Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.

BACKGROUND: 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 (<90 mg/dL), following a treat-to-target algorithm, for 52 weeks. The primary efficacy endpoint was non-inferiority of tirzepatide 10 mg or 15 mg, or both, versus insulin degludec in mean change from baseline in HbA1c at week 52. Key secondary efficacy endpoints were non-inferiority of tirzepatide 5 mg versus insulin degludec in mean change from baseline in HbA1c at week 52, superiority of all doses of tirzepatide versus insulin degludec in mean change from baseline in HbA1c and bodyweight, and the proportion of participants achieving HbA1c of less than 7·0% (<53 mmol/mol) at week 52. We used a boundary of 0·3% to establish non-inferiority in HbA1c difference between treatments. Efficacy and safety analyses were assessed in the modified intention-to-treat population (all participants who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, number NCT03882970, and is complete. FINDINGS: Between April 1 and Nov 15, 2019, we assessed 1947 participants for eligibility, 1444 of whom were randomly assigned to treatment. The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups. From a mean baseline HbA1c of 8·17% (SD 0·91), the reductions in HbA1c at week 52 were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec. The non-inferiority margin of 0·3% was met. The estimated treatment difference (ETD) versus insulin degludec ranged from -0·59% to -1·04% for tirzepatide (p<0·0001 for all tirzepatide doses). The proportion of participants achieving a HbA1c of less than 7·0% (<53 mmol/mol) at week 52 was greater (p<0·0001) in all three tirzepatide groups (82%-93%) versus insulin degludec (61%). At week 52, from a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (-7·5 kg to -12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg. The ETD versus insulin degludec ranged from -9·8 kg to -15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses). The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time. A higher incidence of nausea (12-24%), diarrhoea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively). Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec. Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group. Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment. INTERPRETATION: In patients with type 2 diabetes, tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and bodyweight at week 52 and a lower risk of hypoglycaemia. Tirzepatide showed a similar safety profile to that of GLP-1 receptor agonists. FUNDING: Eli Lilly and Company.

Effect of one-anastomosis gastric bypass on cardiovascular risk factors in patients with vitamin D deficiency and morbid obesity: A secondary analysis.

BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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 those <50 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. CONCLUSION: 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).

Comparison of the HAT study, the largest global hypoglycaemia study to date, with similar large real-world studies.

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.

HORMONE SUBSTITUTION AFTER GASTRIC BYPASS SURGERY IN PATIENTS WITH HYPOPITUITARISM SECONDARY TO CRANIOPHARYNGIOMA.

OBJECTIVE: Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis. METHODS: Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months. RESULTS: In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m(2)), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxinebaseline 156 ± 44 µg/day versus levothyroxinefollow-up 150 ± 30 µg/day), hydrocortisone (hydrocortisonebaseline 29 ± 12 mg/day versus hydrocortisonefollow-up 26 ± 2 mg/day), growth-hormone (somatotropinbaseline 0.9 ± 0.5 mg/day versus somatotropinfollow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressinbaseline 222 ± 96 µg/day versus desmopressinfollow-up 222 ± 96 µg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery. CONCLUSION: Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.

Influence of intravenous thiamine supplementation on blood lactate concentration prior to cardiac surgery: A double-blinded, randomised controlled pilot study.

BACKGROUND: Stress related to surgery and critical illness depletes thiamine, essential in energy metabolism, and might result in high blood lactate concentrations and higher mortality. OBJECTIVES: We hypothesised that thiamine supplementation would increase blood concentration of thiamine and reduce blood lactate concentration postoperatively. Moreover, we aimed to identify the prevalence of, and risk factors for, high blood lactate concentrations. DESIGN: This was a double-blind, randomised controlled pilot study from February to July 2012 including 30 patients scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were assigned randomly to receive thiamine (300 mg in 0.9% Normal saline solution) or placebo (0.9% Normal saline) preoperatively. MAIN OUTCOME MEASURES: One arterial blood sample was taken preoperatively and another postoperatively to measure thiamine concentration, and multiple samples were taken during surgery and ICU stay to determine lactate concentrations. Twenty-four hour urine samples were collected to measure urinary thiamine concentration. Preoperatively, we assessed extracellular mass to body cell mass ratio (ECM/BCM). RESULTS: The mean (SD) age of the patients was 58 (12) years, 73% were overweight, 10% were malnourished and the prevalence of thiamine deficiency was 10%. Patients in the thiamine group had significantly higher blood thiamine concentrations 2 days postoperatively [805.2 ± 289.8 ng g(-1) haemoglobin (Hb)] than those in the placebo group (591.2 ± 100.7 ng g(-1) Hb, P < 0.01). The mean blood lactate concentration changed significantly over time, but did not differ significantly between the groups. Patients with ECM/BCM more than 1 had higher lactate concentrations on admission to ICU than those with ECM/BCM less than 1 (2.1 ± 0.7 vs. 1.7 ± 0.6, P = 0.09) and were at a significantly greater risk of having a higher lactate concentration on ICU admission [odds ratio (OR) 13.5, 95% confidence interval (95% CI) 1.0 to 179.4, P < 0.05]. On the basis of these results, a sample size calculation for a larger study has been facilitated. CONCLUSION: Thiamine supplementation caused normalisation of blood and urine concentrations postoperatively but without a significant reduction in lactate concentration or clinical outcome. Body composition played an important role in lactate formation. Further research focusing on preoperative screening and optimal treatment of high lactate concentrations in this specific population is warranted. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01524315.

Perceived Body Size in Relation to 10-Year Weight Change in the Swedish Obese Subjects Intervention Study.

INTRODUCTION: Body size underestimation in patients with obesity may be associated with long-term weight increase. In the current report, we analyse changes in body size perception in patients with obesity undergoing either bariatric surgery or usual obesity care, and in subgroups of patients who gain weight or maintain their body weight over 10 years. MATERIALS AND METHODS: A total of 2,504 patients with obesity from the prospective, controlled Swedish Obese Subjects (SOS) intervention study were included in this report, 1,370 patients underwent bariatric surgery and 1,134 patients were usual care controls. Weight was measured and body size was self-estimated using the Stunkard's figure rating scale at baseline and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years of follow-up. A body perception index (BPI) was calculated as estimated/measured BMI. Weight (re)gain was defined as ≥10% increase between 1 and 10 years of follow-up. RESULTS: Body size was underestimated by 12% in the surgery and 14% in the control group (i.e., >5 BMI units) at baseline and underestimation largely persisted over 10 years in both intervention groups. When stratified by long-term weight development, weight regainers from the surgery group underestimated their body size to a larger degree compared to weight maintainers (12 vs. 9%, p < 0.001) after 10 years. Likewise weight gainers in the control group also underestimated their body size to a larger degree (17% vs. 13%, p < 0.001). In both groups, the change in BPI was significantly different between weight regainers and maintainers during follow-up (time-BPI interactions both p < 0.001). CONCLUSION: Patients with obesity underestimate their body size and this underestimation remains long-term even after major weight loss induced by bariatric surgery. In patients with obesity who maintain their weight, regardless of treatment, underestimation of body size persists but body size perception is slightly more accurate compared to patients who gain or regain weight long-term.

Health information regarding diabetes mellitus reduces misconceptions and underestimation of consequences in the general population.

OBJECTIVE: To 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. DESIGN: Population-based computer-assisted web interview survey, supplemented with a paper-and-pencil survey via post. SETTING: Representative sample of the general Austrian population aged 15 years and older. SUBJECTS: Men (n 1935) and women (n 2065) with and without diabetes mellitus. RESULTS: Some 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. CONCLUSIONS: Health 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.

Are there differences in LDL-C target value attainment in Austrian federal states? Yes!

UNLABELLED: Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences. DESIGN: Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).

[Diabetes education and counseling in adult patients with diabetes (Update 2023)]. / Diabetesschulung und -beratung bei Erwachsenen mit Diabetes (Update 2023).

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 diabetes 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, lipids, 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), the occurrence of diabetic complications and the use of technical devices such as glucose sensor systems and insulin pumps require additional educational measures supported by adequate electronic tools (diabetes apps and diabetes web portals). New data demonstrate the effect of telemedicine and internet-based services for diabetes prevention and management.

[Position statement: surgery and diabetes mellitus (Update 2023)]. / Positionspapier: Operation und Diabetes mellitus (Update 2023).

This position statement reflects the perspective of the Austrian Diabetes Association concerning the perioperative management of people 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 antihyperglycemic and/or insulin therapy.

[Injection therapy of diabetes]. / Injektionstherapie (GLP1-Rezeptor Agonisten und Insulin) bei Typ 2 Diabetes mellitus (Update 2023).

The present article is a recommendation of the Austrian Diabetes Association for the practical use of injection therapy (GLP1-receptor agonists and insulin) in type 2 diabetes.

[Obesity and type 2 diabetes (Update 2023)]. / Adipositas und Typ-2-Diabetes (Update 2023).

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 additional concomitant therapies is increasingly influenced by body weight. The importance of modern GLP­1 agonists and dual GLP­1 GIP agonists increases since these drugs target obesity and type 2 diabetes. Bariatric surgery is at present indicated with a BMI > 35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.

[Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2023)]. / Diagnostik und Therapie des Typ 1 Diabetes mellitus (Update 2023).

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

[Nutrition for diabetic patients (Update 2023)]. / Ernährungsempfehlungen für Menschen mit Diabetes (Update 2023).

All patients with diabetes require individual and personalized nutritional consultation with professionals. The patient's needs should be the primary focus of the dietary therapy, taking their lifestyle and the type of diabetes into consideration. With the recommendations to the patient's diet, there need to be specific metabolic goals to reduce the disease's progression and to avoid long term health effects. Therefore, practical guidelines such as portion size and meal planning tips should be the main focus.According to the latest national and international standards, patients suffering from diabetes should have access to nutrition consulting and nutritional training. During consultation they can be supported on- how to manage their health condition and choosing food and beverage to improve their health.These practical recommendations sum up the latest literature on nutritional aspects of diabetes treatment.

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

OBJECTIVE: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. METHODS: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation. RESULTS: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. CONCLUSIONS: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2023)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2023).

Hyperglycemia significantly contributes to 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 as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

[Overweight and obesity in adults: general principles of treatment and conservative management]. / Übergewicht und Adipositas bei Erwachsenen: allgemeine Behandlungsgrundsätze und konservatives Management.

The prevalence of overweight and obesity is steadily increasing in Austria as well as internationally. Obesity in particular is associated with multiple health risks, comorbidities, functional disability, and social stigma. Obesity is an independent, complex, chronic disease and should be treated as such by a multidisciplinary team of appropriately qualified personnel. In addition to recent international guidelines, this consensus paper outlines the overall principles of the management of overweight and obesity and provides guidance for the diagnosis and conservative treatment, focusing on lifestyle modifications and pharmacotherapy. Using the "5A" framework of behavioral health intervention, guidelines for a structured, pragmatic, and patient-centered medical care of adults with overweight or obesity are presented.

[A female patient with earache, polyuria and polydipsia]. / Eine Patientin mit Ohrenschmerzen Polyurie und Polydipsie.

INTRODUCTION: 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. HISTORY: 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. FINDINGS AND DIAGNOSIS: 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. THERAPY AND COURSE: Besides systemic chemotherapy with cytarabine, the patient also received denosumab and desmopressin. CONCLUSION: 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.

The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients.

BACKGROUND: Growth 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. METHODS: We 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. RESULTS: Obese 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 A(1c), 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). CONCLUSIONS: The 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.