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Biomedical subjects

P Fasching

Publications and source records attributed to P Fasching.

33 records · Page 2Linked to original sources
PubMed1996

Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus.

To better understand potential associations of circulating adhesion molecules (cAMs) with diabetic microangiopathy, circulating serum concentrations of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), and endothelial leukocyte adhesion molecule-1 (cELAM-1) were determined in patients with insulin-dependent diabetes mellitus (IDDM) (n = 70) presenting with varying degree of metabolic control and status of diabetic late complications, and were compared with age-matched healthy subjects (n = 70) in a cross-sectional study. Concentrations of cICAM-1 and cVCAM-1 were elevated in IDDM vs. age-matched controls (cICAM-1: 276 +/- 71 vs. 212 +/- 57 ng/mL; P < 0.0001; cVCAM-1: 781 +/- 245 vs. 615 +/- 151 ng/mL; P < 0.0001), whereas cELAM-1 did not differ between the groups (cELAM-1: 50 +/- 25 vs. 46 +/- 23 ng/mL, P = 0.31). The levels of cVCAM-1 were more markedly elevated in IDDM patients with diabetic retinopathy (n = 32) than in those without (n = 38) (cVCAM-1: 848 +/- 281 vs. 724 +/- 197 ng/mL, P < 0.05), as well as in patients with micro- or macroalbuminuria (n = 10) vs. those without (n = 60) (cVCAM-1: 947 +/- 256 ng/mL vs. 753 +/- 234 ng/mL, P < 0.05), whereas no difference in cICAM-1 and cELAM-1 was apparent regarding the clinical status of diabetic microangiopathy. No correlations were found between hemoglobin A1e and cAMs in the individual subgroups of patients and healthy subjects. Interestingly, however, low density lipoprotein cholesterol correlated with cVCAM-1 (r = 0.38, P = 0.03) in IDDM patients with diabetic microangiopathy (n = 33), but not in healthy controls or patients without microangiopathy (n = 37). Analyzing the pooled data of diabetic patients and healthy subjects (n = 140), concentrations of cICAM-1 were markedly related to cVCAM-1 (r = 0.45, P < 0.0001) and cELAM-1 (r = 0.31, P < 0.0002), whereas cVCAM-1 was related less to cELAM-1 (r = 0.19, P = 0.03), respectively. We conclude that, irrespective of actual metabolic control, serum concentrations of cICAM-1 and cVCAM-1 but not cELAM-1 are elevated in patients with IDDM, reflecting ongoing endothelial cell stimulation and leukocyte activation. More specifically, more marked elevation of cVCAM-1 may even hint at clinically manifest diabetic microangiopathy.

Adolescent↗
PubMed1996

Elevated circulating P-selectin in insulin dependent diabetes mellitus.

Based on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients. The aim of this study was to compare the plasma levels of cP-selectin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays. Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p > 0.05). In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

Adolescent↗
PubMed1995

Nitric oxide mediates microvascular permeability in the isolated perfused rat mesentery?

The permeability influencing effect of nitric oxide was studied by means of an isolated perfused mesentery preparation in combination with a intravital/fluorescence microscopic set up. As a fluorescent marker served FITC-dextran mol wt 70,000 daltons. Tissue treatment was performed by application of NO-donors like SNP or GTN. Additionally the effects of bradykinin, L-nitroarginine or the combination of both were tested in regard to a permeability modulation. The results point out that NO-donors did not enhance microvascular permeability, whereas the permeability increasing effect of bradykinin is mediated by an NO-independent pathway.

Animals↗
PubMed1995

Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis.

The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6 +/- 0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3 +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n = 6). Administration of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2-response to reperfusion (n = 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.

Adult↗
PubMed1995

Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function.

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 +/- 6 vs. 13 +/- 5%, P < 0.05) and a lower PFR (5.9 +/- 0.8 vs. 7.3 +/- 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

3-Iodobenzylguanidine↗
PubMed1994

Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/- 3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/- 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13 +/- 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRCP] x total incremental area under the curve of plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM, 206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1 [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2 [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/- 0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Estimated glucose requirement following massive insulin overdose in a patient with type 1 diabetes.

A well-documented case of a 35-year-old male Type 1 diabetic patient who was admitted as an emergency after having injected 1500 international units (IU) of insulin (750 IU regular insulin,750 IU NPH-insulin) subcutaneously as a suicidal attempt is reported. Computing disappearance rates of glucose from its infused amounts necessary to maintain euglycaemia during 65 h after the insulin injection in analogy to experimental hyperinsulinaemic euglycaemic clamp examinations, a glucose consumption of 55.6 mumol kg-1 min-1 was found at peak serum insulin concentrations of about 14,400 pmol l-1. The insulin-induced glucose dynamics resemble closely those seen in healthy persons and Type 1 diabetic subjects during a 10 mU kg-1 min-1 euglycaemic clamp. This information may be useful in the handling of similar cases of insulin intoxication.

Adult↗
PubMed1994

Feasibility and efficacy of intensive insulin therapy in type 1 diabetes mellitus in primary care.

To determine the feasibility and efficacy of structured education in intensive insulin therapy (IIT) in patients with Type 1 diabetes mellitus commonly attended by primary care physicians, a prospective case-control study was carried out in co-operation with 26 general practitioners in rural Alpine region and the diabetes service at the University of Vienna, Medical School, Austria. From 89 rural Type 1 diabetic patients on conventional insulin therapy (CIT), those volunteering for better diabetes care (n = 52) were trained in IIT in the diabetes education centre and subsequently received their outpatient service by their general practitioners, as did those remaining on CIT (n = 37). Patients were matched as case-controls (n = 36 in each therapy group) for metabolic control at baseline (IIT/CIT: HbA1c 8.2 +/- 1.8 vs 8.1 +/- 2.0%, ns), age, duration of diabetes, incidence of retinopathy and nephropathy. Analysing an observation period of > 4.5 years, patients trained in IIT presented with improved metabolic control as compared to those on CIT (Mean HbA1c: IIT, 6.9 +/- 1.0%; CIT, 7.9 +/- 1.3%, p < 0.05, ANOVA). No difference between groups was, however, observed at the end-point of the study in HbA1c (IIT, 7.3 +/- 1.3%; CIT, 7.8 +/- 1.4%; IIT vs CIT, p = 0.14) and in the development of diabetic microangiopathy, frequency of reported severe hypoglycaemic episodes, and increase in body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Both acute and chronic near-normoglycaemia are required to improve insulin resistance in type 1 (insulin-dependent) diabetes mellitus.

To determine the impact of both short- and long-term "near-normoglycaemia" on insulin resistance in Type 1 (insulin-dependent) diabetes hepatic glucose production (mg.kg-1.min-1) and peripheral glucose utilisation ("M-value", mg.kg-1.min-1) were estimated during an euglycaemic hyperinsulinaemic clamp (10 mU.kg.min) in patients with either good (HbA1c < 5.8%, groups A and B) or poor (HbA1c > 7.5%, groups C and D) long-term metabolic control (time > 12 months) and in healthy subjects (HbA1c: 5.08 +/- 0.20%; n = 8). To this end blood glucose was stabilized at 6.7 mmol/l by overnight (t = 12 h) i.v. regular insulin in groups (n = 8 each) A (HbA1c: 5.49 +/- 0.46%) and C (HbA1c: 8.83 +/- 1.20%), while groups B (HbA1c: 5.55 +/- 0.19%) and D (HbA1c: 8.51 +/- 1.09%) were kept overnight on long-acting insulin without feed-back control of blood glucose before euglycaemic clamping. Thereby, pre-equilibration of blood glucose at 6.7 mmol/l was shown to normalize basal hepatic glucose production (A: 2.27 +/- 0.48; C 2.50 +/- 0.57 mg.kg-1.min-1) despite different HbA1c values, whereas basal hepatic glucose production stayed elevated in groups B (3.09 +/- 0.38 mg.kg-1.min-1) and D (3.21 +/- 0.58 mg.kg-1.min-1) with poor actual glycaemia (B: 10.9 +/- 4.6; D: 12.1 +/- 4.6 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Monitoring daily insulin needs--an important follow-up parameter in late pregnancy in diabetic mothers?].

Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range < 5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near-normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus.

To determine the therapeutic effect of the carinitine palmitoyltransferase I (CPT-I) inhibitor, etomoxir, eight hospitalized obese non-insulin-dependent diabetes mellitus (NIDDM) patients were studied (body mass index [BMI], 28.7 +/- 1.3 kg/m2; age, 54 +/- 8 years [means +/- SE]) at baseline (placebo = t1), and after oral etomoxir (50 mg/d = t2, 100 mg = 3, 150 mg = t4, 200 mg = t5, placebo = t6). Fasting blood glucose (mmol/L), triglycerides (mmol/L), cholesterol (mmol/L), free fatty acids (mumol/L), beta-hydroxybutyrate (mumol/L), and alanine aminotransferase (GPT, U/L) were determined (t1 to t6), as were glucose utilization (M value; indirect calorimetry) and hepatic glucose production during a 10 mU/kg.min euglycemic clamp (t1 and t4). A dose-dependent decrease was induced by etomoxir in fasting blood glucose (t1 to t5: 9.5 +/- 0.7, 8.7 +/- 1.0, 8.3 +/- 1.1 [P v t1 less than .05], 7.8 +/- 0.9, [P v t1 less than .01], 7.9 +/- 1.1 [P v t1 less than .05]), which was reversible in t6 (9.9 +/- 1.1). Mean plasma lipids were reduced (t1 v t5) for triglycerides (-54%, P v t1 less than .01), cholesterol (-24%, P v t1 less than .05), and beta-hydroxybutyrate (-44%, P v t2 less than .01), while free fatty acids increased by 52% (P v t1 less than .05), as did GPT (t1: 17 +/- 3; t5: 32 +/- 7 U/L [P v t1 less than .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1991

Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance.

To determine the impact of fish-oil supplementation on glucose and lipid metabolism in patients with impaired glucose tolerance (IGT), 30 ml fish oil containing 3.8 g eicosapentaenoic acid (EPA; 20:5 omega 3) and 2.5 g docosahexaenoic acid (DHA; 22:5 omega 3) were given to eight obese subjects with IGT (mean +/- SD age 50.3 +/- 8.0 yr) in addition to their regular diet for 2 wk. Studies were performed in randomized order versus an isocaloric control period with a washout phase of 3 wk. Hyperinsulinemic clamp examinations (1 and 10 mU.kg-1.min-1) were performed. Glucose disposal rate (M value) rose from basal 14.3 +/- 5.1 to 17.9 +/- 4.4 mumol.kg-1.min-1 after fish oil (P less than 0.001) during the 1-mU clamp, whereas no change was seen during the 10-mU clamp (without fish oil, 42.2 +/- 8.9 mumol.kg-1.min-1; with fish oil, 45.1 +/- 9.8 mumol.kg-1.min-1;NS). Basal hepatic glucose output remained unaffected by fish oil, whereas fractional glucose clearance after intravenous glucose loading (2.4 mmol/kg body wt, t = 30 min) tended to increase (K value: without fish oil, 2.15 +/- 1.02%/min; with fish oil, 2.74 +/- 1.26%/min; NS). Neither the fasting concentrations of glucose and insulin nor induced glycemia and insulin response during intravenous glucose loading calculated as incremental area under the curve changed after fish-oil supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗