[Treatment of obesity--where are we today?].
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Anti-Obesity Agents↗
Biomedical subjects
H Hauner
Publications and source records attributed to H Hauner.
[Antioxidants in nutrition and arteriosclerosis].
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Antioxidants↗
[Non-drug therapy of obesity].
BACKGROUND: The current epidemic of obesity is primarily a consequence of the modern lifestyle characterized by a hypercaloric, high-fat diet and lack of physical activity. INTEGRATED TREATMENT CONCEPT: In order to establish a treatment strategy oriented at the pathogenesis of the disorder it is necessary to strive for a long-term change in lifestyle. The modern best-practice treatment of obesity includes a healthy, low-fat diet, an increase in physical activity and behavior modification. This integrated treatment concept aims at decreasing body weight by 5-19% and at obtaining long-term weight management.
Behavior Therapy↗
Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation.
OBJECTIVE: To develop and to characterize a human preadipocyte cell strain with high capacity for adipose differentiation serving as a model for studying human adipocyte development and metabolism in vitro. METHODS: Cells were derived from the stromal cells fraction of subcutaneous adipose tissue of an infant with Simpson-Golabi-Behmel syndrome (SGBS). Adipose differentiation was induced under serum-free culture conditions by exposure to 10 nM insulin, 200 pM triiodothyronine, 1 microM cortisol and 2 microM BRL 49653, a PPAR gamma agonist. RESULTS: During the differentiation process SGBS cells developed a gene expression pattern similar to that found in differentiating human preadipocytes with a characteristic increase in fat cell-specific mRNAs encoding lipoprotein lipase (LPL), glycero-3-phosphate dehydrogenase (GPDH), GLUT4, leptin and others. Differentiated SGBS cells exhibited an increase in glucose uptake upon insulin stimulation and in glycerol release upon catecholamine exposure. SGBS adipocytes were morphologically, biochemically and functionally identical to in vitro differentiated adipocytes from healthy subjects. However, while preadipocytes from healthy control infants rapidly lost their capacity to differentiate after a few cell divisions in culture, SGBS cells maintained their differentiation capacity over many generations: upon appropriate stimulation 95% of SGBS cells of generation 30 developed into adipocytes. A mutation in the glypican 3 gene was not detected in the patient. Thus, it remains unclear whether the molecular alteration in SGBS cells is also responsible for the high differentiation capacity and further investigations are required. CONCLUSION: The human cell strain described here provides an almost unlimited source of human preadipocytes with high capacity for adipose differentiation and may, therefore, represent a unique tool for studying human fat cell development and metabolism. International Journal of Obesity (2001) 25, 8-15
Adipocytes↗
Current pharmacological approaches to the treatment of obesity.
Although comprehensive obesity treatment programmes were shown to induce weight loss and to improve risk factors and comorbidities, the weight reduction is moderate and most patients will rapidly regain weight. For these reasons, drugs have been developed or are in development to support and maintain weight loss. At present, two drugs are available for the adjunct treatment of obesity. Sibutramine is a centrally acting inhibitor of noradrenaline and serotonine reuptake, thereby decreasing caloric intake and increasing energy expenditure. Orlistat is a specific lipase inhibitor that impairs fat absorption, thereby reducing fat uptake. Both drugs have been found to be effective and safe in a number of clinical studies for up to two years. The current experience with these drugs raises questions related to the long-term efficacy with particular reference to cardiovascular end-points. In addition, other current and future pharmacological principles for weight reduction are discussed. There is no doubt that an evidence-based rational pharmacological treatment of obesity is still in an early stage.
Anti-Obesity Agents↗
Effects of leptin on the differentiation and metabolism of human adipocytes.
BACKGROUND: Leptin is an adipose protein regulating food intake in the hypothalamus. Animal studies have suggested that leptin also acts in an auto-/paracrine fashion on adipose cell function. OBJECTIVE: The aim of this study was to investigate the effects of leptin on the differentiation and metabolism of cultured human adipocytes. MATERIAL: Adipose tissue from young healthy, lean women (body mass index (BMI) <27 kg/m(2)) undergoing elective mammary reduction surgery and young obese individuals (BMI>40 kg/m(2)) undergoing laparoscopic gastric banding. METHODS: Human preadipocytes in primary culture were induced to undergo differentiation by defined adipogenic factors. Mature adipocytes were isolated by collagenase digestion and kept in culture suspension. Glycero-3-phosphate dehydrogenase (GPDH) activity was used as a marker of adipose differentiation; glucose uptake, lipolysis and PAI-1 secretion were measured as parameters of fat cell function. RESULTS: Human preadipocytes and adipocytes from lean and obese subjects expressed the long leptin receptor isoform and two of the three short forms as assessed by polymerase chain reaction (PCR). Leptin at a supraphysiological concentration induced a transient increase of GPDH activity, but had no effect on glucose uptake and PAI-1 secretion from human adipocytes. In addition, basal and isoproterenol-stimulated lipolysis as well as the antilipolytic action of insulin in human adipocytes was not significantly affected by leptin exposure. CONCLUSION: In contrast to animal data, the results of our experiments do not demonstrate significant effects of leptin on main metabolic functions of human adipocytes arguing against a local auto-/paracrine action of leptin in human adipose tissue.
Adipocytes↗
Effect of acarbose on weight maintenance after dietary weight loss in obese subjects.
AIMS: Acarbose is a well established antidiabetic drug and is known to exert a modest weight-lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects. DESIGN: Randomised, double-blind, placebo-controlled trial of the effect of acarbose on weight change over a 6-month follow-up period. PATIENTS AND METHODS: One hundred and ten obese subjects with a BMI > or = 32 and < or = 38 kg/m2 were included in the study and underwent a 10-16-week very-low-calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 +/- 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per-protocol population (n = 75). RESULTS: After an initial mean weight loss of 10.0 +/- 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow-up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable). CONCLUSION: In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.
Acarbose↗
The beta3-adrenergic receptor Trp64Arg mutation is not associated with coronary artery disease.
There is some evidence that the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. The objective of this cross-sectional study was to investigate the relationship between the Trp64Arg polymorphism and coronary artery disease (CAD). A total of 1,000 consecutive patients with angiographically confirmed CAD and 1,000 controls, carefully matched for age and sex, were genotyped for the Trp64Arg polymorphism by polymerase chain restriction and subsequent restriction fragment length polymorphism analysis. Among cases with CAD, 83.3% were wild-type Trp/Trp, 15.8% were heterozygotes, and 0.9% were homozygous Arg/Arg compared with 82.3%, 17.3%, and 0.4%, respectively, among controls (P = .27). The odds ratios for the presence of Trp/Arg and Arg/Arg in cases and controls were 0.90 (95% confidence interval [CI] 0.7 to 1.2; P = .40) and 2.2 (95% CI 0.7 to 7.2; P = .17), respectively. There was no effect modification by gender and atherogenic risk factors, including diabetes, hypercholesterolemia, hypertension, and smoking. Furthermore, there was no evidence of an association with premature disease onset (< 40 years) or extent of disease. In conclusion, the results of this study in a large sample of clinically well-characterized patients indicate that neither the Trp/Arg nor the Arg/Arg genotype represents a major risk factor for angiographically confirmed coronary artery disease.
Amino Acid Substitution↗
Effect of angiotensin peptides on PAI-1 expression and production in human adipocytes.
Angiotensin (Ang) II is the active component of the renin-angiotensin-system (RAS), but its degradation products have also been shown to exhibit biological activity. This system, which mainly controls blood pressure and electrolyte homeostasis, was recently found to be completely expressed in human adipose tissue. The major determinant in the fibrinolytic system is the plasminogen activator inhibitor-1 (PAI-1). Both PAI-1 and components of the RAS are over-expressed in the obese state. We have recently shown that Ang II is able to induce PAI-1 expression and release via the AT1-receptor in human fat cells in primary culture, and have provided the first evidence that two metabolites, Ang III and Ang IV, may have a similar stimulatory effect on PAI-1 release. We have now performed additional experiments to further characterize the role of the angiotensin peptides in the production of PAI-1. Ang III and Ang IV showed a time- and dose-dependent stimulation of PAI-1 protein release. Concomitantly, mRNA-levels were markedly elevated. Using specific receptor blockers, all angiotensin peptides seem to induce PAI-1 expression via the angiotensin receptor subtype 1. However, components of the renin-angiotensin-system seem to play an important role in the control of fibrinolysis in adipose tissue. We conclude that PAI-1 production by adipose tissue may contribute to the elevated thromboembolic risk in obesity.
Adipocytes↗
Undiagnosed diabetes mellitus and metabolic control assessed by HbA(1c) among residents of nursing homes.
AIMS/HYPOTHESIS: Diabetes prevalence and diabetes care in residents of nursing homes is a neglected area of research although the growing number of elderly people with diabetes represents a growing challenge for health care in most countries. In this study, we used HbA(1c) measurement to estimate the percentage of residents with undiagnosed diabetes and the quality of metabolic control of subjects with known diabetes in nursing homes. METHODS: All 41 nursing homes in the county of Heinsberg in Northrhine-Westfalia were asked to complete a structured questionnaire on the prevalence of known diabetes among all residents. In addition, all residents were offered measurement of glycated haemoglobin A1c (HbA(1c)) from a capillary blood sample. Undiagnosed diabetes was defined by a HbA(1c) level greater than 6.0%. RESULTS: 39 nursing homes participated in the study comprising 99.6% of all residents. Among the 1936 residents 507 (26.2%) were known to suffer from diabetes. Among the latter 37.0% were under insulin treatment. Blood samples for the determination of HbA(1c) were obtained from 979 subjects from 20 nursing homes. Among those 60 years old or above (n = 843) the mean level of HbA(1c) in those with known diabetes was 7.3 +/- 1.5% and in those without 6.1 +/- 0.9%. Only 16.7% of the subjects with known diabetes had a HbA(1c) greater than 8.5% indicating poor metabolic control. Among the residents previously not known to have diabetes 47.2% had a HbA(1c) equal to or greater than 6.1%, but among those only 8.5% had a HbA(1c) greater than 7.0%. CONCLUSIONS/INTERPRETATION: Although the prevalence of undiagnosed diabetes mellitus defined by HbA(1c) above the normal range in elderly nursing home residents is high, only few may require treatment. The quality of metabolic control among those with known diabetes mellitus is better than expected.
Aged↗
Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture.
Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and was recently shown to be produced by adipose cells. Obesity is associated with an increased production and release of PAI-1 protein. The aim of this study was to investigate the role of angiotensin (Ang) II and its degradation products for PAI-1 release from human adipose cells. For this purpose, we used the model of in vitro differentiated human adipocytes in primary culture. Exposure of human adipocytes to Ang II resulted in a dose- and time-dependent stimulation of PAI-1 release into the culture medium. The maximum effect of Ang II was found at a concentration of 10(-5) mol/L for 48 hours, increasing PAI-1 release by 276+/-53% compared with control cultures (P<0.05). This stimulation was preceded by an increase in specific PAI-1 mRNA copies by 65+/-12% (P<0.05), with a maximum after 6 hours. Incubation of adipocytes with 10(-5) mol/L Ang III and Ang IV, respectively, also resulted in a stimulation of PAI-1 release into the medium by 195+/-60% (P<0.05) and 142+/-24% (P<0.05), respectively, compared with control cultures. Addition of the angiotensin-receptor subtype 1 (AT(1)) blocker candesartan abolished the stimulatory action of Ang II and its metabolites, indicating that this effect is mediated by AT(1). Addition of the AT(1) blocker alone to unstimulated cultures reduced PAI-1 release by 41%+/-25% (P<0.05), suggesting that endogenous Ang II synthesis contributes to PAI-1 secretion from adipose tissue in an autocrine/paracrine manner. In conclusion, Ang II and its metabolites promote PAI-1 production and release by human fat cells and may contribute to the impairment of the fibrinolytic system typical for obesity. AT(1) receptor blockade reduces basal and abolishes Ang II-stimulated PAI-1 release from human adipocytes.
Adipose Tissue↗
Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function.
Adipocytes produce the inflammatory cytokine interleukin-6 (IL-6); however, it is not known whether these cells express the IL-6 receptor system, how the secretion of this cytokine is regulated, and whether it has a function within adipose tissue. Using cultured human breast adipocytes, we investigated the expression of IL-6 and its receptor system, the effects of IL-6 on main adipocyte functions, and the regulation of IL-6 secretion by catecholamines and glucocorticoids. In the culture system, immunohistochemistry demonstrated expression of IL-6 and its receptor system, consisting of the ligand-binding IL-6 receptor and the signal-transducing protein gp130, in mature adipocytes, but not in undifferentiated adipocyte precursor cells. In freshly isolated adipocytes, RT-PCR detected messenger ribonucleic acids encoding the above proteins. Chronic incubation of adipocytes with 1 nmol/L IL-6 during adipose differentiation reduced glycero-3-phosphate dehydrogenase (GPDH) activity, a marker of adipocyte differentiation, and triglyceride synthesis to 67 +/- 9% of the basal level (mean +/- SEM; P < 0.05) only on day 21. Incubation of differentiated adipocytes with 10 nmol/L IL-6 for 24 h also resulted in a reduction of GPDH activity to 81 +/- 5% (P < 0.05). On the other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol release by 42 +/- 12% (P < 0.01) and isoproterenol-induced glycerol release by 21 +/- 6% (P < 0.05). The same concentration of IL-6, however, did not alter basal or insulin-stimulated glucose transport. IL-6 secretion was acutely and chronically stimulated by 1 micromol/L isoproterenol (peak of 6.2-fold after 3 h; P < 0.001) and only moderately suppressed by 100 nmol/L cortisol (-36 +/- 10%; P < 0.001). In conclusion, human breast adipocytes release substantial amounts of IL-6 and express IL-6 receptor and gp130. The secretion of IL-6 by adipocytes is strongly stimulated by beta-adrenergic activation and is modestly suppressed by glucocorticoids. IL-6 reduces GPDH activity and stimulates lipolysis, suggesting an autocrine/paracrine role of this cytokine in human adipose breast tissue.
Adipocytes↗
Cultures of human adipose precursor cells.
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Adipocytes↗
[Management of diabetic patients in inpatient nursing care facilities in the Heinsberg district].
BACKGROUND AND OBJECTIVE: Little information is available on the diabetes management of elderly people under institutional care. It was therefore aim of this study to assess the quality of diabetes care in this patient group. PATIENTS AND METHODS: In the county of Heinsberg, North Rhine-Westphalia, after agreement in the local public health conference, all 41 nursing homes were addressed and asked to fill out a structured, detailed questionnaire. Thirty-nine institutions participated in the study representing 99.6% of all patients under such care. RESULTS: Out of the 1936 residents 507 had known diabetes mellitus (prevalence 26.2%) with an age-dependent decrease. 37.0% of the diabetic subjects were treated with insulin, 46.7% received oral hypoglycemic agents. Advanced late complications were reported in a minority of patients (3.4% amputations, 13.6% blindness or severe visual impairment, 1.0% hemodialysis). In the majority of patients, the metabolic control was assessed by blood glucose measurement, but only in low frequency. Eye examination within the previous 12 months was reported for only 50.0% of the diabetic subjects. Although the diabetics were frequently seen by their doctors (48.1% > 2 consultations/month, 48.7% with 1 to 2 consultations/month), 30.8% had at least 1 hospital stay during the previous 12 months. Among the 834 nurses with the full dataset only 4 had a special training in diabetology. CONCLUSION: The results of this study indicate that the diabetes management of patients living in nursing homes only partially fulfills the current requirements for diabetes care. There appears to be a particular need to improve the nurses training in diabetes as well as the communication between nursing homes and doctors.
Aged↗
[Do we need nutrition medicine?].
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Cardiovascular Diseases↗
[Care of elderly diabetics by ambulatory nursing in the Heinsberg region].
OBJECTIVE: The number of elderly people with chronic diseases receiving ambulant nursing care in the German population is continually increasing. However, little information is available on the quality of care of elderly diabetic patients. The aim of this study was to investigate the pattern of care provided for this group by such ambulatory nursing services. PATIENTS AND METHODS: All ambulant nursing services in the county of Heinsberg, North-Rhine-Westphalia, were contacted and asked to answer a standardized questionnaire. 23 of the 24 services participated in the study and provided suitable answers. The study was conducted between October 1998 and March 1999. RESULTS: All services together took care of 337 persons with known diabetes mellitus, of whom 79.6% were female and 20.4% were male. The total diabetes prevalence among all patients was 27.2%. 231 diabetic persons (68.5%) were treated with insulin. Nurses administered insulin to 84.8% of the patients. As expected many diabetics had severe late complications (7.4% amputation, 20.8% blindness, 4.2% renal failure). In the majority of patients, blood glucose was monitored, but only occasionally, whereas urinary glucose was checked in only a few cases. Foot inspection and care were provided regularly. 115 diabetics (34.1%) had at least one hospital stay during the previous 12-months period. CONCLUSION: The results of this study indicate that ambulatory nursing services care mainly for insulin-treated diabetic patients in late stages of the disease. The current organisational structure not meet the requirements of modern diabetes management.
Aged↗
[Obesity--the new challenge].
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Anti-Obesity Agents↗
[Diabetic muscle infarct].
HISTORY AND CLINICAL FINDINGS: A 64-year-old diabetic man with secondary failure of treatment with oral hypoglycemic agents was admitted to our clinical department to initiate insulin therapy. The patient was otherwise in good health. Before his dismissal he acutely developed symptoms of pain in his left calf. In addition, the patient was unable to move his left leg and presented palpable pea-sized nodules of his left calf. INVESTIGATIONS: Laboratory investigations revealed elevated serum creatine kinase levels on day two after the onset of clinical symptoms (peak value: 2238 U/I). There was evidence for antinuclear antibodies, c-reactive protein was normal. An ultrasound investigation showed a focal edema or bleeding located to the musculus gastrocnemius. Duplex-sonography excluded thrombosis or embolisation. Magnetic resonance imaging showed a diffuse enhancement of signal intensity within the musculus soleus and in areals of the musculus gastrocnemius, as signs of increased blood supply. All clinical findings were consistent with the diagnosis of diabetic muscle infarction. TREATMENT AND COURSE: Under symptomatic treatment with tramadol, diclofenac ointment, and fragmented heparin serum creatine kinase returned to normal levels (105 U/I) within 14 days. In accordance, symptoms of local pain disappeared completely. After two weeks of treatment the patient was able to move his leg without pain. CONCLUSION: This is the first presentation of a patient with diabetic muscle infarction from the onset of symptoms until full recovery. In addition, this case confirms previous descriptions that this condition can be diagnosed by clinical and sonographic findings in combination with magnetic resonance imaging without invasive histologic techniques.
Diabetes Mellitus, Type 2↗