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Biomedical subjects

H J Augustin

Publications and source records attributed to H J Augustin.

At least 19 recordsLinked to original sources
PubMed1999

Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.

Alpha-lipoic acid (ALA), a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models. Clinical studies described an increase of insulin sensitivity after acute and short-term (10 d) parenteral administration of ALA. The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled, multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity. Seventy-four patients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment in various doses of 600 mg once daily (n = 19), twice daily (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid. An isoglycemic glucose-clamp was done on days 0 (pre) and 29 (post). In this explorative study, analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment. Furthermore, the effects of active vs. placebo treatment on insulin sensitivity was compared. All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline. When compared to placebo, significantly more subjects had an increase in insulin-stimulated glucose disposal (MCR) after ALA treatment in each group. As there was no dose effect seen in the three different alpha-lipoic acid groups, all subjects receiving ALA were combined in the "active" group and then compared to placebo. This revealed significantly different changes in MCR after treatment (+27% vs. placebo; p < .01). This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations.

Administration, Oral↗
PubMed1996

Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. This pilot study was initiated to see whether this compound also augments glucose disposal in humans after repeated treatment. Twenty patients with NIDDM received TA (500 mg/ 500 ml NaCl, 0.9%) as daily infusions over a period of ten days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11. Parenteral administration of TA resulted in a significant increase of insulin-stimulated glucose-disposal by about 30% (metabolic clearance rate for glucose, 2.5 +/- 0.3 vs. 3.2 +/- 0.4 ml/kg/min and insulin-sensitivity-index: 3.5 +/- 0.5 vs. 4.7 +/- 0.4 mg/kg/microU/ml; p < 0.05, Wilcoxon-Rank-Sum-Test). There were no changes in fasting plasma levels for glucose or insulin; this can be explained, however, by the short period of treatment and observation. This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM. Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound.

Aged↗
PubMed1996

Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism.

Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole-body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

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. DESIGN: A multicenter double-blind randomized study. SUBJECTS AND METHODS: Seventy-two non-diabetic hypertensive patients were randomly assigned to treatment with either carvedilol or metoprolol. An isoglycemic, hyperinsulinemic glucose clamp was conducted before and after 12 weeks of treatment; the metabolic clearance rate for glucose was taken as an indicator of insulin sensitivity. RESULTS: The two groups did not differ in age, sex, body mass index, blood pressure or lipids, and treatment effectively lowered blood pressure. In both groups, insulin sensitivity was impaired at baseline. After metoprolol treatment, insulin sensitivity further decreased significantly by about 14%, whereas it increased after carvedilol. There was also a decrease in high-density lipoprotein and an increase in triglycerides levels in patients in the metoprolol-treated group, whereas these parameters remained unchanged in patients in the carvedilol-treated group. CONCLUSION: This study confirms previous findings of a reduction in insulin sensitivity after chronic metoprolol treatment. Carvedilol treatment, however, resulted in a small amelioration of insulin resistance and a better lipid profile [corrected]. We thus demonstrate that a beta-blocker with alpha 1-blocking properties has favorable effects on glucose metabolism, suggesting a potentially important role of peripheral blood flow in regulating glucose uptake. These findings imply that beta-blocker treatment, when combined with alpha 1-blocking activity has advantageous effects on insulin sensitivity and lipids and could therefore be suitable for patients with the metabolic syndrome.

Adrenergic beta-Antagonists↗
PubMed1996

Improvement of glucose metabolism in patients with type II diabetes after treatment with a hemodialysate.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Previous studies have shown that Actovegin, a hemodialysate of calf blood, which has been used for treatment of circulatory disorders for many years, improves glucose tolerance in NIDDM without affecting insulin levels; in vitro studies found an improvement of insulin-stimulated glucose uptake in adipocytes. This pilot study was initiated to see whether this compound augments insulin sensitivity after repeated treatment. Ten patients with NIDDM received the hemodialysate (Actovegin 2.000 pro infusions, 500 ml as daily infusions) over a period of 10 days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11; oral glucose tolerance test (oGTT) was done on day -4 and day 12. Parenteral administration of the hemodialysate markedly augmented insulin stimulated glucose disposal (glucose infusion rate and metabolic clearance rate) by more than 80% (p < 0.003 day 11 vs. day 0). Although tested 44 h after the last infusion, oGTT also improved significantly, as documented by the diminished area under the curve (AUC) for glucose, whereas the AUC for insulin remained unchanged. This is the first clinical study to show that parenteral administration of the tested hemodialysate results in a significant increase of insulin-stimulated glucose disposal in NIDDM. The exact mode of action of the hemodialysate in improving insulin sensitivity is currently not known. The hemodialysate possibly acts via a supplementation of inositol-phosphate-oligosaccharides (IPO), as in experimental studies IPOs isolated from the hemodialysate improved glucose uptake in adipocytes in an insulin-independent manner. Further studies are needed to elucidate the underlying mechanisms.

Aged↗
PubMed1995

Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal; metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/kg/min = pre vs. 5.82 ml/kg/min = post, p < 0.05), whereas the control group did not show any significant change (3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation.

Aged↗
PubMed1991

[Chronic fascioliasis with destructive cholangitis].

A 56-year-old Greek working in an electroplating shop, in Germany since 1965, had experienced abdominal pain with weight loss for about 16 years. He had received treatment for a variety of diagnoses. With the aid of ERC and aspired bile, the diagnosis of chronic fascioliasis was finally established.

Bile↗
PubMed1981

The influence of angiotensin II antagonist postischemic acute renal failure.

In 34 dogs the effect of a 90-min period of warm ischemia on renal perfusion and function was studied with and without (Sar1, Ile8) angiotensin II treatment. In the first 3 h after the release of renal arterial occlusion, a significant influence of the angiotensin II antagonist on changes in postischemic vascular resistance, intrarenal hemodynamics and renal function could be demonstrated, all being well preserved in the treated group.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1981

Changes in renal hemodynamics in experimental hydronephrosis.

We measured mean renal blood flow and intrarenal blood flow distribution in 40 dogs using the xenon-133 washout technique 3 and 7 hr; 1, 2, and 3 weeks; and 4 and 6 months after unilateral complete ligation of the ureter. Mean renal blood flow rapidly decreased before renal atrophy. The data show an early redistribution of intrarenal hemodynamics with a predominant decrease in compartment I flow. These data are discussed with respect to possible ischemic atrophy especially in the renal cortex.

Animals↗
PubMed1980

Effect of angiotensin II antagonist, alpha-receptor blockage, and denervation on blood flow reduction in experimental, chronic hydronephrosis.

We studied the mechanism of elevated vascular resistance in 34 dogs with unilateral hydronephrotic kidneys. Neither an alpha-receptor blocking agent nor angiotensin II-antagonist reversed renal blood flow reduction 7 hr, 1, 2, and 3 weeks after complete unilateral ureteral ligation. We conclude that blood flow reduction is the same in the denervated hydronephrotic kidney as in the innervated obstructed kidney.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1980

[Effect of dopamine on renal and intrarenal hemodynamics in unilateral ureteral occlusion].

Renal and intrarenal hemodynamics were studied over a period of 6 months in the hydronephrotic dog kidney after unilateral complete ligation of the ureter. Already 7 hours after ligation renal blood flow was reduced. The intrarenal blood flow distribution changed with a massive reduction in cortical and only slight decrease in medullary perfusion. This alteration of intrarenal blood flow resulted in a change of the compartment fractions. Dopamine, applied intravenously in a dose of 4 micrograms kg-1 min-1, induced a vasodiilation of the obstructed kidney during the whole period of investigation. Especially the reduced cortical blood flow could be improved by the application of dopamine.

Animals↗
PubMed1980

[Amino acid kinetics during hemodialysis].

The kinetic of essential amino acids as well as of histidine and alanine in bilateral nephrectomized rabbits was investigated during a 3 hours hemodialysis. Dialysis, elimination and incorporation rates into plasma proteins were determined for all applied amino acids. Total elimination rates of all the investigated amino acids varied. From 5.31% (leucine) to 75.51% (alanine) of the injected labelled amino acids were eliminated in the dialysate. There was an exponential decrease in the dialysis of essential amino acids and histidine during the period of investigation due to the high incorporation rate into plasma proteins. The kinetic of alanine was different due to a slow incorporation rate leading to a higher elimination rate. The fast incorporation of intravenously applied essential amino acids and histidine during dialysis demonstrates that the existing protein deficiency in renal failure can be influenced positively by infusion of amino acids.

Amino Acids, Essential↗
PubMed1979

[G. I. diagnostics; its ranking and interdisciplinary organisation (author's transl)].

The complicated and expensive diagnostic apparatus available today has to be applied in an orderly sequence. This order depends on certain prerequisites, e.g. on the disease, urgent complications, patient tolerance, apparatus potential, hospital structure and organisation etc. The more rational the indication is to use certain methods, the more efficient will be the results. The appropriate concepts and suggestions for certain general and specific examples, used by us at present are demonstrated. Complicated and expensive diagnostic procedures have to be decided primarily on an interdisciplinary level. The increased costs of these procedure are balanced by a decrease in hospital stay and fewer operative explorations too. At other places different actions will be taken for equally good reasons.

Gastrointestinal Diseases↗
PubMed1978

[The bilateral nephrectomy in terminal renal disease (author's transl)].

45 cases of nephrectomy are reported. Mortality was 8.9%. Thirty-one had a drug-resistant, severe hypertension, three had infected kidneys, and in eleven cases nephrectomy was performed prior to transplantation. Although blood pressure improved in all patients, of the first group 24% died within one year after nephrectomy, which shows unsatisfactory prognosis of malignant nephrosclerosis. Only early nephrectomy can lead to better results. Routine nephrectomy before transplantation should be avoided. Indications for this group are discussed.

Adult↗
PubMed1977

The vasoconstrictive effect of dopamine in the isolated, perfused rat kidney after catecholamine depletion.

In the isolated, perfused kidney of untreated and catcholamine-depleted rats (by 6-hydroxydopamine and reserpine), dopamine (DA) caused a dose-dependent increase in vascular resistance which could be prevented by prior blockade of the alpha-adreno-receptors. The DA-induced vasoconstriction thus appears to be due to a direct stimulation of alpha-receptors in the kidney rather than an indirect sympathomimetic effect through release of noradrena-line from local adrenergic nerve terminals. The effectiveness of the chemical sympathectomy accomplished with 6-hydroxydopamine and reserpine was evaluated by chemical; histochemical and electron microscopical methods.

Adrenergic alpha-Antagonists↗