[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.

Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis.

Liver transplantation provides a unique opportunity to investigate the contribution in vivo of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. We have determined the genetic polymorphisms plasma proteins. We have determined the genetic polymorphisms of apo A-IV, apo E, and of the Lp(a) glycoprotein (apo (a] in the plasma of subjects undergoing liver transplantation and in respective organ donors. The results show that in humans, greater than 90% of the plasma apo E and virtually all apo (a) are liver derived, whereas this organ does not significantly contribute to plasma apo A-IV levels.

Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a).

Patients with terminal renal insufficiency suffer from an increased incidence of atherosclerotic diseases. Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases. Variable alleles at the apo(a) gene locus determine to a large extent the Lp(a) concentration in the general population. In addition, other genetic and nongenetic factors also contribute to the plasma concentrations of Lp(a). We therefore investigated Apo(a) phenotypes and Lp(a) plasma concentrations in a large group of patients with end-stage renal disease (ESRD) and in a control group. Lp(a) concentrations were significantly elevated in ESRD patients (20.1 +/- 20.3 mg/dl) as compared with the controls (12.1 +/- 15.5 mg/dl, P < 0.001). However, no difference was found in apo(a) isoform frequency between the ESRD group and the controls. Interestingly, only patients with large size apo(a) isoforms exhibited two- to fourfold elevated levels of Lp(a), whereas the small-size isoforms had similar concentrations in ESRD patients and controls. Beside elevated Lp(a) concentrations, ESRD patients had lower levels of plasma cholesterol and apolipoprotein B. These results show that elevated Lp(a) plasma levels might significantly contribute to the risk for atherosclerotic diseases in ESRD. They further indicate that nongenetic factors related to renal insufficiency or other genes beside the apo(a) structural gene locus must be responsible for the high Lp(a) levels.

Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels.

To study the influence of thyroid hormone on Lp(a) plasma concentration we measured Lp(a), total cholesterol, LDL-C, HDL-C, triglycerides and fT4 levels and determined apo(a) phenotypes in 26 patients with hyperthyroidism in a follow-up study before and after thyreostatic treatment. The pretreatment values of total cholesterol (TC), LDL-C, and Lp(a) were significantly reduced as compared with those of healthy controls. The reduced mean Lp(a) concentrations could not be explained by a difference of apo(a) 'size allele' frequencies between patients and controls. During thyreostatic treatment mean concentrations of TC, LDL-C, and HDL-C increased significantly. The mean Lp(a) value was not changed after 4 weeks of treatment. The individual changes of Lp(a), however, correlated significantly with those of LDL-C levels (R = 0.40, P = 0.04). Eighty-one per cent of the patients showed an increase of Lp(a) or no change of the Lp(a) level and 19% reacted with a decrease upon thyreostatic treatment. The observed lipid and lipoprotein changes were not different in patients with Graves disease or multifocal toxic goiter. The results indicate that Lp(a) plasma levels are decreased in the hyperthyroid state irrespective of the pathogenic mechanism.

Changes of serum antibodies to heat-shock protein 65 in coronary heart disease and acute myocardial infarction.

Accumulating evidence indicates the involvement of heat shock proteins (hsp), a family of stress-inducible proteins, in atherosclerosis. For carotid atherosclerosis an association with an increase in hsp65 antibodies has been demonstrated. To investigate whether such antibodies are also associated with coronary heart disease (CHD) and acute myocardial infarction (MI), an age- and sex-matched study with patients suffering from CHD (n = 114) and MI (n = 89) and healthy controls (n = 76) was performed. All study participants (n = 279) were consecutively recruited according to typical diagnostic criteria. Determination of antibody titres to hsp65 was performed by an enzyme-linked immunosorbent assay (ELISA). Hsp65 antibody titres in CHD showed a significant increase compared to the healthy control group (P = 0.029), however, hsp65 antibody titres were found to be significantly lower in acute MI, compared to CHD (P = 0.005). Alteration in hsp65 antibody titres showed no correlation to established cardiovascular risk factors, e.g. serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood pressure, smoking, alcohol intake and body weight. In conclusion, serum concentrations of hsp65 antibodies were elevated independently in coronary heart diseases and declined in patients with acute myocardial infarction, indicating a possible involvement of the antibodies in the pathogenesis of this disease.

Lipoprotein(a) is increased in triglyceride-rich lipoproteins in men with coronary heart disease, but does not change acutely following oral fat ingestion.

Association of apo(a)/Lp(a) with triglyceride-rich lipoproteins (TGR-Lps) is determined by different factors that are poorly understood. Some previous studies suggested that apo(a) in TGR-Lps may affect the atherogenicity of the TGR particles. To study whether there are any peculiarities in postprandial (pp) Lp(a) metabolism, we have determined apo(a) phenotypes and Lp(a) concentrations in 46 subjects with coronary heart disease (CHD) and in six normolipidemic individuals at different time points (4, 6 and 8 h) following an oral fat tolerance test. While mean triglyceride concentration reached its maximum 6 h after a standardized fat meal, no change in total cholesterol and in mean Lp(a) plasma concentration was detected at any time point after the fat load. In 6 normolipidemic probands and in 8 patients with CHD, who were matched for apo(a) phenotype, lipoprotein levels, age and body weight, we followed the distribution of apo(a) in plasma density gradient fractions in the fasting and pp state. In the CHD patients a significant larger percentage of apo(a) reactivity was detected in TGR-Lps in the pre- as well as in the postprandial state, compared to control subjects. The fat intake did not induce a significant change of apo(a) reactivity in the TGR-Lp fractions in both groups. The apo(a) isoform-size and the Lp(a) plasma concentration in the fasting state had no influence on the individual variation of the Lp(a) concentration in pp TGR-Lp fractions. Our results provide evidence that TGR-Lp fractions of CHD patients are enriched in apo(a) reactivity compared to healthy controls, but do not support the hypothesis that Lp(a) acts atherogenically through a pp increase of its plasma concentration.

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.

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.

The immunosuppressive substance 2-chloro-2-deoxyadenosine modulates lipoprotein metabolism in a murine macrophage cell line (P388 cells).

A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2-CdA), was reported to inhibit monocyte functions at low concentration. Because macrophages play a key role in the formation of atherosclerotic plaques, it was of interest to study the effect of 2-CdA on cellular lipid metabolism. For this purpose we have used a macrophage cell line (P388) to perform incubation studies in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose-dependent decrease in cellular cholesterol content and in the amount of extracellular [14C]oleic acid (OA) incorporated into the cholesteryl ester (CE) fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in cholesterol esterification compared to controls (P < 0.008). To evaluate the mechanism of interaction of 2-CdA with cellular lipid metabolism, deoxycytidine (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect of 2-CdA in different ways, were co-administered with 2-CdA. dCyt, a competitive inhibitor of dCyt kinase, which catalyzes phosphorylation to the active metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly greater incorporation of extracellular [14C]OA into the CE fraction than in the presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP-ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2-CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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).

[Snuff aspiration as a cause of recurrent pulmonary infiltrations in a 60-year-old patient with chronic renal failure]. / Schnupftabakaspiration als Ursache rezidivierender pulmonaler Infiltrate bei einem 60jährigen Patienten mit chronischer Niereninsuffizienz.

Pulmonary infiltrations associated with renal failure demand several diagnostic procedures to exclude autoimmune disorders affecting both organ systems or to find an infectious cause of the disease. We report the case of a 60 year-old man with chronic renal failure and recurring pulmonary infiltrations. On admission to hospital all diagnostic parameters for systemic vasculitis, infectious or neoplastic disease were negative, including the histological report on transbronchial biopsies. Eventually, follow-up biopsies taken 3 months later showed vegetable fibres and necrosis due to intensive snuff abuse during the previous months. After the patient stopped taking snuff the pulmonary infiltrations improved quickly. Uraemic neuropathy, which may have facilitated aspiration, as well as the reduced pulmonary and systemic defence mechanisms due to chronic renal failure probably contributed to a considerable degree to the development of pulmonary infiltration.

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

[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.

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.

[Pravastatin, a new cholesterol synthesis inhibitor for lowering increased serum cholesterol]. / Pravastatin, ein neuer Cholesterinsynthesehemmer zur Senkung erhöhten Serumcholesterins.

The association between increased risk for coronary artery disease (CAD) and elevated plasma cholesterol has been firmly established. The beneficial effect of cholesterol lowering treatment modalities was confirmed in both primary and secondary intervention trials. Because long-term treatment is usually required for lipid lowering therapies the drugs used for lipid reduction have to be not only efficacious but also safe. Inhibitors of cholesterol synthesis that have become clinically available during the last few years, can reduce plasma levels of total cholesterol and low density lipoprotein (LDL)-cholesterol very effectively. In the Familial Atherosclerosis Treatment Study (FATS) an intensive cholesterol lowering treatment modality consisting of a combination of an inhibitor of cholesterol synthesis and colestipol reduced the progression of coronary lesions and caused a partial regression of such lesions. Among the various inhibitors of cholesterol synthesis developed recently, pravastatin appears to be tissue-specific because of its hydrophilic property.