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W Krone

Publications and source records attributed to W Krone.

At least 19 recordsLinked to original sources
PubMed2006

The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians.

The K121Q polymorphism of the human plasma cell membrane glycoprotein 1 (PC-1) gene is known to be associated with diabetes mellitus type 2 in some populations studied, with contradictory results. The purpose of the present study was to examine a possible association between the presence of diabetes and the PC-1 K121Q polymorphism in a German Caucasian population. Associations between the polymorphism and various metabolic and anthropometric parameters were also examined. The presence of the K121Q variant was investigated using polymerase chain reaction restriction fragment-length polymorphism in 402 subjects with diabetes (231 men, 171 women, age 63+/-11 yrs, body mass index 28.7+/-5.1 kg/m2) and in 432 age- and sex-matched controls (247 men, 185 women, age 64+/-7 yrs, BMI 26.5+/-3.7 kg/m2). Ninety-seven subjects were carriers of the K121Q polymorphism in the control and 110 in the diabetic group (allelic frequency 11.9% and 14.7%, respectively, P=0.25). The polymorphism had no significant influence on the presence of atherosclerotic disease, body mass index, and blood pressure, both, in diabetics and in non-diabetic controls. Our data suggest that the K121Q polymorphism of the PC-1 gene is not associated with diabetes, obesity, hypertension or atherosclerosis in a German Caucasian population.

Adult↗
PubMed2006

[Favorable effects of decreasing lipids in patients with diabetes mellitus].

Patients with diabetes mellitus are patients at high risk for cardiovascular events. There is only limited number of studies examining the effects of lipid lowering specifically in diabetics. The majority of evidence is derived from subgroup analyses of large intervention trials. Patients with diabetes mellitus benefit from a therapy with statins, independently from the starting LDL cholesterol concentrations. Furthermore, recent studies strongly suggest that for high risk patients such as diabetics regarding LDL "the lower is the better" The data for the benefits of fibrate therapy is not as robust as those available for statins. Therefore, at present no specific recommendation for treatment of diabetics with fibrates can be made.

Anticholesteremic Agents↗
PubMed2006

Association of the promoter polymorphism -232C/G of the phosphoenolpyruvate carboxykinase gene (PCK1) with Type 2 diabetes mellitus.

AIMS: The phosphoenolpyruvate carboxykinase gene (PCK1) is a potential candidate gene in the pathogenesis of Type 2 diabetes mellitus. A -232C/G promoter polymorphism of PCK1 has been associated with an increased risk of Type 2 diabetes in a Canadian population. The purpose of the present study was to examine this association in a German Caucasian population. METHODS: We investigated 397 subjects with Type 2 diabetes [227 men, 170 women, age 63 +/- 11 years, body mass index (BMI) 28.7 +/- 5.1 kg/m2] and 431 control subjects without diabetes (247 men, 184 women, age 64 +/- 7 years, BMI 26.5 +/- 3.7 kg/m2) matched for sex and age. RESULTS: In the diabetic and control groups, the CC genotype frequencies were 18.1 and 18.3%, the CG 48.6 and 48.7% and the GG 33.2 and 32.9%, respectively (P = 0.995). The allelic frequencies were 0.51 and 0.57 for the G allele and 0.49 and 0.43 for the C allele, respectively. In a logistic regression model only BMI and family history, but not the polymorphism, were predictors of Type 2 diabetes. In both the control and diabetic subjects, there were no significant differences in BMI or blood pressure between the groups with or without the polymorphism. The variant also had no significant influence on the presence of atherosclerotic disease, while the influence of other known cardiovascular risk factors was confirmed. CONCLUSIONS: The present data suggest that, in a German Caucasian population, the -232C/G polymorphism of the PEPCK gene is not associated with Type 2 diabetes.

Aged↗
PubMed2005

Hypertriglyceridemia-why, when and how should it be treated?

The relationship between serum triglyceride levels and cardiovascular disease has remained enigmatic despite four decades of research. The majority of the available evidence tends to support the role of hypertriglyceridemia as an independent risk factor for cardiovascular disease. However, there are no guidelines recommending a target triglyceride level for prevention of cardiovascular disease. The focus of lipid lowering therapy still remains the reduction of global cardiovascular risk by optimizing LDL cholesterol levels. Therapeutic options for triglyceride-lowering include lifestyle modification and pharmacological agents, such as fibrates, omega 3 fatty acids and niacin. Post-hoc analyses of the Helsinki Heart Study, Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial and Bezafibrate Infarction Prevention Study suggest a beneficial effect of the treatment of hypertriglyceridemia with fibrates, mainly in obese subjects with insulin resistance. However, in order to establish the actual clinical relevance of lowering triglyceride levels, prospective trials need to be conducted with the specific purpose of studying the effects of triglyceride reduction on clinical end points, i. e. coronary events and stroke.

Cardiovascular Diseases↗
PubMed2005

Autoimmune polyglandular syndrome associated with idiopathic giant cell myocarditis.

The autoimmune polyglandular syndrome (APS) is characterized by a variable coexistence of several autoimmune diseases, affecting predominantly endocrine glands. In general two types of APS are distinguished. Type 1 APS is an autosomal recessive disorder often leading to insufficiency of the adrenal cortex, the parathyroid glands, and/or the gonads. This type of APS often affects the skin in form of chronic mucocutaneous candidiasis and ectodermal dystrophies (vitiligo, alopecia, keratopathy, dystrophy of dental enamel and nails). The second form of APS is a polygenic disease which usually involves the adrenal gland, the thyroid and the pancreatic beta-cells. In rare cases APS type 2 is associated with myasthenia gravis, autoimmune thrombocytopenic purpura, Sjogren's syndrome or rheumatoid arthritis. Here we describe a case of APS with the unusual combination of type 1 diabetes, secondary adrenocortical insufficiency, growth hormone deficiency, and primary hypothyroidism associated with lethal idiopathic giant cell myocarditis. The combination of APS and idiopathic giant cell myocarditis which is a rare, frequently fatal autoimmune disorder of myocardium affecting most commonly young individuals has not been reported so far.

Adrenal Cortex Diseases↗
PubMed2005

The Pro387Leu variant of protein tyrosine phosphatase-1B is not associated with diabetes mellitus type 2 in a German population.

OBJECTIVES: Diabetes mellitus type 2 (DM-2) is a complex disorder with a strong genetic background. Protein tyrosine phosphatase-1B (PTP-1B) dephosphorylates various receptor protein kinases in vitro, including the beta subunit of the insulin receptor, therefore representing a potential candidate to be involved in the polygenic pathogenesis of DM-2. Recently a Pro387Leu variant of the PTP-1B gene has been associated with an increased risk of DM-2 in a Danish population. Reports from China and Finland failed to confirm this association. DESIGN, SETTING AND SUBJECTS: The purpose of the present study was to examine the possible association between the presence of DM-2 and the Pro387Leu polymorphism in a German Caucasian population. A total of 836 subjects (age 20-92 years) participated in the study. The presence of the Pro387Leu variant of the PTP-1B gene was investigated using polymerase chain reaction (PCR) restriction fragment-length polymorphism in 402 subjects with DM-2 (231 men, 171 women, age 63.1 +/- 10.8 years, BMI 28.7 +/- 5.1 kg m(-2)) and in 434 normoglycemic age- and sex-matched control subjects (248 men, 186 women, age 64.4 +/- 6.5 years, BMI 26.5 +/- 3.7 kg m(-2)). RESULTS: Nine subjects in the control group and nine in the diabetic group (allelic frequency 0.99% in both groups) carried the Pro387Leu polymorphism. A meta-analysis on published data of >3000 subjects including our own data did not find an association between the polymorphism and DM-2. In addition, the polymorphism had no significant influence on the presence of atherosclerotic disease, whilst the influence of other known cardiovascular risk factors was confirmed. Furthermore, the impact of the mutation on metabolic and anthropometric parameters in both groups was examined. Amongst the controls there were no significant differences in BMI, HDL and LDL cholesterol or blood pressure between the two groups with or without the Pro387Leu polymorphism. The same was true for the diabetic group. Interestingly, in both diabetics and controls, Pro387Leu carriers had significantly higher triglycerides. In a logistic regression model only BMI and family history but not polymorphism were predictors of DM-2. CONCLUSIONS: In conclusion, the present data suggest that in a German Caucasian population the Pro387Leu polymorphism of the PTP-1B gene is not associated with DM-2 but may play a role in other metabolic phenotypes.

Adult↗
PubMed2005

Resistin gene 3'-untranslated region +62G-->A polymorphism is associated with hypertension but not diabetes mellitus type 2 in a German population.

OBJECTIVES: Resistin, a peptide hormone produced by adipocytes, has been associated with diabetes mellitus type 2 (DM-2) in some rodent models. In humans the exact function of resistin remains unknown. Some, but not all studies have found associations between polymorphisms in the resistin gene with DM-2. Recently a 3'-untranslated region +62G-->A polymorphism of the resistin gene has been associated with decreased risk for DM-2 and for hypertension in diabetics in a Chinese population. Purpose of the present study was to examine for the first time in a German Caucasian population the possible association between this polymorphism and DM-2, hypertension, lipoprotein levels, resistin levels as well as atherosclerosis. DESIGN, SETTING AND SUBJECTS: A total of 818 subjects participated in the study. The presence of the +62G-->A polymorphism of the resistin gene was investigated using polymerase chain reaction-restriction fragment length polymorphism in 384 subjects with DM-2 [224 men, 160 women, age 63.4 +/- 10.6 years, body mass index (BMI) 28.7 +/- 5.1 kg m(-2)] and in 434 nondiabetic age- and sex-matched control subjects (248 men, 186 women, age 64.4 +/- 6.5 years, BMI 26.5 +/- 3.7 kg m(-2)). RESULTS: Thirty-four subjects were found to be carrying the +62G-->A polymorphism in the control and 24 in the diabetic group (allelic frequencies 4% and 3.2% respectively). Subjects with DM-2 were not found to have a different frequency of the genotypes (93.75% and 6.258%, for GG:GA/AA respectively) than the control subjects (92.2% and 7.8% for GG:GA/AA respectively) (OR 0.75, 95% CI 0.44-1.3, P = 0.31). In the total cohort, carriers of the A allele had a higher prevalence of hypertension (OR 1.82, 95% CI 1.03-3.21, P = 0.039). When analysed separately, the control group showed a strong association between the presence of the A allele and hypertension (OR 2.92, 95% CI 1.38-6.15, P = 0.005), whilst no such association could be established in the diabetic group (OR 1.05, 95% CI 0.43-2.54, P = 0.92). Multiple regression analysis confirmed that the presence of the A variant is associated with hypertension in control but not in diabetic subjects, independent of age and BMI. The polymorphism had no significant influence on the presence of atherosclerotic disease, BMI, and on triglyceride, HDL and LDL cholesterol levels, both, in the control and the diabetic groups. There was no difference in the serum resistin levels between the 62G-->A variant carriers and noncarriers. CONCLUSIONS: In conclusion, the present data suggest that in a German Caucasian population the +62G-->A polymorphism of the resistin gene is associated with hypertension but not with DM-2.

Aged↗
PubMed2005

Transgenic and knockout mice in diabetes research: novel insights into pathophysiology, limitations, and perspectives.

Insulin resistance and type 2 diabetes are serious public health threats. Although enormous research efforts have been focused on the pathogenesis of these diseases, the underlying mechanisms remain only partly understood. Here we review mouse phenotypes resulting from inactivation of molecules responsible for the control of glucose metabolism that have led to novel insights into insulin action and the development of insulin resistance. In addition, more sophisticated strategies to manipulate genes in mice in the future are presented.

Animals↗
PubMed2005

Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis.

The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARs heterodimerize with the retinoid X receptor (RXR) and modulate the function of many target genes. They were originally described as regulators of various metabolic, pathways, but have been recently found to also exert modulating actions in the vascular wall. PPARalpha is activated by endogenous ligands, such as polyunsaturated fatty acids and by synthetic agonists such as the fibrates. PPARalpha is expressed mainly in the liver, kidney and skeletal muscle and is involved in fatty acid oxidation. However, it is also expressed in vascular cells such as the endothelial cells, vascular smooth muscle cells and macrophages, where it exerts anti-inflammatory and antioxidant effects. Since atherosclerosis is both a chronic inflammatory and a lipid disorder and since PPARalpha is expressed in vascular cells and regulates the expression of genes involved in lipid metabolism and inflammation, PPARalpha activators may constitute useful agents for the prevention of atherosclerosis, beyond their effects on lipid metabolism. This review will focus on the functions of PPARalpha on lipid metabolism, on vascular inflammation and its relationship to atherosclerosis. Furthermore, the currently available preclinical and clinical data on PPARalpha activators as well as their future perspectives will be discussed.

Animals↗
PubMed2004

[Diabetes mellitus needs unrestricted evaluation of patient data to yield treatment progress. The DUTY Register].

Patients with diabetes mellitus require consistent risk management that fulfills risk reduction guidelines for patients suffering from CHD (coronary heart disease). The aim of the DUTY Registry (diabetes mellitus needs unrestricted evaluation of patient data to yield treatment progress) was to show whether the guidelines of the Deutsche Diabetes-Gesellschaft (DDG) are incorporated consistently into daily practice. Therefore 59,035 patients suffering from diabetes mellitus type 1 and type 2 were examined by general practitioners. The physician was requested to enter 20 consecutive patients with existing or newly diagnosed diabetes mellitus into the registry. A total of 45,605 patients showed up for the final examination after 9 months. The results presented show that too many patients suffering from diabetes mellitus do not receive consistent therapy for cardiovascular risk factors according to guidelines and therefore the required target values were rarely reached.

Cause of Death↗
PubMed2004

Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism.

In an open-label, randomized, prospective trial, we investigated pharmacokinetics and several efficacy and safety parameters of a novel, long-acting testosterone (T) undecanoate (TU) formulation in 40 hypogonadal men (serum testosterone concentrations < 5 nmol/liter). For the first 30 wk (comparative study), the patients were randomly assigned to receive either 10 x 250 mg T enanthate (TE) im every 3 wk (n = 20) or 3 x 1000 mg TU im every 6 wk (loading dose) followed by 1 x 1000 mg after an additional 9 wk (n = 20). In a follow-up study, observation continued in those patients who completed the comparative part and opted for TU treatment (8 x 1000 mg TU every 12 wk in former TU patients and 2 x 1000 mg TU every 8 wk plus 6 x 1000 mg every 12 wk in former TE patients) for an additional 20-21 months. Here we report only the pharmacokinetic aspects of the new TU formulation for the first approximately 2.5 yr of treatment. At baseline, serum T concentrations did not significantly differ between the two study groups. In the TE group, mean trough levels of serum T were always less than 10 nmol/liter before the next injection, whereas in the TU group, mean trough levels of serum T were 14.1 +/- 4.5 nmol/liter after the first two doses (6-wk intervals) and 16.3 +/- 5.7 nmol/liter after the 9-wk interval at wk 30. The mean serum levels of dihydrotestosterone and estradiol also increased in parallel to the serum T pattern and remained within the normal range. In the follow-up study, the former TU patients (n = 20) received eight TU injections at 12-wk intervals, and the TE patients (n = 16) switched to TU and initially received two TU injections at 8-wk intervals (loading) and continued with six TU injections at 12-wk intervals (maintenance). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 +/- 5.2 to 16.5 +/- 8.0 nmol/liter) and estradiol (ranging from 98.5 +/- 45.2 to 80.4 +/- 14.4 pmol/liter). The present study has shown that 1000 mg TU injected into male patients with hypogonadism at 12-wk intervals is well tolerated and leads to T levels within normal ranges, using four instead of 17 or more TE injections per year. An initial loading dose of either 3 x 1000 mg TU every 6 wk at the beginning of hormone substitution or 2 x 1000 mg TU every 8 wk after switching from the short-acting TE to TU were found to be a adequate dosing regimens for starting of treatment with the long-acting TU preparation.

Adolescent↗
PubMed2003

[End-organ damage in hyperlipidemias].

Epidemiological and experimental data have clearly demonstrated a strong association between elevated LDL-cholesterol levels and coronary heart disease. In concordance lipid-lowering trials with statins have shown a significant reduction of cardiovascular events. Although stroke is mainly caused by atherosclerotic vascular events, epidemiolgical data have so far failed to show a significant relationship between elevated lipid levels and stroke incidence. However, recent lipid intervention trials with statins have clearly demonstrated a significant reduction in stroke incidence. Moreover, elevated cholesterol levels are thought to contribute to progression of chronic renal insufficiency. In addition, cholesterol crystal emboli are a rare but frequently serious complication of vascular catheter interventions. Significant hypertriglyceridemia carries a significant risk of acute pancreatitis and is thought to contribute to the development of fatty liver disease.

Adult↗
PubMed2003

Genetic manipulation of the insulin signalling cascade in mice--potential insight into the pathomechanism of type 2 diabetes.

To understand the mechanism of insulin signalling and insulin resistance in the development of type 2 diabetes, it is necessary to elucidate the role of insulin and related signal molecules in normal cellular development and functions. A technique for addressing this problem, which is growing more and more important, is the generation and characterization of knockout animal models; such models allow in vivo study of the effects of a lack of a certain gene product, for example, a hormone or intracellular signalling molecule, on the viability, development and physiology of the animal. Besides the conventional form of knockout-which abolishes expression of the gene of interest in every cell of the body and during embryonic development-more recent technology permits the selective inactivation of genes in a tissue-specific and even time-controlled manner. With these techniques, it has become possible not only to examine the function of genes whose conventional inactivation would be lethal for the animal, but also to examine the specific functions that these genes have in certain tissues or at certain developmental stages. Here, we review the phenotype of mice resulting from both conventional and conditional inactivation of molecules in the insulin signalling cascade; this work has led to novel concepts in the understanding of insulin action and the development of insulin resistance.

Animals↗
PubMed2002

Identification of a novel mutation in the arginine vasopressin-neurophysin II gene in familial central diabetes insipidus.

Familial central diabetes insipidus is an inherited disease of predominant autosomal dominant trait characterized by a deficiency of arginine vasopressin. The arginine vasopressin-neurophysin II ( AVP-NPII) gene consists of three exons and is located on chromosome 20p13 encoding for the precursor protein of AVP. We investigated two Caucasian families with a typical autosomal dominant trait of familial central diabetes insipidus, defined by deficiency of arginine vasopressin. After PCR amplification of exon 1 and exon 2/3, fragments were pooled and purified. Nucleotide sequencing was performed with the Taq DyeDeoxy-terminator cycle sequencing method using nested primers. Two mutations in the coding region of NPII were identified. In family C we found a heterozygous G ==> C missense mutation (AA61) in exon 2 leading to the substitution of cystein with serine. In family D a novel heterozygous nonsense mutation in exon 3 (AA 83, GAG ==> TAG) was indentified, leading to a stop codon instead of glutamine. Both mutations were confirmed by restriction analysis and were found in all affected but not in healthy family members or control subjects. We therefore have identified a missense mutation of the AVP-NPII gene and a novel mutation predicting a truncated protein.

Adult↗
PubMed2002

[Assessment of endocrine disorders of the hypothalamic-pituitary axis by nuclear medicine techniques].

The following article reviews nuclear medicine techniques which can be used for assessment of endocrine disorders of the hypothalamic-pituitary axis. For planar and SPECT imaging somatostatin-receptor- and dopamine-D2-receptor-scintigraphy are the most widely distributed techniques. These nuclear medicine techniques may be indicated in selected cases to answer differential diagnostic problems. They can be helpful to search for presence and localization of receptor positive tissue. Furthermore they can detect metastasis in the rare cases of a pituitary carcinoma. Scintigraphy with Gallium-67 is suitable for further diagnostic evaluation in suspected hypophysitis. Other SPECT radiopharmaca do not have relevant clinical significance. F-18-FDG as PET radiopharmacon is not ideal because obvious pituitary adenomas could not be visualized. Other PET radiopharmaca including C-11-methionine, C-11-tyrosine, F-18-fluoroethylspiperone, C-11-methylspiperone, and C-11-raclopride are available in specialized centers only. Overall indications for nuclear medicine in studies for the assessment of endocrine disorders of the hypothalamic-pituitary-axis are rare. Original studies often report only about a small number of patients. According to the authors' opinion the relevance of nuclear medicine in studies of clinically important endocrinologic fields, e.g. localization of small ACTH-producing pituitary adenomas, tumor localization in ectopic ACTH syndrome, localization of recurrent pituitary tissue, assessment of small incidentalomas, can not be definitely given yet.

Humans↗