Biomedical subjects

Raimund Weitgasser

Publications and source records attributed to Raimund Weitgasser.

9 recordsLinked to original sources

PubMed2004

Evaluation of a new insulinotropic agent by using an innovative technology: efficacy and safety of nateglinide determined by continuous glucose monitoring.

Nateglinide, a new insulinotropic agent, specifically targets prandial glycemic excursions. Recently, innovative technologies have become available that provide the possibility to measure 72-h blood glucose values continuously. The aim of this study was to evaluate the effects of nateglinide on 24-h blood glucose profiles in diabetic patients. Eighteen patients with type 2 diabetes mellitus--seven on diet only and 11 on metformin monotherapy--participated in the study. Mean age was 60 years, mean diabetes' duration was 7.4 years, and mean hemoglobin A1c was 8.4%. They underwent a 72-h glucose monitoring using a continuous glucose monitoring system (CGMS, Medtronic MiniMed, Northridge, CA) under their usual diabetes therapy and a standardized breakfast. After this period, therapy with nateglinide, 120 mg three times a day before meals, was initiated. Three days later patients again underwent 72-h glucose monitoring. Mean blood glucose values and mean fasting blood glucose values decreased significantly, from 172 mg/dL before to 131 mg/dL (P< 0.0004) and from 172 mg/dL before to 126 mg/dL (P< 0.0005), respectively, with nateglinide therapy. Postprandial hyperglycemia, expressed as mean blood glucose over a time period of 2 h after a meal, declined significantly after all three daily meals. The number of blood glucose values above 140 mg/dL decreased from 207 without to 98 during nateglinide therapy. Nateglinide was not associated with hypoglycemia or other adverse events. We found in this study, using CGMS, that nateglinide has a glucose-lowering potency that not only affects postprandial hyperglycemia, but also overnight and fasting blood glucose values.

Blood Glucose↗

PubMed2004

Neuroendocrine cell markers for pancreatic islets and tumors.

The authors review the application of a variety of neuroendocrine cell markers to identify pancreatic islet cells and tumors. In the past, several empiric histochemical techniques had been used to demonstrate neuroendocrine cells, particularly the Grimelius argyrophilic stain. The development of immunohistochemistry made it possible to demonstrate specific cell products such as regulatory peptides, thus allowing the classification of pancreatic neuroendocrine tumors with a view to clinical symptoms. However, it is not always possible to visualize regulatory peptides in these tumors. It is therefore important to use broad-spectrum neuroendocrine cell markers to identify the neuroendocrine nature. These markers are proteins localized in the secretory granules (core- or membrane-related), in the cytosol, or in the cellular membrane. The markers most commonly used in routine histopathology are the secretory granule proteins chromogranin A and synaptophysin and the cytosolic enzyme neuronspecific enolase. Other new markers (e.g., synaptic vesicle protein 2) are of general diagnostic value. Region-specific antibodies to chromogranin A can be valuable in differentiating between benign and malignant neuroendocrine tumors. Some markers may be related to the functioning characteristics of pancreatic neuroendocrine tumors, such as prohormone convertases. In addition, markers giving further complementary information have been identified, such as five somatostatin receptor subtypes, the expression of which varies markedly in pancreatic neuroendocrine tumors. Antibodies against all somatostatin receptor subtypes are now commercially available, and immunohistochemical investigation of its expression should be routinely applied when considering treatment with somatostatin analogs.

Biomarkers↗

PubMed2004

Complex haplotypes of the PGC-1alpha gene are associated with carbohydrate metabolism and type 2 diabetes.

Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator implicated in transcriptional programs of hepatic gluconeogenesis, oxidative phosphorylation, and insulin release by beta-cells. To study associations of the PGC-1alpha gene locus with carbohydrate metabolism and type 2 diabetes in humans, we identified several polymorphisms in the promoter region that were located in a haplotype block distinct from a second haplotype block containing part of intron 2 and extending beyond exon 13. Each block contained five common haplotypes. Oral glucose tolerance testing revealed associations of promoter haplotype combinations with 30- and 60-min postload plasma glucose levels, whereas haplotypes in both blocks were associated with indexes of beta-cell function. The associations of promoter haplotypes are supported by functional studies showing that some polymorphisms are located in transcription factor binding sites and affect transactivation in an allele-specific manner. By comparing patients with type 2 diabetes and control subjects, we observed borderline significant differences of four-loci haplotype distributions in the downstream haplotype block. Moreover, the haplotype that was associated with the strongest insulin response to glucose conferred the lowest risk of type 2 diabetes (P < 0.01). Thus, the PGC-1alpha gene locus influences carbohydrate metabolism and contributes to type 2 diabetes in the population studied.

Aged↗

PubMed2004

[Life-style modification].

Diabetes education, nutritional advice, exercise recommendations and training for smoking cessation comprise the mainstay of diabetes treatment before starting drug therapy. Prevention as well as treatment of diabetes mellitus is positively influenced by life-style modification. In addition cardiovascular risk factors can be reduced by such measures. The article gives in brief recommendations leading towards life-style modification based on current evidence.

Diabetes Mellitus↗

PubMed2004

[Therapy with oral antidiabetic drugs].

Hyperglycemia contributes to morbidity and mortality in diabetic patients. Reaching treatment targets with regard to control of glycemia is thus a central goal in the treatment of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of oral antidiabetic drugs according to current scientific evidence.

Administration, Oral↗

PubMed2004

[Therapy with insulin].

Austria↗

PubMed2003

Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.

Sulphonylureas are effective and well tolerated in patients with Type 2 diabetes, but may be associated with weight gain, and lack of compliance due to multiple daily dosing. This open, uncontrolled surveillance study examined the efficacy and safety of glimepiride, a new sulphonylurea, administered once daily in patients with Type 2 diabetes. A total of 1,770 patients were enrolled in the study, and 284 patients were selected for follow-up. Patients received 0.5 to >4 mg glimepiride once daily for 1.5 years. HbA(1c) was reduced from 8.4% at baseline to 7.1% after 4 months and 6.9% after 1 and 1.5 years (median intra-individual change from baseline: -1.4, -1.5, and -1.7%, respectively; P<0.0001). Treatment with glimepiride also resulted in significant and stable weight loss relative to baseline, with the exception of patients with a body mass index of <25 kg/m(2). Mean body weight was reduced from 79.8 kg at baseline to 77.9 kg after 4 months, 77.2 kg after 1 year, and 76.9 kg after 1.5 years (mean intra-individual change from baseline: -1.9 kg, P<0.0001; -2.9 kg, P<0.05; -3.0 kg, P<0.005, respectively). Therefore, once daily glimepiride provides effective glycaemic control, and may have advantages over other sulphonylureas, because it exhibits weight neutralizing/reducing effects in patients with Type 2 diabetes.

Adult↗

PubMed2003

Candida-induced stomatopyrosis and its relation to diabetes mellitus.

BACKGROUND: Glycaemic disorders and oral candidosis can be accompanied by burning mouth sensations. However, no clear relation between all three disorders is known. METHODS: Seventy-two native Upper-Austrians with burning mouth sensations were examined and smears for Candida estimation were taken from the spots where the sensations were felt. All patients with previously unknown diabetes mellitus (DM) were subjected to an oral glucose tolerance test (OGTT). Use of glucocorticoid-containing anti-asthmatic sprays and the body mass index (BMI) were determined. RESULTS: Of the examined non-inhalers of sprays, 52% had increased candidal density. A correlation between that increase and type 2 DM was found. The burning sensations in all patients with increased candidal density subsided completely after anti-mycotic therapy. CONCLUSION: The perception of burning sensations was hypothesised to occur via stimulation of the capsaicin (vanilloid) receptor by Candida metabolites. The Candida-induced stomatopyrosis should be regarded as a single symptom indicating (predisposition to or established) type 2 DM in non-inhalers of the concerned population.

Administration, Inhalation↗

PubMed2002

A functional polymorphism in the promoter of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle-aged humans.

Obesity is frequently associated with type 2 diabetes. We previously observed an association of a functional G/A polymorphism in the uncoupling protein 2 (UCP2) promoter with obesity. The wild-type G allele was associated with reduced adipose tissue mRNA expression in vivo, reduced transcriptional activity in vitro, and increased risk of obesity. On the other hand, studies in animal and cell culture models identified pancreatic beta-cell UCP2 expression as a main determinant of the insulin secretory response to glucose. We therefore ascertained associations of the -866G/A polymorphism with beta-cell function and diabetes risk in obesity. We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the beta-cell line INS1-E. By studying 39 obese nondiabetic humans, we observed genotype differences in beta-cell function; wild-type subjects displayed a greater disposition index (the product of insulin sensitivity and acute insulin response to glucose) than subjects with the variant allele (P < 0.03). By comparing obese subjects with and without type 2 diabetes, we observed genotype-associated differences in diabetes prevalence that translated into a twofold age-adjusted risk reduction in wild-type subjects. Thus, the more common UCP2 promoter G allele, while being conducive for obesity, affords relative protection against type 2 diabetes.

Adipose Tissue↗