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Langerhans cell histiocytosis is a rare inflammatory bone marrow neoplasia that frequently affects bone, lung, skin and pituitary gland. Due to its broad spectrum of clinical presentation, an appropriate diagnosis might be difficult.A 54-year-old female patient complained of pain in her right ear for 5 months. On account of similar complaints, a mastoidectomy had already been performed 3 years ago. Histology at that time revealed nonspecific inflammation. Furthermore, she reported excessive thirst.Computed tomography of the temporal bones showed osteolysis in the mastoid. Magnetic resonance imaging and bone scintigraphy assessed these changes as uncharacteristically inflammatory. Polydipsia proved to be a symptom of central diabetes insipidus in the water deprivation test. Finally, remastoidectomy provided histologic evidence of Langerhans cell histiocytosis.Besides systemic chemotherapy with cytarabine, the patient also received denosumab and desmopressin.Langerhans cell histiocytosis involving cranial bones is often associated with diabetes Insipidus. Knowledge about the distinctive constellation may lead to a more rapid diagnosis and improved prognosis.Die Langerhans-Zell-Histiozytose ist eine seltene inflammatorische Knochenmarks-Neoplasie, die häufig Knochen, Lunge, Haut und Hypophyse befällt. Aufgrund der vielfältigen Klinik wird die Diagnose meist spät gestellt.Eine 54-jährige Patientin klagte über Ohrenschmerzen rechts seit 5 Monaten. Wegen ähnlicher Beschwerden wurde vor 3 Jahren bereits eine Mastoidektomie durchgeführt. Die Histologie ergab damals eine unspezifische Entzündung. Neu aufgetreten war eine Polydipsie.Die Computertomografie der Schläfenbeine ergab Osteolysen im Mastoid. In der Magnetresonanztomografie und Knochenszintigrafie wurden diese Veränderungen als uncharakteristisch entzündlich gewertet. Die Polydipsie erwies sich im Durstversuch als Symptom eines zentralen Diabetes insipidus. Schließlich gelang durch die Remastoidektomie der histologische Nachweis einer Langerhans-Zell-Histiozytose.Die Patientin erhielt neben einer systemischen Chemotherapie mit Cytarabin noch Denosumab und Desmopressin.Eine Langerhans-Zell-Histiozytose mit Befall von Schädelknochen geht häufig mit einem Diabetes insipidus einher. Das Wissen um diese typische Konstellation kann zu einer rascheren Diagnosefindung führen und so die Prognose verbessern.

Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

Introduction: While vitamin deficiency after bariatric surgery has been repeatedly described, few studies have focused on adequate micronutrient status. In this study, we examine the prevalence of vitamin and micronutrient deficiency for the first 3 years after surgery. Methods: Out of 1,216 patients undergoing surgery, 485 who underwent postoperative follow-up in an outpatient clinic between 2010 and 2019 were included in this evaluation (76.9% women, mean age 42 ± 12 years, mean BMI: year 1, 33.9 ± 19.2; year 2, 29.7 ± 8.7; year 3, 26.2 ± 4.0). Weight and cardiovascular risk factors as well as ferritin, vitamin B12, folic acid, 25-OH-vitamin D, vitamin A, vitamin E, zinc, copper, and selenium were evaluated. Deficits were defined as follows: ferritin Results: One year after bariatric surgery, 485 patients completed follow-up. This number decreased to 114 patients in year 2, and 80 patients in year 3. Overall, 42.7% (n = 207) underwent sleeve gastrectomy, 43.7% (n = 211) Roux-en-Y-gastric bypass, and 13.9% (n = 67) gastric banding. The following deficits were found (year 1/2/3): ferritin, 21.6/35.0/32.5%; vitamin B12, 14.3/1.8/6.3%; folic acid, 29.7/21.6/15.3%; 25-OH-vitamin D, 70.8/67.0/57.4%; vitamin A, 13.2/8.9/12.8%; vitamin E, 0%; zinc, 1.7/0/1.5%; copper, 10.4/12.2/11.9%; selenium, 11.1/4.3/0%. Conclusion: As seen in other studies, the follow-up frequency decreased over the years. Despite intensive substitution, the extent of some deficiencies increased or did not improve. These results suggest reinforcing measures to motivate patients for regular follow-up visits, considering closer monitoring schedules, and improving supplementation strategies.

Introduction: Stunkard’s figure rating scale is a widely used tool to assess weight status and, more recently, body image perception in people with obesity. However, large population-based studies on Europeans linking this scale’s silhouettes with measured BMI values are lacking. Therefore, we used measured weight and height data from the Swedish Obese Subjects (SOS) reference cohort to assign a mean BMI to each of the 9 Stunkard Scale silhouettes and to define silhouette cutoff values for categorizing people with obesity and overweight. Methods: A total of 1,128 participants from the SOS reference cohort were included (54% females, BMI = 25.2 [ranging from 17.6 to 45.4] ±3.8 kg/m2, and age = 50 [ranging from 36 to 62] ±7 years [means ± standard deviation]). Patients estimated their own body size by choosing a silhouette of the Stunkard Scale. A mean BMI, based on measured weight and height, was assigned to each male and female silhouette of the Stunkard Scale. Measured BMI values were compared with BMI values calculated by simple linear regression analysis. ROC analysis was used to test accuracy of discrimination and the Youden index to assess optimal cutoff. Results: Figure ratings and BMI were strongly correlated in men, r (518) = 0.76, p < 0.001 and women, r (606) = 0.80, p < 0.001. Silhouette selection significantly predicted BMI values in men, β = 16.03, t (518) = 25.30, p < 0.001, and women, β = 12.06, t (606) = 32.98, p < 0.001, and explained a significant proportion of variance in BMI values in men, R2 = 0.55, F (1, 518) = 639.98, p < 0.001, and women, R2 = 0.64, F (1, 606) = 1,087.88, p < 0.001. ROC curve analyses resulted in an optimal cutoff value of 6 for identifying people with obesity and 5 for overweight. Conclusion: Stunkard’s figure rating scale can be used with confidence to assess weight status. Silhouette selection accurately classifies subjects as overweight or obese.

Objectives: The frequency of postprandial hypoglycaemia after different operative procedures of bariatric surgery (BS) is unknown, although this complication is potentially dangerous. Predictors and severity of hypoglycaemia after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and gastric banding were investigated in a large prospective study. Methods: This study was performed at an excellence centre for BS at a tertiary care institution. Data of 333 patients (mean BMI: 44.9 ± 9.6 kg/m2; mean age: 40 ± 10 years; 80.7% women) were analysed in a prospective study with a 2-year observation period after BS. All patients underwent a 2-hour oral glucose tolerance test (OGTT) with measurements of blood glucose (BG) and insulin. For the purpose of this study, hypoglycaemia was defined as a post-challenge BG Results: 72 (25.6%) of 281 patients showed post-challenge hypoglycaemia after surgery. Hypoglycaemia was different after various procedures: 32.6% of patients after RYGB, 22.6% after sleeve gastrectomy, but only 2.3% after gastric banding had hypoglycaemia. In the whole group, patients with hypoglycaemia had lost more weight (p = 0.013), had a slightly greater decrease in BMI (p = 0.037), a greater change in 2-hour post-challenge BG (p = 0.001), and a smaller change in 1-hour post-challenge insulin (p = 0.004) compared to patients without hypoglycaemia. Conclusion: This prospective study shows a higher prevalence of severe hypoglycaemia (25.6%) after BS than anticipated from retrospective registers. A systematic evaluation of glucose and insulin levels by OGTT 2 years post-surgery may help to identify patients at increased risk for symptomatic and asymptomatic hypoglycaemia.

Background and aims Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. Methods and results In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35–63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. Conclusion We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.

Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors. Methods: In this open-label, parallel-group, multicentre (122 sites), multinational (13 countries), phase 3 study, eligible participants (aged ≥18 years) had a baseline glycated haemoglobin (HbA1c) of 7·0-10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec, and were stratified by country, HbA1c, and concomitant use of oral antihyperglycaemic medications. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (

Introduction: Cortisol is involved in the regulation of gluconeogenesis and glucose utilization. In morbid obesity (MO), the association of cortisol excretion with metabolic parameters is not well-characterized. In our study, we evaluated cortisol excretion in nondiabetic subjects with MO and its effect on glucose metabolism. Methods: We included 1,249 nondiabetic patients with MO (79.8% females, mean BMI 44.9 ± 6.5 kg/m2, mean age 38 ± 11 years). Anthropometric data and cardiovascular risk factors were assessed, and an oral glucose tolerance test for calculation of insulin resistance was performed. Cortisol excretion was assessed on 2 consecutive days (24 h urine specimens). Results: Regarding cortisol excretion, patients were divided into 3 tertiles (urinary cortisol ≤51.6, >51.6 and p = 0.003), more obese (BMI: p = 0.040), had lower diastolic blood pressure ([DBP]; p = 0.012), lower total (p = 0.032) and LDL cholesterol (p = 0.021), fasting (p = 0.049) and 2-h glycemia (p = 0.028), 2-h insulinemia (p = 0.020), and HbA1c (p < 0.001), and a higher estimated glomerular filtration rate (eGFR) (p < 0.001). The glucose (p < 0.001) and insulin (p = 0.011) area under the curve (AUC) were also lower. Urinary cortisol excretion adjusted for age, sex, and eGFR was positively correlated with body weight (BW, beta = 0.076, p = 0.004) and overall glucose tolerance (oral disposition index, beta = 0.090, p = 0.011), and negatively with HbA1c (beta = −0.179, p < 0.001), 2-h glycemia (beta = −0.075, p = 0.032), AUC glucose (beta = −0.103, p = 0.002), and DBP (beta = −0.139, p < 0.001). HbA1c, BW, and DBP remained significant after multivariable analysis. Discussion/Conclusion: Despite being more obese, patients with higher cortisol excretion have a more favorable metabolic profile. These results deserve further attention regarding the respective mechanisms.

The changes in depressive symptomatology during the first year following one-anastomosis gastric bypass (OAGB) were evaluated and its association with uric acid (sUA). Fifty patients were included in this analysis. Beck Depression Inventory (BDI) for measuring depressive symptomatology, blood samples, and anthropometric measurements were assessed before (T0), at 6 (T6), and 12 months (T12) after surgery. There was a significant reduction in BDI total score at T6 (− 5.6 (95% CI − 2.1, − 9.1) points; p = 0.001) and at T12 (− 4.3 (95% CI − 0.9, − 7.9) points; p = 0.011). BMI loss was unrelated to depressive symptomatology. Patients with moderate to severe depressive symptomatology presented lower sUA levels than patients with none or minimal to mild (p = 0.028). ROC analysis revealed that sUA levels below 5.0 at T6 and 4.5 mg/dl at T12 had a prognostic accuracy for depression severity. Furthermore, delta sUA was significantly associated with delta BMI (β = 0.473; p = 0.012) and delta waist circumference (β = 0.531; p = 0.003). These findings support an improvement in depressive symptomatology in the first year postoperatively, however, without relation to BMI loss. Patients with moderate to severe depressive symptomatology presented with lower sUA levels over time. Therefore, sUA could be useful to predict moderate to severe depressive symptomatology in patients undergoing OAGB in clinical practice.

Bariatric patients often suffer from vitamin D (VD) deficiency, and both, morbid obesity and VD deficiency, are related to an adverse effect on cardiovascular disease (CVD) risk. Therefore, we assessed the change of known CVD risk factors and its associations during the first 12 months following one-anastomosis gastric bypass (OAGB).In this secondary analysis, CVD risk factors, medical history and anthropometric data were assessed in fifty VD deficient (25-hydroxy-vitamin D (25(OH)D)75 nmol/l) patients, recruited for a randomized controlled trial of VD supplementation. Based on previous results regarding bone-mass loss and the association between VD and CVD risk, the study population was divided into patients with 25(OH)D ≥50 nmol/l (adequate VD group; AVD) and into those50 nmol/l (inadequate VD group; IVD) at 6 and 12 months (T6/12) postoperatively. In the whole cohort, substantial remission rates for hypertension (38%), diabetes (30%), and dyslipidaemia (41%) and a significant reduction in CVD risk factors were observed at T12. Changes of insulin resistance markers were associated with changes of total body fat mass (TBF%), 25(OH)D, and ferritin. Moreover, significant differences in insulin resistance markers between AVD and IVD became evident at T12.These findings show that OAGB leads to a significant reduction in CVD risk factors and amelioration of insulin resistance markers, which might be connected to reduced TBF%, change in 25(OH)D and ferritin levels, as an indicator for subclinical inflammation, and an adequate VD status. REGISTERED AT CLINICALTRIALS.GOV: (Identifier: NCT02092376) and EudraCT (Identifier: 2013-003546-16).

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

Patients with obesity and type 2 diabetes mellitus (T2DM) are regarded to have reduced serum magnesium (Mg) concentrations. We aimed to assess the changes in serum Mg concentrations at 12-month follow-up in patients, with and without T2DM, who underwent one anastomosis gastric bypass surgery. Overall, 50 patients (80% female, age 42.2 (12.5) years) with morbid obesity (mean baseline BMI 43.8 (4.3) kg/m2) were included in the analysis. Half of the included patients had T2DM diagnosed at baseline, and these patients showed lower serum Mg concentration (0.78 (0.07)) vs. 0.83 (0.05) mmol/L, p = 0.006), higher blood glucose levels (129.9 (41.3) vs. 87.6 (8.1) mg/dL, p &lt, 0.001) as well as HbA1c concentrations (6.7 (1.4) vs. 5.3 (0.5)%, 0.001). During follow-up, BMI and glucose levels showed a decrease, however, serum Mg levels remained stable. At baseline 42% of patients were found to be Mg deficient, which was reduced to 33% at six months and to 30% at 12 months follow-up. Moreover, patients with T2DM had an odds ratio of 9.5 (95% CI = 3.0&ndash, 29.7, 0.001) for magnesium deficiency when compared to patients without T2DM. Further research into the role of Mg and its role in T2DM and other obesity-related comorbidities are needed.

Patients with morbid obesity are at an increased risk for cardiovascular and renal complications, which are not only linked to traditional cardiovascular risk factors. Thus, we evaluated (a) the prevalence of albuminuria in non-diabetic and diabetic morbidly obese patients and (b) the effect of weight loss following bariatric surgery. We included 1307 patients (77% women, mean age 40 ± 12 years, BMI 45.6 ± 6.6 kg/m2) in a cross-sectional study. A subgroup (n = 318) was followed up for 2 years after bariatric surgery. Weight, cardiovascular risk markers and a 75-g glucose tolerance test were determined. Albuminuria was assessed by collecting 24-h urine on three consecutive days. In the cross-sectional study, the prevalence of microalbuminuria was 16.0% (n = 209), of macroalbuminuria 3.1% (n = 41). The chi-square for the association of albuminuria and diabetes was 31.937 (p

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

Evidence demonstrates that medical diabetes treatment has to be accompanied by lifestyle modifications. Structured nutrition interventions and increased physical activity will help patients to normalise, respectively maintain their body weight.The main target of a medical nutrition therapy aims at achieving normal or nearly normal blood glucose levels, prevention of delay of diabetes associated complications.

Diabetes education and self-management play a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and subsequent treatment modification as well as the ability of patients to integrate diabetes into their daily life and to appropriately adapt it to their life style situation. Diabetes education has to be made accessible for all persons with the disease. In order to be able to provide a structured and validated education program, adequate personnel as well as space, organizational and financial prerequisites are required. Besides an increase in knowledge about the disease it has been shown that a structured diabetes education is able to improve diabetes outcome as measured by parameters, such as blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes into everyday life, stress physical activity besides healthy eating as important components of life style therapy and use interactive methods in order to increase the acceptance of personal responsibility. Specific situations (e. g. impaired hypoglycemia awareness, illness, travel) and technical innovations, such as glucose sensor systems and insulin pumps require additional educational measures by information exchange in small groups supported by adequate electronic tools (diabetes apps and diabetes web portals).

The article deals with the demographic data of migration in Austria and with therapeutic advice concerning drug therapy and diabetes education for patients with migration background. In this context sociocultural specifics are discussed. These suggestions are seen complementary to the general treatment guidelines of the Austrian Diabetes Association.The fasting month Ramadan is widely practiced by the Muslim population worldwide. Ensuring the optimal care of the many people with diabetes who fast during Ramadan is crucial. The IDF-DAR Practical Guidelines (International Diabetes Federation - Diabetes and Ramadan International Alliance) provide healthcare professionals with relevant background information and practical recommendations to enable them to help patients with diabetes participate in fasting during Ramadan while minimizing the risk of complications.

This guideline summarizes diagnosis of type 1 diabetes, including accompanying autoimmune disorders, insulin therapy regimens and glycemic target values.

For several years obesity and type 2 diabetes have been increasingly summarized under the name "diabesity". This is due to the fact that in most cases obesity precedes diabetes and is the most important risk factor for the worldwide increase of type 2 diabetes. The body mass index (BMI) is a very crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of a lack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e. g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type 2 diabetes, body weight is increasingly used as a secondary target parameter. The choice of anti-diabetic treatment and also concomitant treatment is increasingly influenced by body weight. The significance of anti-obesity medications in the treatment of type 2 diabetes will have to be clarified by future studies with body weight as the primary endpoint. Bariatric surgery is at present indicated with a BMI35 kg/m

Objective: Structured obesity treatment programs at primary care level are becoming increasingly important. However, evidence from current treatment approaches in the long term is lacking. In view of this fact we evaluated a standardized, meal replacement-based weight loss program (myLINE®; AENGUS, Graz, Austria) according to the currently applicable guidelines. Methods: Data of overweight and obese individuals (n = 70) who participated at least 36 months in the program were analyzed. Data were collected at baseline (T0) as well as after 1, 3, 6, 12, 24, and 36 (T1-T36) months. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis. Results: Compared to T0, a maximum weight, BMI, fat mass, absolute body cell mass (BCM) reduction and an increase of relative BCM could be seen at T6. Subsequently, the findings reveal a significant reduction of body weight and body fat and a satisfying development of body cell mass during the observation period of 36 months. Conclusion: The evaluated program complies with national and international guidelines for the therapy of obesity in adults and is efficient and meaningful for a long-term therapeutic use in primary care..

Summary In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The “Austrian Lipid Consensus – 2016 update” provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

Background Morbidly obese patients are at risk for non-alcoholic fatty liver disease (NAFLD) and vitamin D deficiency (VDD). Non-alcoholic steatohepatitis (NASH) is the progressive variant of NAFLD and can advance to fibrosis, cirrhosis, and liver cancer. We aimed to examine prevalence of liver fibrosis and its non-invasive predictors in bariatric patients with VDD (

Summary Background Semaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) analogue for type 2 diabetes. Few clinical trials have reported on the concomitant use of GLP-1 receptor agonists with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We aimed to investigate the efficacy and safety of semaglutide when added to SGLT-2 inhibitor therapy in patients with inadequately controlled type 2 diabetes. Methods The SUSTAIN 9 double-blind, parallel-group trial was done at 61 centres in six countries (Austria, Canada, Japan, Norway, Russia, and the USA). Adults with type 2 diabetes and HbA1c 7·0–10·0% (53–86 mmol/mol), despite at least 90 days of treatment with an SGLT-2 inhibitor, were randomly assigned (1:1) to receive subcutaneous semaglutide 1·0 mg or volume-matched placebo once weekly for 30 weeks, after a dose-escalation schedule of 4 weeks of 0·25 mg semaglutide or placebo and 4 weeks of 0·5 mg semaglutide or placebo. Existing antidiabetic medications, including SGLT-2 inhibitor treatment, were continued for the duration of the trial. Rescue medication, defined as intensification of background antidiabetic treatment or the initiation of new glucose-lowering medications, could be given to patients meeting specific criteria at the discretion of the investigator. The primary outcome was change in HbA1c from baseline at week 30, assessed in the full analysis set (all patients randomly allocated to treatment) using on-treatment data collected before rescue medication was started. The confirmatory secondary outcome was change in bodyweight from baseline to week 30. Safety was also assessed in the safety analysis set (all patients who received at least one dose of treatment). The trial was registered with ClinicalTrials.gov ( NCT03086330 ). Findings Between March 15, and Dec 4, 2017, 302 patients were enrolled and randomly assigned to receive semaglutide 1·0 mg or placebo (full analysis set), of whom 301 received at least one dose of treatment (safety analysis set). One patient was assigned to semaglutide but was not treated (reason unknown). 294 (97·4%) patients completed the trial and 267 (88·4%) completed treatment. Baseline characteristics were generally comparable between groups. In addition to randomised medication and SGLT-2 inhibitor, 216 (71·5%) patients were taking metformin and 39 (12·9%) were taking sulphonylurea. Patients given semaglutide had greater reductions in HbA1c (estimated treatment difference −1·42% [95% CI −1·61 to −1·24]; −15·55 mmol/mol [–17·54 to −13·56]) and bodyweight (−3·81 kg [–4·70 to −2·93]) versus those randomised to placebo (both p Interpretation Adding semaglutide to SGLT-2 inhibitor therapy significantly improves glycaemic control and reduces bodyweight in patients with inadequately controlled type 2 diabetes, and is generally well tolerated. Funding Novo Nordisk.

Little is known about changes in bone mineral density (BMD) following weight loss after one-anastomosis gastric bypass (OAGB) and the role of serum vitamin D and its supplementation on bone metabolism. We evaluated BMD after OAGB as a function of vitamin D supplementation with respect to a minimum threshold of 25-hydroxy-vitamin-D [25(OH)D] concentration, which could prevent or decelerate an eventual bone loss. Fifty bariatric patients who participated in the randomized controlled trial were included in this analysis. BMD and anthropometric measurements by DXA and laboratory parameters were assessed before (T0), at 6 (T6), and 12 months (T12) after surgery. OAGB resulted in a 36% total body weight loss with a decrease in body fat and an increase in lean body mass. A significant decrease in BMD was seen in lumbar spine by 7%, left hip 13%, and total body 1%, but not in forearm. Bone turnover markers increased significantly but with normal parathyroid hormone concentrations. Weight loss was not associated with changes in BMD. A serum 25(OH)D concentration > 50 nmol/l at T6 and T12 (adequate-vitamin-D-group; AVD) showed a significant lower bone loss, compared to the inadequate-vitamin-D-group (IVD

The prevalence of obesity is growing worldwide, and strategies to overcome this epidemic need to be developed urgently. Bariatric surgery is a very effective treatment option to reduce excess weight and often performed in women of reproductive age. Weight loss influences fertility positively and can resolve hormonal imbalance. So far, guidelines suggest conceiving after losing maximum weight and thus recommend conception at least 12–24 months after surgery. As limited data of these suggestions exist, further evidence is urgently needed as well for weight gain in pregnancy. Oral glucose tolerance tests for the diagnosis of gestational diabetes mellitus (GDM) should not be performed after bariatric procedures due to potential hypoglycaemic adverse events and high variability of glucose levels after glucose load. This challenges the utility of the usual diagnostic criteria for GDM in accurate prediction of complications. Furthermore, recommendations on essential nutrient supplementation in pregnancy and lactation in women after bariatric surgery are scarce. In addition, nutritional deficiencies or daily intake recommendations in pregnant women after bariatric surgery are not well investigated. This review summarizes current evidence, proposes clinical recommendations in pregnant women after bariatric surgery, and highlights areas of lack of evidence and the resulting urgent need for more clinical investigations.

Recently, SFRP4 was identified as a molecular link between islet inflammation and defective insulin secretion. Gene co-expression analysis detected a molecule associated with type 2 diabetes mellitus (T2D), elevated HbA1c, and reduced insulin secretion in mice as well as in a pilot sample of humans. To our knowledge SFRP4 has never been investigated in patients with different types of diabetes. We included 179 patients: 46 with type 1 diabetes (T1D), 30 age matched healthy controls for patients with T1D (CO-T1D), 55 with T2D, 37 with latent autoimmune diabetes of the adult (LADA) and 30 healthy controls (CO) for patients with T2D and LADA. Apart from anthropometric data, lipids and renal parameters were assessed. SFRP4 levels were measured by a commercial ELISA. Patients with diabetes had significant higher SFRP4 levels than CO: T2D vs. CO: 37.1±26.7 vs. 8.8±3.0 ng/ml, p0.001; LADA vs. CO: 15.6±6.2 vs. 8.7±3.0 ng/ml, p0.001; T1D vs. CO-T1D: 24.6±17.9 vs. 16.9±4.5 ng/ml, p=0.011. SFRP4 levels were correlated with age, BMI, HbA1c, HDL-cholesterol, and triglycerides. A multivariate model revealed HDL-cholesterol, triglycerides and BMI as predictors for SFRP4. This is the first study demonstrating that SFRP4 is significantly increased in patients with different types of diabetes suggesting that this protein is generally involved in islet dysfunction and potentially subclinical inflammation irrespective of type of diabetes.

Aims: Optimal diabetes care requires clear understanding of the incidence of hypoglycaemia in real-world clinical practice. Current data on hypoglycaemia are generally limited to those reported from randomised controlled clinical trials. The Hypoglycaemia Assessment Tool (HAT) study, a non-interventional real-world study of hypoglycaemia, assessed hypoglycaemia in 27 585 individuals across 24 countries. The present study compared the incidence of hypoglycaemia from the HAT study with other similarly designed, large, real-world studies. Materials and Methods: A literature search of PubMed (1995-2017) for population-based studies of insulin-treated patients with type 1 or type 2 diabetes (T1D, T2D), excluding clinical trials and reviews, identified comparable population-based studies reporting the incidence of hypoglycaemia. Results: The 24 comparative studies, including more than 24 000 participants with T1D and more than 160 000 participants with T2D, varied in design, size, inclusion criteria, definitions of hypoglycaemia and method of recording hypoglycaemia. Reported rates (events per patient-year [PPY]) of hypoglycaemia were higher in patients with T1D than in those with T2D (overall T1D, 21.8-73.3 and T2D, 1.3-37.7; mild/non-severe T1D, 29.0-126.7 and T2D, 1.3-41.5; severe T1D, 0.7-5.8 and T2D, 0.0-2.5; nocturnal T1D, 2.6-11.3 and T2D, 0.38-9.7) and were similar to the ranges found in the HAT study. Conclusions: The HAT data on hypoglycaemia incidence were comparable with those from other real-world studies and indicate a high incidence of hypoglycaemia among insulin-treated patients. Differences in rates among studies are mostly explained by differences in patient populations and study methodology. The goal of reducing hypoglycaemia should be a target for continued educational and evidence-based pharmacological interventions.

Summary Background Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. Methods AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg, dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Findings Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to dulaglutide 1·5 mg (n=142), dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger in patients receiving dulaglutide (least squares mean [LSM] for dulaglutide 1·5 mg −1·34% [SE 0·06] or −14·7 mmol/mol [0·6]; dulaglutide 0·75 mg −1·21% [0·06] or −13·2 mmol/mol [0·6]) than in patients receiving placebo (−0·54% [0·06] or −5·9 mmol/mol [0·6]; p vs placebo). The LSM differences were −0·79% (95% CI −0·97 to −0·61) or −8·6 mmol/mol (−10·6 to −6·7) for dulaglutide 1·5 mg and −0·66% (−0·84 to −0·49) or −7·2 mmol/mol (−9·2 to −5·4) for dulaglutide 0·75 mg (p vs seven [5%] in the dulaglutide 0·75 mg group vs five [4%] in the placebo group), diarrhoea (eight [6%] vs 14 [10%] vs four [3%]), and vomiting (five [4%] vs four [3%] vs one [1%]) were more common with dulaglutide than with placebo. One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group. Two (1%) patients receiving dulaglutide 1·5 mg died, but these deaths were not considered to be related to study drug; no deaths occurred in the other groups. Interpretation Dulaglutide as add-on treatment to SGLT2 inhibitors (with or without metformin) resulted in significant and clinically relevant improvements in glycaemic control, with acceptable tolerability that is consistent with the established safety profile of dulaglutide. Funding Eli Lilly and Company.

Postoperative micronutrient deficiency is a known side effect of bariatric surgery. In this study, we examined the prevalence of micronutrient deficiency in patients with morbid obesity (MO) preoperatively. A total of 1732 patients with MO wishing to undergo bariatric surgery (age: 40 ± 12 years, mean BMI: 44 ± 9 kg/m2, means ± SD, 77.3% female) were analyzed in this cross-sectional examination. Iron state, vitamin B12, folic acid, 25hydroxy(OH)-vitamin D, PTH, vitamin A, and vitamin E levels were determined. Subsequently, patients underwent nutritional counseling and were substituted accordingly. A total of 63.2% (n = 1094) of the patients had a deficit in folic acid ( 56.9 pg/ml). A total of 5.1% (n = 88) of the patients presented with a deficit in vitamin B12 (

Summary Introduction The purpose of this study was the evaluation of a weight loss program in primary care settings with respect to the European Clinical Practice Guidelines for the Management of Obesity in Adults with regard to the long-term success of changes in body weight and composition. Methods Overweight and obese patients (n = 1167) who underwent a standardized meal replacement-based weight loss program (myLINE®, AENGUS, Austria) in primary care settings were included in this evaluation. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis (AKERN BIA101®, BIACORPUS RX4000®, SoftwareBodycomp Version 8.4 Professional). Data of patients who participated at least 12 months in the program were analyzed retrospectively and compared with their baseline data. Results After 12 months, a weight loss of 8.6 ± 7.5 kg (mean ± standard deviation) or 8.2 ± 7.8 % from baseline was seen (p p p p Conclusion The evaluated program complies with the European Clinical Practice Guidelines for Management of Obesity in Adults (2008), which recommend a weight reduction of 5–15 % from initial weight within 6 months. Furthermore, the data showed a significant reduction of body fat and a relative increase of body cell mass.

Objective: Cushing's syndrome (CS) is extremely rare in morbidly obese patients. To date, no occurrences in obese patients with BMI above 60 kg/m2 have been reported in the literature. Case Report: This case report describes a patient who was admitted to the ward of the Clinical Division of Endocrinology and Metabolism of the Medical University of Vienna in preparation for bariatric surgery. The patient was a 49-year-old female who showed morbid obesity (BMI 61.6 kg/m2), hypertension, and substituted hypothyroidism. Preoperative work-up revealed CS due to an adrenal adenoma. Therefore, the patient underwent unilateral adrenalectomy followed by bariatric surgery 6 months later. Conclusion: Since undiagnosed CS might result in severe perioperative complications in a population already at increased risk, this case report underlines the importance of careful endocrine evaluation of morbidly obese patients. After all, even rare endocrine causes should be excluded.

Background Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level. Method An analysis of 40 patients who had had detailed longitudinal studies for 12 months. Results Twenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of −15 ± 2.1 mmol/mol (−1.39 ± 0.20%), −16 ± 2.2 mmol/mol (−1.48 ± 0.20%) and −14 ± 3.0 mmol/mol (−1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of −7 ± 1.7 mmol/mol (−0.66 ± 0.16%), −5 ± 1.6 mmol/mol (−0.44 ± 0.18%) and −5 ± 1.7 mmol/mol (−0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P

Background Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients. Methods In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit. Results Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14). Conclusions Our findings indicate that a high vitamin D3 loading dose, in the first month postoperatively, with subsequent maintenance dose is effective and safe in achieving higher vitamin D concentrations in OLGB patients. Unexpectedly, it is more effective in patients with significant liver fibrosis which is of potentially high clinical relevance and requires further investigation. Electronic supplementary material The online version of this article (doi:10.1007/s11695-016-2437-0) contains supplementary material, which is available to authorized users.

Hyperglycemia contributes to morbidity and mortality in patients with diabetes. Thus, reaching treatment targets with regard to control of glycemia is a central goal in the therapy of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of insulin according to current scientific evidence and clinical studies.

This position statement reflects the opinion of the Austrian Diabetes Association concerning the perioperative management of patients with diabetes mellitus based on the available scientific evidence. The paper covers necessary preoperative examinations from an internal/diabetological point of view as well as the perioperative metabolic control by means of oral antidiabetics and/or insulin therapy.

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

Evidence demonstrates that medical diabetes treatment has to be accompanied by lifestyle modifications. Structured nutrition interventions and increased physical activity will help patients to normalise, respectively maintain their body weight. The main target of a diabetes therapy is aimed at achieving normal or nearly normal blood glucose levels. Reaching this goal may be facilitated by the following nutritional patterns: Using mainly carbohydrates from vegetables, whole grains, legumes and fruits, Restriction of mono- and disaccharides are often important factors in normalising body weight and blood glucose, Reduction of dietary fat could be indicated. However, the primary goal is the limitation of saturated fatty acids which to high percentage are consumed with animal products. There is not sufficient evidence to recommend a dietary protein consumption of more than 20% of energy intake. Individuals with diabetes should be aware of the importance of acquiring daily vitamin and mineral requirements. Natural food sources should be preferred.

Obesity and Type 2 Diabetes are nowadays summarized as "diabesity". That is due to the fact that obesity is frequently preceding and the most important risk factor in the increase of Type 2 Diabetes. The body mass index (BMI) is a crude measure of body fatness. Even normal weight persons can have lack in muscles (sarcopenia), which leads to the recommendation to measure waist und body fatness (e.g. BIA). Lifestyle management including nutrition and physical activity are important for diabetes prevention. In the therapy of Type 2 Diabetes body weight is increasingly used as secondary target. Also the choice of the anti-diabetic medication and concomitant medications is increasingly influenced by body weight. The significance of anti-obesity medications in the therapy of type 2 diabetes will have to be clarified by future studies. Bariatric surgery is at present indicated with a BMI above BMI 35 kg/m(2) and can lead at least to partial diabetes remission but has to be part of a lifelong care concept.

Background Omega-loop gastric bypass (OLGB) results in weight loss (WL) but data on its impact on liver and glucose metabolism compared to Roux-en-Y gastric bypass (RYGB) is lacking. Therefore, the aim of this study was to compare the development of hepatic and metabolic markers as well as WL between the above-mentioned surgical groups during the first postoperative year. Methods We retrospectively evaluated the respective parameters in non-diabetic morbidly obese patients who underwent either RYGB (n = 25) or OLGB (n = 25). Results Compared to RYGB, OLGB showed a greater WL percentage. Liver transaminases dropped in RYGB, while rose in OLGB. No correlation between aspartate transaminase, alanine transaminase, and WL could be detected. Gamma-glutamyltransferase decreased significantly in RYGB over the first 3 months, while it increased in OLGB. We found higher levels of triglycerides, insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), and liver fat percentage in RYGB at baseline, despite matching the groups for age, sex, and BMI. Those differences disappeared, except for triglycerides, within 1 year. All metabolic parameters correlated with WL. Conclusion OLGB results in greater WL but transiently deteriorated several liver parameters in the first postoperative year. This was not associated with WL. The impact of these results on hepatic outcomes such as non-alcoholic steatohepatitis and fibrosis progression requires further studies. In both groups, improved insulin resistance and sensitivity were correlated with higher WL and lower liver fat percentage, respectively.

ObjectiveTo evaluate self-assessed knowledge about diabetes mellitus, to assess determinants of health knowledge and to evaluate consequences of health knowledge on appraisal about consequences of the disease.DesignPopulation-based computer-assisted web interview survey, supplemented with a paper-and-pencil survey via post.SettingRepresentative sample of the general Austrian population aged 15 years and older.SubjectsMen (n 1935) and women (n 2065) with and without diabetes mellitus.ResultsSome 20·5 % of men and 17·7 % of women with diabetes, and 46·2 % of men and 36·7 % of women without diabetes, rated their knowledge about diabetes mellitus to be ‘very bad’ or ‘rather bad’. Individuals with diabetes and individuals with a family member with diabetes rated their information level more often as ‘very good’ or ‘rather good’, with adjusted OR (95 % CI) of 1·7 (1·1, 2·8) and 2·1 (1·6, 2·7), respectively, in men and 2·7 (1·5, 4·8) and 2·7 (2·1, 3·5), respectively, in women. Additional significant influencing factors on diabetes knowledge were age and educational level in both sexes, and city size in men. Independent of personal diabetes status, diabetes knowledge was associated with a lower perception of restrictions on daily life of diabetes patients and with a lower probability of underestimating health consequences of diabetes.ConclusionsHealth knowledge is associated with fewer misconceptions and less underestimation of health consequences in individuals both with and without diabetes mellitus. Thus health information about diabetes is important on the individual level towards disease management as well as on the public health level towards disease prevention.

The aim of the study was to investigate, whether type 2 diabetes independently influences adipokines and inflammatory markers in patients with metabolic syndrome.36 patients with metabolic syndrome without type 2 diabetes and 39 patients with metabolic syndrome with type 2 diabetes, carefully matched for age, sex, and BMI, were investigated. Primary outcome measures were circulating adipokines and inflammatory markers (adiponectin, leptin, visfatin, vaspin, resistin, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), retinol binding protein 4 (RBP-4), growth differentiation factor-15 (GDF-15)). In addition, we determined parameters of glucose and lipid metabolism.Patients with metabolic syndrome and type 2 diabetes had significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides (p0.05). They displayed higher GDF-15 concentrations (1,113 ± 135 vs. 656 ± 63 pg/ml, p = 0.005) and lower visfatin concentrations (3.7 ± 0.3 vs. 4.8 ± 0.2 ng/ml, p = 0.009). There were no differences in other adipokines and inflammatory markers between both groups.In patients with metabolic syndrome, type 2 diabetes leads to decreased visfatin and increased GDF-15 serum levels when compared to carefully matched non-diabetic subjects. Whether the increase in GDF-15 is an indicator or a causal factor for the increased cardiovascular risk in diabetic subjects remains to be investigated in further studies.

BACKGROUNDGrowth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events.METHODSWe evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery.RESULTSObese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001).CONCLUSIONSThe associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

Due to excellent efficacy for weight loss in the short-term follow-up, sleeve gastrectomy (SG) has gained enormous popularity as bariatric procedure, not only as first step in high-risk or super-obese patients but mainly as a sole and definitive operation in morbidly obese. In contrast to a large number of short and intermediate-term results, no series of SG with a follow-up of 5 years or more has been published so far.We report on the weight loss results of our first consecutive 26 patients with a complete follow-up of 5 years. Furthermore in a subgroup of 12 patients, plasma ghrelin levels were measured preoperatively, and up to 5 years following SG.Weight loss defined as mean percent excess weight loss (%EWL) was found as 57.5 +/- 4.5, 60.3 +/- 5.0, 60.0 +/- 5.7, 58.4 +/- 5.4, and 55.0 +/- 6.8 (not converted, n = 21) for the first 5 years. Weight regain of more than 10 kg from nadir was observed in five (19.2%) of the 26 patients. Four of the patients (15.4%) were converted to gastric bypass due to severe reflux (n = 1, 3.8%) and weight loss failure (n = 3, 11.5%). A total of eight patients (30.8%) were at chronic need for proton pump inhibitor medication due to severe reflux. Plasma ghrelin levels were reduced from 593 +/- 52 to 219 +/- 23 pg/ml 12 months postoperatively, with a slightly, non-significant increase toward the 5-years values of mean 257 +/- 23 pg/ml.At 5-year follow-up, a mean EWL of 55.0 +/- 6.8% was achieved, indicating that SG leads to stable weight loss. Beside significant weight regain, severe reflux might necessitate conversion to gastric bypass or duodenal switch. After an immediate reduction postoperatively, plasma ghrelin levels remained low for the first 5 years postoperatively.

Circulating endothelial progenitor cells (EPCs), responsible for neoangiogenesis and vascular repair, negatively correlate with vascular dysfunction and atherosclerotic risk factors. Because obesity may have a crucial role in the development of endothelial dysfunction, this study evaluated the number and proliferative activity of circulating human EPCs in obese (body mass index (BMI)=48+/-9, n=45) compared with lean (23+/-2, n=45) volunteers.EPCs were quantified after isolation of peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analyses. In addition, plated PBMCs developed colony-forming units (CFUs) from which 'outgrowth' endothelial cells (OECs) sprouted and differentiated into mature endothelial cells. Growth rates were monitored by periodical microscopic evaluation. Cell-cycle protein expression was determined by western blot analyses.BMI negatively correlated (P0.01) with the number of CD34(+)/CD133(+)/KDR(+) (r=-0.442), CD34(+)/KDR(+) (r=-0.500) and CD133(+)/KDR(+) (r=-0.282) EPCs. Insulin, leptin, HbA(1c), high-sensitivity C-reactive protein and hypertension, as well as diminished high-density lipoprotein and apolipoprotein A1, were not only associated with obesity but also with significantly reduced EPC levels. Applying selective culture conditions, EPC-CFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.9+/-2.2% vs lean: 30.9+/-3.2% grown area per week, P0.01). The reduced proliferation was reflected by decreased (P0.05, n=24 for each group) expression of cell-cycle-promoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (P0.05, n=24 for each group) expression of the cell-cycle inhibitor p21(WAF-1/Cip1).Reduced numbers of EPCs along with their premature senescence, as shown in this study, could function as early contributors to the development and progression of vascular dysfunction in obesity.

Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p

The TANTALUS system (MetaCure Ltd.) is a minimally invasive implantable gastric stimulation modality that does not exhibit malabsorptive or restrictive characteristics. The device applies gastric contractility modulation (GCM) signals to the stomach antrum. The signals are delivered in synchronization to the native electrical activity of the stomach during meals. Retrospective analysis of previous studies indicated that type 2 diabetes mellitus (T2DM) subjects on oral medication with hemoglobin A1c (HbA1c) between 7.5% and 9.5% are the population with most potential benefit from the treatment. The current study includes subjects enrolled prospectively within that range of HbA1c.To prospectively investigate the potential effect of the TANTALUS system on glycemic control and weight in overweight subjects with T2DM.In this European multicenter, open-label study, 13 T2DM obese (6 male, 7 female, BMI 37.2 +/- 1.0 kg/m(2), range 30.4-44.0 kg/m(2)) subjects treated with oral antidiabetic medications but with poor glycemic control (HbA1cor = 7%, range 7.3-9.5%) were implanted laparoscopically with the TANTALUS system.Thirteen subjects that had completed 3 months of treatment showed a significant reduction in HbA1c from 8.0 +/- 0.2% to 6.9 +/- 0.1% (p0.05), whereas fasting blood glucose decreased from 175 +/- 6 mg/dL to 127 +/- 8 mg/dL (p0.05). The glycemic improvement was accompanied by reduction in weight from 104.4 +/- 4.4 kg to 99.7 +/- 4.8 kg, and in waist circumference from 122.3 +/- 3.2 cm to 117.0 +/- 3.0 cm.Interim results with the TANTALUS system suggest that this stimulation regime can potentially improve glucose levels and induce moderate weight loss in obese T2DM subjects on oral antidiabetic therapy with poor glycemic control. Further evaluation is required to determine whether this effect is due to induced weight loss and/or due to direct signal-dependent mechanisms.

Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined.sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression.Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression.Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.

Beside complications like band migration, pouch-enlargement, esophageal dilation, or port-site infections, laparoscopic adjustable gastric banding (LAGB) has shown poor long-term outcome in a growing number of patients, due to primary inadequate weight loss or secondary weight regain. The aim of this study was to assess the safety and efficacy of laparoscopic conversion to Roux-en-Y gastric bypass (RYGBP) in these two indications.A total of 25 patients, who underwent laparoscopic conversion to RYGBP due to inadequate weight loss (n = 10) or uncontrollable weight regain (n = 15) following LAGB, were included to this prospective study analyzing weight loss and postoperative complications.All procedures were completed laparoscopically within a mean duration of 219 +/- 52 (135-375) min. Mean body weight was reduced from 131 +/- 22 kg (range 95-194) at time of the RYGBP to 113 +/- 25, 107 +/- 22, and 100 +/- 21 kg at 3, 6, and 12 months, respectively, which results in excess weight losses (EWL) of 28.3 +/- 9.9%, 40.5 +/- 12.3%, and 50.8 +/- 15.2%. No statistically significant differences were found comparing weight loss within these two groups.RYGBP was able to achieve EWLs of 37.6 +/- 16.1%, 48.5 +/- 15.1%, and 56.9 +/- 15.0% at 3, 6, and 12 months following conversion, respectively, based on the body weight at LAGB.

OBJECTIVE—Ghrelin and peptide YY (PYY) are both hormones derived from the gastrointestinal tract involved in appetite regulation. The cholinergic part of the vagal nerve is involved in the regulation of glucose and insulin. The aim of this study was to examine the effects of the cholinergic antagonist atropine on ghrelin, PYY, glucose, and insulin under basal conditions and after meal ingestion in lean and obese subjects. REASEARCH DESIGN AND METHODS—Eight lean and eight obese subjects were included in a randomized, double-blind, placebo-controlled crossover study with 4 study days in randomized order (atropine/placebo ± breakfast). Plasma ghrelin, PYY, insulin, and glucose were measured. Hunger and satiety feelings were rated on a 10-cm visual analog scale. RESULTS—In lean individuals, atropine led to a decrease in ghrelin concentrations comparable and nonadditive with breakfast ingestion and a significant decrease in both basal and meal-induced PYY concentrations. In obese subjects, atropine did not significantly change ghrelin or PYY concentrations, whereas it induced a comparable increase in heart rate and meal-induced glucose concentrations in the two study groups. Only lean, not obese, subjects experienced sustained feelings of satiety after breakfast. CONCLUSIONS—The impaired cholinergic regulation of the postprandial drop in ghrelin concentrations and rise in PYY concentrations might be part of the deregulated food intake in obese subjects.