[Newly manifested type IIb diabetes presents with significant hyperinsulinemia].

Background: Data concerning the insulin status in the early phase of NIDDM are controversial.

Patients And Method: Since this has therapeutical implications, ten patients were identified with new-onset type 2 diabetes, defined by fasting blood glucose concentrations below 120 mg/dl, no previous history of diabetes and venous blood glucose concentrations at 120 min of an oral glucose tolerance test above 200 mg/dl (x 262 +/- 15 mg/dl) ("diabetic glucose tolerance"). Ten subjects with normal glucose tolerance and no familial history of NIDDM, who were matched for gender, age (n: 56 +/- 2 years, D: 61 +/- 5) and BMI (n: 28 +/- 1, D: 28 +/- 1), served as control group.

Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study.

Background: Hypertensive patients frequently show resistance to insulin-stimulated glucose uptake and hyperinsulinemia. Diuretics and beta-adrenoceptor blocking agents have been found to decrease insulin sensitivity, whereas alpha 1-blockers and angiotensin converting enzyme inhibitors seem to improve it.

Objective: To compare the effects of a 3 months' antihypertensive treatment with carvedilol, a non-selective beta-adrenoceptor blocker with alpha 1-blocking properties, with the beta 1-selective receptor blocker metoprolol on insulin sensitivity in non-diabetic hypertensive patients.

Insulin-induced glucose transporter (GLUT1 and GLUT4) translocation in cardiac muscle tissue is mimicked by bradykinin.

The effect of bradykinin on glucose transporter translocation in isolated rat heart was compared with the effect of insulin. Hearts from male obese (fa/fa) Zucker rats were perfused under normoxic conditions and constant pressure in a classic Langendorff preparation with 12 mmol/l glucose as substrate, and a set of functional parameters was measured simultaneously. Bradykinin was administered at a concentration (10(-11) mmol/l) that did not increase coronary flow.

Potential role of bradykinin in forearm muscle metabolism in humans.

Using the euglycemic-hyperinsulinemic glucose clamp and the human forearm technique, we have demonstrated that the improved glucose disposal rate observed after the administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril may be primarily due to increased muscle glucose uptake (MGU). These results are not surprising because ACE, which is identical to the bradykinin (BK)-degrading kininase II, is abundantly present in muscle tissue, and its inhibition has been observed to elicit the observed metabolic actions via elevated tissue concentrations of BK and through a BK B2 receptor site in muscle and/or endothelial tissue. These findings are supported by several previous studies.

Hypertension in the non-insulin-dependent diabetes mellitus syndrome: a critical review of therapeutic intervention.

Background: Since it is not yet clear whether and to what degree treatment of mild hypertension will decrease cardiovascular morbidity and mortality in non-insulin-dependent diabetes (NIDDM), decisions concerning the treatment of hypertension diabetics are at present based on data from the non-diabetic population.

Recent Research On Causes Of Diabetes: A large body of recent work on the sequence of events leading from the prediabetic to the hyperglycemic stages of the NIDDM syndrome has suggested that elevated blood pressure and other cardiovascular risk factors may precede NIDDM by many years and that after the onset of NIDDM intervention might be too late to be beneficial.

Prospective Intervention Study In Progress: It is not possible to draw firm conclusions that can be applied to the treatment of hypertensive diabetics before the results of the United Kingdom Prospective Diabetes Study/Hypertension in Diabetes Study are published later this decade.

New aspects of insulin resistance in hypertension.

Primary hypertension is a frequent polygenic disease with strong genetic and environmental components. During the last decade, evidence has been increasing that insulin resistance as a marker of increased risk for Type 2 diabetes and cardiovascular atherosclerotic disease is present not only in individuals with obesity, Type 2 diabetes and impaired glucose tolerance, but also in the majority of the hypertensive population. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism present in the so called 'metabolic syndrome'.

[How can primary prevention of coronary heart disease be improved in general practice?].

Background: The basic issue of primary prevention strategies of coronary heart disease is an individually adapted cardiovascular risk factor management. However, transformation of these strategies by health care professionals is still insufficient, as was demonstrated by three studies performed in private practice.

Methods And Results: In oral glucose tolerance tests performed in 234 patients with essential hypertension who were under regular medical control, 25.

[The metabolic syndrome. Pathophysiologic causes, diagnosis, therapy].

The individual components of the metabolic syndrome such as central obesity, dyslipidemia with increased triglycerides and decreased HDL-cholesterol, hyperuricemia, hypertension and progressive glucose intolerance are markers for an increased risk of atheroma and type 2 (non-insulin-dependent) diabetes. All components, with the exception of hyperuricemia, are associated with skeletal muscle insulin resistance, leading to compensatory chronic hyperinsulinemia. Insulin resistance/hyperinsulinemia, in turn, is associated with a series of hypertensiogenic and atherogenic side effects, aggravating the individual components of the metabolic syndrome.

Possible synergistic effect of ACE inhibition and calcium-channel blockade on insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.

So-called insulin resistance is a frequent phenomenon and a marker of increased risk for both type II diabetes mellitus and atherosclerosis. Today, insulin resistance is widely understood as a tissue- and pathway-specific defect of insulin-stimulated glucose uptake into skeletal muscle that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated muscle blood flow and cellular kation balance are presently attracting increasing awareness.

What is the clinical significance of insulin resistance?

Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and the majority of the hypertensive population are insulin resistant. Insulin resistance describes a tissue- and pathway-specific defect of glucose metabolism that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes.

Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound.

Fatty infiltration of the liver with cholestasis is one of the complications of total parenteral nutrition (TPN). The cause has not yet been determined. It seems probable, however, that these alterations could be prevented when a mixture of medium- and long-chain triglycerides (MCT/LCT) is used as a fat component instead of the application of long-chain emulsions (LCT) alone.

[Effect of prostaglandin E1 on amino acid metabolism of human skeletal muscle].

The influence of an intraarterial infusion of PGE1 on the amino acid metabolism of human skeletal muscle was examined in healthy volunteers using the forearm technique. A continuous increase of perfusion from 2.9 +/- 0.

[Essential hypertension and diabetes mellitus].

While the incidence of essential hypertension is not increased in type 1 diabetics, it is about three times as high in type 2 diabetics. Since in 50% of the cases, hypertension is present before the metabolic disorder becomes manifest, an association between the etiologies of the two disturbances was suspected as long as 65 years ago. A new understanding of the significance of insulin resistance and hyperinsulinemia suggests that the two conditions are part of a single metabolic disorder.

[ACE-inhibitors and glucose metabolism].

ACE-inhibitors exhibit their blood pressure-lowering activity not only via a reduction of angiotensin II but also via on increase of kinin levels. The latter are known to improve insulin action and hence carbohydrate metabolism in normal volunteers and diabetics. Accordingly, ACE-inhibitors display the same effects.

Clinical studies with CE-inhibitors in diabetes.

Early antihypertensive intervention in diabetes often means intervention in a cluster of cardiovascular risk factors including glucose intolerance per se, hyperlipidemia, obesity and hypertension, which are not just coexistent but may be causally linked together by the resistance of peripheral tissues to the action of insulin. Blood pressure lowering treatment should therefore be metabolically neutral in order to avoid aggravation of this risk factor syndrome. Clinical studies applying CE-inhibitors in type II diabetes are critically reviewed under this aspect.

Effects of beta-blocking agents on insulin secretion and glucose disposal.

Non-selective and to a lesser extent selective beta-blockers are known to slightly deteriorate glucose metabolism. This may be of clinical relevance, since patients with essential hypertension suffer from reduced insulin-sensitivity and some studies showed an increased incidence of diabetes type II with beta-blocker-treated hypertensive patients. However, it is not clear whether this effect is due to hypertension per se or in addition by antihypertensive treatment.

Metabolic effects of kinins: historical and recent developments.

In 1928, Frey and co-workers discovered kallikrein in human urine and described its prolonged hypotensive effect in the dog. Four years later, the same authors first reported a blood glucose-lowering effect of orally administered kallikrein in diabetic patients. However, the observed blood glucose-lowering effect of kallikrein appeared to fade with repeated administration, and therefore its possible metabolic role was not further investigated and fell into disregard.

[Artificial nutrition of diabetic patients].

For total parenteral nutrition in diabetes, the same relation between carbohydrates, fat and protein of 50, 30-35 and 15-20% of total calories as in regular oral feeding has to be taken. For carbohydrates, a 2:1:1 mixture of fructose, glucose and xylitol should be used, since this is to a lesser extent blood glucose level raising as glucose alone and the dose-dependent side effects of the sugar substitutes are negligible. If insulin is infused intravenously, it is important that the carbohydrates are given simultaneously, in order to prevent deleterious hypoglycemnia.

Local generation of kinins in working skeletal muscle tissue in man.

The effect of standardized isometric forearm work on circulating and local kinin concentrations was investigated in 12 healthy volunteers using the forearm catheter technique. Radioimmunological kinin determination in arterial blood and in the venous effluent of forearm muscle tissue was performed using a modification of Shimamoto's technique of blood sampling and kinin extraction. Under basal conditions, there was no arterio-venous difference of kinins.