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Biomedical subjects

R Weitgasser

Publications and source records attributed to R Weitgasser.

At least 19 recordsLinked to original sources
PubMed2006

The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population.

CONTEXT: The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. DESIGN, SETTINGS AND PARTICIPANTS: We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. MAIN OUTCOME MEASURES: Body mass index (BMI), indices of insulin sensitivity and beta-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. RESULTS: Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. CONCLUSIONS: We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.

Adiponectin↗
PubMed2004

Cholesteryl ester transfer protein TaqIB polymorphism and its relation to parameters of the insulin resistance syndrome in an Austrian cohort.

The cholesteryl ester transfer protein (CETP) is responsible for the exchange of triglycerides and cholesteryl esters between lipoprotein particles leading to an increased hepatic clearance of HDL-cholesteryl esters. A high CETP activity reduces serum HDL levels, whereas persons without CETP activity have high HDL levels. We investigated the association of the TaqIB CETP polymorphism and various parameters of the insulin resistance syndrome in a cross sectional population based study. We included 1029 persons without known cardiovascular disease or diabetes mellitus consecutively enrolled in our SAPHIR program (Salzburg Atherosclerosis Prevention program in persons with a High Infarction Risk). Numerous clinical and laboratory data were accomplished. Insulin sensitivity was measured by a short insulin tolerance test. The TaqIB CETP polymorphism was determined by PCR, TaqI restriction and electrophoresis. 35.2% were homozygous for the prevalence (B1B1), 46.7% were heterozygous (B1B2), and 18.1% homozygous for the absence (B2B2) of the restriction site. HDL cholesterol and apolipoprotein A1 were lower and small dense low-density lipoproteins (sdLDL) higher in B1B1 compared to B2B1 and B2B2 persons. In women, we found a significant interaction effect between CETP genotype and adiposity for HDL cholesterol. B1B1 women with a BMI and a waist circumference above the median had 9.7 mg/dl lower HDL than B1B2 and 9.1 mg/dl lower HDL than B2B2 women (P < 0.001). In men, no interaction effect but a marked genotype to HDL correlation was found. There was a high CETP effect on sdLDL detected in men (P = 0.001). B1B1 men had sdLDL in 36%, B1B2 in 24.6%, and B2B2 in only 14.5%. Men with adiposity and insulin resistance had twice as many sdLDL as insulin sensitive men. We found a significant sex specific effect of the TaqIB CETP polymorphism on the insulin resistance parameters HDL-cholesterol and sdLDL in an Austrian population based study.

Adult↗
PubMed2003

Antibodies to heat-shock protein 65 and neopterin levels in patients with type 1 diabetes mellitus.

Antibodies to heat shock protein (hsp) are strongly associated with atherosclerotic cardiovascular disease in the non-diabetic population as well as in patients with type 2 diabetes mellitus. In type 1 diabetes increased antibody titers to hsp were found to be a symptom of the autoimmune disease leading to beta-cell damage. We asked whether hsp antibody titers are related to metabolic control and late complications in type 1 diabetic patients. Serum neopterin, also an indicator of chronic inflammation, was also evaluated. The hsp65 antibody titer was determined in 138 patients with type 1 diabetes, 47 women and 91 men, aged 35.5 +/- 12 years with a mean diabetes duration of 16.6 +/- 10.5 years. A history of diabetic late complications and cardiovascular disease was taken. A fundoscopy and a neurological examination were performed, nephropathy was assessed by measurement of the urinary albumin excretion rate. For the measurement of the hsp antibody titer an enzyme-linked immunosorbent assay (ELISA) was applied, for neopterin a radio-immuno assay (RIA) was used. The hsp65 antibody titer was found to be positively related to the patients' age (r = 0.237; p < 0.035). Patients with retinopathy revealed significantly higher hsp65 antibody titers (307.2 +/- 38.6) than those without retinopathy (150.0 +/- 18.5;p < 0.003). No correlation was found between hsp antibody titer and metabolic control. Serum neopterin levels revealed a trend towards a positive relationship with diabetes duration (r = 0.205; p < 0.0539) and a significant correlation with serum cholesterol levels (r = 0.436; p < 0.001), but not with HbA1 c values. Our data add further information to the role of inflammatory markers in the development of diabetic microangiopathy.

Adult↗
PubMed2002

Candida attachment to oral epithelium.

Inflamed oral mucosa biopsies from patients with thrush and high candidal density were observed in a transmission electron microscope (TEM) using ultra-histochemical staining with ruthenium red for glycocalyx visualization. Fimbriae comprising the glycocalyx and enabling yeast adhesion to epithelial cells were clearly visualized by ruthenium red. All internalized portions of the yeast walls were devoid of glycocalyx, indicating that the growing tips of the hyphae mechanically penetrated the host cells. The attachment of Candida occurred in two ways: by fimbria-mediated adhesion enabling colonization of the epithelial surface, and by invasion of the superficial epithelial cells via hyphae. As the interaction between adhesin receptors and adhesins stimulates the production of proinflammatory cytokines, Candida adhesion itself is assumed to induce mucosal inflammation.

Adult↗
PubMed2002

[Risk status of screened population based on elevated serum cholesterol values].

The mean value of serum total cholesterol was 208 +/- 42 mg/dl for the study population. Sixty-five percent of investigated subjects had elevated cholesterol levels > 200 mg/dl. The percentage of subjects with low to moderate elevated cholesterol levels between 200-250 mg/dl was 40%, and 2% had a cholesterol higher than 300 mg/dl. Grouping the cholesterol levels by age and sex resulted in a high percentage of subjects with serum cholesterol > 200 mg/dl for the cardiovascular high-risk age group of 45-65 years old men and 55-75 years old women. Remarkably high was this percentage for women in this age-group; 71% had a cholesterol level > 200 mg/dl. In 59% of investigated women and 52% of men cholesterol should be lowered.

Adult↗
PubMed2001

High-fructose diet preserves beta-cell mass and prevents diabetes in nonobese diabetic mice: A potential role for increased insulin receptor substrate-2 expression.

We demonstrate that a high-fructose diet reduces the incidence of diabetes in nonobese diabetic (NOD) mice (31.2% v 57.1% on regular chow (RC); P =.009). In a second cohort of mice, we evaluated potential mechanisms for the protective effect of the high-fructose (HF) diet and whether the metabolic changes are strain-specific. Sixty NOD and 60 Balb/c mice were randomized at weaning into HF- and RC-fed groups (30 mice each) and followed for 28 weeks. Glucose tolerance testing demonstrated improved glucose tolerance in HF diet groups (P =.001 in Balb/c; P =.04 in NOD mice at 6 months). beta-cell mass was preserved in NOD mice on the HF diet, but remained unchanged in Balb/c mice. In NOD mice, hepatic insulin receptor substrate (IRS)-2 protein expression increased by 2-fold (P =.01 for 2 v 6 months) in HF-fed mice and was 53% +/- 15% higher (P =.01) in the HF diet versus RC groups at 6 months of age. IRS-2 expression was also increased in skeletal muscle of NOD mice and in both liver and muscle of Balb/c mice. Our data suggest that a HF diet improves glucose tolerance in both NOD and Balb/c mice. The improved glucose tolerance may be related to increased IRS-2 expression and, in NOD mice, preservation of beta-cell mass.

Animals↗
PubMed2001

Immunohistochemical assessment of an asymptomatic glucagonoma in a patient with hypergastrinemia and marked antral angiodysplasia.

A 58-year-old patient had been treated for recurrent gastritis. Numerous gastroscopies indicated hemorrhagic gastritis combined with increasingly severe anemia. The patient was admitted with a hemoglobin of 4.4 g/dL. Gastroscopy showed marked antral angiodysplasia. Serum samples for gastrin were taken and found to be elevated (170-250 U/mL). The search for a gastrin-producing tumor with abdominal ultrasound, computed tomography, octreotide scan, and secretin test was negative, but angiography detected a pancreas tumor with a 2-cm diameter. Partial pancreatectomy and partial gastrectomy were performed. Immunohistochemical examination of the tumor did not show a gastrinoma but did show glucagon-reactive tissue. Further tumors or elevated plasma hormone levels were not detected, and a multiple endocrine neoplasia type I syndrome could be excluded. We thus found antral angiodysplasia with hypergastrinemia leading to detection of a glucagonoma diagnosed by immunohistochemistry. After more than 4 years of follow-up, the patient is without any symptoms or signs of relapse or secondary hormone syndrome.

Diagnosis, Differential↗
PubMed2000

Association of HELLP syndrome with autoimmune antibodies and glucose intolerance.

OBJECTIVE: HELLP syndrome is a severe form of preeclampsia, characterized by hemolysis (H), elevated liver enzymes (EL), and low platelets (LP), whose pathogenesis is unclear. Autoimmunity is thought to play an important role. After the observation of development of type 1 diabetes in a patient with HELLP syndrome, we assumed a possible disease association based on autoimmune reactions. RESEARCH DESIGN AND METHODS: We examined 70 women with HELLP syndrome for the presence of autoimmune markers and glucose intolerance. Free thyroxine, triiodothyronine, thyroid-stimulating hormone, anti-thyroglobulin antibodies, thyroperoxidase antibodies, thyrotropin receptor antibodies, antinuclear antibodies (ANAs) and anti-DNA, islet cell antibodies, GADA, an oral glucose tolerance test, and HbA1c were determined postpartum. Patients with positive autoimmune markers or glucose intolerance were prospectively followed and repeated testing was performed. There were 60 women with a normal course of pregnancy matched for age, BMI, and number of pregnancies, which served as a control group. RESULTS: From the HELLP patients, 22 (31%) compared with only 6 (10%) control subjects had autoimmune antibodies (P < 0.01). There were 16 HELLP patients (23%) who exhibited only 1 kind of autoantibody (5 ANA, 9 thyroid antibodies, and 2 GADA), whereas in 6 HELLP patients (8.5%) 2 different antibodies were found. In all but 4 patients of the study group, these antibodies disappeared during 3 +/- 1.5 years of follow-up. Glucose intolerance was detected in 22 (31%) of the HELLP patients, 17 of them had impaired glucose tolerance (IGT), and 5 had diabetes, whereas only 4 subjects (6.5%) with IGT at postpartum were found in the control group (P < 0.01). During the follow-up, 2 HELLP patients were still diabetic and another 2 HELLP patients (1 GADA positive) had IGT versus 1 control subject. CONCLUSIONS: Our data give evidence that HELLP syndrome is associated with various autoimmune antibodies and glucose intolerance. Because glucose intolerance and/or autoimmune markers persisted during long-term follow-up in 6 patients with HELLP syndrome versus 1 in the control group, it may become advisable to reexamine patients with HELLP syndrome for detection of diabetes and autoimmune disorders.

Adult↗
PubMed1999

Glycaemic disorders in denture stomatitis.

The prevalence of glycaemic disorders was investigated in native Upper-Austrians with Candida-associated denture stomatitis. All patients with previously unknown diabetes mellitus were subjected to an oral glucose tolerance test (OGTT) and as a result diabetes was diagnosed in 13% of the patients over 50 years of age. Thirty-five percent of all inspected patients over 50 years of age with denture stomatitis had type 2 diabetes mellitus and 36% had impaired glucose tolerance (IGT). The correlation between Candida-associated denture stomatitis and diabetes mellitus indicates a means for the early diagnosis of diabetes. Hyperglycaemia could not be a predisposition to denture stomatitis, since all patients with denture stomatitis in the age-bracket 26-50 years were without diabetes and only very few of the older patients with diabetes were obese. The correlation between Candica-associated denture stomatitis and type 2 diabetes mellitus could be traced back to a reduced resistance to Candida that preceded the diabetes.

Adult↗
PubMed1999

Prospective evaluation of urinary N-acetyl-beta-D-glucosaminidase with respect to macrovascular disease in elderly type 2 diabetic patients.

OBJECTIVE: To analyze prospectively the importance of urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker for renal tubular function, in comparison with urinary albumin excretion (UAE), a marker for glomerular renal function, with respect to macrovascular disease in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 124 patients over a mean period of 7.0 +/- 0.5 years. At baseline, urinary NAG, UAE, age, diabetes duration, sex, blood pressure, lipids, and serum creatinine were determined. Also, history of myocardial infarction (MI), stroke, severe peripheral vascular disease (PVD), antidiabetic and concomitant medication, and smoking habits were recorded. After 7 years, patients were reevaluated, and a multivariate logistic regression analysis was used to test risk factors for significance in order to predict macrovascular disease. Subgroups of patients were analyzed with respect to severe macrovascular disease, with a separate analysis for surviving patients. RESULTS: Compared with known cardiovascular risk factors such as microalbuminuria and total cholesterol, urinary NAG was similarly associated with cardiovascular disease for the total cohort (P < 0.05). Analyzing the subgroup of 65 patients still alive after follow-up care, urinary NAG and UAE were significantly elevated at baseline and at the time of follow-up care in patients with MI and PVD, but not in those with stroke (P < 0.01). There was a positive predictive trend of NAG excretion for the development of MI and PVD in our patients (P = 0.07). CONCLUSIONS: Urinary NAG proved comparable to UAE when analyzed with respect to preexistence and development of severe macrovascular disease. It needs to be determined by further studies if urinary NAG will be of value to serve as an adjunct marker to UAE in type 2 diabetic patients.

Acetylglucosaminidase↗
PubMed1999

Newer portable glucose meters--analytical improvement compared with previous generation devices?

BACKGROUND: Newer glucose meters are easier to use, but direct comparisons with older instruments are lacking. We wished to compare analytical performances of four new and four previous generation meters. METHODS: On average, 248 glucose measurements were performed with two of each brand of meter on capillary blood samples from diabetic patients attending our outpatient clinic. Two to three different lots of strips were used. All measurements were performed by one experienced technician, using blood from the same sample for the meters and the comparison method (Beckman Analyzer 2). Results were evaluated by analysis of clinical relevance using the percentage of values within a maximum deviation of 5% from the reference value, by the method of residuals, by error grid analysis, and by the CVs for measurements in series. RESULTS: Altogether, 1987 blood glucose values were obtained with meters compared with the reference values. By error grid analysis, the newer devices gave more accurate results without significant differences within the group (zone A, 98-98.5%). Except for the One Touch II (zone A, 98.5%), the other older devices were less exact (zone A, 87-92.5%), which was also true for all other evaluation procedures. CONCLUSIONS: New generation blood glucose meters are not only smaller and more aesthetically appealing but are more accurate compared with previous generation devices except the One Touch II. The performance of the newer meters improved but did not meet the goals of the latest American Diabetes Association recommendations in the hands of an experienced operator.

Ambulatory Care↗
PubMed1998

[Blood glucose self-monitoring in intensified insulin therapy: acceptance of frequent measurements and effect on quality of diabetic control].

In intensive insulin therapy frequent measurements of blood glucose are necessary for daily insulin adjustments. The aim of our study was to determine acceptance of frequent blood glucose measurements and its relation to quality of glycemic control over a period of 5 years. We report on 57 unselected patients with type 1 diabetes mellitus, who were at least half a year under intensive insulin therapy when entering the study. Mean age was 34 +/- 9, diabetes duration 18 +/- 8 years. The number of daily blood glucose measurements, HbA1c, body mass index, daily insulin dose, routine laboratory values, number of severe hypoglycemic reactions and frequency of retinopathy, nephropathy and neuropathy were determined for year 1 and 5. We found an increase in daily blood glucose measurements from 2.5 to 4.5 per day (year 1 resp. year 5). The frequency of blood glucose measurements at the begin of our study respectively after 5 years was: < or = 2.0/day in 51% vs. 12%, > 2.0 but < 4.0/day in 20% vs. 21% and > or = 4.0/day in 29% vs. 67% of patients. HbA1c decreased from 7.3 +/- 1.2 to 6.4 +/- 1.1% after 5 years (p < 0.001). A comparison of subgroups of patients showed that frequency of blood glucose measurement is not the only cause for this improvement, but adequate education of diabetic patients seems to be most important. Retinopathy and neuropathy increased despite better diabetic control, 2 patients developed microalbuminuria, all other data determined at study entry remained unchanged after 5 years. We conclude that frequent daily blood glucose measurements were accepted by the majority of our patients over a long period of time. Mean blood glucose determined by HbA1c improved under intensive insulin therapy. In our study group with low HbA1c values at baseline this effect was only partly related to the frequency of daily blood glucose measurements.

Adult↗
PubMed1997

[Current portable blood sugar analysis equipment--comparison of the MediSense Card, Glucometer Elite, Hypocount Supreme and Omnican Control with the glucose oxidase reference method].

Patients as well as medical personnel are increasingly confronted with new devices for blood glucose measurement. Devices smaller in size, faster in action and easier to handle are being developed by various companies. We investigated whether precision and accuracy of recently marketed blood glucose meters would be efficient and safe enough for clinical use, and compared the meters MediSense Card, Glucometer Elite, Hypocount Supreme, and Omnican Control with our reference glucose oxidase method. On average 200 pairs of blood glucose values from capillary blood samples of type 1 and 2 diabetic patients were determined using two meters of each make. The measurements were performed by one experienced technician using blood from the same sample for the meter and the Beckman Analyzer 2. For evaluation a linear regression analysis, the percentage of values within a maximum deviation of less than 10% from the reference value, and clinically relevant models such as Clarke's error-grid analysis and Koschinsky's acceptance analysis were used. Combining all analyses, MediSense Card and Glucometer Elite showed the least deviations in all blood glucose ranges. For MediSense Card 56%, for Glucometer Elite 72%, but for Hypocount Supreme and Omnican Control less than 50% of all values were within a +/- 10% range compared with the reference method. Clarke's error-grid analysis reflected the best results for MediSense Card and Glucometer Elite with 96% and 97% respectively of all measurements within the ideal error-grid zone A, whereas this was the case for Hypocount Supreme in 85% and for Omnican Control in only 71%. The coefficient of variance for measurements in series using 3 different blood glucose ranges was acceptable for all devices besides the Hypocount Supreme, but overall performance was poor compared to our reference method. Nevertheless, according to Koschinsky's clinical acceptance scale even Hypocount Supreme and Omnican Control can be classified as clinically acceptable (range 2 from a three point scale). The 1994 criteria of the American Diabetes Association, a maximum deviation of less than 5% in 100% of measurements, were not met by any device, but after training and with proper handling all devices work efficiently enough and are safe for clinical use. Nevertheless, companies are urged to seek new technologies for blood glucose measurement, as all recently developed devices tested in our study did not perform better than known older glucose meters.

Analysis of Variance↗
PubMed1996

Islet transplantation under the kidney capsule fully corrects the impaired skeletal muscle glucose transport system of streptozocin diabetic rats.

Chronic insulin therapy improves but does not restore impaired insulin-mediated muscle glucose uptake in human diabetes or muscle glucose uptake, transport, and transporter translocation in streptozocin diabetic rats. To determine whether this inability is due to inadequate insulin replacement, we studied fasted streptozocin-induced diabetic Lewis rats either untreated or after islet transplantation under the kidney capsule. Plasma glucose was increased in untreated diabetics and normalized by the islet transplantation (110 +/- 5, 452 +/- 9, and 102 +/- 3 mg/dl in controls, untreated diabetics, and transplanted diabetics, respectively). Plasma membrane and intracellular microsomal membrane vesicles were prepared from hindlimb skeletal muscle of basal and maximally insulin-stimulated rats. Islet transplantation normalized plasma membrane carrier-mediated glucose transport Vmax, plasma membrane glucose transporter content, and insulin-induced transporter translocation. There were no differences in transporter intrinsic activity (Vmax/Ro) among the three groups. Microsomal membrane GLUT4 content was reduced by 30% in untreated diabetic rats and normal in transplanted diabetics, whereas the insulin-induced changes in microsomal membrane GLUT4 content were quantitatively similar in the three groups. There were no differences in plasma membrane GLUT1 among the groups and between basal and insulin stimulated states. Microsomal membrane GLUT1 content was increased 60% in untreated diabetics and normalized by the transplantation. In conclusion, an adequate insulin delivery in the peripheral circulation, obtained by islet transplantation, fully restores the muscle glucose transport system to normal in streptozocin diabetic rats.

Animals↗
PubMed1996

Long-term normalization of GLUT-4 protein content in skeletal muscle of diabetic rats following islet transplantation.

Skeletal muscle GLUT-4 content is decreased in streptozotocin (STZ)-diabetic rats. This decrease is associated with impairment in glucose transport across the plasma membrane. In this study we investigated whether islet transplantation might normalize GLUT-4 content. Transplantation of syngeneic islets restored long-term near-normoglycemia in STZ-diabetic Lewis rats. Transplanted rats, followed up to 6 months, maintained slightly but significantly higher fasting and fed glucose levels when compared with age-matched normal controls. Although fasting insulin levels of transplanted rats were significantly higher than those of controls, insulin levels did not increase significantly with feeding. Plasma glucose levels following an oral glucose load (2 g/kg) were only slightly higher than in normal controls 2 months after transplantation, whereas after 6 months more severe glucose intolerance was detected. Transplanted rats completely lost the first-phase insulin release in response to i.v. glucose although they showed an increased second phase and preserved response to arginine. Six months after transplantation, endocrine beta cell mass of the grafts was similar to pretransplantation values. GLUT-4 protein content in skeletal muscle homogenates was reduced in untreated diabetic animals whereas it was completely restored by islet transplantation. In conclusion, achievement of long-term nearnormoglycemia after islet transplantation was associated with complete normalization of skeletal muscle GLUT-4 content in the diabetic animals, even in the presence of abnormal glucose tolerance and an altered pattern of insulin secretion.

Animals↗
PubMed1996

Islet transplantation in diabetic Lewis rats--a comparison of the transplantation sites kidney and spleen capsule.

Animal studies have been used to investigate different transplantation (Tx) sites to find best conditions for Tx in humans. A few long-term experiments of comparisons of different Tx-sites have been published. Therefore the aim of our study was to compare islet grafts transplanted under the kidney capsule (KTx) of male Lewis rats with grafts transplanted under the spleen capsule (STx) and to observe these animals over a period of 6 months. Diabetes was induced by Streptozotocin and rats were each transplanted with 2000 syngeneic islets under the kidney respectively the spleen capsule. 2 weeks after Tx all animals were normoglycemic. Over the following 6 months nearly normal plasma glucose levels could be maintained in the KTx group whereas the STx animals already became diabetic after 3 months. An oral glucose load after 2 months showed slightly elevated plasma glucose levels in the KTx group which only gained statistical significance in a similar test after 6 months. In the STx group definitely impaired glucose tolerance already prevailed at 2 months. An i.v. glucose tolerance test performed 6 months after Tx showed a loss of first phase insulin release in both Tx groups but an increased second phase release and a preserved response to L-arginine compared to controls. Insulin content remained unchanged in the KTx group, but was markedly reduced in the STx group after 6 months. In conclusion we may say that KTx is able to establish near-normoglycemia in streptozotocin-diabetic Lewis rats which can be maintained over a long period of time despite abnormal glucose tolerance and impaired insulin secretion STx could normalize plasma glucose only up to 3 months showing early impairment of glucose and insulin regulation. If KTx has immunological or local advantages (islet vascularization, innervation) compared to STx with higher dispersion of islets in spleen and portal vascular system remains unclear.

Animals↗