Antje Steveling

Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20–79

AIMS Although the association of low serum testosterone levels with mortality has gained strength in recent research, there are few population-based studies on this issue. This study examined whether low serum testosterone levels are a risk factor for all-cause or cause-specific mortality in a population-based sample of men aged 20-79. METHODS AND RESULTS We used data from 1954 men recruited for the prospective population-based Study of Health in Pomerania, with measured serum testosterone levels at baseline and 195 deaths during an average 7.2-year follow-up. A total serum testosterone level of less than 8.7 nmol/L (250 ng/dL) was classified as low. The relationships of low serum testosterone levels with all-cause and cause-specific mortality were analysed by Cox proportional hazards regression models. Men with low serum testosterone levels had a significantly higher mortality from all causes than men with higher serum testosterone levels (HR 2.24; 95% CI 1.41-3.57). After adjusting for waist circumference, smoking habits, high-risk alcohol use, physical activity, renal insufficiency, and levels of dehydroepiandrosterone sulfate, low serum testosterone levels continued to be associated with increased mortality (HR 2.32; 95% CI 1.38-3.89). In cause-specific analyses, low serum testosterone levels predicted increased risk of death from cardiovascular disease (CVD) (HR 2.56; 95% CI 1.15-6.52) and cancer (HR 3.46; 95% CI 1.68-6.68), but not from respiratory diseases or other causes. CONCLUSION Low serum testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. As serum testosterone levels are inversely related to mortality due to CVD and cancer, it may be used as a predictive marker.

Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men

Obesity and metabolic syndrome are associated with low serum testosterone levels. Hepatic steatosis contributes to the metabolic syndrome and might be regarded as its hepatic manifestation. In this study, we sought to investigate the relationship between hepatic steatosis, serum testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in men. This is a cross-sectional population-based study. We used data of 1912 men recruited for the population-based Study of Health in Pomerania, which was conducted in a region with high prevalence of metabolic syndrome and related diseases. Hepatic steatosis was defined according to sonographic criteria. The relationship of hepatic steatosis with serum testosterone and DHEAS levels was analysed by multivariable logistic regression. Men with low serum testosterone levels had a higher risk of hepatic steatosis than men with high serum testosterone levels. Adjustment for age and further confounders attenuated this association, but did not affect statistical significance (odds ratio 2.36; 95% confidence interval 1.66-3.37; p < 0.05). In the full model, the highest risk of hepatic steatosis was found in subjects with the highest serum DHEAS levels (odds ratio 1.59; 95% confidence interval 1.04-2.43; p < 0.05). Exclusion of men with high alcohol consumption did not affect these results substantially. Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels. These associations are independent of alcohol consumption.

Reference Ranges for Serum Dehydroepiandrosterone Sulfate and Testosterone in Adult Men

Dehydroepiandrosterone (DHEA) is the main adrenal androgen, which mostly exists in a sulfated version (DHEAS). Both DHEA and DHEAS are metabolic intermediates in the biosynthesis of the male sex hormone testosterone. In men, testosterone is involved in the regulation of fertility, libido, and muscle mass and is valuable for the assessment of gonadal, adrenal, and pituitary function and for the diagnosis of hypogonadism. The objective of the present study was to calculate age-specific reference ranges for serum DHEAS and serum testosterone using 1) linear regression and the mean +/- 1.96 standard deviation concept and 2) quantile regression. From the cross-sectional Study of Health in Pomerania a total of 1078 men aged 20-79 years were included in the analyses. Serum DHEAS and testosterone levels were quantified using IMMULITE 2500 immunoassays. Linear and quantile regression were performed to calculate age-specific reference ranges. Both statistical methods generated different results: The reference ranges based on linear regression identified 17 men (1.6%) with DHEAS levels and 45 men (4.2%) with serum testosterone levels outside the reference range. Using quantile regression, 54 men (5.0%) and 50 men (4.6%) with serum DHEAS and testosterone levels outside the range were detected, respectively. The present study established age-specific reference ranges for serum DHEAS and testosterone levels for men. Quantile regression should be preferred to calculate reference ranges; a better concordance with original data is possible because no distribution assumption is required and the robustness against outliers is given.

Nutrition in Pancreatic Cancer: A Review.

Background: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival. Key Message: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data. Practical Implications: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and L-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer.

Magnetic Resonance Imaging of Changes in Abdominal Compartments in Obese Diabetics during a Low-Calorie Weight-Loss Program.

Objectives To investigate changes in the fat content of abdominal compartments and muscle area during weight loss using confounder-adjusted chemical-shift-encoded magnetic resonance imaging (MRI) in overweight diabetics. Methods Twenty-nine obese diabetics (10/19 men/women, median age: 59.0 years, median body mass index (BMI): 34.0 kg/m2) prospectively joined a standardized 15-week weight-loss program (six weeks of formula diet exclusively, followed by reintroduction of regular food with gradually increasing energy content over nine weeks) over 15 weeks. All subjects underwent a standardized MRI protocol including a confounder-adjusted chemical-shift-encoded MR sequence with water/fat separation before the program as well at the end of the six weeks of formula diet and at the end of the program at 15 weeks. Fat fractions of abdominal organs and vertebral bone marrow as well as volumes of visceral and subcutaneous fat were determined. Furthermore, muscle area was evaluated using the L4/L5 method. Data were compared using the Wilcoxon signed-rank test for paired samples. Results Median BMI decreased significantly from 34.0 kg/m2 to 29.9 kg/m2 (p < 0.001) at 15 weeks. Liver fat content was normalized (14.2% to 4.1%, p < 0.001) and vertebral bone marrow fat (57.5% to 53.6%, p = 0.018) decreased significantly throughout the program, while fat content of pancreas (9.0%), spleen (0.0%), and psoas muscle (0.0%) did not (p > 0.15). Visceral fat volume (3.2 L to 1.6 L, p < 0.001) and subcutaneous fat diameter (3.0 cm to 2.2 cm, p < 0.001) also decreased significantly. Muscle area declined by 6.8% from 243.9 cm2 to 226.8 cm2. Conclusion MRI allows noninvasive monitoring of changes in abdominal compartments during weight loss. In overweight diabetics, weight loss leads to fat reduction in abdominal compartments, such as visceral fat, as well as liver fat and vertebral bone marrow fat while pancreas fat remains unchanged.

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy.

Early Parenteral Nutrition in Patients with Biliopancreatic Mass Lesions, a Prospective, Randomized Intervention Trial.

Purpose Patients with biliopancreatic tumors frequently suffer from weight loss and cachexia. The in-hospital work-up to differentiate between benign and malignant biliopancreatic lesions requires repeated pre-interventional fasting periods that can aggravate this problem. We conducted a randomized intervention study to test whether routine in-hospital peripheral intravenous nutrition on fasting days (1000 ml/24 h, 700 kcal) has a beneficial effect on body weight and body composition. Material and Methods 168 patients were screened and 100 enrolled in the trial, all undergoing in-hospital work-up for biliopancreatic mass lesions and randomized to either intravenous nutrition or control. Primary endpoint was weight loss at time of hospital discharge; secondary endpoints were parameters determined by bioelectric impedance analysis and quality of life recorded by the EORTC questionnaire. Results Within three months prior to hospital admission patients had a median self-reported loss of 4.0 kg (25*th: -10.0 kg and 75*th* percentile: 0.0kg) of body weight. On a multivariate analysis nutritional intervention increased body weight by 1.7 kg (95% CI: 0.204; 3.210, p = 0.027), particularly in patients with malignant lesions (2.7 kg (95% CI: 0.71; 4.76, p < 0.01). Conclusions In a hospital setting, patients with suspected biliopancreatic mass lesions stabilized their body weight when receiving parenteral nutrition in fasting periods even when no total parenteral nutrition was required. Analysis showed that this effect was greatest in patients with malignant tumors. Further studies will be necessary to see whether patient outcome is affected as well. Trial Registration ClinicalTrials.gov NCT02670265

HbA1c-Bestimmung – ein neues Diagnosekriterium? / HbA1c – The new diagnostic criterion?

Zusammenfassung Entsprechend den aktuellen Leitlinien soll die Diagnosestellung des Typ 2 Diabetes mellitus (T2DM) in Deutschland anhand der Kriterien der American Diabetes Association (ADA) erfolgen, die sich an Kriterien der National Diabetes Data Group (NDDG) und der World Health Organisation (WHO) anlehnen. Zum Screening des T2DM wurde die Bestimmung des HbA1c-Wertes bislang allerdings von der ADA als diagnostischer Parameter abgelehnt, da er als nicht auseichend standardisiert und zu wenig sensitiv eingestuft wurde. In neueren Untersuchungen konnte allerdings eine gute Sensitivität und Spezifität des HbA1c-Wertes zur Diagnostik eines T2DM nachgewiesen werden, so dass zukünftig mit einer steigenden Bedeutung des HbA1c-Wert als Screening-Parameter des T2DM gerechnet werden kann. In der folgenden Übersicht soll deshalb die HbA1c-Bestimmung als mögliches Screeninginstrument und Prädiktor des Erkrankungsverlaufs näher erörtert werden. Abstract According to the current guidelines, in Germany type 2 diabetes mellitus (T2DM) is diagnosed by the criteria of the American Diabetes Association (ADA). Using HbA1c as a screening parameter of T2DM has not been accepted by the ADA until now because of insufficient standardisation and low sensitivity. Nevertheless, since recently published investigations could prove high sensitivity and specificity, HbA1c will gain more attention as a screening parameter. We discuss the meaning of HbA1c as a screening parameter for T2DM and as a predictor of disease progress.

Physical Activity, Energy Expenditure, Nutritional Habits, Quality of Sleep and Stress Levels in Shift-Working Health Care Personnel

Background Among health care personnel working regular hours or rotating shifts can affect parameters of general health and nutrition. We have investigated physical activity, sleep quality, metabolic activity and stress levels in health care workers from both groups. Methods We prospectively recruited 46 volunteer participants from the workforce of a University Medical Department of which 23 worked in rotating shifts (all nursing) and 21 non-shift regular hours (10 nursing, 13 clerical staff). All were investigated over 7 days by multisensory accelerometer (SenseWear Bodymedia® armband) and kept a detailed food diary. Physical activity and resting energy expenditure (REE) were measured in metabolic equivalents of task (METs). Quality of sleep was assessed as Pittsburgh Sleeping Quality Index and stress load using the Trier Inventory for Chronic Stress questionnaire (TICS). Results No significant differences were found for overall physical activity, steps per minute, time of exceeding the 3 METs level or sleep quality. A significant difference for physical activity during working hours was found between shift-workers vs. non-shift-workers (p<0.01) and for shift-working nurses (median = 2.1 METs SE = 0.1) vs. non-shift-working clerical personnel (median = 1.5 METs SE = 0.07, p<0.05). Non-shift-working nurses had a significantly lower REE than the other groups (p<0.05). The proportion of fat in the diet was significantly higher (p<0.05) in the office worker group (median = 42% SE = 1.2) whereas shift-working nurses consumed significantly more carbohydrates (median = 46% SE = 1.4) than clerical staff (median = 41% SE = 1.7). Stress assessment by TICS confirmed a significantly higher level of social overload in the shift working group (p<0.05). Conclusion In this prospective cohort study shift-working had no influence on overall physical activity. Lower physical activity during working hours appears to be compensated for during off-hours. Differences in nutritional habits and stress load warrant larger scale trials to determine the effect on implicit health-associated conditions.

HbA1c determination – A new diagnostic criterion? 1

Abstract According to the current guidelines, in Germany type 2 diabetes mellitus (T2DM) is diagnosed by the criteria of the American Diabetes Association (ADA). Using HbA1c as a screening parameter of T2DM has not been accepted by the ADA until now because of insufficient standardisation and low sensitivity. Nevertheless, since recently published investigations could prove high sensitivity and specificity, HbA1c will gain more attention as a screening parameter. We discuss the meaning of HbA1c as a screening parameter for T2DM and as a predictor of disease progress.