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M S Huijberts

Publications and source records attributed to M S Huijberts.

11 recordsLinked to original sources
PubMed2001

[Disorders of lipid metabolism in 3 patients with diabetes mellitus type 2].

Three patients with diabetes mellitus (type 2) and cardiovascular disease had disturbed lipid concentrations: two women aged 60 and 73 years and one man aged 47 years. The lipid levels were normalised during the 9-18 years of treatment with medication and in this period the patients experienced no cardiovascular events. Disturbances in plasma lipid levels play a major role in the increased risk of cardiovascular disease in patients with diabetes mellitus (type 2). Cholesterol-lowering treatment should be aggressive and based on the lipid profile. Statins reduce cardiovascular events by lowering the concentration of both the total cholesterol and low-density lipoprotein cholesterol whereas fibrates reduce cardiovascular events by increasing high-density lipoprotein cholesterol concentrations and lowering triglyceride concentrations.

Aged↗
PubMed2001

Rosiglitazone.

Type 2 diabetes mellitus is characterised by impaired insulin secretion, diminished peripheral insulin action and increased hepatic glucose production. Clinical trials have indicated that near-normal glucose control may reduce the risk for microvascular and - to a lesser extent - macrovascular complications in Type 2 diabetic patients. Thiazolidinediones improve insulin action by activating a nuclear receptor, PPARgamma. Therefore, these drugs are often referred to as 'insulin sensitisers'. Rosiglitazone is the second compound of this group. Clinical studies with rosiglitazone have shown that it is effective in lowering blood glucose levels in Type 2 diabetic patients treated with either diet alone, sulphonylurea or metformin. Preliminary studies suggest that rosiglitazone also improves glycaemic control in insulin-treated patients while even slightly decreasing insulin dose. The magnitude of the effects is, however, moderate. In diet-treated patients, the reduction of HbA1c levels amounted on average 0.5 - 1.5% and addition to existing sulphonylurea therapy decreased HbA1c by 1.0 - 1.2%. The clinical relevance of additional beneficial effects, i.e., on blood pressure and microalbuminuria, needs to be determined further. Rosiglitazone does not cause hypoglycaemia or gastrointestinal side effects. There is however some concern related to fluid retention, which seems to be an effect of all PPARgamma agonists. In patients treated with rosiglitazone, no severe hepatotoxic side effects have been noticed until now. In the treatment of our patients with Type 2 diabetes, drugs like rosiglitazone which directly reduce insulin resistance are very welcome but more data on its combined use with insulin are needed. Additional studies will also explore its long-term effects in sparing beta-cell function and reducing diabetes-related complications and atherosclerosis.

Animals↗
PubMed1999

Miglitol, a new alpha-glucosidase inhibitor.

Miglitol (Bay m 1099, Bayer) is a second generation alpha-glucosidase inhibitor. It is a derivative of 1-desoxynojirimycin, and binds reversibly to the brushborder alpha-glucosidase enzymes. In contrast to its parent drug (acarbose, Bay g 5421, Bayer), miglitol is almost completely absorbed in the small intestine. It has to be taken with each main meal, and through its effect on carbohydrate digestion it blunts the postprandial blood glucose increase. Miglitol has no or a very small effect on fasting blood glucose levels. The blood-glucose lowering effects of miglitol in patients with Type 2 diabetes are lower than those of the frequently-used sulphonylurea compounds. Long-term studies show that a moderate average reduction of HbA1c of 0.3-0.7% point from baseline can be achieved. An advantage over sulphonylurea is the effect on serum insulin levels: miglitol therapy leads to slightly lower postprandial levels of serum insulin, whereas chronic sulphonylurea treatment usually increases serum insulin levels. This insulin-sparing effect may, in theory, lead to a lesser weight gain or even no weight gain and reduced risk of hypoglycaemia during chronic treatment. Long-term experience in Type 1 diabetic patients is limited. Similarly, miglitol may lead to reduced postprandial glucose excursions, slightly reduced insulin requirements and perhaps, as a consequence, a lower risk of hypoglycaemia. More long-term data are needed to fully assess to the clinical use of miglitol in these patients.

1-Deoxynojirimycin↗
PubMed1998

Breakers of advanced glycation end products restore large artery properties in experimental diabetes.

Glucose and other reducing sugars react with proteins by a nonenzymatic, posttranslational modification process called nonenzymatic glycation. The formation of advanced glycation end products (AGEs) on connective tissue and matrix components accounts largely for the increase in collagen crosslinking that accompanies normal aging and which occurs at an accelerated rate in diabetes, leading to an increase in arterial stiffness. A new class of AGE crosslink "breakers" reacts with and cleaves these covalent, AGE-derived protein crosslinks. Treatment of rats with streptozotocin-induced diabetes with the AGE-breaker ALT-711 for 1-3 weeks reversed the diabetes-induced increase of large artery stiffness as measured by systemic arterial compliance, aortic impedance, and carotid artery compliance and distensibility. These findings will have considerable implications for the treatment of patients with diabetes-related complications and aging.

Animals↗
PubMed1994

Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats.

Advanced glycation end-product-formation is thought to play a role in the development of diabetic angiopathy. By altering the structure of different extracellular matrix components advanced glycation end-products might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation end-product-formation, aminoguanidine, on vascular permeability and the development of albuminuria in streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a control group, a diabetic group, and an aminoguanidine-treated diabetic group. After 8 weeks, 24-h urine collections were taken and rats were implanted with an arterial and a venous catheter. mean arterial blood pressure was determined by intra-arterial measurement. Regional albumin clearances were assessed in the eye, ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial pressure in the diabetic group was significantly lower in the control and aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were significantly increased in all tissues of diabetic rats compared to control rats (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant decrease of regional albumin clearance in all tissues except the lung (p < 0.05, lung p = 0.07). The development of albuminuria in diabetic rats however, was not affected by aminoguanidine.

Albuminuria↗
PubMed1993

Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats.

The accumulation of advanced glycosylation end-products (AGEs) on collagen and the subsequent stiffening of this matrix protein in diabetes has been described many years ago. Structural modification of collagen in the arterial wall might have important effects on arterial elasticity. Aminoguanidine is known to decrease the formation of AGEs. In this study we evaluated the effects of aminoguanidine treatment on different parameters reflecting arterial wall elasticity in diabetic rats. We demonstrated that treatment of diabetic rats with aminoguanidine resulted in a significant increase in carotid static compliance (+39%, P < 0.01 under control conditions, and +27%, P < 0.01 after abolition of vascular tone by KCN), and a decrease in characteristic aortic input impedance (-40%, P < 0.01). The arterial pulse pressure in aminoguanidine-treated rats was decreased (-15%, P < 0.05) and the pulsatile component of left ventricular power output was relatively diminished (-35%, P < 0.05). In addition, we observed a lower fluid filtration across the carotid wall. These results indicate an increased vascular elasticity, an improved left ventricular-arterial coupling, and a decreased vascular permeability in diabetic rats after aminoguanidine treatment, suggesting that AGE-accumulation on collagen negatively affects arterial wall properties in experimental diabetes.

Animals↗
PubMed1992

The microcirculation and hypertension.

AIM: To review published evidence on the effects of arteriolar changes in primary and secondary hypertension. BACKGROUND: Pressure profile analyses have shown that the microcirculation is a major site of vascular resistance. With the recent refinement of intravital microscopy techniques detailed information has become available on mechanisms of the microvascular resistance increase in hypertension. Three mechanisms play an important role: (1) a decrease in arteriolar diameter; (2) arteriolar vessel wall hypertrophy; and (3) small arteriolar and capillary rarefaction. METHOD: The evidence was synthesized into a hypothesis on the role of the microcirculation in primary forms of hypertension. HYPOTHESIS: The hypothesis formulated contains two important elements in that (1) diminished outgrowth of the microvascular bed in different tissues is seen as an important early pathogenic mechanism; and (2) the decreases in arteriolar diameter and vessel wall hypertrophy are seen as adaptive mechanisms that maintain a constant wall stress. The three factors together maintain the increase in vascular resistance that is common to all established forms of primary hypertension.

Animals↗
PubMed1989

Effects of bepridil on conduction properties of the isolated rabbit sinus node and atrial myocardium.

In the isolated rabbit sinus node and right atrial myocardium, the effects of bepridil (1-6 x 10(-6) M) on impulse formation, impulse conduction, and tissue refractoriness were examined. In the sinus node, drug concentrations between 1 and 3 x 10(-6) M were tested. In the border zone of the sinus node, bepridil (3 x 10(-6) M) reduced impulse conduction velocity by 65% and prolonged the effective refractory period by 81% (n = 11). In the center of the sinus node, bepridil in a concentration of 2.5 x 10(-6) M decreased impulse conduction velocity by 78% and prolonged effective refractory period by 77% (n = 9), whereas a drug concentration of 3 x 10(-6) M blocked impulse conduction systematically. Despite these marked effects on nodal conduction properties, only limited effects on sinus rate were found. Conduction properties in the atrium were affected by bepridil as well, but higher concentrations (4-6 x 10(-6) M) were needed. Impulse conduction velocity was decreased by 57%, and the effective refractory period was prolonged by 73% (6 x 10(-6) M; n = 8). At these higher drug concentrations, sinus automaticity decelerated and ceased abruptly, after which only subthreshold oscillations were detectable. From these findings, we concluded that (a) bepridil reduces impulse conduction velocity and prolongs refractoriness in the sinus node, less markedly in the atrial myocardium; (b) bepridil affects nodal impulse conduction prior to nodal impulse formation; and (c) bepridil possesses both "fast channel" and "slow channel" inhibitory properties.

Action Potentials↗
PubMedDate not supplied

Peripheral vascular disease and type 2 diabetes mellitus.

Patients with Type 2 diabetes mellitus frequently have peripheral vascular disease, with a predilection for the lower legs. In this review potential mechanisms for this high prevalence and altered distribution are explored. It is hypothesised that the metabolic abnormalities in the prediabetic phase predispose to a more distal and aggressive atherosclerosis. Once diabetes has developed this process is accelerated due to chronic hyperglycaemia. Furthermore, endothelial damage, non-enzymatic glycosylation and polyneuropathy could lead to impaired vascular remodelling and collateral formation.

Diabetes Mellitus, Type 2↗