree of insulinopenia and hyperglycemia, nor the myocardial energy metabolism during ischemia-reperfusion. 4. The results suggest that the gliclazide treatment has a cardioprotective effect on basal and post-ischemic cardiac functions of chronic diabetes.
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PMID:Chronic gliclazide treatment affects basal and post-ischemic cardiac function in diabetic rats. 795 31


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