[Gender aspects of malnutrition and associated sequelae. Prevention and therapy]. / Genderaspekte der Malnutrition und assoziierte Folgeerkrankungen : Prävention und Therapie.

Malnutrition is related to a range of secondary complications. The prevalence of many of these sequelae is higher in elderly women than in men, thus resulting in a higher level of impairment and reduced quality of life. Multiple factors lead to the development of malnutrition and socioeconomic causes, such as poverty among the elderly and isolation, are more common in elderly women. The age-associated loss of muscle mass is more pronounced in women than in men and the risk of developing sarcopenia and frailty is increased. The prevalence of sarcopenic obesity is higher in women than in men. Malnutrition increases the risk of osteoporosis and about 80 % of all osteoporosis patients are women. Furthermore, low serum levels of vitamin D correlate more closely to a poorer cognitive outcome in elderly women than they do in men. The prevention, early diagnosis and therapy of malnutrition is of great clinical importance, particularly to preserve physical functional capacity and thus quality of life in elderly women.

[Diabetes and osteoporosis: pathophysiological interactions and clinical importance for geriatric patients]. / Diabetes und Osteoporose: Pathophysiologische Interaktionen und klinische Bedeutung für geriatrische Patienten.

Osteoporosis is an age-associated disease, resulting in impaired bone quality and increased risk for bone fractures. Patients with type 2 diabetes mellitus have--despite a normal or even increased bone mineral density--an increased risk for fractures, which is related to an imbalance between osteoblastic bone formation and osteoclastic resorption. Complex pathophysiological mechanisms associated with insulin resistance and hyperglycemia are involved in the deleterious effects on osteoblast function and bone formation. The quality and regimen of antidiabetic therapy are discussed as modulators of bone metabolism. Of great clinical importance is an assessment of the fall risk especially for diabetic patients, because late complications, such as neuropathy, but also side effects of medication can result in a significantly increased risk for falls. Lifestyle intervention is of advantage with respect to diabetes and osteoporosis prevention and therapy. Vitamin D supplementation results in favorable effects with a reduced risk for falls and also improvements of insulin sensitivity. According to published data, the safety and efficacy of specific medication for the treatment of osteoporosis (bisphosphonates, denosumab, selective estrogen receptor modulators) reveal no difference between patients with and without diabetes mellitus.

Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment.

PURPOSE: Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. METHODS: Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16). RESULTS: Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p

The metabolic syndrome as a link between smoking and cardiovascular disease.

OBJECTIVE: Smoking is associated with a significant increase in the cardiovascular risk. The possible relationship of smoking with insulin resistance might further enhance the cardiovascular risk of the patients and is therefore of great clinical interest. DESIGN, SETTING AND SUBJECTS: We have retrospectively evaluated data of 3804 non-diabetic men attending a medical outdoor clinic. Clinical [body mass index (BMI), percentage of body fat, waist-to-hip ratio] and laboratory results were compared between smokers (n = 124) and non-smokers (n = 1915) without cardiovascular disease, as well as between smokers (n = 759) and non-smokers (n = 1006) with cardiovascular disease. RESULTS: Smokers without clinically manifest cardiovascular disease revealed significantly higher fasting glucose (5.8 +/- 0.6 mmol/l) and triglyceride levels (1.8 +/- 0.9 mmol/l) than non-smokers (fasting glucose: 5.1 +/- 0.7 mmol/l, p < 0.010; triglycerides: 1.5 +/- 0.8 mmol/l, p < 0.030). The adverse metabolic profile of smokers was even more pronounced in patients with cardiovascular disease. An age-matched analysis of smokers could demonstrate that cardiovascular patients revealed higher BMI values (27.3 +/- 2.4 kg/m2) and a higher percentage of body fat (25.5 +/- 5.5%) than those without cardiovascular disease (BMI: 25.7 +/- 2.2 kg/m2, p < 0.010; percentage of body fat: 23.0 +/- 5.5%, p < 0.030). CONCLUSION: In men with and without clinically manifest cardiovascular disease, smoking was associated with a metabolic profile indicating a higher degree of insulin resistance.

Antibodies to heat-shock protein 65 and neopterin levels in patients with type 1 diabetes mellitus.

Antibodies to heat shock protein (hsp) are strongly associated with atherosclerotic cardiovascular disease in the non-diabetic population as well as in patients with type 2 diabetes mellitus. In type 1 diabetes increased antibody titers to hsp were found to be a symptom of the autoimmune disease leading to beta-cell damage. We asked whether hsp antibody titers are related to metabolic control and late complications in type 1 diabetic patients. Serum neopterin, also an indicator of chronic inflammation, was also evaluated. The hsp65 antibody titer was determined in 138 patients with type 1 diabetes, 47 women and 91 men, aged 35.5 +/- 12 years with a mean diabetes duration of 16.6 +/- 10.5 years. A history of diabetic late complications and cardiovascular disease was taken. A fundoscopy and a neurological examination were performed, nephropathy was assessed by measurement of the urinary albumin excretion rate. For the measurement of the hsp antibody titer an enzyme-linked immunosorbent assay (ELISA) was applied, for neopterin a radio-immuno assay (RIA) was used. The hsp65 antibody titer was found to be positively related to the patients' age (r = 0.237; p < 0.035). Patients with retinopathy revealed significantly higher hsp65 antibody titers (307.2 +/- 38.6) than those without retinopathy (150.0 +/- 18.5;p < 0.003). No correlation was found between hsp antibody titer and metabolic control. Serum neopterin levels revealed a trend towards a positive relationship with diabetes duration (r = 0.205; p < 0.0539) and a significant correlation with serum cholesterol levels (r = 0.436; p < 0.001), but not with HbA1 c values. Our data add further information to the role of inflammatory markers in the development of diabetic microangiopathy.

The influence of obesity on the frequency and distribution of medication.

Obesity is a serious health problem in industrialized countries and is associated with a significant increase in total health care costs. Only few data are available about the costs of drug therapies in patients with an increased body weight treated under clinical routine procedures. Such data could support efforts to intensify obesity prevention and treatment programmes in order to reduce comorbidities and costs. We have evaluated body mass index (BMI), diagnosis, and medication in 3360 outpatients (2175 women and 1185 men; mean age: 56.7 +/- 17.5 years). All patients underwent physical examinations, including BMI determination, and provided a detailed record concerning medication. In 1809 patients, the percentage of body fat content was measured with a bioimpedance method (OMRON BF 302 body fat monitor). Continuous variables were compared using the t-test or Wilcoxon U-test. Frequency distributions were compared using chi-squared tests. With respect to BMI, most of the patients (n = 1793; 53 %) were overweight or obese, 1349 (40 %) showed a normal BMI and 218 (7 %) a low BMI. The majority of cardiovascular (61 %), rheumatological (61.1 %) and metabolic (60.4 %) medication was administered to overweight and obese patients. Parallel findings could be obtained by analysing the percentage of body fat and the frequency of medication. Overall, 82.5 % of all medication was given to patients with a body fat content >20 %. Our results support the importance of weight-reduction programmes in order to prevent an overall increase in the costs of medication as a consequence of overweight and obesity.

Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years.

AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved in the development of obesity-linked insulin resistance. TNF-alpha plasma levels rise with increasing age and might thus also be related to metabolic control in Type 2 diabetes mellitus. We have studied the relationship of TNF-alpha plasma levels to glycaemic control in elderly patients with Type 2 diabetes over 2 years. METHODS: Clinical and laboratory data of 53 patients (26 women, 27 men) with Type 2 diabetes (mean age 71.6 +/- 5.6 years) were regularly evaluated over 2 years, and the relationship to anti-diabetic treatment regimens analysed. TNF-alpha plasma level was measured by a solid-phase enzyme amplified sensitivity immunoassay. RESULTS: TNF-alpha plasma levels increased significantly from 16.2 +/- 9.6 pg/ml at baseline to 28.0 +/- 13.8 pg/ml after 2 years (P = 0.028). HbA1c values also increased from 6.4 +/- 1.2% to 7.7 +/- 1.6% (P = 0.046). Mean body mass index of the patients remained almost constant, while a moderate increase in the percentage of body fat (34.5 +/- 7.0% to 35.3 +/- 6.9%; P= 0.061) and in waist-hip ratio was observed (0.86 +/- 0.04 to 0.88 +/- 0.04; P= 0.052). After adjustment for covariates multivariate analysis demonstrated that TNF-alpha plasma levels are positively related to the HbA1c values of the whole study population at the baseline control and after 2 years. TNF-alpha also revealed a positive correlation to the percentage of body fat. CONCLUSIONS: In elderly patients with Type 2 diabetes TNF-alpha plasma levels revealed a continuous increase during an observation period of 2 years. This increase in TNF-alpha plasma levels might add another aspect to the worsening of glycaemic control in the progression of Type 2 diabetes.

Counseling programs and the outcome of gestational diabetes in Austrian and Mediterranean Turkish women.

An increasing number of patients from different ethnic groups is admitted to European diabetes treatment centers. Counseling programs are of central importance in disease treatment, especially in gestational diabetes where counseling is of influence also on the outcome of pregnancy. We report about the outcome of gestational diabetes in 39 Mediterranean Turkish and 72 Caucasian Austrian women treated at our outpatient clinic. Both groups of patients underwent repeated counseling including information about the cause of gestational diabetes and therapeutic instructions with an emphasis on dietary recommendations adapted to the eating habits. Individually adapted and repeated instructions with the help of trained translators were of great importance for the Turkish women because nearly one third of them turned out to be illiterates. Under comparable treatment modalities, Turkish and Austrian women revealed no differences in metabolic control, the mean birth weight of the children was 3311+/-467 and 3370+/-600g, respectively, and 12.8% of the Turkish and 16.6% of the Austrian children still had a birth weight above 4000g. These results suggest that women with gestational diabetes and different ethnicity reveal a comparable outcome of gestational diabetes when therapeutic instructions are adapted to the social and cultural background as well as to the individual need of the patient.

Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factors.

OBJECTIVES: Diabetic patients reveal a significant increase in their cardiovascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis factor-alpha (TNF-alpha), might offer a tool to determine patients at high risk. The cytokine TNF-alpha reveals a complex relationship with diabetes. It is involved in beta-cell damage leading to type 1 diabetes, causes insulin resistance associated with obesity and is of influence in the formation of atherosclerotic vascular lesions. We were interested in the possible association of this cytokine with metabolic control and cardiovascular risk factors in patients with type 1 diabetes. DESIGN AND SUBJECTS: TNF-alpha plasma levels were determined in 44 outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration 11.2 +/- 8.7 years) and in 24 healthy controls by use of a solid phase enzyme amplified sensitivity immunoassay (TNF-alpha ELISA, Biosource Fleurus, Belgium). None of our study participants suffered from inflammatory or other concurrent diseases. Relationships between variables were evaluated by non-parametric Spearman correlation coefficients. RESULTS: TNF-alpha plasma levels were significantly higher in diabetic patients (19.3 +/- 7.5 pg mL-1) than in non-diabetic subjects (11.1 +/- 5.8 pg mL-1; P < 0. 023), and revealed a significant positive correlation with glycated haemoglobin (HbA1c) (r = 0.43; P < 0.004) and fructosamine (r = 0. 31; P < 0.049) values, and a negative correlation with HDL cholesterol (r = -0.36; P < 0.018) and apoAI-levels (r = -0.37; P < 0.015). These relationships could be observed in patients with a duration of diabetes for more than 5 years, as well as in patients with a shorter duration of diabetes. In the male group, TNF-alpha plasma levels revealed a significant positive correlation with plasma levels of thiobarbituric acid reacting substances (r = 0.61; P < 0.001). Plasma levels of thiobarbituric acid reacting substances showed a positive correlation with the duration of diabetes (r = 0. 58; P < 0.008), as well as with the serum levels of the vascular adhesion molecules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion molecule (VCAM) (r = 0.30; P < 0.052). CONCLUSIONS: Our data indicate that TNF-alpha plasma levels are increased in type 1 diabetes mellitus and reveal a significant association with metabolic long-term control parameters, HbA1c and fructosamine for glycaemic control, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation.

The correlation of office blood pressure and 24-hour ambulatory measurements in hypertensive patients - comparison between non-pharmacological treatment and antihypertensive medication.

Blood pressure control in many hypertensive patients remains imperfect, also because routine office blood pressure can only give limited information about diurnal variations and nocturnal dipping. It was the aim of our evaluation to study the efficacy of antihypertensive therapy and the correlation between repeated office blood pressure values and 24-hour ambulatory measurements in hypertensive outdoor patients treated by life-style modification and antihypertensive medication. Clinical data and blood pressure values in 343 outdoor patients who were admitted to the medical centre for diagnostic and therapeutic procedures in hypertension were evaluated. Database was created from 1991 to 1998. The study population (mean age 59.5 +/- 11.6 years) comprised 153 men and 190 women, 141 (41%) were treated by life-style modification, 202 (59%) received antihypertensive medication. 57 patients showed symptoms of a metabolic syndrome, 62 suffered from manifest diabetes mellitus type 2. - Repeated office blood pressure measurements showed a significant positive correlation to the systolic and diastolic values obtained by 24-hour blood controls. While diastolic night minima revealed a positive correlation to office measurements (R = 0. 211; P <0.05), systolic night minima showed no correlation to office pressure control. In the whole study population and in subgroups (metabolic syndrome, diabetes mellitus) patients under antihypertensive medication still revealed significantly higher mean 24-hour systolic blood pressure values (140.5 +/- 16.9 mm Hg) than patients treated by life-style modification (133.0 +/- 14.4 mm Hg; P <0.001). Diastolic day- and night-time difference (dipping) was less pronounced in patients with antihypertensive medication. For appropriate antihypertensive therapy 24-hour blood pressure measurements are thus of advantage to repeated office controls especially to optimize medication for high systolic blood pressure values and adapt therapy to the nocturnal decrease of blood pressure values (dipping).

Prognostic value of antibody titre to heat-shock protein 65 on cardiovascular events.

Accumulating evidence suggests that the immune system is involved in atherogenesis, such as the correlation of the antibody titre to heat shock protein (hsp) with atherosclerotic lesions in the carotid and coronary arteries. Because the prognostic value of the hsp antibody titre for future cardiovascular events has not been evaluated until now, we performed a follow-up study on 195 subjects without a history of established cardiovascular risk factors (e.g. hypercholesterolaemia, diabetes, smoking), recruited for hsp antibody titre determination in 1995. Cardiovascular events were defined as unstable angina with the need for hospitalisation, myocardial infarction, re-vascularisation (PTCA, bypass), stroke and cardiovascular death. Among 79 men with coronary artery disease defined by coronary angiography, hsp antibody titres were significantly higher in those with future cardiovascular events (467.0 +/- 56.3) than in patients without further events (351.0 +/- 23.3; p < 0.049). Because anti-hsp-antibody titres might be of prognostic value for coronary artery disease, patients with an increased hsp antibody titre should obtain intensive management of classical risk factors.

[Evaluating genetics and environment in development of obesity]. / Bewertung von Genetik und Umwelt für die Entstehung von Ubergewicht.

Previous studies with twins had demonstrated that heredity exerts a definite impact on the development of overweight even more than environmental conditions of nutrition. In recent years studies of molecular genetics in imbred obese mice lead to the discovery of the ob-gene coding for the expression of the ob-protein (leptin) in adipose tissue. Mutation of this gene and also of other genes coding for the expression of receptor proteines for leptin were also discovered in obese mice. In humans, however, mutations of the ob-gene were found only in a few families with hereditary obesity obviously as rarities as compared to a huge number of overweight people with high leptin of normal structure in western societies. About the molecular structure of leptin receptors or its possible mutation in obesity are no human results are available at the present time. In this survey further observations about genetics and mutations of transmitters regulating feeding and for energy expenditure are reported. Although all these results come from animals it may be presumed that they will provide an experimental basis for a better understanding of genetic mechanisms leading to obesity in humans and also for future development of drugs interfering with these mechanisms thus offering a chance for medical treatment of obesity.