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Diagnosis, Prevention and Treatment of Cardiovascular Disease in People with Diabetes and Prediabetes Abstract. Diabetes is associated with an increased cardiovascular risk. In addition to optimizing glycemia, timely diagnosis and stringent control of cardiovascular risk factors is essential for individuals with diabetes. Therapeutic options include lifestyle-optimization, individualized drug therapy and targeted treatment of concomitant or secondary cardiovascular disease. Cardiovascular disease occurs more often in individuals with diabetes and includes heart failure, atrial fibrillation, coronary heart disease and sudden cardiac death. The correct choice of antidiabetic drugs and interventions can control cardiovascular risk factors, reduce cardiovascular risk and treat concomitant or secondary diseases in a targeted manner. This review is intended to provide guidance on diagnosis, treatment and choice of therapy for individuals with type 2 diabetes without and with concomitant or secondary cardiovascular disease.

Zusammenfassung. Mit dem künstlichen Pankreas (auch closed-loop-System genannt) wird der jahrzehntelange Traum einer automatisierten Insulindosierung Realität. Das System steuert die subkutane Insulinzufuhr automatisch anhand eines Kontrollalgorithmus, der Bezug nimmt auf die aktuelle Glukosekonzentration. Closed-loop-Systeme werden seit 2011 bei Patienten mit Typ-1-Diabetes in klinischen Studien getestet. Dabei konnten gegenüber der konventionellen Pumpentherapie deutliche Reduktionen von Über- und Unterzuckerungen sowie eine geringere Blutzuckervariabilität erreicht werden. Im Jahre 2016 wurde das erste hybrid-closed-loop-System zur Therapie des Typ-1-Diabetes von den amerikanischen Behörden zugelassen. Hybrid-closed-loop-Systeme arbeiten noch nicht vollautomatisch. Nutzer müssen bei der Insulindosierung für Mahlzeiten und Korrekturen aktiv mitwirken. Herausforderungen wie der verzögerte Wirkungseintritt subkutan verabreichten Insulins und das Tragen einer Vielzahl medizinischer Geräte am Körper bleiben weiterhin bestehen. Die folgende Übersichtsarbeit illustriert den aktuellen Stand der Entwicklung von closed-loop-Systemen in der Diabetestherapie. Dabei wird auf das Therapie-Konzept, die einzelnen technischen Komponenten, die Evidenzlage sowie auf heute oder in naher Zukunft verfügbare Systeme eingegangen.

Objective To estimate the prevalence of diabetes due to diseases of the exocrine pancreas (DEP) using data of the multicentre diabetes patient follow-up registry. Moreover, we aimed at comparing individuals with diabetes due to DEP to individuals with type 1 and type 2 diabetes. Methods Individuals with DEP, type 1 or type 2 diabetes ≥18 years of age were studied. We aggregated the most recent treatment year per patient and used propensity scores to match diabetes due to DEP to type 1 and type 2 diabetes. Matching was conducted one-to-one with sex, age, diabetes duration, migration background and the German index of socioeconomic deprivation as covariates. Results We identified 7,093 (1.6%) individuals with diabetes due to DEP. In the matched cohort DEP-type 1 diabetes we observed a similar daily insulin dose (0.62 IU/kg (95% confidence interval:0.60–0.63), 0.60 IU/kg (0.58–0.62)) and significant differences regarding microvascular (41.0% (39.7–42.2), 45.3% (44.0–46.6)), and macrovascular disease (16.6% (15.7–17.6), 14.7% (13.8–15.6)). HbA1c (8.2% (8.1–8.3), 7.9% (7.8–8.0)), daily insulin dose (0.60 IU/kg (0.58–0.62), 0.56 IU/kg (0.54–0.58)) and event rates of severe hypoglycemia (23.9 events/100 PY (21.4–26.8), (9.5 events/100 PY (8.0–11.2)) were significantly higher in individuals with diabetes due to DEP compared to type 2 diabetes. Conclusions Using registry data, rare diabetes types such as diabetes due to DEP can be studied with a significant sample size. Our study identified differences and similarities between adult individuals with DEP related diabetes and type 1 or type 2 diabetes.

Das kunstliche Pankreas (auch Closed-loop-System genannt) bringt uns dem jahrzehntelangen Traum einer automatisierten Insulindosierung einen Schritt naher. Das System steuert die subkutane Insulinzufuhr mit einem Kontrollalgorithmus entsprechend der Glukosekonzentration. Die Studienlage zeigt, dass damit die Blutzuckerkontrolle und Lebensqualitat Betroffener deutlich verbessert werden konnen. Vollautomatische Closed-loop-Systeme sind jedoch noch nicht erhaltlich. Patienten mussen bei der Insulindosierung fur Mahlzeiten und Korrekturen zusatzlich aktiv mitwirken. Die folgende Ubersichtsarbeit zeigt den aktuellen Entwicklungsstand des kunstlichen Pankreas in der Diabetestherapie auf.

Aims To examine the association of frozen shoulder (FS) with demographic and diabetes-related outcomes in individuals with type 1 (T1D) or type 2 (T2D) diabetes aged ≥30 years. Materials and methods Multivariable logistic regression models, adjusted for demographics were used to calculate the proportion of FS in association with age, gender, diabetes duration, body mass index (BMI), haemoglobin A1C (HbA1c) and diabetes treatment. Results The unadjusted percentage of FS was higher in T1D compared to T2D (0.22% vs. 0.06%). In T1D, adjusted regression models revealed higher prevalence of FS in women than men (0.26 [0.20–0.34] % vs. 0.15 [0.11–0.21] %, p=0.010). No significant relationship of age and BMI with FS was found in both diabetes types. Longer diabetes duration was associated with a higher proportion of FS in T1D (p7% was related to a higher proportion of FS compared to HbA1c ≤7% (0.25 [0.19–0.32] vs. 0.12 [0.08–0.20] %, p=0.007), while an inverse relationship was found in T2D (HbA1c ≤7%: 0.08 [0.07–0.10] vs. HbA1c >7%: 0.05 [0.04–0.06] %, p=0.001). Conclusions Different associations of FS with gender and HbA1c were observed for T1D and T2D; however, longer diabetes duration increases the risk for FS independent of diabetes type. Musculoskeletal diseases are still underreported in individuals with diabetes and awareness should be raised for FS as a specific diabetes complication.

OBJECTIVE To investigate temporal trends and contemporary use of insulin pump therapy and glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS In a population-based study, we analyzed the use of insulin pump therapy, continuous glucose monitoring (CGM), and self-monitoring of blood glucose (SMBG) from 1995 to 2017 in patients with type 1 diabetes identified from the Diabetes Prospective Follow-up (DPV) database in Germany and Austria. Patients were stratified by age, sex, migration background, and country. RESULTS Among 96,547 patients with type 1 diabetes (median age 17.9 years, 53% males), the percentage using insulin pump therapy increased from 1% in 1995 to 53% in 2017, with the highest rates in the youngest patients (92% in preschoolers, 74% in children, 56% in adolescents aged CONCLUSIONS Since 1995, insulin pump use has continuously increased, and insulin pump therapy is now standard in patients aged

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes, based on current evidence.

OBJECTIVE Concerning diabetes mellitus, one of the greatest burdens in public health in the 21st century, epidemiological data in Switzerland are scarce. To address this issue, this study intended to use a little-known but convenient way to quantify the prevalence of diabetes mellitus in the Swiss region of Bern-Mittelland. METHODS In a population of approximately 330,000 people, the prevalence for the years 2010–2014 in adult persons was estimated using the capture-recapture method based on data collected routinely at the University Hospital in Bern (Inselspital) using outpatient lists and the registry of persons insured with Helsana Insurance Group. RESULTS The estimated prevalence of diabetes mellitus was 3.97% (95% confidence interval [CI] 3.41–4.53%) in 2010, with a slight decrease to 3.65% (95% CI 3.24–4.06%) in 2014. An average of 3430 patients with diabetes or 26% of the total number appeared on at least one patient list. The remaining 74% were unknown patients identified by the capture-recapture method. CONCLUSIONS The estimated prevalence of diabetes mellitus was in a range comparable to national and international studies. Thus, administratively collected data in clinics and insurance companies constitute a convenient data source for epidemiological studies. In conjunction with the capture-recapture method an approach with comparatively low effort and costs for the surveillance of chronic disease can be provided.

OBJECTIVE While the adjustment of insulin is an established strategy to reduce the risk of exercise-associated hypoglycemia for individuals with type 1 diabetes, it is not easily feasible for those treated with ultra-long-acting basal insulin. The current study determined whether pre-exercise intake of fructose attenuates the risk of exercise-induced hypoglycemia in individuals with type 1 diabetes using insulin degludec. RESEARCH DESIGN AND METHODS Fourteen male adults with type 1 diabetes completed two 60-min aerobic cycling sessions with or without prior intake (30 min) of 20 g of fructose, in a randomized two-period crossover design. Exercise was performed in the morning in a fasted state without prior insulin reduction and after 48 h of standardized diet. The primary outcome was time to hypoglycemia (plasma glucose ≤3.9 mmol/L) during exercise. RESULTS Intake of fructose resulted in one hypoglycemic event at 60 min compared with six hypoglycemic events at 27.5 ± 9.4 min of exercise in the control condition, translating into a risk reduction of 87.8% (hazard ratio 0.12 [95% CI 0.02, 0.66]; P = 0.015). Mean plasma glucose during exercise was 7.3 ± 1.4 mmol/L with fructose and 5.5 ± 1.1 mmol/L in the control group (P < 0.001). Lactate levels were higher at rest in the 30 min following fructose intake (P < 0.001) but were not significantly different from the control group during exercise (P = 0.32). Substrate oxidation during exercise did not significantly differ between the conditions (P = 0.73 for carbohydrate and P = 0.48 for fat oxidation). Fructose was well tolerated. CONCLUSIONS Pre-exercise intake of fructose is an easily feasible, effective, and well-tolerated strategy to alleviate the risk of exercise-induced hypoglycemia while avoiding hyperglycemia in individuals with type 1 diabetes on ultra-long-acting insulin.

Background White coat adherence (WCA) is defined as an increased adherence to treatment regimens directly before a visit with a healthcare provider. Little is known on the effect of WCA on glucose control in adult patients with diabetes mellitus. Methods The present study is based on 618 CGM-observations of 276 patients with diabetes treated between January 2013 and July 2018. The analysis compares data from the 3 days prior to a visit (p1) with the preceding 25 days (p2). Results Sensor use was higher during p1 than p2 (92.8±7.3% vs 88.8±7.5%; p 7% [53mmol/mol]. Conclusion This study reveals a WCA effect on pre-visit glucose control in adult patients with diabetes. The effect was most pronounced in patients with moderate to poor glycemic control. In these patients, analysis of CGM data should encompass a minimum of 1 to 2 weeks prior to a consultation., Diabetes Research and Clinical Practice, 168

Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.

Background The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. Methods 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. Results 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. Conclusions While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166

We investigated the short-term effects of dapagliflozin as adjunct to insulin on insulin sensitivity, postprandial glucose excursions and ketone body production in type 1 diabetes mellitus (T1DM). A total of seven male patients completed the randomized, double-blind, placebo-controlled cross-over trial, receiving 10 mg of dapagliflozin daily for 3 days, followed by placebo, or the reverse. At Day 3, hyperinsulinaemic, euglycaemic clamps and oral glucose tolerance test clamps with repeated blood sampling were performed. Required glucose infusion and blood glucose excursions did not differ significantly between dapagliflozin treatment and placebo (P = 0.491; P = 0.342). Prior to oral glucose, total ketone bodies showed a higher trend following dapagliflozin treatment (P = 0.051). Following oral glucose, total ketone bodies decreased while concentrations of total GLP-1 were higher following dapagliflozin (P = 0.009). Non-esterified free fatty acids did not differ between dapagliflozin treatment and placebo and ketonuria was absent under both conditions. In T1DM, short-term addition of dapagliflozin to insulin influenced neither postprandial glucose excursions nor insulin sensitivity. Following oral glucose, total ketone bodies decreased in parallel with an increase in GLP-1 concentrations, which were higher under dapagliflozin treatment as compared with placebo.

Zusammenfassung. Körperliche Aktivität und Training sind wichtige Bausteine eines gesunden Lebensstils, auch oder vor allem bei Personen mit Diabetes mellitus. Eine Reduktion des kardiovaskulären Risikos sowie eine Verbesserung zahlreicher weiterer Parameter durch Bewegung konnte sowohl bei Personen ohne Diabetes als auch bei Patientinnen und Patienten mit Diabetes in Studien gezeigt werden. Beim Typ-2-Diabetes wird daher – zum Teil auch noch bei Vorhandensein von Spätkomplikationen – ein mehrmals wöchentlich durchgeführtes Ausdauer- als auch Krafttraining zur Verbesserung der glykämischen Kontrolle und Reduktion des kardiovaskulären Risikos empfohlen. Bereits kurze Trainingseinheiten haben einen nachhaltig positiven Effekt auf den Organismus, die Überwindung der Inaktivität und Ausübung von Sport ist aber im Alltag häufig mit gewissen Schwierigkeiten verbunden. Unterschiedliche Trainingstypen haben differierende Auswirkungen auf den Blutzuckerspiegel, dies ist vor allem bei Patientinnen und Patienten mit Insulintherapie zu beachten. Bei Patientinnen und Patienten mit Typ-1-Diabetes gelten per se dieselben Aktivitätsziele. Sport birgt bei diesen Patienten nebst den günstigen Effekten aber auch die Gefahr einer Destabilisierung der glykämischen Kontrolle, insbesondere ist das während des Sports erhöhte Hypoglykämierisiko relevant. Durch adäquate blutzuckeradaptierte Therapiemodifikationen und unter Einsatz moderner technologischer Hilfsmittel kann dem aber wirksam entgegengewirkt werden.

BACKGROUND According to the current evidence, behavior modifications are an effective part of a non-surgical multiprofessional obesity treatment program (MOTP). The purpose of the present study was to report changes in weight as well in psychological variables during a one year MOTP. We aimed to identify the associations of emotional state and patients' emotion regulation skills with weight change. METHODS Prospective interventional study. Data of participants attending the one year obesity treatment in either a group or individual structured MOTP were analyzed. Weight, BMI (Body Mass Index) and measures on psychosomatic variables, emotion regulation skills, affective state, shame and guilt were collected at baseline, after three months and after one year. Mixed-effects models were used for the statistical analysis of BMI. RESULTS We included 238 patients at baseline (t1), 234 after three months (t2) and 179 after one year (t3). A drop in BMI measurements of at least 5% was observed in 20.6% of participants at t2 and 41.4% of participants at t3. After three months, participants showed significant improvements in the following psychosomatic variables: somatisation (p

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.

Studies on CGM assume equal glycemic control between MDI and CSII. However, observation periods are often short and the impact of hypoglycemia on glycemic control and variability is unclear. In this study, we analyzed 12846 days (35 years; CSII 2232 days [6 years]; MDI 10614 days [29 years]) of CGM readings obtained from 99 patients with T1D. In the overall analysis mean glucose was 169.6 ± 18.9mg/dl for CSII and 175.0 ± 29.5 mg/dl for MDI. Estimated A1c was 7.54 ± 0.66% (CSII) and 7.7 ± 1.0% (MDI). Percentage of readings in target range (70-180mg/dL) was 54.0 ± 15.5% for CSII and 57.4 ± 11.4% for MDI. In total, 3.1/2.2% of readings were < 54 mg/dL and 14.9/12.4% were > 250mg/dL for CSII and MDI, respectively. In total, 464 hypoglycemic events (< 54mg/dL) occurred in CSII (day: 305 [64%]; night: 170 [36%]), corresponding to 0.21 hypoglycemic events daily. In MDI, 2297 hypoglycemic events occurred (day: 1507/66%; night: 783/34%), corresponding to 0.22 hypoglycemic events daily. Mean duration of hypoglycemia was 146.5 ± 65.9 minutes (CSII) and 132.8 ± 42.8 minutes (MDI); 233 (CSII) vs. 982 (MDI) events were prolonged (>120 minutes). CV was 41.1 ± 6.7% for CSII and 40.8 ± 3.8% for MDI. In the 24 hours prior to hypoglycemia, mean glucose was higher (182.9 ± 30.5 vs. 166.9 ± 26.6mg/dl; p Disclosure A. Melmer: None. T. Züger: None. T. Pöttler: None. H. Kojzar: None. M. Cigler: None. F. Aberer: None. M. Laimer: None. J.K. Mader: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Prediktor Medical, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; decide Clinical Software GmbH.

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. METHODS: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA1c of 7·5-9·5% (58-80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. FINDINGS: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89-6·70, p

We aimed to assess the risk of developing diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors (NET). Methods: NET patients received somatostatin radiopeptide therapy with yttrium-90-DOTATOC and/or lutetium-177-DOTATOC. The incidence of diabetes mellitus and its mortality were assessed using univariate and multivariate regression. Results: Overall, 1535 NET patients were enrolled, and received 3807 treatment cycles. After treatment, 72 patients developed diabetes mellitus, including 47 cases after yttrium-90-DOTATOC and 25 cases after combined treatment. The diabetes mellitus risk was higher before than after DOTATOC (Estimate: 0.0032, P < 0.001), and overall survival was similar in patients with and without diabetes mellitus (HR: 1.13, 95%CI: 0.91-1.39, n = 1535, P = 0.27). Conclusion: Radiopeptide therapy does not appear to increase the risk of developing diabetes mellitus in NET patients, while diabetes mellitus does not appear to increase the mortality of NET patients undergoing receptor-targeted radiopeptide therapy.

Das Positionspapier reprasentiert die Empfehlungen der ODG zur diagnostischen und therapeutischen Anwendung der kontinuierlichen Glukosemessung bei Erwachsenen und Kindern mit Diabetes mellitus, basierend auf der zurzeit zur Verfugung stehenden Evidenz.

BACKGROUND We investigated the rate of severe hypoglycemic events and confounding factors in patients with type-2-diabetes treated with sulfonylurea (SU) at specialized diabetes centers, documented in the German/Austrian DPV-Wiss-database. METHODS Data from 29,485 SU-treated patients were analyzed (median[IQR] age 70.8[62.2-77.8]yrs, diabetes-duration 8.2[4.3-12.8]yrs). The primary objective was to estimate the event-rate of severe hypoglycemia (requiring external help, causing unconsciousness/coma/convulsion and/or emergency.hospitalization). Secondary objectives included exploration of confounding risk-factors through group-comparison and Poisson-regression. RESULTS Severe hypoglycemic events were reported in 826(2.8%) of all patients during their most recent year of SU-treatment. Of these, n = 531(1.8%) had coma, n = 501(1.7%) were hospitalized at least once. The adjusted event-rate of severe hypoglycemia [95%CI] was 3.9[3.7-4.2] events/100 patient-years (coma: 1.9[1.8-2.1]; hospitalization: 1.6[1.5-1.8]). Adjusted event-rates by diabetes-treatment were 6.7 (SU + insulin), 4.9 (SU + insulin + other OAD), 3.1 (SU + other OAD), and 3.8 (SU only). Patients with ≥1 severe event were older (p 60 mL/min: 3.9). CONCLUSIONS These real-life data showed a rate of severe hypoglycemia of 3.9/100 patient-years in SU-treated patients from specialized diabetes centers. Higher risk was associated with known risk-factors including lack of diabetes-education, older age, and decreased eGFR, but also with lower BMI and lower triglyceride-levels, suggesting that SU-treatment in those patients should be considered with caution. This article is protected by copyright. All rights reserved.

Smartphone-App zur Kohlenhydratberechnung Neue Technologien wie Blutzuckersensoren und moderne Insulinpumpen prägten die Therapie des Typ-1-Diabetes (T1D) in den letzten Jahren in wesentlichem Ausmaß. Smartphones sind aufgrund ihrer rasanten technischen Entwicklung eine weitere Plattform für Applikationen zur Therapieunterstützung bei T1D. GoCARB Hierbei handelt es sich um ein zur Kohlenhydratberechnung entwickeltes System für Personen mit T1D. Die Basis für Endanwender stellt ein Smartphone mit Kamera dar. Zur Berechnung werden 2 mit dem Smartphone aus verschiedenen Winkeln aufgenommene Fotografien einer auf einem Teller angerichteten Mahlzeit benötigt. Zusätzlich ist eine neben dem Teller platzierte Referenzkarte erforderlich. Die Grundlage für die Kohlenhydratberechnung ist ein Computer-Vision-gestütztes Programm, das die Mahlzeiten aufgrund ihrer Farbe und Textur erkennt. Das Volumen der Mahlzeit wird mit Hilfe eines dreidimensional errechneten Modells bestimmt. Durch das Erkennen der Art der Mahlzeiten sowie deren Volumen kann GoCARB den Kohlenhydratanteil unter Einbeziehung von Nährwerttabellen berechnen. Für die Entwicklung des Systems wurde eine Bilddatenbank von mehr als 5000 Mahlzeiten erstellt und genutzt. Resümee Das GoCARB-System befindet sich aktuell in klinischer Evaluierung und ist noch nicht für Patienten verfügbar., Smartphone app for carbohydrate calculation In recent years, new glucose monitoring devices and insulin delivery systems have significantly enhanced diabetes self-management. In parallel, recent advances in smartphone technology has permitted the introduction of a broad spectrum of applications to support diabetic patients in their everyday routine. GoCARB The scope of the GoCARB is the automatic and near real-time estimation of a meal’s carbohydrate content for individuals with type 1 diabetes based on computer vision and smartphone technologies. The user places a credit card-sized reference object next to the meal and acquires two images using a smartphone from different viewing angles. Then, a number of computer vision steps is executed. Initially, the food items on the plate are segmented and recognized while their 3D shape is reconstructed. Based on shape, segmentation results, and reference object, the volume of each item is estimated. Finally, the carbohydrate content is calculated by combining the food type with its volume, and using nutritional databases. For the design and development of GoCARB, a database of more than 5000 meal images has been created and used. Conclusion Currently, the GoCARB system is under clinical evaluation, and therefore not yet accessible for public use.

Der progressive Charakter des Typ-2-Diabetes mellitus führt in vielen Fällen nach Ausschöpfen der oralen antidiabetischen Therapie zum Einsatz von Insulin. Insulin kann aber durchaus auch in der Frühphase direkt nach Diabetesdiagnose oder intermittierend bei Verschlechterung der glykämischen Kontrolle im Rahmen von Infekten oder Medikamenteneinnahmen (wie z.B. Kortison) hilfreich und indiziert sein. Auf jeden Fall stellt die Insulintherapie keine Einbahnstrasse dar und kann gerade in diesen Fällen durchaus auch wieder sistiert werden. Der Beginn einer Insulintherapie soll eher vorsichtig mit einer bedarfsmässigen Anpassung im Verlauf erfolgen. Diese Anpassung kann nach entsprechender Schulung durchaus auch durch den Patienten selbst erfolgen.

Objective: Pronounced weight loss after bariatric surgery was demonstrated to have significant beneficial effects on surrogates of early atherosclerosis. The aim of this prospective examination was to investigate whether these improvements of endothelial function and vascular structure are persistent in the long-term. Design and Methods: A total of 52 obese adults were examined before and 5 years after bariatric surgery. Carotid intima media thickness (IMT), brachial flow-mediated dilation (FMD), abdominal fat distribution, and metabolic parameters were determined. Additional 18 months data were available from 27 patients. Results: After 5 years, mean weight loss ± SD of 25% ± 12 in all subjects was accompanied by known improvements in metabolism. Change in IMT was −0.02 mm ± 0.007, whereas FMD improved by +1.5% ± 0.5. In the subgroup IMT decreased by 0.04 mm ± 0.06 within the first 18 months, whereas no significant change was observed between 18 month and 5 years. FMD improved by 3.8% ± 0.6 after 18 months followed by a nonsignificant decrease of −1.4% ± 0.9. Conclusions: These long-term results demonstrate that bariatric surgery-induced weight loss improves both functional and structural markers of early atherosclerosis providing further evidence for the beneficial effects of weight loss on obesity-associated alterations of the vasculature.

Objective: The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice. Design and Methods: Thus, we evaluated the strength of BAI and other indexes to relate with anthropometric parameters, adipocytokines, blood lipids, parameters of glucose-homeostasis and blood pressure in 1,770 patients from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study in a crosssectional design. Measurements were BAI, BMI, WHR, WHtR, abdominal subcutaneous and visceral adipose tissue (aSAT and VAT), total body adipose tissue mass, body weight, waist- and hip circumference (WC and HC), leptin, adiponectin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), fasting plasma glucose, fasting plasma insulin, the homeostasis model assessment of insulin resistance (HOMAIR), systolic and diastolic blood pressure. Results and Conclusions: BAI was significantly associated with leptin and HC. We conclude that BAI was the best calculator for leptin. BAI was inferior to BMI to predict anthropometric parameters other than HC, adiponectin, blood lipids, parameters of glucose homeostasis, and blood pressure in this cross-sectional study.

Accurate carbohydrate (CHO) counting to achieve satisfactory glucose control in type 1 diabetes (T1D) remains challenging in practice, and thus novel approaches are still needed (1,2). GoCARB is a computer vision-based application installed in a smartphone device that provides users with CHO content estimations from photos taken of plated meals (3). We present the results of a pilot prospective randomized controlled crossover study (NCT02546063) evaluating the effects of GoCARB on postprandial and overall glucose control in individuals with T1D using sensor-augmented insulin pump (SAP) therapy. One week of GoCARB use was compared with conventional methods to estimate meal CHO content in 20 adults with T1D using SAP therapy (mean age 35 ± 14 years, BMI 25.5 ± 3.8 kg/m2, HbA1c 7.5 ± 0.6% [58.7 ± 5.9 mmol/mol], duration of diabetes 17 ± 10 years, …

The quality of glycaemic control in diabetes mellitus relies on accurate individualization of available treatment options. Treatment targets depend on the type and duration of diabetes, the patients' abilities and characteristics and the individual risk for acute and/or late-stage complications. These complications include hypoglycaemia, which can be severe and life threatening, hyperglycaemia, which is a main factor for the development of cardiovascular disease, and macrovascular and microvascular disease, both of which are hallmark features of diabetes-associated constraints. Moreover, other treatment goals in diabetic patients influence both glycaemic control and quality of life. Lipoproteins, blood pressure, weight control, mental health and lifestyle are important factors that contribute to the frequency of diabetes-associated complications.

Wernicke encephalopathy (WE) is a serious complication of bariatric surgery with significant morbidity and mortality. A few cases have been reported in the literature, mainly in patients after a Roux-en-Y gastric bypass. Since sleeve gastrectomy (SG) has become a more established and popular bariatric procedure, WE is expected to appear more frequently after SG. We performed a literature review on WE after SG, and 13 cases have been found to be sufficiently documented. The risk of WE needs to be considered in patients with a prolonged vomiting episode and any type of neurological symptoms, independent of the presence of any surgical complications.

Background Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. Materials and Methods BR profiles of 3118 female and 2427 male patients from the “Diabetes-Patienten-Verlaufsdokumentation” registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The “variability index” was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. Results The variability Index correlated positively with severe hypoglycemia (r = .06; p

Obesity is often associated with an atherogenic dyslipidemia such as high LDL levels, low HDL levels and hypertriglyceridemia. The noninterventional treatment of obesity by lifestyle modification and pharmacological intervention results in moderate weight loss and is mostly unsatisfactory with respect to long-term success. Bariatric surgery, by contrast, results in profound and long-term weight loss. Several studies report higher HDL-C levels and lower levels of LDL-C and triglycerides, and a less atherogenic composition of the respective lipoproteins following bariatric surgery-induced weight loss. In addition, structural and functional markers for early atherosclerosis such as flow-mediated dilation and carotid artery intima–media thickness improve. Most studies found a greater efficiency with respect to weight loss and resolution of comorbidities after malabsorptive and combination operations compared with restrictive operations, although the former led to more serious surgical and nutritional complica...

Eur J Clin Invest 2011; 41 (9): 937–942 Abstract Background Cumulating evidence suggests that the broadly acting neurotrophic pigment epithelium-derived factor is associated with visceral adiposity, the metabolic syndrome, diabetes and exerts beneficial effects on atherosclerosis. To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor. Materials and methods Thirty-six severely obese adults were examined before and 18 months after bariatric surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters by standard methods, pro-inflammatory biomarkers and serum pigment epithelium-derived factor levels by enzyme-linked immunosorbent assay. Results Bariatric surgery resulted in a mean body mass index (BMI) reduction of 9·0 ± 5·0 kg m−2 and concomitant improvements in glucose homoeostasis and lipid profile. Pigment epithelium-derived factor serum levels decreased from a median 11·0 μg mL−1 (interquartile range: 3·8) to 9·2 μg mL−1 (interquartile range: 4·5) (P 0·370, P

Background. Matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitor of metalloproteinases [TIMPs]), are involved in adipogenesis, angiogenesis and remodeling of extracellular matrix. MMPs and TIMPs have been shown to be associated with various diseases such as neurological disorders, malignancies and cardiovascular disease. MMPs and TIMPs are thought to play a major role in extensive reorganization of the adipose tissue in obesity. Methods and materials. To test whether significant weight loss alters circulating MMPs and TIMPs, 18 morbidly obese women, who underwent bariatric surgery for weight loss, were investigated before and one year after surgery in a prospective design study. Body composition, glucose and lipid metabolism parameters were determined in all study subjects before and after weight loss. Circulating MMP-2, -3, -7 and TIMP-1, -2 and -4 serum levels were measured using commercially available, enzyme-linked immunoassays. Results. Pronounced weight loss was accompanied by improvements in glucose homeostasis and lipid parameters. In the mean time MMP-2 and MMP-3, as well as TIMP-1, -2 and TIMP-4 concentrations were not affected by significant weight loss, and circulating MMP-7 increased significantly after bariatric surgery, although without reaching the standard levels as determined in 18, lean, healthy women. Conclusion. Our data indicate that reduced MMP-7 levels in obesity might be restored by significant weight loss, suggesting that the reorganization of adipose tissue in obesity might be partially reversible by weight reduction. We hypothesize that increased circulating MMP-7 might indicate enhanced adipocyte differentiation in subjects who had undergone bariatric surgery.

Adipocyte fatty acid binding protein (A-FABP) has been suggested to play an important role in fat metabolism linking obesity and the metabolic syndrome. Increasing A-FABP plasma levels were observed during greatest weight loss after bariatric surgery suggesting that A-FABP may indicate changes in fat mass in dynamic situations. As there are no data on weight gain, we investigated the effect of refeeding anorexic patients on body composition and A-FABP plasma levels. Parameters of glucose and lipid metabolism as well as plasma levels of leptin and A-FABP were prospectively assessed in 16 female patients with anorexia nervosa during inpatient weight restoration. Body composition was determined by multifrequency body impedance analysis. After 28 days, fat mass increased from 4.4 ± 2.5 kg at baseline to 5.5 ± 2.2 kg (P

SummaryValproic acid (VPA) is an effective and widely used anticonvulsant, associated with metabolic adverse effects such as weight gain, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia. The aim of this study was to evaluate the influence of VPA and topiramate (TPM) on adiponectin binding receptors, adipoR1 and adipoR2, in human liver cancer cells, HepG2. AdipoR1 but not adipoR2 gene expression was upregulated by VPA treatment. TPM did neither affect adipoR1 nor adipoR2 gene expression. Given the tight association between VPA treatment, metabolic side effects and the adipocytokine-axis, upregulation of adipoR1 possibly represents a favoured and insulin-sensitizing mechanism.

Brain natriuretic peptide(BNP) and the N-terminal pro-brain natriuretic peptide (NTproBNP)are important cardiac biomarkers secreted by the heart in response to increased ventricular wall stress associated with heart failure. The aim of our case series was to prospectively evaluate the influence of vagus nerve stimulation (VNS) on the release of NTproBNP.Three children with medically refractory epilepsy and scheduled for implantation of the VNS device were included. Pre-implantation,NT-proBNP measurements were taken at two different occasions after seizure-free periods of at least three days. After implantation,NT-proBNP measurements were taken every 2 to 4 weeks, immediately before and immediately after up-regulation of the VNS. After VNS implantation, the pattern of NT-proBNP increase was consistent for all children. In a 12 year-old girl, NT-proBNP concentrations reached a maximum of an almost 10-fold increase. Thereafter, NTproBNP concentrations returned continuously to baseline. In a three year-old boy, NT-proBNP concentrations reached a maximum of an almost 7-fold increase, accompanied by manifestation of side effects(voice alterations, snoring).Thereafter, NT-proBNP concentrations decreased to almost 4-fold those at baseline. In an 8 year-old girl, NT-proBNP concentrations increased slightly without yet reaching a plateau. This case series suggests that NT-proBNP concentrations increase in response to VNS-induced autonomic influences involving endocrinological stress-response mechanisms typically associated with cardiac injury.Especially in patients with pre-existing cardiovascular dysfunction,measurement of NT-proBNP concentrations may help to identify patients with high baseline concentrations and possibly at greater risk for cardiac side effects.

The metabolic syndrome is associated with low high-density lipoprotein-cholesterol (HDL-C) and decreased low-density lipoprotein (LDL) particle size. The Taq1B-polymorphism in the cholesteryl ester-transfer protein (CETP)-gene influences HDL-C, CETP concentration, and LDL-size. We investigated the effect of the Taq1B-polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme-linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B-polymorphism influenced significantly CETP concentrations, HDL-C levels, and LDL-size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51-0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53-0.92), P = 0.01) and after further adjustment for body mass index, waist-to-hip ratio, blood pressure, insulin resistance (IR), HDL-C, and triglycerides (TGs) (OR 0.43 (0.26-0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.

The use of second-generation antipsychotics (SGAs) is associated with metabolic side effects including weight gain, diabetes mellitus and an atherogenic lipid profile. These adverse effects are not only the risk factors for cardiovascular disease, insulin resistance and diabetes mellitus leading to increased morbidity and mortality but may also impair the patient's adherence to treatment. SGAs in particular are associated with significant weight gain with clozapine and olanzapine carrying the highest risk, whereas newer agents, such as risperidone and aripiprazole, are considered to be less prone to cause weight gain. Consequently, a consensus development conference convened issuing recommendations on patient monitoring when treated with SGAs. The metabolic effects of antipsychotic drugs should be of concern when planning a patient's treatment strategy. Baseline screening and regular follow-up monitoring whose intervals should depend on the individual predisposition are advised. Possible therapeutical strategies for the management of drug-induced obesity include therapeutic approaches, such as life style change and pharmaceutical intervention. Drugs with a weight reducing effect become more important because of the lack of compliance with behavioural intervention. Topiramate, histamine-antagonists, dopaminergic- and serotoninergic agents have shown positive results in the management of psychotropic medication induced weight gain. However, further trials are required to support a specific therapeutical approach as well as studies to investigate the underlying mechanisms for future drug development.

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters. Research Methods and Procedures: Thirteen severely obese female subjects were examined before and 1 year after surgical treatment. Total adiponectin was determined by radioimmunosorbent assay, and oligomer composition was detected by nondenaturing Western blot. Results: BMI decreased substantially (p < 0.001), which was associated with an increase of total adiponectin from 12.9 ± 5.9 to 14.3 ± 6.1 μg/mL (p = 0.055). Medium molecular weight (MMW) adiponectin increased from 7.5 ± 3.6 to 9.1 ± 4.1 μg/mL (p = 0.009), whereas high (HMW) and low molecular weight adiponectin remained unchanged. Δ values of total adiponectin correlated significantly with Δ values of anthropometric parameters. Similar correlations were found for Δ values of MMW (Δ weight: r2 = 0.4132, p = 0.0178; Δ BMI: r2 = 0.3319, p = 0.0393; Δ fat mass: r2 = 0.5202, p = 0.0054). Discussion: Thus, profound weight loss was associated with an increase in total adiponectin, which was mainly and consistently caused by increases in MMW adiponectin (p = 0.009). These changes result in a shift from low molecular weight to MMW and HMW adiponectin isoforms, which may be related to improvements in both anthropometric and metabolic parameters.

PURPOSE OF REVIEW The primary focus of this review is threefold: first, to summarize available knowledge on exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus (T1DM); second, to elucidate physiological mechanisms predisposing to glycemic variations in patients in T1DM; and third, to describe novel approaches derived from physiological perceptions applicable to stabilize exercise-related glycemia in individuals with T1DM. RECENT FINDINGS Recent studies corroborate the concept that despite partial differences in counter-regulatory mechanisms individuals with T1DM do not fundamentally differ in their glucose response to exercise when compared with healthy individuals if studies are performed under standardized conditions with insulin and glucose levels held close to physiological ranges. Novel approaches derived from a better understanding of exercise-associated glucose metabolism (e.g., the concept of intermittent high-intensity exercise) may provide alternative ways to master the challenges imposed by exercise to individuals with T1DM. SUMMARY Exercise still imposes high demands on patients with T1DM and increases risks for hypoglycemia and hyperglycemia. Deeper insight into the associated metabolic pathways has revealed novel options to stabilize exercise-associated glucose levels in these patients.

Obesity contributes to telomere attrition. Studies focusing on short-term effects of weight loss have been unable to identify protection of telomere length. This study investigates long-term effects of pronounced weight loss induced by bariatric surgery on telomere length.One hundred forty-two patients were recruited in a prospective, controlled intervention study, follow-up investigations were done after 10.46±1.48 years. A control group of normal weight participants was recruited and followed from 1995 to 2005 in the Bruneck Study. A total of 110 participants from each study was matched by age and sex to compare changes in telomere length. Quantitative PCR was used to determine telomere length.Telomere length increased significantly by 0.024±0.14 (P=0.047) in 142 bariatric patients within 10 years after surgery. The increase was different from telomere attrition in an age- and sex-matched cohort population of the Bruneck Study (-0.057±0.18; β=0.08; P=0.003). Significant changes in telomere length disappeared after adjusting for baseline body mass index (BMI) because of general differences in BMI and telomere length between the two study populations (β=0.07; P=0.06). Age was proportional to telomere length in matched bariatric patients (r=0.188; P=0.049) but inversely correlated with telomere length in participants of the Bruneck Study (r=-0.197; P=0.039). There was no association between percent BMI/excess weight loss and telomere attrition in bariatric patients. Baseline telomere length in bariatric patients was inversely associated with baseline plasma cholesterol and triglyceride concentrations. Telomere shortening was associated with lower high-density lipoprotein cholesterol and higher fasting glucose concentration at baseline in bariatric patients.Increases in relative telomere length were found after bariatric surgery in the long term, presumably due to amelioration of metabolic traits. This may overrule the influence of age and baseline telomere length and facilitate telomere protection in patients experiencing pronounced weight loss.

OBJECTIVE Low high-density lipoprotein cholesterol (HDL-C), hypertriglyceridemia, and small dense-low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG-rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL-C and small dense-LDL. The aim of this study was to investigate the role of CETP in subjects with MS. RESEARCH METHODS AND PROCEDURES In a cross-sectional cohort of 234 middle-aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme-linked immunosorbent assay and LDL size-by-gradient polyacrylamide gel electrophoresis. RESULTS Men and women with MS had lower HDL-C (45 +/- 7 vs. 58 +/- 13 and 48 +/- 10 vs. 71 +/- 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 +/- 71 vs. 98 +/- 54 and 167 +/- 67 vs. 90 +/- 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 +/- 11 A vs. 267 +/- 11 A and 262 +/- 10 A vs. 273 +/- 8 A for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 +/- 0.78 vs. 1.40 +/- 0.65 mug/mL; p < 0.001) but not in women (1.74 +/- 0.79 vs. 1.62 +/- 0.62 mug/mL). CETP mass correlated inversely with LDL size in both men and women (r = -0.19, p < 0.01 and r = -0.13, p < 0.05 in men and women, respectively). DISCUSSION MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL-C and reduced LDL particle diameter in MS.

Objective Weight gain is a common side effect of psychotropic medications. Mirtazapine, a widely used antidepressant, induces adverse metabolic effects such as an increase in body weight. The aim of this study was to investigate the influence of mirtazapine treatment on body weight, body fat mass, glucose metabolism, lipoprotein profile, and leptin and its soluble receptor in a prospective, controlled study design. Method Seven women who met the ICD-10 diagnostic criteria for a depressive episode (ICD-10: F31-F33) were assigned to monotherapy with mirtazapine and observed for a 6-week period. Seven mentally and physically healthy female volunteers matched for age and body weight served as a control group. Data were collected from November 2002 to December 2003. Results The mean +/- SD body weight increased from 63.6 +/- 13.1 kg to 66.6 +/- 11.9 kg during mirtazapine treatment (p = .027). Fat mass increased in study subjects from 20.9 +/- 9.6 kg to 22.1 +/- 9.3 kg (p = .018). Insulin, glucose, and the homeostasis model assessment (HOMA) index for insulin resistance and lipid parameters remained stable. Leptin concentrations increased from 23.0 +/- 17.1 ng/mL to 40.9 +/- 27.2 ng/mL (p = .018), whereas the soluble leptin receptor concentrations remained stable during mirtazapine treatment. In the control subjects, the investigated parameters remained stable. Between-group analyses of change scores revealed significant differences for body weight (p = .010), body mass index (p = .013), fat mass (p = .035), and leptin (p = .013). Conclusion The antidepressant therapy with mirtazapine was associated with a significant increase in body weight, body fat mass, and leptin concentration. In contrast to other psychotropic medications inducing weight gain, such as some second-generation antipsychotics, mirtazapine treatment did not influence the glucose homeostasis.

Second-generation antipsychotic agents (SGAs) are increasingly replacing first-generation antipsychotic agents due to their superior activity against the negative symptoms of schizophrenia, decreased extrapyramidal symptoms and better tolerability. However, some SGAs are associated with adverse metabolic effects as significant weight gain, lipid disorders and diabetes mellitus. The pathogenesis of SGA-induced disturbances of glucose homeostasis is unclear. In vivo studies suggest a direct influence of SGAs on peripheral insulin resistance. To this end, we analyzed whether olanzapine might alter glycogen synthesis and the insulin-signaling cascade in L6 myotubes. Glycogen content was diminished in a dose- and time-dependent manner. Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. IRS-1-associated PI3K activity was stimulated by insulin three-fold in L6 myotubes. Olanzapine inhibited insulin-stimulated IRS-1-associated PI3K activity in a dose-dependent manner. Protein mass of AKT, GSK-3 and GS was unaltered, whereas phosphorylation of AKT and GSK-3 was diminished, and pGS was increased. Finally, we compared olanzapine with amisulpride, an SGA clinically not associated with the induction of diabetes mellitus. Glycogen content was diminished in olanzapine-preincubated L6 cells, whereas this effect was not observed under the amisulpride conditions. We conclude that olanzapine impairs glycogen synthesis via inhibition of the classical insulin-signaling cascade and that this inhibitory effect may lead to the induction of insulin resistance in olanzapine-treated patients.

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.

Background: The aim of this study was to compare glucose metabolism in patients with schizophrenia receiving olanzapine with that in control subjects. Method: We conducted a prospective, controlled, open study comparing body weight, fat mass, and indices of insulin resistance/ sensitivity in 10 olanzapine-treated patients with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a group of 10 mentally and physically healthy volunteers. Weight, fat mass, and indices of insulin resistance/sensitivity were assessed over individual 8-week observation periods from November 1997 to October 1999. Results: Fasting serum glucose and fasting serum insulin increased significantly in the olanzapine-treated patients (p = .008 for glucose and p = .006 for insulin). The homeostasis model assessment (HOMA) index for beta cell function did not change significantly in the olanzapine-treated patients, whereas the HOMA index for insulin resistance did increase (p = .006). In the control group, these parameters were stable. A significant increase in body weight (p = .001) and body fat (p = .004) was seen in patients treated with olanzapine, while the control group showed no significant changes. Conclusion: This study indicates that the disturbances in glucose homeostasis during antipsychotic treatment with olanzapine are mainly due to insulin resistance. However, beta cell function remains unaltered in olanzapine-treated patients. We conclude that treatment with some second-generation antipsychotic drugs may lead to insulin resistance.

Objective: In obesity, plasma leptin is high and soluble leptin receptor (sOb-R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb-R concentration and the bound-free ratio of leptin. Research Methods and Procedures: sOb-R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle-aged obese or overweight men. Results: Concentration of sOb-R and soluble receptor-bound fraction of leptin were lowest in the highest tertile of HOMA-IR. sOb-R and the bound-free ratio of leptin correlated with HOMA-IR, leptin concentration, and waist-to-hip ratio independently of age, BMI, and fat mass. Leptin and waist-to-hip ratio were the sole independent determinants of sOb-R concentration, and BMI, HOMA-IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb-R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb-R concentration and a lower fraction of bound leptin in men with the MS. Discussion: IR and abdominal obesity are associated with low sOb-R concentration and low bound-free ratio of leptin independent of fat mass. Low sOb-R concentration and low bound-free ratio of leptin segregate with components of the MS. We suggest that low sOb-R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS.

Objective: Soluble leptin receptor (sOB-R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction. Research Methods and Procedures: A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB-R concentrations before and 1 year after Swedish adjustable gastric banding. Results: Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 ± 5.6 to 32.9 ± 6.0 kg/m2 (mean ± SD)]. Fat mass decreased from 56.3 ± 9.0 to 33.9 ± 12.5 kg. Plasma leptin concentration decreased from 44.6 ± 18.0 to 20.0 ± 13.1 ng/mL (p < 0.001), whereas the sOB-R levels increased from 11.1 ± 3.6 to 16.6 ± 6.0 U/mL after weight-reducing surgery. Thus, the sOB-R bound fraction of leptin increased from 7% to 33%. Discussion: This work demonstrates a relationship between weight loss, leptin, and sOB-R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB-R levels and the receptor bound fraction of leptin increased. Thus, sOB-R may negatively regulate free leptin.