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Objectives Left atrial appendage (LAA) amputation concomitant to coronary artery bypass grafting (CABG) has become an increasingly performed technique in patients with atrial fibrillation (AF) or with sinus rhythm and a CHA2DS2-VASc score ≥2. However, LAA amputation has come under suspicion to cause postoperative atrial fibrillation (POAF) due to left atrial (LA) dilation. This study aims to assess this assumption in patients undergoing CABG in off-pump technique with and without amputation of the LAA. Methods Patients who underwent isolated CABG in off-pump technique without history of AF were retrospectively examined. Cohorts were divided according to the concomitant execution of LAA amputation. LA volume was measured by transthoracic echocardiography and rhythm was analyzed by electrocardiography, medication protocol, and visit documentation. Propensity score (PS) matching was performed based on 20 preoperative risk variables to correct for selection bias. Results A total of 1,522 patients were enrolled, with 1,267 in the control group and 255 in the LAA amputation group. Occurrence of POAF was compared in 243 PS-matched patient pairs. Neither the unmatched cohort (odds ratio [OR] 0.82; 95% confidence interval or CI [0.61; 1.11], p = 0.19) nor the PS-matched cohort (OR 0.94; 95% CI [0.62; 1.41], p = 0.75) showed significant differences in POAF occurrence. Subgroup analysis of sex, use of β-blockers, pulmonary disease, ejection fraction, and CHA2DS2-VASc-Score also showed no tendencies. LA volume did not change significantly (p = 0.18, 95% CI [−0.29; 1.51]). Conclusion Surgical amputation of the LAA concomitant to CABG did not lead to LA dilation and has no significant impact on the occurrence of POAF.

Purpose The aim of this study was to examine the mediation of body mass index (BMI) on the association between per capita sugar consumption and diabetes prevalence using country-related data. Research design and methods In this ecological study, based on 192 countries, data on per capita sugar consumption were obtained from the Food and Agriculture Organization of the United Nations (FAO), on BMI from the World Health Organization and on diabetes prevalence from the International Diabetes Federation. Data on demography and economic factors were obtained from the Central Intelligence Agency, the United Nations and the FAO. Multiple linear regression analysis was performed to investigate the association between per capita sugar consumption and diabetes prevalence, and mediation analysis to detect the mediated percentage of BMI on this association. Results Each increase of 100 kcal/day per capita sugar consumption was associated with a 1.62% higher diabetes prevalence [adjusted β-estimator (95% CI): 1.62 (0.71, 2.53)]. Mediation analysis using BMI as the mediator demonstrated an adjusted direct association of 0.55 (95% CI: − 0.22, 1.32) and an adjusted indirect association of 1.07 (95% CI: 0.54, 1.68). Accordingly, the BMI explained 66% (95% CI: 34%, 100%) of the association between per capita sugar consumption on diabetes prevalence. Conclusions These findings indicate that the association between dietary sugar intake and the occurrence of diabetes is mediated by BMI to a large proportion. However, it seems that other mechanisms may explain the association between sugar consumption and development of type 2 diabetes.

HINTERGRUND: In der NAKO Gesundheitsstudie liegen die Daten zu selbstberichteten Krebserkrankungen der ersten Hälfte der Teilnehmenden vor. ZIEL: Beschreibung der Methoden zur Erfassung selbstberichteter Krebserkrankungen und Tumorlokalisationen in der NAKO und Darstellung erster Ergebnisse. MATERIAL UND METHODEN: In einem computergestützten, standardisierten persönlichen Interview wurden 101.787 Teilnehmende (54.526 Frauen, 47.261 Männer) gefragt, ob bei ihnen jemals eine Krebserkrankung (bösartiger Tumor einschließlich in situ) ärztlich diagnostiziert wurde und wie viele Krebserkrankungen sie hatten. Anhand einer Liste wurde die Tumorlokalisation erfragt. Absolute und relative Häufigkeiten von Selbstangaben zu Krebserkrankungen insgesamt und einzelnen Tumorlokalisationen wurden berechnet und mit krebsregisterbasierten Daten verglichen. ERGEBNISSE: Eine ärztlich diagnostizierte Krebserkrankung wurde von 9,4 % der Frauen und 7,0 % der Männer berichtet. Von den Personen, die eine Krebserkrankung berichteten, gaben 88,3 % der Teilnehmenden an, nur eine Krebserkrankung gehabt zu haben. Bei Frauen war die häufigste bösartige Krebserkrankung Brustkrebs, gefolgt von Gebärmutterhalskrebs und malignem Melanom, bei Männern Prostatakrebs, gefolgt von malignem Melanom und Darmkrebs. Beim Vergleich der Krebserkrankungen, die von 45- bis 74-jährigen NAKO-Teilnehmenden in den letzten fünf Jahren berichtet wurden, mit krebsregisterbasierten 5‑Jahres-Prävalenzen wurden für die meisten Tumorlokalisationen in der NAKO niedrigere relative Häufigkeiten beobachtet. Vergleichsweise häufiger traten das maligne Melanom sowie Gebärmutterhalskrebs und Leberkrebs bei Frauen und Harnblasenkrebs und Brustkrebs bei Männern auf. DISKUSSION: Die NAKO ist eine reichhaltige Datenbasis für die zukünftige Untersuchung inzidenter Krebserkrankungen. BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIAL AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5‑year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer.

Die korperliche Aktivitat stellt ein komplexes Verhalten dar, dessen valide und reliable Erfassung in gros angelegten populationsbasierten Studien mit besonderen Herausforderungen einhergeht. In der bundesweiten NAKO Gesundheitsstudie liegen zur Halbzeit der Basiserhebung die Daten zur korperlichen Aktivitat fur 100.000 Teilnehmende vor. Beschreibung der Erfassung der korperlichen Aktivitat und Prasentation erster deskriptiver Ergebnisse. Das multimodale Erhebungskonzept bestand aus zwei Fragebogen, dem Questionnaire on Annual Physical Activity Pattern (QUAP) und dem Global Physical Activity Questionnaire (GPAQ), einem computerbasierten Erinnerungsprotokoll der vergangenen 24 h (cpar24) und einer 7‑Tage-Akzelerometrie (Actigraph GT3X/+; Fa. ActiGraph, Pensacola, FL, USA). Fur die einzelnen Erhebungsmodule lagen auswertbare Datensatze in unterschiedlicher Zahl vor (QUAP: n = 16.372; GPAQ: n = 90.900; cpar24: n = 23.989; Akzelerometrie: n = 35.218). Die Analysen der einzelnen Module ergaben unterschiedliche Durchschnittswerte fur die moderate oder intensive korperliche Gesamtaktivitat der Teilnehmenden: Bei Frauen wurden 75–216 min/Tag gemessen, bei Mannern 73–224 min/Tag. Personen der Altersgruppe 20–39 Jahre verbrachten 66–200 min/Tag in moderater oder intensiver korperlicher Gesamtaktivitat, wahrend Personen der Altersgruppe 40–69 Jahre 78–244 min/Tag aufwendeten. Erste modulubergreifende Analysen der korperlichen Aktivitat in der NAKO zeigen den Nutzen komplementar eingesetzter Erhebungsmethoden. Die umfangreichen Daten stellen eine wertvolle Ressource fur die Charakterisierung der Zusammenhange zwischen korperlicher Aktivitat und Krankheitspravention dar, die in der Zukunft erfolgen soll.

Context/Objective Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D. Design/Patients Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n = 14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging. Results T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P Conclusions Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.

Background Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. Methods Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score–matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). Results Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84–1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85–3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41–9.68]). Conclusions Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations.

IntroductionAs chronic systemic autoimmune disease, which can affect every organ, SLE is creating significant burden and increased mortality. Despite better outcomes over the past decades by optimising standard of care, new interventions are needed for further improvements. Changing strategy to ‘treat-to-target’ (T2T) may be a promising concept proven successful in other chronic diseases.Methods and analysisIn this cluster-randomised trial, SLE centres will be assigned 1:1:1 to standard of care (SoC), remission (no clinical disease activity+prednisolone ≤5 mg/day+Physician Global Assessment (PGA 0–3) ConclusionsThis is the first trial to assess if the implementation of a T2T concept in clinical care minimises damage accrual and improves HRQoL in patients with SLE. Comparison of remission and LLDAS will help to identify the target with the best benefit–risk ratio concerning attainability, adverse events and damage. The emphasis on SDM will strengthen patient autonomy and will improve both their satisfaction and medical condition.

IntroductionWomen with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus compared with women who never had GDM. Consequently, the question of structured aftercare for GDM has emerged. In all probability, many women do not receive care according to the guidelines. In particular, the process and interaction between obstetrical, diabetic, gynaecological, paediatric and general practitioner care lacks clear definitions. Thus, our first goal is to analyse the current aftercare situation for women with GDM in Germany, for example, the participation rate in aftercare diabetes screening, as well as reasons and attitudes stated by healthcare providers to offer these services and by patients to participate (or not). Second, we want to develop an appropriate, effective and patient-centred care model.Methods and analysisThis is a population-based mixed methods study using both quantitative and qualitative research approaches. In various working packages, we evaluate data of the GestDiab register, of the Association of Statutory Health Insurance Physicians of North Rhine and the participating insurance companies (AOK Rheinland/Hamburg, BARMER, DAK Gesundheit, IKK classic, pronova BKK). In addition, quantitative (postal surveys) and qualitative (interviews) surveys will be conducted with randomly selected healthcare providers (diabetologists, gynaecologists, paediatricians and midwives) and affected women, to be subsequently analysed. All results will then be jointly examined and evaluated.Ethics and disseminationThe study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (Ethics Committee No.: 2019-738). Participants of the postal surveys and interviews will be informed in detail about the study and the use of data as well as the underlying data protection regulations before voluntarily participating. The study results will be disseminated through peer-reviewed journals, conferences and public information.Trial registration numberDRKS00020283.

Purpose The aims of this study were to analyze the prevalence and course of disordered eating behavior (DEB) in adolescents with intensively treated type I diabetes, describe differences in age-specific DEB symptoms, and identify predictors of current DEB. Methods Data were taken from 332/218 11- to 27-year-old participants (55.7% girls/women, mean age [SD] 17.8 [3.4] years, mean diabetes duration 14.9 [3.0] years) of two/three surveys of a Germany-wide longitudinal study on early-onset and long duration diabetes, respectively. A diabetes-adapted version of the SCOFF questionnaire was used to assess DEB. Both screening-based overall and age- and sex-specific prevalence of DEB and its symptoms were determined. To estimate transition probabilities between DEB states, first-order Markov transition models were implemented adjusting for previous sociodemographic, socioeconomic, and diabetes-specific covariates. Results The overall screening-based DEB prevalence among all 1,318 observations was 10.8% (95% confidence interval [CI]: 9.2%, 12.6%) with age-specific differences in symptom prevalence. Transition probabilities for developing/persistent DEB were twofold higher among female than male participants (risk ratio [RR] 2.3 [1.4, 3.9]/2.1 [1.3, 3.4]). In multiple adjusted regression, previous DEB (odds ratio [OR] 2.8 [95% CI 1.4, 5.6]), follow-up time (ORper 1-year increase 3.4 [1.4, 8.0]), and sex (ORgirls/women 2.1 [1.1, 3.9]) were the most important predictors of current DEB with further weaker associations for previous age and HbA1c. Conclusions Our results contribute to better understanding the course of DEB in patients with early-onset diabetes and emphasize the relevance of regular DEB screenings including the age group of young adults.

OBJECTIVE To evaluate whether the sodium–glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute change of −1.8% (95% CI −3.4, −0.2; P = 0.02) and relative change in LFC of −22% (−36, −7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change −2.5 kg [−3.7, −1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (−74 mol/L [−108, −42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.

Summary Background Cluster analyses have proposed different diabetes phenotypes using age, BMI, glycaemia, homoeostasis model estimates, and islet autoantibodies. We tested whether comprehensive phenotyping validates and further characterises these clusters at diagnosis and whether relevant diabetes-related complications differ among these clusters, during 5-years of follow-up. Methods Patients with newly diagnosed type 1 or type 2 diabetes in the German Diabetes Study underwent comprehensive phenotyping and assessment of laboratory variables. Insulin sensitivity was assessed using hyperinsulinaemic-euglycaemic clamps, hepatocellular lipid content using magnetic resonance spectroscopy, hepatic fibrosis using non-invasive scores, and peripheral and autonomic neuropathy using functional and clinical criteria. Patients were reassessed after 5 years. The German Diabetes Study is registered with ClinicalTrials.gov , number NCT01055093 , and is ongoing. Findings 1105 patients were classified at baseline into five clusters, with 386 (35%) assigned to mild age-related diabetes (MARD), 323 (29%) to mild obesity-related diabetes (MOD), 247 (22%) to severe autoimmune diabetes (SAID), 121 (11%) to severe insulin-resistant diabetes (SIRD), and 28 (3%) to severe insulin-deficient diabetes (SIDD). At 5-year follow-up, 367 patients were reassessed, 128 (35%) with MARD, 106 (29%) with MOD, 88 (24%) with SAID, 35 (10%) with SIRD, and ten (3%) with SIDD. Whole-body insulin sensitivity was lowest in patients with SIRD at baseline (mean 4·3 mg/kg per min [SD 2·0]) compared with those with SAID (8·4 mg/kg per min [3·2]; p Interpretation Cluster analysis can characterise cohorts with different degrees of whole-body and adipose-tissue insulin resistance. Specific diabetes clusters show different prevalence of diabetes complications at early stages of non-alcoholic fatty liver disease and diabetic neuropathy. These findings could help improve targeted prevention and treatment and enable precision medicine for diabetes and its comorbidities. Funding German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, Research Network SFB 1116 of the German Research Foundation, and Schmutzler Stiftung.

Background Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM). Methods To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m2) received Boost®high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2) ingested either Boost®high Protein 20 g protein or the isocaloric Boost®high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV). Results Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%). Conclusion MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses. Trial registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093

Background There is limited knowledge about mortality risk in persons with increased haemoglobin A(1c)(HbA(1c)) levels below the diabetes threshold. Moreover, little is known about how associations between increased HbA(1c)and mortality depend on the length of follow-up. Therefore, we studied associations between HbA(1c)and mortality over long-term follow-up in persons with and without known diabetes. Methods We used data from two German population-based cohort studies: KORA S4 Study (Southern Germany, n = 1458, baseline visits in 1999 to 2001, baseline age 55 to 74 years, mortality follow-up 16.8 years) and Heinz Nixdorf Recall (HNR) Study (Ruhr area, n = 4613, baseline visits in 2000 to 2003, baseline age 45 to 75 years, mortality follow-up 17.8 years). Adjusted log-linear models were fitted to estimate relative risks (RRs) with 95% confidence intervals (CI). Results In both cohorts, participants with HbA(1c)39 to 41 mmol/mol (5.7%-5.9%) and HbA(1c)42 to 46 mmol/mol (6.0% to 6.4%) did not have a larger overall mortality risk than participants with HbA(1c) < 39 mmol/mol (5.7%): the corresponding adjusted RRs were 1.00 (95% CI: 0.83-1.21) and 1.01 (0.80-1.27) in KORA and 0.99 (0.82-1.21) and 0.83 (0.65-1.07) in the HNR Study. For the pooled cohorts, the RR for HbA(1c)39 to 46 mmol/mol (5.7%-6.4%) was 0.96 (0.85-1.07). Associations between newly detected diabetes (HbA(1c) >= 6.5%) and mortality were weak after 4 and 8 years of follow-up, but were stronger after 12 years of follow-up, whereas associations between previously known diabetes (baseline) and mortality decreased. Conclusions HbA(1c)-defined pre-diabetes is not associated with overall mortality. For newly detected and previously known diabetes, mortality risks vary with length of follow-up.

In a non-interventional study of older persons, we assessed the impact of changes in BMI and waist circumference (WC) on reversion from glucose- and HbA1c-defined prediabetes to normoglycaemia (in short: reversion) and on persistence of normoglycaemia. Moreover, we studied whether reversion reduced cardiovascular risk.From the population-based KORA S4/F4/FF4 cohort study conducted in Southern Germany, we utilized data from the second and third visit to the study center (median follow-up 6.5 years). We used two overlapping data sets, one with 563 persons with HbA1c6.5% (mean age 69 years, 51.5% men), one with 510 persons with glucose-based prediabetes or normal glucose tolerance. We calculated proportions of reversion, and estimated adjusted relative risks for the association between initial BMI/WC and change of BMI/WC, respectively, and reversion (and persistence of normoglycaemia, respectively). We estimated 10-year cardiovascular risks using the Framingham 2008 score. Overall, 27.3% of persons with HbA1c-defined prediabetes and 9.2% of persons with glucose-based prediabetes returned to normoglycaemia during follow-up. Lower initial BMI/WC and reduction of BMI/WC were associated with larger probabilities of returning to normoglycaemia (e.g., for HbA1c 5.7-6.4%, RR = 1.24 (95% CI: 1.09-1.41) per 1 kg/mIn older adults, even moderate weight reduction contributes to reversion from prediabetes to normoglycaemia and to maintaining normoglycaemia.

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal mitochondrial capacity. While oxidative capacity can be increased in steatosis, hepatic ATP decreases in long-standing diabetes. However, longitudinal studies on diabetes-related NAFLD and its relationship to hepatic energy metabolism are lacking.This prospective study comprised volunteers with type 1 (T1DM, n = 30) and type 2 (T2DM, n = 37) diabetes. At diagnosis and 5 years later, we usedAt diagnosis, individuals with T2DM had higher HCL and adipose tissue volumes, but lower whole-body insulin sensitivity than those with T1DM, despite comparable glycemic control. NAFLD was present in 38% of individuals with T2DM and 7% with T1DM. After 5 years, visceral adipose tissue only increased in individuals with T2DM, while HCL almost doubled in this group (p0.001), resulting in a 70% prevalence of NAFLD (independent of diabetes treatment). Changes in HCL correlated with adipose tissue volume and insulin resistance (r = 0.50 and r = 0.44, both p0.05). Pi decreased by 17% and 10% in individuals with T2DM and T1DM (p0.05), respectively. In T1DM, HCL did not change, whereas γATP decreased by 10% and correlated negatively with glycated hemoglobin (r = -0.56, p0.05).The rapid increase in HCL during the early course of T2DM likely results from enlarging adipose tissue volume and insulin resistance in response to impaired hepatic mitochondrial adaptation. The decrease of phosphorus metabolites in T1DM may be due to pharmacological insulin supply.Previous studies suggested that the impaired function of mitochondria, the power plants of cells, can promote fatty liver and type 2 diabetes mellitus. This study now shows that during the first 5 years of type 2 diabetes the increase in body fat content rapidly leads to a doubling of liver fat content, whereas the energy metabolism of the patients' livers progressively declines. These data suggest that fat tissue mass and liver mitochondria have an important role in the development of fatty liver disease in humans with diabetes.NCT01055093.

Objectives We assessed disagreements between nonrandomized controlled studies based on real-world data (NRCS-RWDs) and randomized controlled trials (RCTs). Study Design and Setting We systematically searched for studies that compared treatment effect estimates from NRCS-RWDs and RCTs on the same clinical question. We assessed the potential difference between NRCS-RWDs and RCTs related to internal and external validity. We calculated various meta-epidemiological measures to assess agreement. In case of disagreements, we tried to identify the probable causes of disagreements. Results We included 12 studies comparing 15 treatment effect estimates of NRCS-RWDs and RCTs. There were many potential causes of disagreement. Ninety-five percent confidence intervals overlapped for 12 of 15 treatment effect estimates. Our analysis on predicted vs. observed overlap showed that there were no more disagreements than expected by chance. We observed only two substantial differences between the 15 treatment effect estimates. In both cases, we identified risk of bias in the NRCS-RWDs as the most probable cause of disagreement. Conclusion Our findings suggest that there are clinical questions where the difference in risk of bias between a well-conducted NRCS-RWD and an RCT is negligible. In our analysis, threats to external validity appeared to have no or only a weak impact on the disagreements of treatment effect estimates.

Using data from DISCOVER (NCT02322762; NCT02226822), a 3-year, global, observational study programme of patients with type 2 diabetes initiating second-line glucose-lowering therapy, we assessed socioeconomic factors associated with hypoglycaemic events and fear of hypoglycaemia.Data were collected at baseline (second-line therapy initiation) and 6, 12 and 24 months. Factors associated with experiencing a hypoglycaemic event at baseline or during follow-up were determined using a hierarchical logistic regression model and an interval-censored survival analysis, respectively. Fear of hypoglycaemia was assessed using the hypoglycaemia fear survey-II (HFS-II).The overall proportion of patients reporting hypoglycaemic events during follow-up was 7.3%; this was higher in middle-income countries than in high-income countries (8.4% vs 5.8%, p 0.001). Factors associated with an increased risk of hypoglycaemia during follow-up included living in a country with a low gross national income, use of glucose-monitoring equipment and second-line treatment with insulin, meglitinides or sulphonylureas (versus metformin). Experiencing hypoglycaemia was associated with increased HFS-II worry and overall scores.Our results highlight the global inequity in the treatment of type 2 diabetes. Increased risk of hypoglycaemia in middle-income countries may be explained by limited treatment options and may be underestimated because of limited access to glucose-monitoring equipment.

HINTERGRUND: Muskuloskelettale Symptome und Erkrankungen sind in der Bevölkerung sehr weit verbreitet und verursachen hohe Kosten in Gesundheitswesen und Volkswirtschaft. ZIEL DER ARBEIT: Die Häufigkeit muskuloskelettaler Symptome und Erkrankungen aus den Bereichen Rückenschmerzen, Osteoporose, Arthrose und Arthritis wurde auf Basis von Daten der bevölkerungsbasierten NAKO Gesundheitsstudie beschrieben. MATERIAL UND METHODEN: Die Daten wurden in der ersten Hälfte der NAKO-Basiserhebung von März 2014 bis März 2017 bei Erwachsenen im Alter von 20–75 Jahren erhoben. In die Analysen gingen Daten von 101.779 Interviewteilnehmenden sowie von 9370 Teilnehmenden aus zwei klinischen Untersuchungen ein. Mittels der klinischen Handuntersuchung wurden tastbar geschwollene Gelenke sowie auf Druck schmerzhafte Gelenke identifiziert. Die Winkelstuhluntersuchung lieferte Daten zu Ruheschmerzen am Knie- und Hüftgelenk. Häufigkeiten wurden auf die deutsche Standardbevölkerung 2011 gewichtet. ERGEBNISSE: In den Selbstberichten der Teilnehmenden im Interview wurden am häufigsten jemals diagnostizierte andauernde Rückenschmerzen (22,5 %) und Arthrosen (20,6 %) angegeben, seltener Osteoporose (2,9 %) und rheumatoide Arthritis (1,9 %). In der Handuntersuchung wurden bei 6,0 % Schmerzen an mindestens einem Fingergelenk festgestellt. Laut Winkelstuhluntersuchung waren 8,2 % von einem Ruheschmerz in mindestens einem Knie betroffen sowie 5,1 % an der Hüfte. Frauen berichteten insgesamt häufiger muskuloskelettale Erkrankungen und Symptome als Männer, der Anteil Betroffener nahm mit dem Alter deutlich zu. DISKUSSION: Die Ergebnisse belegen die große Verbreitung vieler muskuloskelettaler Erkrankungen. Die berichtete Beschwerdelast ist mit Ergebnissen aus früheren bevölkerungsbezogenen Erhebungen vergleichbar. BACKGROUND: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy. OBJECTIVES: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis. MATERIAL AND METHODS: Data were collected from March 2014 to March 2017 in adults aged 20–75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011. RESULTS: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age. CONCLUSION: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20–69 years derived from random samples of the German general population were recruited in 18 study centers (2014–2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases. HINTERGRUND: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinäres Forschungsvorhaben mit dem Ziel, die Ursachen für chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Überblick über das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre Qualitätssicherung zur Halbzeit der Basiserhebung. METHODEN: Für die Basiserhebung wurden mehr als 200.000 Frauen und Männer im Alter von 20–69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014–2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien für alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm für mindestens 20 % (Level 2) und eine Magnetresonanztomografie (MRT) für 30.000 Teilnehmerinnen und Teilnehmer. Sekundär- und Registerdaten werden über Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. ERGEBNISSE: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18 %. Die Teilnahme an den Untersuchungen lag überwiegend bei mehr als 95 %. Bei 96 % der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollständig durchgeführt werden. Der Erschließung und wissenschaftlichen Nutzung ergänzender Sekundär- und Registerdaten stimmten mehr als 90 % der Teilnehmerinnen und Teilnehmer zu. DISKUSSION: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzuführen, war trotz des zeitlichen Aufwandes außerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource für die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur Früherkennung, Vorhersage und Primärprävention chronischer Krankheiten zu entwickeln.

Übergewicht und Adipositas sind bedeutende Risikofaktoren für verschiedene Erkrankungen. Als Maß zu ihrer Bestimmung wurde in früheren Studien meist nur der Body-Mass-Index (BMI) verwendet. Der BMI ist allerdings ein Marker, der den Einfluss auf das Krankheitsrisiko nur unzureichend erfasst. In groß angelegten, bevölkerungsbasierten Studien besteht daher ein vordringlicher Bedarf, verbesserte Messmethoden der Körperzusammensetzung und -fettverteilung einzusetzen. Der vorliegende Beitrag stellt die in der NAKO (Nationale Kohorte) Gesundheitsstudie eingesetzten Messverfahren zur Beschreibung von Körperzusammensetzung und -fettverteilung und die ersten deskriptiven Ergebnisse vor. Diese beziehen sich auf die Daten zur Halbzeit der Basiserhebung, welche 101.817 Teilnehmende einschließt, die in 18 Studienzentren in Deutschland zwischen März 2014 und März 2017 untersucht worden sind. Die anthropometrischen Messungen umfassten Körpergewicht, Körpergröße und -umfänge, bioelektrische Impedanzanalyse (BIA), Sonographie des Abdominalfettes, 3‑D-Bodyscanner und Magnetresonanztomographie. Die Analyse des BMI zeigte, dass 46,2 % der Männer sowie 29,7 % der Frauen übergewichtig und 23,5 % der Männer und 21,2 % der Frauen adipös waren. Frauen wiesen im Mittel in fast allen Altersgruppen eine höhere Schichtdicke an subkutanem Fettgewebe auf als Männer. Die mittlere Schichtdicke des viszeralen Fettgewebes lag hingegen bei den Männern in allen Altersgruppen über den Werten der Frauen und stieg bei beiden Geschlechtern über die Altersgruppen kontinuierlich an. Die umfassenden Daten über die Körperfettverteilung und -zusammensetzung ermöglichen es zukünftig, den Einfluss von Übergewicht und Adipositas auf die Entstehung von chronischen Erkrankungen im Detail zu analysieren. High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here – for example on determinants of susceptibility to self-reported infections – can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed. HINTERGRUND: Infektionen spielen für das Krankheitsempfinden, für gesundheitsökonomische Überlegungen sowie Public Health in Deutschland weiterhin eine wichtige Rolle. Sie wurden in den letzten Jahren außerdem mit der Entstehung von nichtübertragbaren Erkrankungen in Zusammenhang gebracht. Die NAKO Gesundheitsstudie kann Erkenntnisse auf diesem Gebiet vertiefen und damit zielgenaueren präventiven Ansätzen den Weg bereiten. ZIEL: Die infektionsbezogenen Erhebungsinstrumente sollen beschrieben und in Bezug zu Erhebungsarten anderer deutscher Studien gesetzt werden. Zudem werden erste Daten zur Häufigkeit von Infektionskrankheiten berichtet. METHODEN: Fragen zu Infektionskrankheiten wurden in der NAKO-Basiserhebung sowohl im Interview als auch im Selbstausfüllerfragebogen (Touchscreen) gestellt. Es wurden die Daten der ersten 101.787 Teilnehmenden ausgewertet. ERGEBNISSE: Das Auftreten von Herpes Zoster (HZ), Post-Zoster-Neuralgie (bei Angabe von HZ), Hepatitis B/C, HIV/Aids und Tuberkulose im Sinne einer ärztlichen Diagnose bzw. von Sepsis als Grund für eine stationäre Behandlung wurde von 0,2 % (HIV/Aids) bis 8,6 % (HZ) der Befragten im Interview angegeben. Im Touchscreenmodul wurde das mindestens einmalige Auftreten einer Infektion der oberen Atemwege (IOA), der unteren Atemwege, des Magen-Darm-Traktes, der Harnblase oder von Fieber in den letzten 12 Monaten von 12 % (Zystitis) bis 81 % (IOA) berichtet. AUSBLICK: Weitere Ergebnisse anhand von Daten aus den hier vorgestellten Fragebögen sind im Querschnittsdesign – beispielsweise zu Determinanten der Anfälligkeit für selbst berichtete Infektionen – ab 2021 zu erwarten. Die Bearbeitung darüber hinausgehender Forschungsfragen der Infektionsepidemiologie wird insbesondere nach Analysen von NAKO-Bioproben möglich sein.

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time. HINTERGRUND: Asthma bronchiale stellt über alle Bildungsschichten hinweg eine der häufigsten chronischen Erkrankungen im Kindes- und Erwachsenenalter dar. Im Erwachsenenalter erstmals auftretendes Asthma (Adult-onset Asthma, AOA) ist im Vergleich zu Childhood-onset Asthma (COA) mit einer schlechteren Prognose assoziiert, was verstärkte Untersuchungen in diesem Bereich erfordert. Ziel der Arbeit war es, Häufigkeiten und das Alter bei Erstdiagnose aus Selbstangaben zu Asthma bei Erwachsenen in der NAKO Gesundheitsstudie darzustellen und mit Daten der Studie zur Gesundheit Erwachsener in Deutschland (DEGS) zu vergleichen. MATERIAL UND METHODEN: Unsere Analyse beruht auf einem Datensatz zur Halbzeit der NAKO-Basiserhebung mit 101.284 Personen. Verwendete Variablen waren die Selbstangabe zum jemals ärztlich diagnostizierten Asthma, Alter bei Erstdiagnose, Behandlung in den letzten 12 Monaten, Alter und Geschlecht. ERGEBNISSE: Laut Datenbasis zur Halbzeit berichteten in der NAKO 8,7 % der Frauen und 7,0 % der Männer, dass bei ihnen jemals Asthma diagnostiziert wurde. Etwa bei einem Drittel der Teilnehmenden mit Asthma wurde die Diagnose bereits im Kindes‑/Jugendalter (

Die körperliche Fitness ist das Maß für die individuelle Fähigkeit, körperlich aktiv zu sein. Ihre wesentlichen Komponenten sind die kardiorespiratorische Fitness (Cardiorespiratory Fitness, CRF), die Muskelkraft und die Beweglichkeit. Neben der körperlichen Aktivität ist die körperliche Fitness ein wesentlicher Prädiktor für Morbidität und Mortalität. Ziel der Arbeit sind die Beschreibung der Erhebungsmethoden körperlicher Fitness in der NAKO Gesundheitsstudie und die Darstellung erster deskriptiver Ergebnisse. In der NAKO-Basiserhebung wurden die maximale Handgreifkraft (Grip Strength, GS) und die CRF als Komponenten der körperlichen Fitness über ein Handdynamometer bzw. über einen Fahrradergometertest mit submaximaler Belastung erhoben. Daraus wurde die maximale Sauerstoffaufnahme (VO2max) zur Beurteilung der CRF abgeleitet. Die Ergebnisse von insgesamt 99.068 GS-Messungen und 3094 Messungen der CRF beruhen auf einem Datensatz zur Halbzeit der Basiserhebung der NAKO (Alter 20–73 Jahre, 47 % Männer). Männer zeigten im Vergleich zu Frauen höhere Werte der körperlichen Fitness (Männer: GS = 47,8 kg, VO2max = 36,4 ml·min−1 · kg−1; Frauen: GS = 29,9 kg, VO2max = 32,3 ml·min−1 · kg−1). Ungefähr ab dem 50. Lebensjahr konnte ein Rückgang der GS verzeichnet werden, wohingegen die CRF ab der Altersgruppe 20–29 Jahre bis zu den ≥60-Jährigen kontinuierlich abfiel. Die GS und die VO2max zeigten nach Korrektur für das Körpergewicht einen linear positiven Zusammenhang (Männer β = 0,21; Frauen β = 0,35). Die Analysen zeigten eine gute Übereinstimmung der Verteilung der körperlichen Fitness in der NAKO im Vergleich zu anderen bevölkerungsbasierten Studien. Zukünftige Auswertungen werden insbesondere die unabhängige Bedeutung der GS und CRF bei der Prädiktion von Morbidität und Mortalität beleuchten. Physical fitness is defined as an individual’s ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality. The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort. In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20–73 years, 47% men). Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min−1 · kg−1; females: GS = 29.9 kg, VO2max = 32.3 ml · min−1 · kg−1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20–29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35). These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.

BACKGROUND: Data on self-reported cardiovascular and metabolic diseases are available for the first 100,000 participants of the population-based German National Cohort (GNC, NAKO Gesundheitsstudie). OBJECTIVES: To describe assessment methods and the frequency of self-reported cardiovascular and metabolic diseases in the German National Cohort. MATERIALS AND METHODS: Using a computer-based, standardized personal interview, 101,806 participants (20–75 years, 46% men) from 18 nationwide study centres were asked to use a predefined list to report medical conditions ever diagnosed by a physician, including cardiovascular or metabolic diseases. For the latter, we calculated sex-stratified relative frequencies and compared these with reference data. RESULTS: With regard to cardiovascular diseases, 3.5% of men and 0.8% of women reported to have ever been diagnosed with a myocardial infarction, 4.8% and 1.5% with angina pectoris, 3.5% and 2.5% with heart failure, 10.1% and 10.4% with cardiac arrhythmia, 2.7% and 1.8% with claudicatio intermittens, and 34.6% and 27.0% with arterial hypertension. The frequencies of self-reported diagnosed metabolic diseases were 8.1% and 5.8% for diabetes mellitus, 28.6% and 24.5% for hyperlipidaemia, 7.9% and 2.4% for gout, and 10.1% and 34.3% for thyroid diseases. Observed disease frequencies were lower than reference data for Germany. CONCLUSIONS: In the German National Cohort, self-reported cardiovascular and metabolic diseases diagnosed by a physician are assessed from all participants, therefore representing a data source for future cardio-metabolic research in this cohort. HINTERGRUND: Aus der NAKO Gesundheitsstudie, der größten deutschen bevölkerungsbasierten Studie zur Gesundheit, liegen die Daten zu selbst berichteten kardiovaskulären und metabolischen Erkrankungen der ersten ca. 100.000 Teilnehmenden vor. ZIEL: Beschreibung der Methoden zur Erhebung sowie Berechnung der Häufigkeit kardiovaskulärer und metabolischer Erkrankungen in der NAKO. MATERIAL UND METHODEN: 101.806 Teilnehmende (20–75 Jahre, 46 % Männer) aus 18 bundesweiten Studienzentren wurden in einem computergestützten, standardisierten persönlichen Interview gebeten, anhand einer vorgegebenen Liste anzugeben, welche Erkrankungen bei ihnen jemals ärztlich diagnostiziert wurden, darunter auch kardiovaskuläre und metabolische Erkrankungen. Für Letztere wurden deren geschlechtsspezifische relative Häufigkeiten berechnet und diese mit Referenzzahlen verglichen. ERGEBNISSE: Bezogen auf die kardiovaskulären Erkrankungen berichteten 3,5 % der Männer und 0,8 % der Frauen, jemals einen Herzinfarkt diagnostiziert bekommen zu haben, 4,8 % bzw. 1,5 % eine Angina pectoris, 3,5 % bzw. 2,5 % eine Herzinsuffizienz, 10,1 % bzw. 10,4 % Herzrhythmusstörungen, 2,7 % bzw. 1,8 % eine Claudicatio intermittens und 34,6 % bzw. 27,0 % eine arterielle Hypertonie. Die Häufigkeit berichteter diagnostizierter metabolischer Erkrankungen lag bei 8,1 % bzw. 5,8 % für Diabetes mellitus, bei 28,6 % bzw. 24,5 % für Hyperlipidämie, bei 7,9 % bzw. 2,4 % für Gicht und bei 10,1 % bzw. 34,3 % für Schilddrüsenerkrankungen. Die beobachteten Häufigkeiten lagen insgesamt etwas niedriger als Vergleichsdaten für Deutschland. DISKUSSION: Die NAKO erhebt von allen Teilnehmenden selbst berichtete, ärztlich diagnostizierte kardiovaskuläre und metabolische Erkrankungen und stellt damit eine Datenressource für weitergehende kardiometabolische Forschungsfragestellungen dar.

HINTERGRUND: Arterielle Hypertonie ist einwichtiger Risikofaktor für Herz-Kreislauf-Er-krankungen. Epidemiologische Studien führen meist drei konsekutive Blutdruckmessungen durch. Der 1. Messwert wird für Auswertungen verworfen, da dieser am stärksten durch vorhergehende Aktivitäten beeinflusst sein kann. Aus zeitlichen Gründen wurden in der NAKO Gesundheitsstudie nur zwei Messungen durchgeführt. FRAGESTELLUNG: Die vorliegende Analyse untersucht Auswirkungen methodischer Unterschiede bei der Blutdruckmessungauf die Hypertoniehäufigkeit und mittlere Blutdruckwerte anhand eines Vergleichsder ersten Hälfte der NAKO-Teilnehmenden(nur 2 Messungen) mit 5 deutschen populationsbasierten Studien (3 Messungen). MATERIAL UND METHODEN: Es wurden Daten der Teilnehmenden aus der NAKO (erste 101.816 Personen), der bundesweiten Studie zur Gesundheit Erwachsener des Robert Koch-Instituts (DEGS1) und aus 4 regionalen populationsbasierten Kohortenstudien (CARLA, HNR, KORA, SHIP) analysiert. Alters- und geschlechtsspezifische mittlere Blutdruckwerte und Hypertoniehäufigkeiten wurden auf Basis des 2. Messwertes, des Mittelwerts aus 1. und 2. sowie aus 2. und 3. Messung berechnet. ERGEBNISSE: Die mittleren Blutdruckwerte der beiden aktuellsten Studien (NAKO und DEGS1) sind sehr ähnlich und niedriger als in den anderen Studien. Die Differenz zwischen dem 2. Messwert und dem Mittelwert aus 2. und 3. Messung ist gering (maximale mittlere Abweichung: 1,5mmHg systolisch), jedoch ist die mittels des 2. Messwertes berechnete Hypertoniehäufigkeit der Bevölkerung höher als bei Verwendung des Mittelwertsaus 2. und 3. Messung. DISKUSSION: Die Ergebnisse der vorliegenden Analyse zeigen, dass für die wissenschaftliche Auswertung der NAKO-Daten die Verwendung des 2. Blutdruckmesswerts zu empfehlen ist. BACKGROUND: Arterial hypertension is an important risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. OBJECTIVES. The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). MATERIALS AND METHODS: Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate age-and sex-specific mean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). RESULTS: The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mmHg systolic blood pressure), but leads to higher estimated hypertension frequencies. CONCLUSIONS: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data.

Aims/hypothesis Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death. Methods This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool. Results A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19. Conclusions/interpretation Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted. Registration PROSPERO registration ID CRD42020193692. Graphical abstract

Objective To analyze the interrelationship of metabolic control, age- and sex-adjusted body mass index, and daily insulin dose and to identify heterogeneous multivariate developmental curves from childhood to young adulthood in a large cohort of children with type 1 diabetes (T1D) Study design Data were extracted from the diabetes follow-up registry DPV. Longitudinal data from 9239 participants with T1D age 8-18 years with diabetes duration ≥2 years and ≥5 years of follow-up were analyzed. We applied group-based multitrajectory modeling to identify latent groups of subjects following similar developmental curves across outcomes (hemoglobin A1c [HbA1c], age/sex-standardized body mass index [BMI-SDS], daily insulin dose per kg). Group number was based on Bayes information criterion and group size (≥5%). Results The group-based multitrajectory approach revealed 5 heterogeneous 3-variate trajectories during puberty. Individuals with stable good metabolic control, high-normal increasing BMI-SDS, and rising insulin dose patterns were classified as group 1 (33%). Group 2 (20%) comprised youths with intermediate-increasing HbA1c, low BMI-SDS, and steeply increasing insulin dose trajectories. Group 3 (11%) followed intermediate-rising HbA1c and high-normal increasing BMI-SDS developmental curves, while insulin dose increased steeply. In group 4 (14%), both high-increasing HbA1c and insulin dose trajectories were observed, while BMI-SDS was stable-normal. Group 5 (22%) included subjects with intermediate-rising HbA1c patterns, high-increasing BMI-SDS, and increasing insulin dose patterns. Conclusions This study identified 5 distinct 3-variate curves of HbA1c, BMI-SDS, and insulin dose during puberty among youths with T1D. This approach demonstrates a considerable heterogeneity highlighting the importance of personalized medical care.

In systematic reviews, meta-analyses are routinely applied to summarize the results of the relevant studies for a specific research question. If one can assume that in all studies the same true effect is estimated, the application of a meta-analysis with common effect (commonly referred to as fixed-effect meta-analysis) is adequate. If between-study heterogeneity is expected to be present, the method of choice is a meta-analysis with random effects. The widely used DerSimonian and Laird method for meta-analyses with random effects has been criticized due to its unfavorable statistical properties, especially in the case of very few studies. A working group of the Cochrane Collaboration recommended the use of the Knapp-Hartung method for meta-analyses with random effects. However, as heterogeneity cannot be reliably estimated if only very few studies are available, the Knapp-Hartung method, while correctly accounting for the corresponding uncertainty, has very low power. Our aim is to summarize possible methods to perform meaningful evidence syntheses in the situation with only very few (ie, 2-4) studies. Some general recommendations are provided on which method should be used when. Our recommendations are based on the existing literature on methods for meta-analysis with very few studies and consensus of the authors. The recommendations are illustrated by 2 examples coming from dossier assessments of the Institute for Quality and Efficiency in Health Care.

Aims There is still debate on the optimal threshold for population-based screening of diabetes (diagnosed by the oral glucose tolerance test) using tests like HbA1c or fasting plasma glucose. Meta-analyses provide meaningful input in such situations. The aim of this article is to perform a meta-analysis that includes the complete information reported in the individual studies of two existing systematic reviews. Methods We screened the individual studies from two systematic reviews and reconstructed the full four-fold tables for every reported threshold. Using a recently proposed meta-analysis model for the comparison of two diagnostic tests, we compared HbA1c with fasting plasma glucose, and estimated meta-analytic receiver operating characteristic curves for both tests using the 11.1 mmol/l threshold of the 2-h post-challenge glucose level (2 h-PG) as the gold standard. Results We included nine studies from two existing systematic reviews in our analysis. Based on our data set, the optimal threshold lies between 42 and 44 mmol/mol (6.0–6.2%) for HbA1c, and 6.2–6.4 mmol/l for fasting plasma glucose choosing the Youden index as the technical criterion. In addition, we found that there is no relevant difference in the performance of HbA1c and fasting plasma glucose. Conclusions In our meta-analysis, we found that the optimal threshold with reference to the 2 h-PG should be chosen between 42 and 44 mmol/mol (6.0–6.2%) for HbA1c, and 6.2–6.4 mmol/l for fasting plasma glucose on the basis of maximal sensitivity and specificity.

OBJECTIVE In Germany, as in many other countries, nationwide data on mortality attributable to diagnosed diabetes are not available. This study estimated the absolute number of excess deaths associated with diabetes (all types) and type 2 diabetes in Germany. RESEARCH DESIGN AND METHODS A prevalence approach that included nationwide routine data from 64.9 million people insured in the German statutory health insurance system in 2010 was used for the calculation. Because nationwide data on diabetes mortality are lacking in Germany, the mortality rate ratio from the Danish National Diabetes Register was used. The absolute number of excess deaths associated with diabetes was calculated as the number of deaths due to diabetes minus the number of deaths due to diabetes with a mortality that was as high as in the population without diabetes. Furthermore, the mortality population-attributable fraction was calculated. RESULTS A total of 174,627 excess deaths were due to diabetes in 2010, including 137,950 due to type 2 diabetes. Overall, 21% of all deaths in Germany were attributable to diabetes and 16% were attributable to type 2 diabetes. Most of the excess deaths (34% each) occurred in the 70- to 89-year-old age-group. CONCLUSIONS In this first nationwide calculation of excess deaths related to diabetes in Germany, the results suggest that the official German estimates that rely on information from death certificates are grossly underestimated. Countries without national cohorts or diabetes registries could easily use this method to estimate the number of excess deaths due to diabetes.

Aim The diet of people with type 1 diabetes may differ from that of healthy peers due to disease-related factors that may affect the course of diabetes. This cross-sectional study sought to compare meal and snacking frequency and corresponding carbohydrate intake among adolescents with intensively-treated type 1 diabetes and healthy peers and to analyze their association with glycemic control among diabetes patients. Methods Nutritional data of 712 11- to Results After comprehensive adjustment, diabetes patients had, on average, 4.6 [95% confidence interval 3.6, 5.5] more meals or snacks/week but consumed 75.9 [64.5, 87.3] fewer grams of carbohydrates/day than the comparison group. Diabetes subjects also consumed breakfast, lunch, dinner, and snacks more frequently but ate fewer carbohydrates at all eating occasions. Total carbohydrate intake and carbohydrate intake at breakfast were associated with higher HbA1c levels, while increased breakfast frequency was associated with lower HbA1c levels. Conclusion Eating frequency and carbohydrate intake differed between adolescents with early-onset type 1 diabetes and non-diabetic peers. The observed associations with glycemic control challenge the concept of a completely unregulated eating frequency and carbohydrate intake for people on intensified insulin therapy.

SummaryBackground The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. Objective To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. Methods In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers® on Scanpor® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. Results Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: −8% to 26%) for nickel sulfate and 23% (95%CI: −16% to 63%) for potassium dichromate, both favouring the strip patch test. Conclusions The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative.

OBJECTIVE Worsening of glycemic control in type 1 diabetes during puberty is a common observation. However, HbA1c remains stable or even improves for some youths. The aim is to identify distinct patterns of glycemic control in type 1 diabetes from childhood to young adulthood. RESEARCH DESIGN AND METHODS A total of 6,433 patients with type 1 diabetes were selected from the prospective, multicenter diabetes patient registry Diabetes-Patienten-Verlaufsdokumentation (DPV) (follow-up from age 8 to 19 years, baseline diabetes duration ≥2 years, HbA1c aggregated per year of life). We used latent class growth modeling as the trajectory approach to determine distinct subgroups following a similar trajectory for HbA1c over time. RESULTS Five distinct longitudinal trajectories of HbA1c were determined, comprising group 1 = 40%, group 2 = 27%, group 3 = 15%, group 4 = 13%, and group 5 = 5% of patients. Groups 1–3 indicated stable glycemic control at different HbA1c levels. At baseline, similar HbA1c was observed in group 1 and group 4, but HbA1c deteriorated in group 4 from age 8 to 19 years. Similar patterns were present in group 3 and group 5. We observed differences in self-monitoring of blood glucose, insulin therapy, daily insulin dose, physical activity, BMI SD score, body-height SD score, and migration background across all HbA1c trajectories (all P ≤ 0.001). No sex differences were present. Comparing groups with similar initial HbA1c but different patterns, groups with higher HbA1c increase were characterized by lower frequency of self-monitoring of blood glucose and physical activity and reduced height (all P < 0.01). CONCLUSIONS Using a trajectory approach, we determined five distinct longitudinal patterns of glycemic control from childhood to early adulthood. Diabetes self-care, treatment differences, and demographics were related to different HbA1c courses.

AIM For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany. METHODS Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population. Age- and sex-specific incidence and prevalence in 2014/2015, based on claims data from statutory health insurance (n= 69 000 000, ~85% of the German population), and the age pyramid for Germany in 2015 were used for the calculation. Age at Type 2 diabetes diagnosis was stratified by sex. CIs were estimated using bootstrap methods. In addition, the age range in which 50% of the population received a diagnosis of Type 2 diabetes was calculated (the interquartile range). RESULTS The mean ± sd age at Type 2 diabetes diagnosis in 2015 was 61.0 ± 13.4 years (95% CI 60.9-61.0) in men. Women were diagnosed ~2 years later than men (mean age 63.4 ± 14.9 years; 95% CI 63.4-63.5). The age range in which 50% of the population was diagnosed with diabetes was 53-72 years for men and 54-76 years for women. CONCLUSIONS The sex differences are mainly attributable to a higher incidence of Type 2 diabetes in men than women during middle age and the higher absolute number of women in the older ages. The early age at diabetes diagnosis compared to average life expectancy means that the risk of diabetes-related complications is increased.

Cluster analysis using age, BMI, glycemia and homeostasis model estimates (HOMA-IR, -B) revealed distinct risk profiles for progression of diabetic nephropathy in large cohorts, but its relevance for other diabetes-related comorbidities remains unclear. We aimed to (i) examine whether intensified phenotyping would confirm the results of this cluster analysis and (ii) test the hypothesis that liver fat content (HCL), as marker of nonalcoholic fatty liver disease (NAFLD), differs among clusters at diabetes diagnosis and during follow-up. Thus, this cluster analysis was applied to recent-onset patients with non-autoimmune diabetes of the German Diabetes Study. This identified 286 mild age-related (MARD, 44%), 268 mild obesity-related (MOD, 42%), 66 severe insulin-resistant (SIRD, 10%) and 27 severe insulin-deficient (SIDD, 4%) diabetes patients. Furthermore, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, HCL by magnetic resonance spectroscopy and hepatic fibrosis by a noninvasive score (NAFLD-FS). Congruently, whole-body insulin sensitivity was lowest in SIRD compared to MOD, SIDD and MARD (4.3±2.0 vs. 5.6±2.4, 6.5±2.6, 7.6±2.8 mg*kg-¹*min-¹, all p0.6) was highest in SIRD (21%) compared to SIDD (0%), MOD (16%) and MARD (11%). In conclusion, patients of the SIRD cluster exhibit higher prevalence of steatosis at diagnosis and increased risk of NAFLD progression over 5 years. Disclosure O.P. Zaharia: None. K. Strassburger: None. Y. Kupriyanova: None. Y. Karusheva: None. S. Antoniou: None. K. Bodis: None. O. Asplund: Research Support; Self; Eli Lilly and Company. V. Burkart: None. K. Muessig: None. J. Hwang: None. O. Kuss: None. L. Groop: None. E. Ahlqvist: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. Funding German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research

Type 2 diabetes (T2D) associates with nonalcoholic fatty liver disease (NAFLD), which itself contributes to both insulin resistance and excessive cardiovascular risk of diabetes. Nevertheless, there is currently no established therapy for NAFLD in T2D. This trial examined whether treatment with the sodium glucose transporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (HCL, primary outcome) in metabolically well-controlled patients with short known disease duration. T2D patients (n=84; 63±8 years; body mass index (BMI) 32.2±4.5 kg/m2, HbA1c 6.6±0.5%, disease duration 38±27 months) were randomly assigned to 24-week treatment with either EMPA 25 mg per day or placebo (PLAC). HCL was measured by 1H-magnetic resonance (MR) spectroscopy (STEAM) and fat-selective MR imaging (IDEAL). Statistical analysis was done by ANCOVA adjusted for the respective baseline value, age, sex and BMI. After treatment, HCL was reduced compared to baseline (relative change (RC) EMPA -33%[95% confidence interval -43;-23], p In conclusion, empagliflozin effectively reduces HCL in well-controlled T2D patients and increases serum adiponectin with beneficial effects on hepatocellular integrity. Thus, empagliflozin may improve NAFLD via distinct different mechanisms. Disclosure S. Kahl: None. S. Gancheva: None. K. Strassburger: None. C. Herder: None. J. Machann: None. H. Katsuyama: None. S. Kabisch: Research Support; Self; California Walnut Commission, Institute for Grain Processing, Nuthetal, J. Rettenmaier Söhne, Südzucker / Beneo. Other Relationship; Self; Berlin-Chemie AG, Sanofi. E. Henkel: None. S. Kopf: None. K. Kantartzis: None. Y. Kupriyanova: None. O. Kuss: None. J. Hwang: None. C. Kasperk: None. N. Stefan: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Sanofi. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. A.L. Birkenfeld: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. Funding Boehringer Ingelheim Pharma GmbH

Worsening metabolic control, weight changes and increasing insulin dose during puberty have emerged as a challenge in diabetes care. However, individual variation is large. Data from the German/Austrian/Luxembourgian diabetes registry DPV were used to identify distinct patterns of hemoglobin A1c (HbA1c), age/sex-standardized body mass index (BMI-SDS) and daily insulin dose from childhood to young adulthood. Longitudinal data from 9,239 participants with T1D aged 8 to 18 years with duration >=2 years and >=5 years of follow-up were analyzed. We applied group-based multitrajectory (GBMT) modeling, a generalization of the group-based trajectory approach, to identify latent groups of subjects following similar developmental curves over time across multiple variables (Nagin, 2018). The GBMT approach revealed five unique groups of heterogeneous HbA1c, BMI-SDS and insulin dose patterns over time (Fig1). Differences in age at onset, gender, migration background as well as height-SDS, insulin pump and CGM usage, frequency of SMBG and physical activity were found across all groups. The present study identified for the first time five distinct multitrajectories of HbA1c, BMI-SDS and insulin dose during puberty. This approach demonstrates that variability between individuals is obscured by statistics on central tendency. Disclosure A. Schwandt: None. O. Kuss: None. D.P. Dunstheimer: None. B. Karges: None. T.M. Kapellen: None. T. Meissner: None. M. Witsch: None. M. Flury: Other Relationship; Self; Pfizer Inc. S. Straubinger: None. R.W. Holl: None. Funding German Center for Diabetes Research; Robert Koch Institute; German Diabetes Association

In Germany, the nationwide population-based mammography screening program (MSP) was introduced in 2005 and is full-running since 2010. By 2014, incidence rates for invasive breast cancer were very similar to those of the pre-screening era. Therefore, the ongoing effect of the MSP on breast cancer surgery rates can now be investigated. We analyzed population-based breast-conserving (BCS) and mastectomy (MET) surgery rates (per 100,000) among women aged

We used data from the GUIDANCE Study to determine the care of people with type 2 diabetes according to age and accompanying cardiovascular diseases and to assess indicators of overtreatment of glycaemia. The GUIDANCE study was a retrospective, cross-sectional study from 2009–2010 based on the records of 7597 people in France, Belgium, Italy, the Netherlands, Sweden, UK, Ireland and Germany. We analysed the level of metabolic control achieved and blood glucose-lowering medication used in different age groups and in relation to accompanying diseases. 4.459 patients (59.1%) were 65 years or older. Their HbA1c levels were similar to those with

A low within-country variability and a large between-country variability in cancer incidence may indicate that ecologic factors are involved in the etiology of the disease. The aim of this study is to explore the within- and between-country variability of cancer incidence to motivate high-quality ecologic studies. We extracted age-standardized incidence rate estimates (world standard population) from 135 regions for the ten most frequent invasive cancers in Europe for non-Hispanic white populations from Cancer Incidence in Five Continents, Volume X. We fitted weighted multilevel Poisson regression models with random country effects for each cancer and sex. We estimated intraclass correlation coefficients (ICCs) and 95% confidence intervals (95% CIs). A high ICC indicates a low within- and a high between-country variability of rates. The two cancer sites with the highest ICC among men were prostate cancer (0.96, 95% CI: 0.92-0.99) and skin melanoma (0.78, 0.64-0.93). Among women, high ICCs were observed for lung cancer (0.84, 0.73-0.95) and breast cancer (0.80, 0.69-0.91). The two most prominent sex differences for ICC occurred for cancers of the head and neck (men: 0.70, 0.55-0.85, women: 0.19, 0.08-0.30) and breast cancer (men: 0.04, 0.01-0.07, women: 0.80, 0.69-0.91). ICCs were relatively low for pancreatic cancer (men: 0.23, 0.10-0.35; women: 0.13, 0.04-0.21) and leukemia (men: 0.12, 0.04-0.21; women: 0.08, 0.02-0.14). For cancers with high ICC for which systematic factors of the health care system, screening and diagnostic activities are not plausible explanations for between-country variations in incidence, cross-country sex-specific ecologic studies may be especially promising.

Purpose Recent studies highlighted that early diabetic neurodegeneration is present before microvascular changes are visible. Retinal neurodegeneration can decrease retinal layer thickness. We aimed to determine whether decreased retinal layer thickness is present already in the early time course of disease. Methods A cross-sectional analysis of patients and healthy adults from the German Diabetes Study (GDS, ClinicalTrials.gov Identifier number: CT01055093, https://clinicaltrials.gov/ct2/show/NCT01055093). Inclusion criteria were a diagnosis of diabetes mellitus (DM) within the last 12 months. Retinal layers thickness in the nasal pericentral segment was measured by spectral domain ocular coherence tomography (SD-OCT). For statistical analysis proc mixed (sas-version 9.4) was used. Results One hundred and seventy-eight eyes of 89 patients with type 1 DM (58 males, age 36 ± 11 years, BMI 25.5 ± 4.2 kg/m²) and 242 eyes of 121 patients with type 2 DM (84 males, age 53 ± 10 years, BMI 31.9 ± 6.3 kg/m²) with a disease duration of less than 1 year were compared to 76 eyes of 38 controls (27 males, age 41 ± 16 years, BMI 27.3 ± 6.4 kg/m²). Analysis of retinal layer thickness and visual function did not reveal a significant difference between patients and controls. Conclusion In the early course of DM potential, neurodegeneration does not relate to measureable changes of retinal layer thickness.

The aim of this study was to investigate the modifying effect of the glucose transporter (GLUT2) gene SLC2A2 (rs8192675) variant on the glycaemic response to metformin in individuals recently diagnosed with type 2 diabetes. Individuals with type 2 diabetes (n = 508) from the prospective German Diabetes Study (age [mean ± SD] 53 ± 10 years; 65% male; BMI 32 ± 6 kg/m2, metformin use 57%) underwent detailed metabolic characterisation (hyperinsulinaemic–euglycaemic clamp, IVGTT) during the first year after diagnosis. Participants provided self-reported data from the time of diagnosis. The change in fasting glucose was assessed in relation to SLC2A2 genotype and glucose-lowering treatment using two-way ANCOVA with gene×treatment interactions adjusted for age, sex, BMI and diabetes duration. The C variant allele of rs8192675 was associated with a higher prevalence of diabetes symptoms at diabetes diagnosis. In the metformin monotherapy group only, patients with a C allele showed a larger adjusted blood glucose reduction during the first year after diabetes diagnosis than patients with the TT genotype (6.3 mmol/l vs 3.9 mmol/l; genotype difference 2.4 mmol/l, p = 0.02; p value for genotype interaction [metformin monotherapy vs non-pharmacological therapy]

The American Diabetes Association (ADA) Expert Committee introduced impaired fasting glucose (IFG: 100–125 mg/dL [5.6–6.9 mmol/L]) as a category with an increased risk for diabetes (1). The World Health Organization (WHO) defined a higher IFG cut point of 110 mg/dL (6.1 mmol/L) because using the lower cut point would substantially increase IFG prevalence and there was no evidence it would lead to reduced progression to diabetes (2). Our aim was to estimate the long-term incidence of type 2 diabetes in people with isolated IFG (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT. Contrary to previous studies, we split IFG into two subcategories (i-IFGlow: 100 to

Given the short-comings of randomized controlled trials, such as low numbers of patients and events, we aimed to perform a network meta-analysis of observational trials on the effects of non-insulin glucose-lowering drugs on all-cause and cardiovascular mortality in type 2 diabetes. We searched MEDLINE and EMBASE through August 2017. From the 38 eligible studies, we extracted patient characteristics, exposure, outcome, confounder-adjusted effect measures, and risk of bias. All-cause and cardiovascular mortality risk were assessed with random-effects network meta-analysis. In 32 studies reporting on all-cause mortality (1,661,945 persons) and in 11 studies on cardiovascular mortality (358,784 persons), 119,591 (7.2%) and 9,221 (2.6%) persons, respectively, died during follow-up. Compared to metformin, sulfonylurea drugs (SU) increased all-cause mortality risk (HR: 1.42 (95% CI: 1.29-1.56)). Dipeptidyl peptidase-4 inhibitors (DDP4i) added to metformin significantly decreased all-cause mortality risk compared to metformin monotherapy (HR: 0.76 (0.63-0.93)), any other drug class as monotherapy, and SU + metformin dual therapy (HR: 0.69 (0.60-0.79)). DPP-4i + metformin dual therapy was associated with even larger reductions in risk of cardiovascular mortality; HR: 0.40 (0.21-0.79) when compared to metformin monotherapy, and HR: 0.41 (0.23-0.74) when compared to SU + metformin dual therapy. Glucagon-like-peptide-1 receptor agonists + metformin dual therapy tended to, but did not significantly, decrease mortality risk when compared to metformin monotherapy (all-cause mortality, HR: 0.88 (0.53-1.47); cardiovascular mortality, HR: 0.74 (0.30-1.82)). In conclusion, this large network meta-analysis evidently confirmed that SU, compared to metformin, increased all-cause mortality risk. DPP-4i + metformin dual therapy, compared to other treatments, resulted in a consistent risk reduction of both all-cause and cardiovascular mortality. Disclosure B. Bongaerts: None. L.M. Lindner: None. A. Hoyer: None. O. Kuss: None. C. Herder: Other Relationship; Self; Sanofi, Eli Lilly and Company. H. Al-Hasani: None. K. Müssig: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. W. Rathmann: Advisory Panel; Self; AstraZeneca. Research Support; Self; Novo Nordisk A/S.

Aims. To estimate the risk of microvascular complications and macrovascular risk factors among persons with early-onset (diagnosed at ages 0 to Methods. We conducted three population-based cross-sectional surveys in Germany (N=1789) to obtain information on exposures and five outcomes (retinopathy, nephropathy, dyslipidemia, hypertension, and a composite endpoint combining all four outcomes). For each outcome, log-binomial spline regression was applied to estimate the risk and dose-response relationship with diabetes duration and exposures. Results. The risk for microvascular complications increased after 14 years since diabetes diagnosis whereas dyslipidemia and hypertension were already prevalent at 10 years. The 15-year risk (95% confidence interval) of the composite endpoint for female and male patients was 22.9% (18.8%–27.9%) and 19.2% (15.5%–23.8%), respectively. Temporal trends suggested a decreasing risk between 2009 and 2016. Glycemic control, lifestyle-related factors, and SES, but not health care-related factors, were associated with the risk of the composite endpoint. Conclusions. In early-onset type 1 diabetes, there exists a considerable risk of complications and comorbidities already in young ages. Future research should focus on prevention of diabetic complications in young patients and clarification of pathways of the associations found.

PurposeTo analyse the association of area-level deprivation (German Index of Multiple Deprivation, GIMD 2010) with health- and disease-related quality of life (QoL) and glycaemic control (HbA1c) jointly with individual-level socioeconomic status (SES) in young patients with preschool-onset type 1 diabetes.MethodsA total of 425 male and 414 female patients aged 11-21years from a Germany-wide population-based survey completed the generic KINDL-R, the DISABKIDS chronic-generic module (DCGM-12), and the DISABKIDS diabetes-specific module with impact and treatment scales (QoL indicators; range 0-100 with higher scores representing better QoL). To analyse the association of area-level deprivation and SES with QoL and HbA1c, multiple linear regression models were applied adjusting for sociodemographic and health-related variables.ResultsMean QoL scores (SD) were 73.2 (12.2) for the KINDL-R, 76.1 (16.1) for the DCGM-12, 66.2 (19.9) for diabetes impact, and 56.4 (27.3) for diabetes treatment (DISABKIDS). Mean HbA1c was 8.3 (1.4)%. While both QoL outcomes and HbA1c level improved with increasing individual SES, no association was observed between area-level deprivation (GIMD 2010) and either outcome.ConclusionsCompared with individual SES, area-level deprivation seems to be of minor importance for QoL and glycaemic control in young people with early-onset type 1 diabetes.