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P Fasching

Publications and source records attributed to P Fasching.

At least 19 recordsLinked to original sources
PubMed2002

The impact of diabetes mellitus at the time of heart transplantation on long-term survival.

AIMS/HYPOTHESIS: To analyse the impact of diabetes mellitus (DM) at the time of heart transplantation on long-term survival and incidence of transplant coronary artery disease (TxCAD). METHODS: We analysed 773 consecutive adult heart transplant recipients who underwent primary heart transplantation from May 1986 until December 2000. The cohort consisted of 140 patients with diabetes mellitus (with DM, men 82%) and 633 patients without (wo DM, men 84%) diabetes mellitus at the time of transplantation. The patients were documented as to survival and incidence of TxCAD. RESULTS: Patients with diabetes mellitus were older compared to those without diabetes mellitus (with DM 54.9+/-6.8a vs wo DM 49.7+/-10.8a; p=0.0001), they had a higher incidence of ischaemic cardiomyopathy prior to transplantation (with DM 52% vs wo DM 30%; p=0.0001), but reduced long-term survival (10 year survival: with DM 40% vs wo DM 58%; log-rank=0.025). Surprisingly, the incidence of transplant coronary artery disease (TxCAD) was comparable at 10 years (with DM 28% vs wo DM 22%; log-rank=0.625). In multivariate Cox proportional hazard analysis, diabetes mellitus present at the time of heart transplantation (HR 1.594; 95%CI 1.009-2.518; p=0.045), but not age (HR 0.990; 95%CI 0.965-1.014; p=0.404) was an independent predictor affecting long-term survival. CONCLUSION/INTERPRETATION: The presence of diabetes mellitus at the time of heart transplantation adversely affects long-term patient survival, but does not predict the occurrence of transplant coronary artery disease. The definite mechanisms of adverse survival primarily seem to relate to generally impaired global organ function. Despite a less favourable long-term outcome, our data still justify heart transplantation in end-stage heart failure patients with diabetes mellitus.

Adult↗
PubMed2002

[Effect of age on glucose tolerance and cardiovascular risk factors--results of the Diabetes Infobus tour 1998/99 ].

In 19,219 individuals (45.4% male, 54.6% female) with an age range from 10 to 95 years average body weight, body mass index (BMI), serum cholesterol and arterial blood pressure showed typical age-dependent changes. In the middle-aged between 45 and 65 years the high percentage of total cholesterol levels over 200 mg/dl (male: 58.3%; female 70.7%) seems alarming. In very old persons over 80 years the predictive value of those cardiovascular risk factors for increased mortality might be reversed, since in several epidemiological observations higher total cholesterol values and a high systolic blood pressure were associated with a longer survival. Average random blood glucose concentration is steadily rising with age. In good comparison with results from US American and European studies the age-matched relative risk for known myocardial infarction and stroke is twice to four times higher in individuals with known diabetes mellitus than in those without. These findings underline the urgent need for broadly based screening programs looking for metabolic and cardiovascular risk factors and for early disturbances of carbohydrate metabolism particularly in middle-aged groups, and for manifest diabetes mellitus in persons over 65 years of age.

Adolescent↗
PubMed2000

Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells.

Incubation of bovine aortic endothelial cells (BAECs) with erythrocytes from patients with type 2 diabetes induced an increase in endothelin 1 (ET-1) production. The effect of erythrocytes on ET-1 synthesis was dependent on glycemic control. ET-1 levels after incubation with erythrocytes derived from patients with HbA(1c) levels <6% were just half the levels observed after incubation with erythrocytes from patients with HbA(1c) levels >8%. Nepsilon-(carboxymethyl)lysine (CML)-containing protein isolated from patients' erythrocytes induced ET-1, and CML-containing protein-dependent ET-1 induction was blocked by the recombinant decoy peptide soluble receptor for advanced glycation end products (AGEs), which comprises the NH2-terminal Ig domain of the receptor for AGEs. In vitro-generated AGEs induced ET-1 mRNA transcription (nuclear run-on assay and Northern blot) in a time- and dose-dependent manner. Transient transfection of BAECs with a chimeric construct containing the 5' promoter region of the ET-1 gene linked to a reporter gene confirmed that AGE induced ET-1 promoter activity. Electrophoretic mobility shift assay confirmed AGE-inducible binding of members of the nuclear factor-kappab (NF-kappaB) family to a potential binding site at -2,090 bp. Binding was functionally significant because overexpression of the cytoplasmic inhibitor of NF-kappaB or deletion of the NF-kappaB binding site reduced ET-1 induction, whereas overexpression of NF-kappaB p65 induced ET-1 even in the absence of AGEs. Thus, ET-1 transcription is controlled by the AGE-inducible redox-sensitive transcription factor NF-kappaB.

Animals↗
PubMed1999

Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

Adult↗
PubMed1998

Previous episodes of hypoglycemic coma are not associated with permanent cognitive brain dysfunction in IDDM patients on intensive insulin treatment.

Intensive insulin treatment of IDDM is associated with increased frequency of hypoglycemic coma. The extent of possible cerebral sequelae after recovery is still unknown. We studied the impact of previous hypoglycemic coma on neurophysiological measures of cognitive brain function in 108 patients with adult-onset IDDM receiving intensive insulin treatment. In the study, 55 IDDM patients (age 38 +/- 14 years, mean +/- SD) who had a history of > or =1 (median 3, range 1-35) comatose hypoglycemic event were compared with 53 IDDM patients (age 34 +/- 12 years) with no history of hypoglycemic events using P300 event-related potentials and psychometric tests (the Mini-Mental State Exam and trailmaking test, part A). Findings on these patients were compared with those from 108 matched healthy control subjects. No difference was observed in P300 latencies and psychometric tests between patients with and without a history of hypoglycemic coma (P300 latency, 346 vs. 342 ms; trailmaking test, 31 vs. 30 s; Mini-Mental State Exam, 29.5 vs. 29.6; NS). In diabetic patients, however, P300 latencies were delayed compared with those of healthy control subjects (344 vs. 332 ms; P < 0.001) and were correlated to diabetes duration but not to total hypoglycemic episodes. Scores on the Mini-Mental State Exam (29.5 vs. 29.6; P = 0.59) and trailmaking test (31 vs. 28 s; P = 0.10) were not different between patients and control subjects. In conclusion, previous episodes of hypoglycemic coma are not associated with permanent impairment of cognitive brain function in patients with adult-onset IDDM receiving intensive insulin treatment compared with patients without such episodes. Cognitive brain function, however, is subclinically impaired in relation to duration of diabetes.

Adult↗
PubMed1997

Ocular and systemic reactivity to isoprenaline in patients with insulin-dependent diabetes mellitus.

There is experimental evidence of decreased beta-adrenergic myocardial sensitivity in patients with insulin-dependent diabetes mellitus (IDDM). In the present study we hypothesized that the ocular response to isoprenaline, as a consequence of increased arterial vessel rigidity, might also be blunted in patients with IDDM. We therefore compared the correlation between systemic pulse pressure amplitude (PPA) and fundus pulsation amplitude (FPA) during intravenous isoprenaline administration in 11 otherwise healthy IDDM patients and 11 healthy control subjects. Ocular fundus pulsations were measured by a recently developed laser interferometric method. Isoprenaline increased PPA in both study groups in a dose-dependent way, but the response was significantly less in IDDM patients (at 0.8 microgram min-1: +38% in control subjects, +27% in IDDM patients, P < 0.05 between groups). Moreover, a dose-dependent increase in FPA was observed, which again was more pronounced in healthy subjects (at 0.8 microgram min-1: +45% in controls, +17% in IDDM patients, P < 0.005 between groups). The regression line between PPA and FPA was very close to the 45 degrees line in healthy subjects, whereas it was significantly flattened in IDDM patients. In conclusion, linear regression between PPA and FPA during isoprenaline suggests arterial stiffening in patients with IDDM. Hence, comparison of systemic PPA and FPA during isoprenaline provocation may be a useful method of estimating changes in arterial capacitance in patients with diabetes mellitus.

Adrenergic beta-Agonists↗
PubMed1997

Inhibition of paracrine angiotensin-converting enzyme in vivo: effects on interstitial glucose and lactate concentrations in human skeletal muscle.

Microdialysis was used to selectively assess the effect of the paracrine renin-angiotensin system (RAS) on interstitial glucose and lactate concentration profiles in skeletal muscle of healthy volunteers (n = 8) during basal and insulin-stimulated conditions. Paracrine RAS was selectively inhibited by local retrodialysis with enalaprilate. Under basal conditions, local administration of enalaprilate (2 micrograms mL-1) increased interstitial dialysate glucose concentration from 0.71 +/- 0.14 mmol L-1 to 0.84 +/- 0.14 mmol L-1 and decreased the serum interstitial gradient (SIGglu) compared with baseline (P < 0.02). Under clamp conditions, enalaprilate, even at the lowest concentration (0.02 microgram mL-1), increased interstitial dialysate glucose concentration from 0.77 +/- 0.11 mmol L-1 to 1.02 +/- 0.09 mmol L-1 and decreased SIGglu compared with baseline (P < 0.01). Interstitial lactate concentrations slightly increased during basal as well as during clamp conditions (P < 0.05 vs. baseline). Selective inhibition of paracrine muscle angiotensin-converting enzyme (ACE) increases interstitial glucose and lactate concentrations and decreases SIGglu in muscle by facilitating transcapillary glucose transport. This effect is more pronounced during hyperinsulinaemia and may be of clinical relevance in diabetic patients treated with therapeutic doses of enalapril.

Adult↗
PubMed1997

Persistent elevation and metabolic dependence of circulating E-selectin after delivery in women with gestational diabetes mellitus.

The increased risk of premature atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM) might be related in part to augmented expression of endothelial adhesion molecules (AMs). So far it is, however, unknown whether increased circulating (c) AMs in NIDDM are only a consequence of this disease or also involved in its sequelae. To determine the presence of cAMs in a population at increased risk for subsequent development of NIDDM, we analyzed fasting and postprandial [oral glucose tolerance test (OGTT): 100 g] serum concentrations of circulating E-selectin, vascular cell adhesion molecule-1 (cVCAM-1), and intercellular adhesion molecule-1 (cICAM-1) in pregnant women with either gestational diabetes (GDM) or normal glucose tolerance (NT) before and after delivery vs. nonpregnant healthy women (C). During pregnancy cE-selectin and cVCAM-1 were elevated in both GDM and NT vs. nonpregnant females (P < 0.01 vs. C). Following delivery, all GDM females regained normal glucose tolerance according to OGTT criteria, but showed slightly higher postprandial [area under the curve (AUC)180 min] glycemia and HbA1c values than nonpregnant healthy women (P < 0.05), indicating persisting subtle abnormalities in carbohydrate metabolism. cE-selectin and cVCAM-1 remained increased in GDM (P < 0.01 vs.C) after delivery, but fell to normal in NT (P < 0.05 before vs. after delivery). Furthermore, a correlation was seen in GDM females between cE-selectin and HbA1c (P < 0.005), fasting glucose (P < 0.01), and insulin (P < 0.05) as well as postprandial (AUC180 min) glucose and insulin concentrations (P < 0.05) during OGTTs, both before and after delivery. ICAM-1, however, did not differ significantly between groups. In summary, GDM is characterized by persistently raised levels of cE-selectin and cVCAM-1 12 weeks after delivery. Whether these persistent elevations of cE-selectin and cVCAM-1 reflect early vascular injury or represent a risk factor for atherosclerosis in women at increased risk for NIDDM remains to be determined.

Adult↗
PubMed1997

Renal and ocular hemodynamic effects of insulin.

There is evidence that the vasodilator action of insulin is mediated by the release of nitric oxide (NO). We hypothesized that euglycemic hyperinsulinemia might increase renal and ocular blood flow, and that the vasodilator capacity of insulin might be NO-dependent. Euglycemic insulin clamps were performed in 10 healthy subjects. Sixty minutes after the start of insulin administration, an intravenous coinfusion of N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, or of norepinephrine (NE), an endothelium-independent vasoconstrictor, was started. Renal plasma flow was measured by para-aminohippurate (PAH) clearance method. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. Renal plasma flow and ocular fundus pulsations were increased by insulin. L-NMMA almost completely abolished the vasodilative effects of insulin, whereas the effects of combined infusion of insulin and NE were approximately the sum of the hemodynamic changes induced by each agent alone. The results show that during euglycemic hyperinsulinemia, renal and ocular blood flow are increased, which may be mediated either by a local vasodilator effect or a systemic increase in flow. The hemodynamic effects of insulin in the kidney and the eye are at least partially dependent on NO synthesis. Because the insulin plasma levels we obtained are in the high physiological range, it may be assumed that insulin plays a role in renal and ocular blood flow regulation.

Adult↗
PubMed1997

Nitric oxide and ocular blood flow in patients with IDDM.

Endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disorders such as diabetic retinopathy. We hypothesized that either local endogenous nitric oxide (NO) synthesis or local reactivity to endogenous NO might be impaired in patients with IDDM and that this may contribute to the development of diabetic retinopathy. Ten otherwise healthy patients with long-standing IDDM and ten healthy control subjects were studied according to an open randomized two-way cross-over design. Subjects received intravenous infusions of either N(G)-monomethyl-L-arginine, an inhibitor of NO-synthase, or L-arginine, the precursor of NO synthesis, on two separate study days. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine decreased fundus pulsations and blood flow velocity in the ophthalmic artery and increased blood pressure in healthy subjects. The responses to NO-synthase inhibition were significantly less in diabetic subjects. In contrast, L-arginine caused a comparable increase in fundus pulsations and decrease in blood pressure in both cohorts. These results indicate that systemic and ocular hemodynamic reactivity to NO-synthase inhibition is reduced in patients with long-standing IDDM, compared with healthy control subjects. Thus, this study indicates that either NO-synthase activity is increased or NO sensitivity is decreased in patients with IDDM and supports the concept of an involvement of the L-arginine-NO system in the pathophysiology of diabetic retinopathy.

Adult↗
PubMed1997

[Functional insulin therapy and pregnancy].

Pregnant type-I diabetic women have to be treated in an experienced diabetes center where optimal cooperation and exchange of knowledge between obstetrician, diabetologist and neonatologist is guaranteed. Given optimal preconceptional metabolic control and thorough guidance throughout pregnancy maternal and fetal risk of type-I diabetic patients without severe diabetic late complications is similar to that of healthy pregnant women. "Near-normoglycemic" metabolic control and meticulous prevention of severe and long-standing hypoglycemic episodes can be achieved throughout pregnancy by functional insulin therapy employing a basis-bolus regime of insulin administration with frequent blood glucose self control (more than 6 times a day). Non-compliant diabetic patients and those with severe diabetic late complications represent a high-risk group for complications in pregnancy. To avoid such risks special care and preconceptional information is mandatory.

Adult↗
PubMed1996

[Secondary prevention of diabetic retinopathy in type I diabetes mellitus. Dependence on retinopathy status before the intervention].

OBJECTIVE: To assess prospectively the effect of improving the metabolic state on the course of diabetic retinopathy in relation to the extent of retinal changes before intervention. PATIENTS AND METHODS: 140 patients with type I (insulin-dependent) diabetes mellitus (IDDM) (55 men, 85 women; mean age 30 +/- 11 years; mean duration of illness 11 +/- 8 years), underwent intensified insulin treatment and were then followed for 4 years. At the beginning of the trial fundoscopy was unremarkable in 68 patients (stage 0), a few microaneurysms and (or) punctate bleeding (stage 1) in 21, nonproliferative retinopathy (stage 2) in 27, preproliferative retinopathy (stage 3) in six, proliferative retinopathy (stage 4) in 14, and proliferative retinopathy with complications (stage 5) in four. The average retinopathy stage was 1.2 +/- 1.0, mean HbA1c value 7.0 +/- 1.3%). RESULTS: The retinopathy remained unchanged in 94 patients (group A), it improved in 16 (group B), and deteriorated in 30 (group C). There was no significant change in mean HbA1c value in any of the groups (A: 6.2 +/- 0.9%; B: 6.4 +/- 1.0%; C: 6.3 +/- 6.0%). There were also no differences with respect to blood glucose, M-value according to Schlichtkrull, frequency of hypoglycaemia, serum lipids, blood pressure and renal biopsy parameters. However, significant differences (P < 0.001 C vs. A and B) were found in relation to duration of diabetes (A: 9.3 +/- 7.2 years; B: 8.8 +/- 8.6 years; C: 16.9 +/- 7.8 years) and mean retinopathy stage at beginning of the study (A: 0.8 +/- 0.8; B: 1.2 +/- 0.7; C: 2.4 +/- 1.6). CONCLUSION: Decisive for the course of retinopathy in patients with IDDM of long duration and secondarily optimised metabolic state is the duration of illness and especially the degree of fundal changes when intensified insulin treatment is undertaken.

Adult↗
PubMed1996

Fish oil supplementation versus gemfibrozil treatment in hyperlipidemic NIDDM. A randomized crossover study.

To compare the impact of dietary fish oil supplementation (FO, 22 ml daily, containing 4.6 g of n-3 (omega-3) fatty acids, equalling 14.4 mmol) on carbohydrate and lipid metabolism with that of conventional lipostatic therapy (Gemfibrozil (G), 900 mg daily, equalling 3.6 mmol) on hyperlipidemic non-insulin dependent diabetes mellitus (NIDDM), 10 patients were selected for a randomized, short-time, cross-over study. Each patient was treated for a duration of 2 weeks, with an individual washout period of 8 weeks. Metabolic variables and intravenous glucose tolerances (1.2 mmol/kg body weight, t = 30 min) were determined on days 1 and 15 of each treatment period. Plasma lipid concentrations were identical at baseline, but were reduced more markedly following G as against FO exposure (% change vs. baseline: total cholesterol (chol), - 13**/-6* (G vs FO: p = 0.05); total triglycerides (TG), -39**/-18** (p < 0.05); APO B, -17**/- 10* (N.S.); LDL-chol, -15**/0 (p < 0.02); VLDL-chol, -50***/- 34*** (N.S.); VLDL-TG, -44***/-27** (N.S.); (p vs. baseline: * < 0.05, ** < 0.01, *** < 0.001). Total-HDL, HDL2, HDL3 and APO A were not influenced by either FO or G. Neither FO nor G induced a change in intravenous glucose tolerances or associated basal and incremental concentrations of insulin and C-peptide. We concluded, based on short-time applications, that (a) neither treatment affected the carbohydrate metabolism in patients with NIDDM, and (b) a greater hypolipidemic efficacy had to be assigned to Gemfibrozil than to fish oil. It would therefore appear that Gemfibrozil acts as a useful lipostatic pharmacologic compound, whilst fish oil could serve as a potential ingredient of a prudent cardio-protective diet which favours the low plasma triglyceride concentrations found in NIDDM patients.

Aged↗
PubMed1996

No effect of short-term dietary supplementation of saturated and poly- and monounsaturated fatty acids on insulin secretion and sensitivity in healthy men.

To evaluate the short-term influence of fatty acids with different grades of saturation on insulin secretion and sensitivity, 8 healthy males (age 26 +/- 3.5 years, body mass index 22.4 +/- 1.8 kg/m2) were provided with 800 kcal daily of either carbohydrates (CH; 200 g), or fat (90 g) enriched either with saturated fatty acids (SAFA; 72%) or (omega-6) polyunsaturated fatty acids (PUFA; 60%) or cis-monounsaturated fatty acids (MUFA; 40%; n = 5) in addition to a standard diet (2,000 kcal/ day; 50% CH, 15% protein, and 35% fat; 33% SAFA, MUFA, and PUFA each) for 1 week in a randomized order (washout period 2 weeks). The stimulated insulin secretion was quantified by the frequently sampled intravenous glucose tolerance test (FSIGT; 0.3 g glucose/kg body weight), while the insulin sensitivity was determined by an euglycemic-hyperinsulinemic 5-mU clamp. In parallel, basal and stimulated carbohydrate and fat oxidation rates were estimated by indirect calorimetry. One week of defined fat exposure failed to significantly affect the glucose-induced insulin secretion during FSIGT and insulin-dependent glucose disposal during an euglycemic clamp (M values: CH 9.6 +/- 1.6 mg/kg.min, SAFA 9.7 +/- 2.2, PUFA 9.8 +/- 2.5, and MUFA 11.5 +/- 3.2 mg/kg.min; NS). In addition, oxidation rates for fat and glucose in the postabsorptive state and during hyperinsulinemia did not differ between the different diets. We conclude that short-term (1-week) isocaloric supplementation of a standard diet with fatty acids of varying degree of saturation does not affect either insulin secretion or insulin sensitivity in healthy men, due to the compensatory metabolic capacity of healthy subjects.

Adult↗