Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

High Thyroid-Stimulating Hormone and Low Free Triiodothyronine Levels Are Associated with Chronic Kidney Disease in Three Population-Based Studies from Germany.

High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. We used cross-sectional data from 7933 individuals aged 20 to 93 years of the Berlin Aging Study II and the Study of Health in Pomerania to associate serum TSH, fT3, and fT4 levels with eGFR and albuminuria. In multivariable analyses adjusted for confounding, we found inverse non-linear associations of serum TSH levels with eGFR, while serum fT3 levels showed a positive association with eGFR. High as well as low serum fT4 levels were associated with a lower eGFR. Age but not sex modified the association between thyroid hormone levels and eGFR. The inverse associations between serum TSH levels and eGFR were strongest in the youngest age groups, while the positive associations between serum fT3 levels and eGFR were strongest in older individuals. No significant associations between thyroid hormone levels and albuminuria were found. Our results indicate that hypothyroidism might be associated with a reduced kidney function. Thyroid function might be more tightly related to the eGFR than to albuminuria in the general population.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Effects of body mass index on the immune response within the first days after major stroke in humans.

INTRODUCTION: Immunological alterations associated with increased susceptibility to infection are an essential aspect of stroke pathophysiology. Several immunological functions of adipose tissue are altered by obesity and are accompanied by chronic immune activation. The purpose of this study was to examine immune function (monocytes, granulocytes, cytokines) as a function of body mass index (BMI: 1st group: 25; 2nd group: 25 BMI 30; 3rd group: 30) and changes in body weight post stroke. METHOD: Fat status was assessed using standardized weight measurements on days 1, 2, 3, 4, 5, and 7 after ischemic stroke in a cohort of 40 stroke patients and 16 control patients. Liver fat and visceral fat were assessed by MRI on day 1 or 2 [I] and on day 5 or 7 [II]. Leukocyte subpopulations in peripheral blood, cytokines, chemokines, and adipokine concentrations in sera were quantified. In a second cohort (stroke and control group, n = 17), multiple regression analysis was used to identify correlations between BMI and monocyte and granulocyte subpopulations. RESULTS: Weight and fat loss occurred from the day of admission to day 1 after stroke without further reduction in the postischemic course. No significant changes in liver or visceral fat were observed between MRI I and MRI II. BMI was inversely associated with IL-6 levels, while proinflammatory cytokines such as eotaxin, IFN-ß, IFN -γ and TNF-α were upregulated when BMI increased. The numbers of anti-inflammatory CD14+CD16+ monocytes and CD16+CD62L- granulocytes were reduced in patients with higher BMI values, while that of proinflammatory CD16dimCD62L+ granulocytes was increased. CONCLUSION: A small weight loss in stroke patients was detectable. The data demonstrate a positive correlation between BMI and a proinflammatory poststroke immune response. This provides a potential link to how obesity may affect the clinical outcome of stroke patients.

Associations of age, sex, and socioeconomic status with adherence to guideline recommendations on protein intake and micronutrient supplementation in patients with sleeve gastrectomy or Roux-en-Y gastric bypass.

INTRODUCTION: Patients with bariatric surgery often show poor long-term compliance to recommendations for prevention of nutrient deficiency but it is unclear which factors contribute. We investigated the associations of age, sex, and socioeconomic status (SES) with adherence to guideline recommendations on protein intake and micronutrient supplementation. METHODS: In a monocentric cross-sectional study we prospectively recruited patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) and a minimum postoperative period of 6 months. Clinical and demographic data were obtained from the patients' medical files and by questionnaire. Patients reported on supplement usage, recorded their dietary intake for seven days and underwent physical examinations including blood testing. RESULTS: We included 35 patients (SG: n = 25, RYGB: n = 10) with a mean (+SD) postoperative period of 20.2 (±10.4) months. Distributions of age, sex and SES were comparable between the SG and RYGB groups. Non-adherence to recommended protein intake was associated with age ≥ 50 years (p = 0.041) but not sex or SES. Protein intake inversely correlated with markers of obesity. There were no significant associations of age or sex with micronutrient supplementation. Only for vitamins A (p = 0.049) and B1 (p = 0.047) higher SES was associated with greater compliance. The only manifest deficiency associated with non-adherence to micronutrient supplementation was that for folic acid (p = 0.044). CONCLUSION: In patients after bariatric surgery, those of older age and of lower SES might have a greater risk of unfavorable outcome and may require greater attention to micronutrient and protein supplementation.

Serum Uromodulin in Children and Adolescents with Type 1 Diabetes Mellitus and Controls: Its Potential Role in Kidney Health.

INTRODUCTION: Uromodulin is a kidney-specific tubular protein, and its assessment in serum (sUMOD) reveals the potential as a novel marker for function and the integrity of renal parenchymal cells and does not directly depend on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are not able to diagnose structural lesions. Recent data show that sUMOD is linked to glucose intolerance in adults. Thus, we launched to assess the hypothesis that sUMOD is also associated with kidney function, biometric data, and quality of metabolic control in children/adolescents with type 1 diabetes. PATIENTS AND METHODS: Patients with type 1 diabetes (n=135) and healthy controls (n=69) were recruited to participate in the trial. Clinical, biometrical data, sUMOD, and other laboratory parameters were assessed. RESULTS: The mean concentrations of sUMOD in diabetic patients and controls were comparable (201.19±103.22 vs. 198.32±84.27 ng/mL, p=0.832). However, in contrast to healthy controls, sUMOD levels in patients with diabetes were associated with serum-creatinine (r=-0.368, p<0.0001), age (r=-0.350, p<0.0001), height (r=-0.379, p<0.0001), body weight (r=-0.394, p<0.0001), Body mass index (r=-0.292, p=0.001), daily insulin dosage (r=-0.300, p<0.0001), HbA1c (%) (r=-0.190, p=0.027), standardized HbA1c/IFCC (mmol/mol) (r=-0.189, p=0.028), and systolic (r=-0.299, p<0.0001) and diastolic (r=-0.235, p=0.006) arterial blood pressure. CONCLUSIONS: Our study shows that children/adolescents with type 1 diabetes disclose similar sUMOD concentrations as healthy controls. Serum UMOD appears to indicate higher risks for kidney tissue remodeling and possibly subsequent cardiovascular alterations. However, further studies are mandatory to settle these findings.

Abdominal Morphologic Changes in MRI during Gastric Balloon Therapy.

INTRODUCTION: Adiposity and excessive weight are on the rise in western industrialized countries. In cases where conservative measures fail and surgical interventions are not (yet) desired, gastric balloon therapy has proven to be a safe and reversible endoscopic method. METHODS: Aside from weight progression under gastric balloon therapy and by using MRI, our research paper describes the behavior of different abdominal body fat compartments at the beginning and at the end of the gastric balloon therapy. Additionally, the volume of the left liver lobe as well as the fill volume and performance of the gastric balloon were analyzed over the duration of treatment. For assessing potential impacts of weight reduction on the muscle mass, we determined the area of the m. psoas on a comparable cross-sectional area at the beginning and at the end of the therapy. RESULTS: We were able to verify a significant reduction of the layer of subcutaneous fat, adipose capsule of the kidney, and intra-abdominal fatty tissue during the therapy. The volume of the left liver lobe was shrinking in addition to a muscle loss during the balloon therapy. The volume of the gastric balloon remained stable (not hyperinflation). There were variable gas bubbles in the gastric balloon. CONCLUSION: The gastric balloon is a temporary and successful option for weight reduction by reducing body fat, liver volume, but also muscle mass.

Malnutrition Is Highly Prevalent in Patients With Chronic Pancreatitis and Characterized by Loss of Skeletal Muscle Mass but Absence of Impaired Physical Function.

Background/Aims: Patients with chronic pancreatitis (CP) have an increased risk of malnutrition, a condition linked to reduced muscle mass and physical performance. We have investigated the risk factors, phenotypic presentation, and health implications associated with malnutrition in CP. Materials and Methods: In a multicenter cross-sectional study we recruited patients with confirmed CP and healthy volunteers as a control group. Malnutrition was diagnosed according to the criteria proposed by the Global Leadership Initiative on Malnutrition. We performed detailed examinations of body composition and physical function as well as testing of routine blood parameters and markers of inflammation. Results: We included 66 patients [mean (±SD) age: 56.0 (±14.5) years; 51 males] and an equal number of age- and sex-matched controls. Moderate malnutrition was diagnosed in 21% (n = 14) and severe malnutrition in 42% (n = 28) of patients. Besides weight loss malnourished patients showed lower fat and skeletal muscle mass compared to both non-malnourished subjects and healthy controls. Only in severe malnutrition, blood parameters reflected elevated inflammation and reduced muscle reserves. Handgrip strength in patients did not differ by nutritional status but there was a significant correlation (rho = 0.705, p < 0.001) with skeletal muscle mass. Although 20 patients (30%) had pathologically reduced skeletal muscle mass, only two individuals (3%) had sarcopenia with concomitantly reduced handgrip strength. Conclusion: Malnutrition is a frequent complication of CP characterized by loss of skeletal muscle mass. As this condition becomes evident only at an advanced stage, regular testing for altered body composition is recommended. Suitable biomarkers and the link between loss of muscle mass and physical function require further investigation. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04474743], identifier [NCT04474743].

Association between thyroid function and assessment of hepatic fat and iron contents by magnetic resonance imaging.

The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

Associations of liver volume and other markers of hepatic steatosis with all-cause mortality in the general population.

AIMS: We examined the associations between liver volume and other quantitative and qualitative markers of hepatic steatosis with all-cause mortality in the general population. METHODS: We included 2769 German middle-aged individuals with a median follow-up of 8.9 years (23,898 person-years). Quantitative markers used were serum liver enzymes and FIB-4 score, while qualitative markers of hepatic steatosis included magnetic resonance imaging (MRI) measurements of liver fat content and total liver volume. Cox proportional hazards models, adjusted for confounding factors, were undertaken to investigate the associations of liver volume and other markers of hepatic steatosis with all-cause mortality. RESULTS: A larger MRI-assessed liver volume was associated with a nearly three-fold increased risk of all-cause mortality (Hazard Ratio = 3.16; 95% confidence interval 1.88; 5.30), independent of age, sex, body mass index, food frequency score, alcohol consumption and education level. This association was consistent in all subgroups considered (men vs. women; presence or absence of overweight/obesity, metabolic syndrome or diabetes). Higher serum liver enzyme levels and FIB-4 score were also significantly associated with higher all-cause mortality in the total population and in all subgroups. No independent associations were found between other quantitative and qualitative markers of hepatic steatosis and the risk of all-cause mortality. CONCLUSIONS: We showed for the first time that larger liver volume was associated with a three-fold increase in long-term risk of all-cause mortality. This association remained significant after adjustment for age, sex, alcohol consumption, obesity and other coexisting metabolic disorders.

Gastric Balloon Implantation as Part of Morbid Adiposity Therapy Changes the Structure of the Stomach Wall.

PURPOSE: The implantation of a gastric balloon (also known as intragastric balloon) is an established and reversible endoscopic procedure for adiposity therapy. Structural changes of the stomach wall are expected to occur with gastric balloon implantation; however, until now these changes have rarely been investigated. METHODS: We compared the histological structure of the stomach wall after gastric-sleeve resection in a group of patients following gastric balloon implantation and a group without previous gastric balloon implantation. RESULTS: Following gastric balloon implantation, the tunica muscularis was found to be significantly thicker than without gastric balloon implantation. The enlarging of the tunica muscularis is not caused by hyperplasia of the leiomyocytes, but by hypertrophy of the leiomyocytes and an increase in collagen fibers (fibrosis). CONCLUSION: A longer-lasting hypertrophy of the tunica muscularis, particularly in the corpus, should be taken into account when surgical treatment follows gastric balloon implantation. The staple suture height should be adjusted to the altered tissue composition since reduced tissue elasticity must be expected due to fibrosis.

Excess Body Weight and Pancreatic Disease.

BACKGROUND: Excess body weight (EBW) is a risk factor for various acute and chronic conditions. Conversely, the "obesity paradox" suggests a protective effect of higher body weight on some disease outcomes. This article discusses the role of EBW along the disease continuum of pancreatitis and pancreatic cancer (PC) in terms of incidence and outcome. SUMMARY: Comparison of findings is hampered by the use of different methods to assess EBW. Nevertheless, in acute pancreatitis (AP) and PC, EBW, especially visceral obesity, presents a distinct risk factor and predictor of a negative outcome. Findings of a protective effect likely result from nonconsideration of fat distribution or other confounders. Regarding chronic pancreatitis (CP), few studies indicate lower incidence and a better outcome with higher body mass. However, there is insufficient evidence to confirm the existence of an obesity paradox. The precise mechanisms of how EBW affects the disease continuum require further elucidation but both common and disease-specific effects seem involved. KEY MESSAGES: EBW is associated with higher incidence and a negative outcome in AP and PC. The association with CP is less conclusive. Thus, maintaining normal weight is advisable at any stage of the disease continuum.

Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly.

Previous studies on the association between thyroid function and body composition are conflicting and showed strong differences across age groups. Our aim was to clarify age-specific associations of serum thyroid-stimulating hormone (TSH) levels with markers of body composition including body mass index (BMI), waist circumference, fat mass (FM), fat-free mass (FFM) and body cell mass (BCM). We used data from two independent population-based cohorts within the framework of the Study of Health in Pomerania. The study population included 5656 individuals aged 20 to 90 years. Markers of body composition were measured by bioelectrical impedance analysis. Serum TSH levels were significantly positively associated with BMI (ß = 0.16; 95% confidence interval [CI]: 0.06 to 0.27), waist circumference (ß = 0.35; 95% CI: 0.08 to 0.62) and FM (ß = 0.32; 95% CI: 0.12 to 0.52), but not with FFM and BCM. Interaction analysis revealed positive associations of serum TSH levels with BMI, waist circumference, FM, FFM and BCM in individuals older than 60 years, while no such associations were observed in younger individuals. We demonstrated that lower serum TSH levels were accompanied with lower values of BMI, waist circumference, FM, FFM, and BCM in the elderly, while no such associations were observed in younger individuals.

Fructose Consumption-Free Sugars and Their Health Effects.

BACKGROUND: The excessive consumption of free sugars, including fructose, is considered a cause of overweight and metabolic syndrome throughout the Western world. In Germany, the prevalence of overweight and obesity among adults (54%, 18%) and children (15%, 6%) has risen in the past few decades and has now become stable at a high level. The causative role of fructose is unclear. METHODS: This review is based on publications retrieved by a selective search in PubMed and the Cochrane Library, with special attention to international guidelines and expert recommendations. RESULTS: The hepatic metabolism of fructose is insulin-independent; because of the lack of a feedback mechanism, it leads to substrate accumulation, with de novo lipogenesis and gluconeogenesis. Recent meta-analyses with observation periods of one to ten weeks have shown that the consumption of fructose in large amounts leads to weight gain (+ 0.5 kg [0.26; 0.79]), elevated triglyceride levels (+ 0.3 mmol/L [0.11; 0.41]), and steatosis hepatis (intrahepatocellular fat content: + 54% [29; 79%]) when it is associated with a positive energy balance (fructose dose + 25-40% of the total caloric requirement). Meta-analyses in the isocaloric setting have not shown any comparable effects. Children, with their preference for sweet foods and drinks, are prone to excessive sugar consumption. Toddlers under age two are especially vulnerable. CONCLUSION: The effects that have been observed with the consumption of large amounts of fructose cannot be reliably distinguished from the effects of a generally excessive caloric intake. Further randomized and controlled intervention trials of high quality are needed in order to determine the metabolic effects of fructose consumed under isocaloric conditions. To lessen individual consumption of sugar, sugary dietary items such as sweetened soft drinks, fruit juice, and smoothies should be avoided in favor of water as a beverage and fresh fruit.

Efficiency of a 15-Week Weight-Loss Program, Including a Low-Calorie Formula Diet, on Glycemic Control in Patients with Type 2 Diabetes Mellitus and Overweight or Obesity.

INTRODUCTION: Patients who are overweight or obese have an increased risk of developing type 2 diabetes mellitus (T2DM). Weight loss can have a positive effect on glycemic control. OBJECTIVE: We aimed to investigate glycemic control in patients with T2DM and overweight or obesity during a structured weight-loss program. METHODS: This was a prospective, interventional study. We recruited 36 patients (14 men and 22 women) with a median age of 58.5 years and median body mass index (BMI) of 34.1, to a 15-week structured weight-loss program with a low-calorie (800 kcal) formula diet for 6 weeks. The primary end point, HbA1c level, and secondary end points, anthropometric data, medication, and safety, were assessed weekly. Laboratory values and quality of life were assessed at baseline and after 15 weeks. RESULTS: HbA1c decreased from 7.3% at baseline to 6.5% at 15 weeks (p < 0.001), median body weight by 11.9 kg (p < 0.001), median BMI by 4.3 (p < 0.001) and median waist circumference by 11.0 cm (p < 0.001). Two participants discontinued insulin therapy, 4 could reduce their dosage of oral antidiabetic agents, and 6 completely discontinued their antidiabetic medication. Insulin dose decreased from 0.63 (0.38-0.89) to 0.39 (0.15-0.70) units/kg body weight (p < 0.001). No patient experienced hypoglycemic episodes or hospital emergency visits. Triglycerides and total cholesterol decreased as well as surrogate markers of liver function. However, the levels of high-density and low-density lipoprotein cholesterol (HDL-C and LDL-C) as well as uric acid remain unchanged. Regarding quality of life, the median physical health score increased from 44.5 (39.7-51.4) at baseline to 48.0 (43.1-55.3; p = 0.007), and the median mental health score decreased from 42.1 (36.1-46.7) to 37.4 (30.3-43.7; p = 0.004). CONCLUSIONS: A structured weight-loss program is effective in the short term in reducing HbA1c, weight, and antidiabetic medication in patients with T2DM who are overweight or obese. Levels of HDL-C and LDL-C were not affected by short-term weight loss. The decline in mental health and the long-term effects of improved glycemic control require further trials.

Quality of life and olfactory function after suprasellar craniopharyngioma surgery-a single-center experience comparing transcranial and endoscopic endonasal approaches.

The endoscopic endonasal approach to suprasellar craniopharyngiomas has become popular as alternative to transcranial approaches. However, the literature lacks data regarding quality of life and olfactory function. The assessment of the long-term quality of life and olfactory function of all patients harboring a suprasellar craniopharyngioma who underwent surgery in our department has been done. Patient characteristics and perioperative data were gathered in a prospectively maintained database. At the last follow-up visit, the olfactory function and the quality of life (ASBQ, SNOT-22) as well as visual and pituitary function were assessed. Thirteen and 17 patients underwent surgery via a transcranial (T) and endonasal (E) route, respectively. No differences were seen in ASBQ, SNOT-22, and olfactory function between T and E, but in E were more full-time worker and less obesity. CSF leaks occurred in 15% of T and 29% of E (p = 0.43). Patients from group E had a superior visual outcome which was most pronounced in the visual field. The degree of new anterior and posterior pituitary gland deficiency after surgery and in the follow-up was lower in group E. The general and sinonasal quality of life and the olfactory function are equal in E and T. E is associated with a superior visual outcome, lower rates of diabetes insipidus, and lower rates of obesity, but has a higher risk for postoperative CSF leaks.

Is the Obesity Paradox in Type 2 Diabetes Due to Artefacts of Biases? An Analysis of Pooled Cohort Data from the Heinz Nixdorf Recall Study and the Study of Health in Pomerania.

AIMS/HYPOTHESIS: There is controversy on whether an obesity paradox exists in type 2 diabetes, ie, that mortality is lowest in overweight or obesity. We examined the role of potential biases in the obesity paradox. METHODS: From two regional population-based German cohort studies - the Heinz Nixdorf Recall Study and the Study of Health in Pomerania (baseline examinations 2000-2003/1997-2001) - 1187 persons with diabetes at baseline were included (mean age 62.6 years, 60.9% males). Diabetes was ascertained by self-report of physician's diagnosis, antidiabetic medication, fasting/random glucose or haemoglobin A1c. Mortality data were assessed for up to 17.7 years. We used restricted cubic splines and Cox regression models to assess associations between body mass index (BMI) and mortality. Sensitivity analyses addressed, inter alia, exclusion of early death cases, of persons with cancer, kidney disease or with history of cardiovascular diseases, and of ever smokers. Furthermore, we examined the role of treatment bias and collider bias for the obesity paradox. RESULTS: In spline models, mortality risk was lowest for BMI at about 31 kg/m2. Sensitivity analyses carried out one after another had hardly any impact on this result. In our cohort, persons with diabetes and BMI ≥30 kg/m2 did not have better treatment than non-obese patients, and we found that collider bias played only a minor role in the obesity paradox. CONCLUSION: In a cohort of 1187 persons with diabetes, mortality risk was lowest in persons with moderate obesity. We cannot explain this result by a variety of sensitivity analyses.

Rehabilitation in Germany 2004-2016 A Multicenter Analysis Over a Period of 13 Years in Children and Adolescents with Diabetes Mellitus.

In the treatment of children/adolescents with diabetes medical rehabilitation plays an important role. It was the aim of the survey to analyze trends in the number of patients admitted to rehabilitation, the quality of diabetes care, the incidence of acute complications, risk factors for cardiovascular co-morbidities like lipids and blood pressure and the familial status nationwide and over a period of 13 years. METHODS: Currently seven hospitals offer in-patient rehabilitation for children/adolescents with diabetes in Germany. Six hospitals participated in the survey. All children/adolescents (n=7.163) who participated in an in-patient rehabilitation 01/01/2004-31/12/2016 were included. Clinical/familial data were assessed: age, sex, family situation, type/duration of diabetes, insulin dosage, self-monitoring, acute complications, height, body weight, blood pressure and laboratory parameters. For collecting and storage of data the computer software DPV® (Diabetes-Patienten-Verlaufsdokumentation, University of Ulm, Germany) was used. Statistical analyses were performed using the programme SAS (Statistical Analysis Software 9.4, SAS Institute Inc, Cary, North Carolina, USA). RESULTS: During the study period 7.163 patients took part in 10.987 in-patient rehabilitation procedures. The yearly number of patients participating in rehabilitation remained stable. There was no change in the quality of diabetes control (HbA1c: p=0.30, fasting blood glucose: p=0.80). The incidence of severe hypoglycaemia decreased (p<0.001). The incidence of ketacidosis remained stable (p=0.18). The frequency of blood glucose self-monitoring increased (p<0.001). The same was true for patients treated with CSII (p<0.001), whereas the numbers of patients treated with CT or ICT decreased (both p<0.001). There was no change in patients' total insulin dose (p=0.01). There was a decrease of the number of patients living with both parents (p<0.001), the percentage of children/adolescents living with mother or father alone increased (p<0.001). The percentage of children/adolescents living in mixed cultural families or having a background of immigration increased (p<0.001). CONCLUSIONS: There is a change in medical rehabilitation: The number is stable, the proportion of patients using CSII increased, the number of patients living with single parents and the percentage of patients from culturally mixed families increased also.

Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP.

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation. Alterations in BDNF signaling are related to the development of cardiovascular disease. Whether BDNF is related to subclinical cardiac remodeling is unclear. We related BDNF with echocardiographic parameters and NTproBNP in a large population-based cohort (n = 2,976, median age 48 years; 45% male). Transthoracic echocardiography was performed on all subjects and BDNF was measured by ELISA. Study participants with severe kidney dysfunction, previous myocardial infarction, and LV ejection fraction <40% were excluded. Linear regression models were adjusted for age, sex, lean mass, fat mass, current smoking, systolic blood pressure and depression. Low BDNF was associated with high NTproBNP. A 10,000 pg/ml lower BDNF was related with a 2.5 g higher (95%-confidence interval [CI]: 0.2 to 4.9; p = 0.036) LV mass, 0.01 cm posterior wall thickness (0.003 to 0.022; p = 0.007) and 0.02 E/A ratio (0.003 to 0.042, p = 0.026). Here we show that low BDNF levels are related with adverse cardiac remodeling and higher levels of NTproBNP. Further research is warranted to assess if BDNF may be used to monitor neuronal-cardiac damage during CVD progression.