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Biomedical subjects

M Stumvoll

Publications and source records attributed to M Stumvoll.

At least 19 recordsLinked to original sources
PubMed2007

[The biology of visceral fat].

Visceral obesity is an independent risk factor for the development of cardiovascular diseases and type 2 diabetes. This is likely to be due to biological characteristics of visceral tissue, which are different from those of subcutaneous adipose tissue in terms of decreased insulin sensitivity and increased lipolytic activity. In addition, the anatomical site of visceral fat could be one potential reason for the increased cardio-metabolic risk associated with visceral obesity. Visceral adipose tissue drains into the portal vein and therefore the liver is exposed to the undiluted metabolites and adipokines released from visceral fat. There are profound differences between visceral and subcutaneous adipocytes in the metabolism, expression of specific receptors and secretion of a specific adipokine pattern, which could contribute to the adverse consequences of visceral obesity.

Adipose Tissue↗
PubMed2006

Evaluation of patients' opinion and metabolic control after transfer of young adults with type 1 diabetes from a pediatric diabetes clinic to adult care.

BACKGROUND: Transferring adolescents with diabetes from pediatric to adult care remains a challenge and the outcome is often unknown. The aims of this study were to determine the patients' perception of transfer arrangements and to analyze health care use and metabolic control. METHODS: A telephone questionnaire was conducted for patients who had been transferred from the pediatric clinic to adult care between 1995 and 2003. Of 161 identified patients, 101 (58 females, 43 males, mean age 22.1 +/- 2.4 years) were interviewed. Pediatric case notes and, if available (n = 44), current notes were analyzed to validate answers from the interview. RESULTS: After transfer, 52.5% of patients changed their health care provider at least once. The mean frequency of changes was 1.47. There was a significant decrease in clinic attendance rate after transition (8.5 +/- 2.3/years vs. 6.7 +/- 3.2/years). Patients criticized the lack of arrangements, poor information about transfer and the specific age for transition (18 years) set by legislation. The transfer was considered a negative experience by 58 patients. The patients assumed their metabolic control (HbA1c) was better than it really was (7.5 +/- 1.3% vs. 8.3 +/- 1.6%, p < 0.05). Actual HbA1c from case notes pre- and post-transfer did not change significantly (8.5 +/- 1.5% vs. 8.4 +/- 1.7%, n = 44, p = 0.441). CONCLUSION: The establishment of transition clinics and closer cooperation between specialists in pediatric and adult medicine is mandatory. Such changes are demanded by patients and would ensure better uptake of health care services after transfer.

Adolescent↗
PubMed2006

Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children.

OBJECTIVE: A Val1483Ile polymorphism in the human fatty acid sythase gene (FAS) has recently been shown to be associated with lower percentage of body fat and substrate oxidation rates in Pima Indians, but its role in other populations has not been described. Here, we investigate the effect of this variant on obesity in Caucasian children and adolescents. SUBJECTS AND METHODS: In total, 738 Caucasian children and adolescents aged 6-17 years of the Leipzig Schoolchildren cohort, which constitutes an unselected representative German population and 205 obese children (body mass index (BMI) 2.71+/-0.04 SDS) were genotyped for genotype-phenotype associations. RESULTS: The frequency of the Ile-allele was lower in German Caucasians compared with Pima Indians (0.03 compared to 0.10). Using generalized linear regression models, there was no effect of the polymorphism on BMI in the whole normal population. However, we identified a significant interaction effect between sex and genotype (P=0.004). Subsequent sex stratified analyses revealed a lower BMI SDS in boys with Ile/Val genotype compared to Val/Val (-0.36+/-0.29 vs 0.09+/-0.05, P<0.05), while an opposite effect was observed in girls (0.48+/-0.19 vs 0.09+/-0.05, P<0.05). In genotype-phenotype associations in obese children, the polymorphism did not affect parameters of insulin, glucose, or lipid metabolism in the whole population. Again, however, obese boys with Ile/Val genotype had significantly higher high-density lipoprotein (HDL) cholesterol levels (1.46+/-0.07 vs 1.23+/-0.03 mmol/l, P<0.05). CONCLUSION: In conclusion, our findings suggest a sex-specific protective effect of the Val1483Ile polymorphism in FAS for obesity in Caucasian boys. In addition, the polymorphism may be associated with a beneficial lipid profile in obese boys.

Adolescent↗
PubMed2006

Central diabetes insipidus in a patient with malaria tropica.

Up to 21% of severe cases of malaria tropica are associated with polyuria and are life-threatening. We describe a 39-yr-old man with malaria tropica who developed disseminated intravascular coagulation, polyuria, and a pituitary lesion. Empiric treatment with vasopressin improved the polyuria. This is the first case of malaria tropica in which central diabetes insipidus has been documented.

Adrenal Insufficiency↗
PubMed2006

[Renal anemia - an important secondary disease in renal insufficiency].

Anemia is as a frequent complication in patients with chronic kidney disease, which gains in importance in the treatment of patients with renal disease. The main cause of renal anemia is the inadequately low production of endogenous erythropoietin. Often the patients develop an additional absolute or functional iron deficiency, which complicates the diagnostic and therapeutic procedures. Substitution of recombinant human erythropoietin (r-HuEPO) is the most effective therapy. The goal is a stable haemoglobin level >11 g/dl. An often additional existing iron deficiency should be balanced adequately according to the guidelines. With consequent and early treatment morbidity, mortality, and quality of life can be effectively improved.

Anemia↗
PubMed2006

The effects of insulin on the central nervous system--focus on appetite regulation.

Appetite and satiety are subject to complex regulation, with neuroendocrine mechanisms playing an important role. The central nervous system is attracting increasing attention as a target tissue for many hormones such as leptin, PYY3-36, ghrelin, glucagon-like-peptide 1 and many others. Among its many well-known functions, insulin is also a potent anorexigenic hormone, and insulin receptors are widely distributed throughout the central nervous system. One way to advance our understanding of central nervous regulation of hunger and satiety in humans is to develop suitable neuroimaging techniques for use in various clinical and experimental conditions. Several studies have been performed using functional magnetic resonance imaging and positron emission tomography to identify areas of the brain that are differentially activated by alteration of the feeding state. These preliminary data are taking shape as a complex neuronal network involving the hypothalamus, thalamus, limbic and paralimbic areas including the insular cortex and the anterior cingulate gyrus and the orbitofrontal cortex. Continuous efforts to understand hormonal effects on these pathways may advance our understanding of human obesity.

Animals↗
PubMed2006

The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and hypoglycemia awareness in patients with type 1 diabetes.

Impaired hypoglycemia awareness affects approximately 25% of all patients with type 1 diabetes (T1DM). Duration of diabetes and tight glycemic control represent main risk factors of impaired hypoglycemia awareness. However, even among patients with good glycemic control and longstanding T1DM, awareness of hypoglycemia may be intact. Genetic factors might explain some of this remaining variability. Recently, the insertion/deletion ( I/ D) polymorphism in angiotensin converting enzyme gene ( ACE) was shown to be associated with significantly higher risk of hypoglycemic events in subjects with T1DM. Here, we studied the effects of genetic polymorphisms in the ACE on impaired hypoglycemia awareness in 231 Caucasian T1DM patients. Hypoglycemia awareness status was determined using standardized questionnaires (Clarke et al. and Edinburgh Hypoglycemia Scale). ACE I/ D genotype was determined by PCR amplification of the respective fragments from intron 16 of the ACE and size fractionation (I allele frequency=0.49; P=0.74 for Hardy-Weinberg equilibrium). In the logistic regression analysis, significant risk factors of impaired hypoglycemia awareness were duration of diabetes, C-peptide and HbA (1c) (all P<0.01). However, no significant effect of the I/ D polymorphism on impaired hypoglycemia awareness was observed with and without adjustment for age, diabetes duration, C-peptide and HbA (1c). Even though the study provides a relatively large dataset, it is possible that small differences may have been missed.

Adult↗
PubMed2006

[Role of muscle and fat tissue in the pathogenesis of type 2 diabetes].

In the last years type 2 diabetes has reached almost epidemic proportions. More than 170 million individuals are affected worldwide, about 6 million in Germany. In the pathogenesis of type 2 diabetes, insulin resistance in liver, fat and muscle as well as the inability of the pancreatic beta-cell to fully compensate for this insulin resistance are the central pathophysiological events. Both genetic and environmental factors, such as lack of physical exercise and hypercaloric nutrition play a major role in this process, although the precise mechanisms for type 2 diabetes development remain largely unknown. In the characterization of the role of liver, adipose tissue and skeletal muscle in the pathogenesis of type 2 diabetes, tissue specific knockout mouse models have challenged our concepts of glucose homeostasis.

Adipose Tissue↗
PubMed2006

Tissue inhibitor of metalloproteinase 1 expression and secretion are induced by beta-adrenergic stimulation in 3T3-L1 adipocytes.

Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocytokine upregulated in obesity which might promote adipose tissue development. In the current study, the impact of the beta-adrenergic agonist isoproterenol on TIMP-1 gene expression and secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol increased TIMP-1 secretion 2.7-fold. Furthermore, isoproterenol induced TIMP-1 mRNA in a time- and dose-dependent fashion with significant effects observed as early as 1 h after effector addition and at concentrations as low as 1 microM isoproterenol. Significant isoproterenol-induced upregulation of TIMP-1 mRNA could also be found in immortalized brown adipocytes. Inhibitor experiments confirmed that the positive effect of isoproterenol on TIMP-1 is mediated via beta-adrenergic receptors and protein kinase A. Moreover, increasing cAMP levels with forskolin or dibutyryl-cAMP was sufficient to stimulate TIMP-1 synthesis. Insulin induced basal TIMP-1 mRNA, but did not significantly influence forskolin-induced TIMP-1 expression. Taken together, we demonstrate that TIMP-1 expression and secretion are selectively upregulated in adipocytes by beta-adrenergic agonists via a classic Gs-protein-coupled pathway.

3T3-L1 Cells↗
PubMed2005

Contraindications can damage your health--is metformin a case in point?

Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.

Acidosis, Lactic↗
PubMed2005

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat.

AIMS/HYPOTHESIS: The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism. MATERIALS AND METHODS: We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity. RESULTS: We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (-8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (-1927 T/C) in intron 1. Subjects carrying the -8503 A and -1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA(1)c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the -8503 A and -1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the -8503 G and -1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat. CONCLUSIONS/INTERPRETATION: The present findings suggest that the -8503 G/A SNP in the promoter or the -1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.

Adipose Tissue↗
PubMed2005

Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis.

CONTEXT: The adipokine adiponectin has insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Mouse and human adiponectin receptor-1 and -2 have been cloned, both of which are expressed in various tissues and mediate effects of globular and full-length adiponectin. Whether adiponectin affects insulin secretion and beta-cell apoptosis and whether plasma adiponectin is associated with beta-cell function in humans is under investigation. DESIGN AND METHODS: In human islets from multiorgan donors, we investigated expression of adiponectin receptor-1 and -2. Furthermore, glucose-stimulated insulin secretion was determined by RIA. In addition, we investigated fatty acid-induced beta-cell apoptosis by terminal dUTP nick end labeling and flow-cytometric cell cycle analysis (sub-G1 formation). In humans in vivo, insulin secretory function was measured during hyperglycemic clamps in 65 normal glucose-tolerant subjects. We determined first and second phase of glucose-stimulated, glucagon-like peptide-1-stimulated, and arginine-stimulated insulin secretion. RESULTS: Adiponectin receptor-1 and -2 are expressed in human islets at the mRNA and protein level. Moreover, full-length adiponectin induces phosphorylation of acetyl coenzyme A carboxylase. However, adiponectin did not affect basal or glucose-stimulated insulin secretion or basal or fatty acid-induced beta-cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucose-stimulated first- and second-phase insulin secretion or with glucagon-like peptide-1- or arginine-stimulated insulin secretion (all P > 0.42). CONCLUSIONS: These data support a regulatory role of adiponectin in human islets; however, adiponectin does not seem to affect insulin secretion or basal/fatty acid-induced beta-cell apoptosis in humans.

Adiponectin↗
PubMed2005

Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians.

AIMS/HYPOTHESIS: Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians. METHODS: The coding and untranslated regions of UCP2, and approximately 1 kb of the 5' upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives. RESULTS: Five variants were identified: (1) a -866G/A in the 5' upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3' untranslated region. Among the 83 subjects whose DNA was sequenced, the -866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the -866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the -866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass). CONCLUSIONS/INTERPRETATION: Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians.

3' Untranslated Regions↗
PubMed2005

Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI/MRS study.

Quantitative measurement of adipose tissue (AT) compartments in the entire body and of lipids in muscle and liver cells by means of MRI and MRS. Assessment of age and gender related differences in AT compartments and determination of cross-correlations between AT compartments in a heterogeneous cohort at increased risk for metabolic diseases. One hundred and fifty healthy volunteers with increased risk to type 2 diabetes were examined. T1-weighted MRI was applied for whole-body adipose tissue quantification. Adipose tissue compartments were subdivided in lower extremities, trunk (abdominal subcutaneous (SCAT) and visceral (VAT) adipose tissue), and upper extremities. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) in tibialis anterior and soleus muscle were determined by volume selective MRS. Females are characterized by lower %VAT (2.8+/-1.3% vs. 4.6+/-1.4%, p<0.001) and higher %SCAT (14.7+/-3.9% vs. 9.3+/-2.9%, p<0.001). There is a strong correlation between %VAT and age (r=0.64/0.60 for females/males), whereas %SCAT remained virtually unchanged in males (r=-0.09) and was only slightly increaseding in females (r =0.30, p<0.01). For IHCL, age related differences were observed in females with significantly increased IHCL in the older women, but not in males. IMCL contents in both muscles were found almost independent of age in both, males and females. Furthermore, VAT and IHCL show significant correlations in both groups. Assessed age and gender related differences, especially the age related significant increase of VAT and IHCL, as well as cross-correlations between different lipid compartments might contribute to a better understanding of the lipid metabolism under normal and pathologic metabolic conditions in humans.

Adipose Tissue↗
PubMed2005

[Genetics of type 2 diabetes].

In the last years type 2 diabetes has reached almost epidemic proportions. More than 170 million individuals are affected worldwide, about 6 million in Germany. Manifestation of type 2 diabetes is determined by both environmental factors such as lack of physical exercise and overeating and a genetic predisposition. Despite enormous efforts in medical research to identify susceptibility loci and high risk alleles, the genetics of common type 2 diabetes (non-MODY) remain unknown. To date, only a few susceptibility genes have been identified (such as PPARG, KCNJ11, CAPN10). However, replication of initial studies is often difficult. This can be explained by both locus and allelic heterogeneity as well as ethnic differences between different populations. Studies in genetically isolated populations such as the Pima Indians are advantageous to identify susceptibility alleles. Despite some recent advances, it is not possible to predict an individual's risk of type 2 diabetes based on the presence of a certain disease-risk allele.

Biomarkers↗
PubMed2005

Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones.

BACKGROUND: Thiazolidinediones as PPARgamma agonists and fibrates as PPARalpha agonists improve insulin sensitivity in insulin-responsive tissues. Recent data show an induction of adiponectin receptor 2 (AdipoR2) by PPARalpha and PPARgamma agonists in human macrophages. OBJECTIVE: In this study, we examined the effects of thiazolidinediones and fibrates on the expression of adiponectin receptors in human skeletal muscle cells, an important cell type in the context of insulin resistance. RESULTS AND METHODS: In vitro differentiated human myotubes treated with troglitazone or rosiglitazone (20 h) showed no significant changes in AdipoR1 and AdipoR2 mRNA expression. PPARgamma activation was controlled by determination of PPARgamma mRNA induction. Likewise, differentiated myotubes treated with Wy-14,643 or fenofibrate (20 h) revealed no significant regulation of AdipoR1 and AdipoR2 mRNA. PPARalpha activation was assessed by measuring PDHK4 mRNA expression. CONCLUSION: Induction of AdipoR gene expression in human skeletal muscle cells is not involved in the insulin-sensitizing effects of thiazolidinediones or fibrates.

Adult↗