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Biomedical subjects

H Hauner

Publications and source records attributed to H Hauner.

At least 37 records · Page 2Linked to original sources
PubMed2004

Weight reduction by sibutramine in obese subjects in primary care medicine: the SAT Study.

BACKGROUND: Sibutramine is a selective serotonin and noradrenaline reuptake inhibitor that is known to reduce body weight. The efficacy of this drug in primary care medicine is currently unknown. OBJECTIVE: To study, in a primary healthcare setting, the effect of a standardized non-pharmacological treatment program and 15 mg sibutramine or placebo on long-term weight reduction in obese subjects with a body mass index >or= 30 and < 40 kg/m(2). DESIGN: A multicentre, double-blind, placebo-controlled, randomized, parallel group comparison over 54 weeks of continuous therapy. SETTING: 33 general practitioners in Germany. SUBJECTS: 389 obese patients were recruited of whom 362 were randomized. MEASUREMENTS: Primary measure was weight reduction at week 54; others included reduction in BMI, waist circumference, waist-hip ratio, blood pressure and blood lipids. RESULTS: 348 obese subjects were analyzed using an intention-to-treat analysis. Mean weight loss in the sibutramine (S) group was 8.1 +/- 8.2 kg vs. 5.1 +/- 6.5 kg in the placebo (P) group (p < 0.001; Intent-to-treat analysis). More subjects lost more than 5 % and 10 % of initial weight with sibutramine than with placebo (5 %, S: 62.6 %, P: 41.4 %, p < 0.001; 10 %, S: 40.8, P: 19.0 %, p < 0.001). Weight loss was accompanied by an improvement in the lipid profile, in particular, an increase in HDL-cholesterol and a decrease in fasting triglycerides. In both groups, systolic and diastolic blood pressure decreased in those with moderate hypertension and remained unchanged in those with normal blood pressure at baseline. There was a modest increase in heart rate in S (1.9 beats/min) vs. P (- 0.9 beats/min) (p < 0.05). CONCLUSIONS: Under primary care conditions, sibutramine 15 mg daily proved to be a safe and effective drug for additional weight loss in obese subjects undergoing a comprehensive weight reduction program.

Adult↗
PubMed2004

Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in patients with mild hypertension.

AIM: Impaired fibrinolysis is frequently observed in patients with the metabolic syndrome. Aim of the study was to examine the short-term effect of angiotensin II receptor blockade on the fibrinolytic system. METHODS: Seventy-four patients with mild hypertension were randomly assigned to a 7-day treatment period with either 16 mg candesartan cilexetil or placebo. Several variables of the fibrinolytic system such as plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity as well as circulating t-PA/PAI-1 complexes were determined. RESULTS: At baseline, the body mass index but not blood pressure was positively associated with PAI-1 antigen (r=0.314, p<0.01) and PAI-1 activity (r=0.425, p<0.01) but negatively with t-PA activity (r=-0.187, p < 0.05). A 7-day treatment with 16 mg candesartan cilexetil resulted in a significant greater reduction of diastolic blood pressure (-10.3 +/- 10.8 mmHg vs.-5.8 +/- 8.5 mmHg, p=0.03). However, there was no significant effect of candesartan on all parameters of the fibrinolytic system under investigation, i.e. circulating PAI-1 antigen, PAI-1 activity, t-PA antigen, t-PA activity and t-PA/PAI-1 complexes. Furthermore, candesartan did not affect the characteristic circadian pattern of the variables of the fibrinolytic system. CONCLUSION: We conclude that short-term blockade of the angiotensin II receptor subtype 1 with candesartan does not have an impact on fibrinolysis in patients with mild hypertension.

Adult↗
PubMed2003

[Outpatient care of patients with diabetes mellitus in 2001. Analysis of a health insurance sample of the AOK in Hesse/KV in Hesse].

AIM: Aim of this retrospective case-control study was to assess the quality of out-patient care in patients with diabetes mellitus by analysing health insurance data from a large cohort of members of a regional statutory health insurance fund in Hesse. METHODS: The study was carried out in the 'Versichertenstichprobe AOK Hessen/KV Hessen', a 18.75% random sample of the AOK Hesse, for the year 2001 corresponding to 306,736 subjects and 26,972 diabetics. All medical services and prescriptions provided by primary-care physicians were documented. RESULTS: Compared to an age- and sex-matched control group patients with diabetes received more out-patient medical services (diabetics: 126 +/- 0.8, controls: 76 +/- 0.4 per year, p < 0.0001) and more prescriptions (diabetics: 39.9 +/- 0.3, controls: 20.0 +/- 0.3 per year, p < 0.0001) in 2001. HbA (1c) measurements were performed in 69.5% of the insulin-treated patients, in 64.3% of the patients under monotherapy with oral hypoglycaemic agents and in 41.1% of the patients under dietary treatment. 78.1% of the insulin-treated patients, 12.0% of those under oral hypoglycaemic agents and 2.0% of patients under dietary treatment received prescriptions for material for blood glucose self-monitoring. In contrast, a retinal examination was performed in only 45.8%, 31.1% and 22.5% of the patients in the three treatment groups throughout the year. The respective figures for screening for microalbuminuria in the three treatment groups were 12.7%, 7.1% and 3.6%. CONCLUSIONS: The results of this retrospective analysis suggest that the out-patient medical care of subjects with diabetes is in some respect unsatisfactory and does not comply with the accepted recommendations for appropriate diabetes care.

Adolescent↗
PubMed2003

[Prevalence of diabetes mellitus in Germany 1998-2001. Secondary data analysis of a health insurance sample of the AOK in Hesse/KV in Hesse].

AIMS: The aim of this population-based study was to assess the prevalence of subjects with diabetes mellitus by retrospectively analysing routine health insurance data. METHODS: This analysis comprised a 18.75% random sample of all members of the largest regional statutory health insurance (Allgemeine Ortskrankenkasse, AOK) in Hesse. Patients with diabetes were identified by criteria such as ICD-10 diagnoses and regular prescriptions of insulin and oral antidiabetic agents. The data were corrected for the age and gender distribution of the German population. RESULTS: Over the 4-year observation period there was a continuous increase in the prevalence of subjects with known diabetes mellitus, from 7.24% in 1998 to 8.79% in 2001. After correction for the German population the last figure corresponded to a prevalence rate of 6.00% in 1998 and 6.91% in 2001. During this period, there was an overproportional increase in the percentage of subjects treated with insulin, from 1.49% in 1998 to 1.91% in 2001, while there was only a moderate increase in the percentage of subjects under oral medication and under dietary treatment, respectively. In the age group of 70 and above roughly 25% of all subjects had known diabetes. In this age group, more than 6% of all people were treated with insulin. CONCLUSIONS: This data suggests that there was a continuous increase in the prevalence of individuals treated for diabetes between 1998 and 2001 in Germany by approximately 5% per year. After correction for the total German population the pre-valence of diagnosed diabetes is nearly 7%.

Adolescent↗
PubMed2003

Human adipocytes secrete mineralocorticoid-releasing factors.

Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.

Adipocytes↗
PubMed2003

[Disease management program (DMP) diabetes mellitus: simulation of therapeutic results of different guidelines. A new diabetes mellitus model (DMM)].

BACKGROUND AND OBJECTIVE: In conjunction with the introduction of disease management programmes in Germany there is an ongoing scientific debate on the desirable goals for HbA1c in the management of patients with type 2 diabetes mellitus. PATIENTS AND METHODS: In this study, a novel computer-based simulation model (diabetes mellitus model = DMM) was used to estimate the consequences of different levels of metabolic control as assessed by HbA1c for the development of short- and long-term complications of this disease. RESULTS: At a mean difference of 1 % the rate of severe hypoglycaemic events over 10 years was by 32-84 % higher in those with a lower HbA1c. In contrast, the incidence of microvascular complications (proliferative retinopathy, end-stage kidney disease, clinical neuropathy) was by 20-33 % lower in the group with the lower as compared to the higher HbA1c level according to the scenario applied. The rates of myocardial infarction and stroke were reduced by 15-20 % under these conditions. CONCLUSIONS: This model calculation suggests that a more strict metabolic control in patients with type 2 diabetes mellitus results in a greater reduction of microvascular complications than of macrovascular complications, but is associated with a higher rate of hypoglycaemic episodes. The diabetes mellitus model is a non-expensive alternative to simulate clinically relevant questions on the management of type 2 diabetes and to provide rapid and realistic answers.

Aged↗
PubMed2003

Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women.

OBJECTIVE: To study the relation between body mass index (BMI) and age on the one hand and total number of human (pre-) adipocytes and preadipocyte differentiation capacity on the other hand. SUBJECTS: In total, 189 women undergoing surgical mammary reduction, age range 16-73 y, BMI range 19.7-39.7 kg/m(2). MEASUREMENTS: Differentiation of preadipocytes in primary culture was assessed by morphological criteria, and determination of glycerol-3-phosphate dehydrogenase after stimulation of the cells by standardized adipogenic conditions containing isobutyl-methylxanthine, troglitazone or both compounds. The total number of stromal cells (ie preadipocytes) and fat cells per gram of adipose tissue and per body as well as mature fat cell volume were calculated from isolated stromal cells and adipocytes, respectively, and anthropometric measures. RESULTS: BMI correlated positively to age, mature fat cell size and total number of adipocytes and stromal cells per body (r varying from 0.22 to 0.54, each P<0.05). In contrast, BMI correlated negatively to the number of adipocytes and stromal cells per gram of adipose tissue and the capacity of preadipocytes to differentiate (r varying from -0.20 to -0.37, each P<0.05). No significant correlation was observed between BMI and the ratio of stromal cells to adipocytes. The sample was also divided into three groups: BMI <25 kg/m(2) (lean), BMI 25-29.9 kg/m(2) (overweight) and BMI >/=30 kg/m(2) (obese). The overweight group showed a larger fat cell size but no increase in total fat cell or stromal cell number when compared to the lean subjects. The obese subjects showed larger stromal and fat cell numbers when compared to the lean subjects. Age did not independently correlate to the number of stromal cells or adipocytes per gram of adipose tissue or total body, nor with the capacity of preadipocytes to undergo differentiation and the ratio of stromal cells to adipocytes. CONCLUSION: There seems to be a constant ratio between the number of adipose tissue stromal cells and adipocytes independently of BMI and age in humans. During adipose tissue expansion, there seems to be both a continuous increase in fat cell size, and in stromal cell and adipocyte number, but the increase in fat cell size apparently precedes the increase in fat cell number. The differentiation capacity of the stromal cells appears to decrease with increasing BMI.

1-Methyl-3-isobutylxanthine↗
PubMed2003

HMG-CoA reductase inhibitor cerivastatin inhibits interleukin-6 expression and secretion in human adipocytes.

Human adipose tissue is a main contributor to plasma levels of pro-inflammatory cytokine IL-6. How IL-6 expression is regulated in adipocytes remains unclear. In the current study, we investigated the effect of the HMG-CoA reductase inhibitor, cerivastatin, on the production of IL-6 from cultured human adipocytes. Cerivastatin reduced both IL-6 mRNA and secretion in a dose- and time-dependent manner. The inhibitory effect on IL-6 mRNA was prevented by the intermediates of the cholesterol synthesis pathway, mevalonate and geranyl-geranyl-phyrophosphate (GGPP) but not by farnesyl-pyrophosphate. This suggests the involvement of geranylgeranyl-modified intermediates in the effect of cerivastatin on IL-6. Moreover, cerivastatin induced an inactivation of the phosphorylation of the p65 subunit of NFkappaB which was prevented by GGPP. Our data suggest that cerivastatin exerts an anti-inflammatory effect by down-regulating IL-6 levels in adipocytes, which seems to be mediated by reduced production of GGPP and interference with the NFkappaB pathway.

Adipocytes↗
PubMed2002

[Diabetes mellitus type 2].

SUMMARY: Type 2 diabetes represents the most common form of carbohydrate disorders affecting at least 5% of the population in the industrialized world. In addition to genetic predisposition obesity and a sedentary lifestyle are the main promoters. Recent data clearly suggest that lifestyle intervention in people at increased risk can potently reduce the incidence of the disease. In overt type 2 diabetes, good glycaemic control and aggressive management of associated cardiovascular risk factors may prevent its multiple and costly complications.

Cardiovascular Diseases↗
PubMed2002

Insulin resistance and the metabolic syndrome-a challenge of the new millennium.

The term metabolic syndrome is used for describing a cluster of cardiovascular risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes mellitus, dyslipidaemia and hypertension. A concomitant presentation of all components of the syndrome is rare, therefore, in the view of most experts three out of the four main components are sufficient for defining the syndrome. Another recently identified component of high clinical significance is the impairment of the fibrinolytic system which is now frequently mentioned in extended definitions. This clustering of metabolic risk factors has been described in various combinations and given different names including insulin resistance syndrome or syndrome X. Unfortunately, there is no generally accepted definition so far. The original mentioning of the syndrome goes back to the late sixties, when the metabolic syndrome was described as a 'disorder of genetic adaptation becoming manifest following unrestricted food intake and/or muscular inacitvity'. In its modern meaning this term was propagated by Hanefeld and Leonhardt and by Kaplan, who also called the syndrome the 'deadly quartet' to emphasize its high atherogenic potential.

Humans↗
PubMed2002

Effects of the G-protein beta3 subunit 825T allele on adipogenesis and lipolysis in cultured human preadipocytes and adipocytes.

The recently discovered C825T polymorphism of the G-protein beta 3 subunit has been reported to be associated with the development of hypertension and obesity. The aim of our study was to investigate the relationship between the C825T polymorphism and functional aspects of human adipose cells, particularly with regard to adipose differentiation and lipolysis. Adipose tissue samples were collected from 65 women with a BMI ranging from 19.7 to 39.7 kg/m 2 undergoing surgical mammary reduction. The stromal cells were allowed to undergo differentiation in primary culture using adipogenic media of defined composition. No significant difference was observed between the CC carriers and the carriers of the T allele under all adipogenic conditions with differentiation capacity related to the genotype. In a subgroup of patients (n = 20), lipolysis in isolated fat cells was determined by measurement of glycerol in the culture medium upon catecholamine exposure. Glycerol release after 10(-7) mmol/l isoproterenol was significantly higher in fat cells from the 10 CC carriers than in adipocytes from the T allele carriers when expressed as percentage of basal glycerol release (increase above baseline: CC: 809 +/- 174 %, T allele carriers: 247 +/- 88 %, p = 0.01), while basal glycerol concentrations were no different according to genotype after controlling for either age or BMI. In conclusion, this study provides the first evidence that the GNB3 825T allele is associated with an impairment of the beta-adrenergic control of lipolysis.

Adipocytes↗
PubMed2001

[Therapy of obesity. Setting realistic goals].

Every third German needs to lose weight for health reasons. Risk assessment of obesity is based on the BMI, the distribution pattern of body fat, and the presence of concomitant diseases and sequelae of obesity. The most important prerequisites are personal motivation and the ability of the patient to self-manage his/her problem. The basic long-term weight-reduction program includes a low-calory diet, increased physical activity, and specific measures aimed at modifying eating habits. Should the basic programs fail to produce the necessary results, the two weight-reducing drugs Sibutramine and Orlistat are available--with appropriate consideration being given to contraindications. Surgical measures, such as gastric banding and gastroplasty are reserved for patients that prove resistant to conservative measures.

Body Mass Index↗
PubMed2001

Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization.

A novel ER-subtype, the ER-beta has recently been characterized in various tissues, furthermore five isoforms of the ER-beta are known (ER-beta1--ER-beta5). Using immunoblotting and real- time RT-PCR, ER-alpha and beta were studied in human adipose tissue. The expression of ER-alpha mRNA was equal in subcutaneous gluteal adipose tissue, subcutaneous abdominal and intra-abdominal adipose tissue, similar findings were obtained at the protein level. In contrast the amount of ER-beta1 (protein and mRNA) was significantly lower in intra-abdominal adipose tissue as compared with the subcutaneous adipose tissue (five-fold lower in women, P<0.005 and three-fold lower in men, P<0.005) whereas the expression of ER-beta4 and -beta5 mRNA isoforms were significantly higher in gluteal adipose tissue compared to subcutaneous abdominal adipose tissue. No significant gender differences in ER expression was detected in any of the fat depots investigated. During adipocyte differentiation the expression of ER-alpha, -beta4 and -beta5 mRNA declined, whereas, the expression of ER-beta1 mRNA was constant. In conclusion, the existence of ER-beta isoforms in human adipose tissue was demonstrated and the amount of these receptors was dependent upon fat depot localization, with much reduced expression of ER-beta1 in intra-abdominal adipose tissue compared to subcutaneous adipose tissue. These findings may indicate that estrogens could have differentiation and depot specific effects in human adipose tissue.

Abdomen↗