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Biomedical subjects

G Schernthaner

Publications and source records attributed to G Schernthaner.

At least 91 records · Page 5Linked to original sources
PubMed1992

Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects.

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1992

The effect of insulin treatment on HbA1c, body weight and lipids in type 2 diabetic patients with secondary-failure to sulfonylureas. A five year follow-up study.

No conclusive data are available about the long-term effect of insulin treatment in type 2 diabetic patients failing to maximal doses of sulfonylureas and caloric restriction. In total 160 non-obese type 2 diabetic patients with secondary failure were substituted with insulin using a diabetic teaching and care program. From these 160 patients 40 died within the observation period of five years; 102 patients had a complete five year follow-up, whereas the remaining 18 patients did not come to regular follow-up visits. Metabolic control parameters improved significantly in the 102 patients with the complete five year follow-up. Postprandial plasma glucose (16.0 mM vs 10.9 mM; p < 0.0001) and HbA1c values (8.7% vs 7.1%, p < 0.0001) decreased significantly from the state before to five years after insulin substitution. In addition, plasma lipid levels could be significantly lowered under insulin therapy (cholesterol 6.2 +/- 1.5 mM vs 5.4 +/- 3.6 mM, p < 0.0002; triglycerides 2.8 +/- 1.6 mM vs 2.4 +/- 2.1 mM, p < 0.01). However, we observed a significant weight gain (mean: 10.6 kg) associated with insulin application during the five year follow-up. Thus, the body-mass-index decreased from 28.9 at onset of type 2 diabetes to 24.5 (p < 0.0001) at time of secondary failure and increased again to 28.5 (p < 0.0001) at five years after onset of insulin treatment. Furthermore, small increases of plasma creatinine from 88.4 microM to 115 microM, as well as systolic (19.3 kPa to 20.7 kPa) and diastolic (10.7 kPa to 11.3 kPa) blood pressures were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.

C-Peptide↗
PubMed1992

Influence of interferon alfa-2b with or without folinic acid on pharmacokinetics of fluorouracil.

Interferon alfa has been demonstrated to enhance the effect of fluorouracil (5-FU) on human colon cancer cell lines as well as in clinical studies. By several authors interest in focussed on the question whether the interaction between these two agents is reflected by changes of 5-FU kinetics. In the present study the pharmacokinetic behavior of 5-FU was investigated in combination with interferon alfa (IFN-alpha-2b) and further after adding the second well-established biomodulating agent folinic acid (FA). Ten patients with advanced gastrointestinal cancer received 5-FU as a weekly bolus injection of 750 mg/m2, IFN-alpha-2b 5 million units three times per week subcutaneously and FA as a short time infusion at 200 mg/m2. 5-FU plasma levels were determined by high performance liquid chromatography as a baseline measurement on day 1 before starting IFN-alpha-2b. Analysis was repeated at the second or third cycle of 5-FU administration 1 hour after the last IFN-alpha-2b injection, and finally after also adding FA immediately infused before 5-FU injection. Biomodulation of 5-FU by IFN-alpha-2b alone resulted in a significant alteration of 5-FU kinetic parameters as demonstrated by an increase of area under the curve by 80%, and of blood concentration (co) by 65%, and a decrease of total clearance at 50%. These data may partly explain the observed enhancement of antiproliferative and toxic effects of this combination. On the other hand, when FA was added to this schedule, no significant changes of 5-FU kinetics could be documented. Therefore the theoretical benefit of such a double modulation cannot be supported by our findings. Further preclinical and clinical investigations are required to define the role of a triple combination of 5-FU with IFN-alpha-2b and FA.

Aged↗
PubMed1992

Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration.

The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.

Female↗
PubMed1992

[Diabetic nephropathy in type 2 diabetes--epidemiology, early diagnosis and therapeutic strategies].

Diabetic nephropathy now accounts for approximately one-third of all patients who develop end-stage renal disease. The realization that half of these individuals suffer from non-insulin-dependent (type-2) diabetes mellitus has sparked increased interest attempts to understand the epidemiology and pathophysiology. In particular, early diagnosis, prevention and intervention in type-2 diabetic patients with micro-albuminuria and incipient diabetic nephropathy is urgently needed, since an early mortality due to cardiovascular complications is well documented in these patients. This review article summarizes most of the new data concerning epidemiology, pathophysiology, early diagnosis and the very few intervention studies in diabetic nephropathy of type-2 diabetic patients.

Albuminuria↗
PubMed1991

[Decreased plasma carnitine in Type I diabetes mellitus].

Realizing the importance of carnitine for the lipid and carbohydrate metabolism and the possible role for glucose utilization and myocardial function carnitine concentrations in type I and type II diabetic patients in plasma, erythrocytes and 24 h urine were determined. The plasma levels of carnitine were significantly diminished in type I diabetic patients compared to controls, while carnitine concentrations in erythrocytes and 24 h urine did not differ from controls. Plasma carnitine levels did not change significantly during the diurnial profile. No correlation between HbA1c and carnitine levels was observed in the diabetic patients.

Adult↗
PubMed1991

Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects.

In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.

Adolescent↗
PubMed1991

Enhanced growth hormone responses to growth hormone releasing hormone in male type I diabetic patients.

In a previous paper we have demonstrated that growth hormone (GH) responses to growth hormone releasing hormone (GHRH) are higher in premenopausal normal women than in age matched healthy men. As in type I diabetes mellitus various disturbances of GH secretion have been reported, the aim of our study was to assess the effect of sex on basal and GHRH stimulated GH secretion in type I diabetes mellitus. In 21 female and 23 male type I diabetic patients and 28 female and 30 male control subjects GH levels were measured before and after stimulation with GHRH (1 microgram/kg body weight i.v.) by radioimmunoassay. GH responses to GHRH were significantly higher in female than in male control subjects (p less than 0.02), whereas the GH levels following GHRH stimulation were similar in female and male type I diabetic patients. GH responses to GHRH were significantly higher in the male type I diabetic patients than in the male control subjects (p less than 0.001); in the female type I diabetic patients and the female control subjects, however, GH responses to GHRH were not statistically different. The absence of an effect of sex on GHRH stimulated GH responses in type I diabetes mellitus provides further evidence of an abnormal GH secretion in this disorder.

Adult↗
PubMed1991

Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus.

Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127 +/- 3 versus 139 +/- 6 mm Hg and 129 +/- 4 versus 142 +/- 4, respectively; p less than 0.05). Fasting blood glucose (190 +/- 21 versus 152 +/- 15 mg/dl; p less than 0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.

Adult↗
PubMed1991

Contribution of postprandial insulin and glucose to glucose disposal in normal and insulin-resistant obese subjects.

We recently found that postprandial hyperinsulinemia does not compensate for the insulin resistance of obese subjects and proposed that postprandial hyperglycemia might be more important in promoting glucose disposal via the mass action effect of glucose. To test this idea we perform oral glucose tolerance tests (OGTT) in six lean and eight obese subjects, measuring glucose and insulin levels. Afterward two insulin infusion studies were performed. During infusion study I, insulin was infused in a dynamic square wave fashion to mimic the individual post-OGTT insulin levels at content euglycemic glucose levels. During study II, glucose and insulin infusions were varied to mimic post-OGTT levels in each subject. Overall glucose turnover was measured isotopically by infusion of [3-3H] glucose. During the OGTT the obese subjects exhibited significantly higher insulin (P less than 0.005) and glucose levels (P less than 0.002). Insulin-stimulated glucose disposal rates and total incremental glucose disposal (IGD) over 4 h during study I at euglycemia were significantly lower in obese compared to lean subjects (area under the curve, 824 +/- 166 vs. 1222 +/- 161 mmol/L.m2; P less than 0.01) despite higher post-OGTT insulin levels in obese subjects. When insulin plus glucose levels were matched to the individual OGTT levels, IGD was not significantly different between obese and control subjects (1712 +/- 253 vs. 1617 +/- 444 mmol/L.m2; P = NS). A significant inverse correlation (r = -0.73; P less than 0.05) existed between the degree of glucose intolerance (OGTT) and the decrease in IGD during the phasic hyperinsulinemic euglycemic study (infusion study I). These data suggest that with increasing insulin resistance, hyperinsulinemia is less effective in compensating for this decrease in insulin action, and hyperglycemia becomes more important in augmenting overall glucose disposal values.

Adult↗
PubMed1991

The effects of ramipril on glucose tolerance, insulin secretion, and insulin sensitivity in patients with hypertension.

To evaluate a possible influence of the angiotensin-converting enzyme inhibitor ramipril on glucose tolerance and insulin sensitivity, an oral glucose tolerance test (oGTT) and an euglycemic clamp were performed in 10 nonobese, nondiabetic patients with mild hypertension before and after treatment with ramipril for 14 days. Following ramipril treatment, systolic and diastolic blood pressures were significantly lower (152.5 +/- 10.6/97.5 +/- 4.3 vs. 136.5 +/- 18.9/79.5 +/- 16.4 mm Hg). Therapy with ramipril showed no influence on glucose tolerance (serum glucose of 106.8 +/- 32.8 vs. 109.1 +/- 33.9 mg/dl at 120 min during the oGTT), insulin secretion (53.0 +/- 45.7 vs. 41.1 +/- 10.6 microU/ml at 120 min), and insulin sensitivity (glucose infusion rate of 180.8 +/- 60.7 vs. 199.8 +/- 77.5 mg/m2/min after 3 h of clamp). In conclusion, short-term treatment of hypertension with ramipril has no influence on glucose metabolism in nondiabetic patients.

Aged↗
PubMed1991

[Pharmacokinetic aspects of the combination of interferon-alpha-2b and folic acid with fluorouracil].

The plasma levels of fluorouracil (5-fluorouracil, 5FU; CAS 51-21-8) after intravenous administration have been monitored without, under influence of interferon-alpha-2b (IFN) and under influence of IFN combined with folic acid (FA). IFN causes a highly significant change of the pharmacokinetic parameters of 5FU (p less than 0.001) compared to 5FU administration without IFN. The bioavailability of 5FU (compared as the AUC0-60 values) is elevated to 80%. In contrary, the combination of IFN with FA leads to a non-significant change of the 5FU pharmacokinetics, although the bioavailability is increased to 18%. The higher plasma levels of 5FU under the influence of IFN might be causes by a changed renal clearance, which is indicated by the reduction of the total plasma clearance at about 53%. The combination IFN/FA did not show a similar effect. Yet, in both cases an improvement of the tumor response and of the clinical picture could be observed.

Aged↗
PubMed1991

[Pharmacokinetics and local availability of mitomycin. The influence of vasoconstriction and chemoembolization].

The influence of the vasopressin-pro-drug glycylpressine (GP) and of a chemoembolisation with Spherex starch-particles (SP) on the availability of mitomycin (CAS 50-07-7, mitomycin C, MMC) was investigated in 30 patients with liver metastases, MMC administration was performed after blocking of the common hepatic artery by different concentrations of SP and after different time-intervals of GP. The comparison of plasma-levels after bolus injection without GP and after administration of MMC after 2, 5 and 15 min of vasoconstriction and after chemoembolisation with 450 mg or 900 mg SP, respectively, showed a remarkable reduction in the systemic circulation of MMC in the blood vessel system at about 40% (GP) and 45% (SP). A statistically significant influence on the pharmacokinetics of MMC with regard to CO, Vd, T 1/2zp, AUC and Cl(tot) was found, but not in t1/2el, t1/2biol and Vl. Both methods cause a distinctly accelerated diffusion of MMC into the tissue of the tumor region by change of the hemodynamics, leading to lowered side-effects. Thus the clinical picture was improved by MMC.

Biological Availability↗
PubMed1991

[Glycosylated hemoglobin and diabetes--self monitoring (compliance) in depressed and non-depressed type I diabetic patients].

128 type I diabetics were examined in view of connections between psychosocial factors and metabolic control. Indications of a direct interaction between depressivity, incidence of complaints and the level of hyperglycemia were found. The prevalence of manifest depression ranges at a total of 25 percent. The results further show connections between coping with the disease and behavior. High recording frequency, frequent measurements and medical consultations are found in active coping. Changes in relations to close persons and frequent change of job are psychosocial effects of the disease manifesting themselves in poorer metabolic control. In conclusion, high-risk groups of depressive diabetes patients and those under particular stress are defined.

Adaptation, Psychological↗
PubMed1990

[Hypertension, insulin resistance and diabetes mellitus: pathophysiological interactions and therapeutic consequences].

The pathophysiological connections between insulin resistance, hypertension and type 2 diabetes are discussed in this review article. Increased blood pressure levels are often found in type 2 diabetic patients long before the diabetes itself is diagnosed. By contrast, in type 1 diabetes hypertension is predominantly the consequence of diabetic glomerulopathy. Non-pharmacological strategies should be favoured in the treatment of hypertension in type 2 diabetic patients before specific pharmacological intervention is started. Antihypertensive treatment with beta-blocking agents and diuretics is criticized by many experts in the field of metabolic disorders, since these drugs induce a deterioration of glycaemic control and lipid metabolism in diabetic patients. Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking agents have no influence on metabolism, these drugs are recommended for the antihypertensive treatment of diabetic patients. Further studies should be undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective effect. Since most type 2 diabetic patients do not develop diabetic nephropathy, a possible nephroprotective effect of ACE inhibitors is only relevant to the antihypertensive treatment of type 1 diabetic patients.

Adrenergic alpha-Antagonists↗
PubMed1990

[Pharmacokinetic aspects of dosage increase of recombinant interferon alpha-2B in patients following intraperitoneal and intra-arterial application].

Interferon-alpha-2 b (IFN) was administered as an i.a. bolus at doses of 3 and 5 million international units (MIU), as an i.a. 24h long-time infusion at 3 and 5 MIU and as an i.p. 90 min short-time infusion at 5, 10 and 15 MIU. Dose escalation of IFN on i.p. administration leads to correspondingly elevated AUC values of IFN (correlating to the dose) in the peritoneal fluid (PF) and blood, with a shift of the steady-state at about 2h. Bioavailability of IFN is 30 times higher for PF than for blood. t1/2 el, Vd and total clearance are not influenced by dose escalation in both compartments due to their dose-independency. IFN is eliminated from the PF with t1/2 el = 10-32h and from the blood with t1/2 el = 5-13h. After an i.a. bolus at either dosage IFN is distributed from the blood with a half-life of below 2h. 24h infusion leads to a steady-state within 4-6h and a cmax of 8.5 or 12.5 units/ml, respectively. IFN is slowly eliminated during infusion with a t1/2 el of 16h.

Dose-Response Relationship, Drug↗