Search

Aims Hemoglobin A1c (HbA1c) has been repeatedly questioned as a valid surrogate marker, especially for patient-relevant outcomes. The aim of this study was to validate the HbA1c value as a surrogate for all-cause mortality in people with type 2 diabetes. Methods The effect estimates for HbA1c lowering after treatment as well as reductions in all-cause mortality of randomized trials were extracted from a systematic review and updated. For the measurement of actual surrogacy, weighted linear regression models with a random intercept for the study effect were used with the all-cause mortality estimate (risk difference and log relative risk) as the outcome and the estimate for HbA1c difference as the covariate. Surrogacy was assessed according to the criteria of Daniels and Hughes. Results A total of 346 HbA1c-mortality-pairs from 205 single randomized trials were included in the analysis. Regarding the risk difference of all-cause mortality, there was no evidence for surrogacy of the HbA1c value. For the log relative risk, a small positive association between HbA1c and the all-cause mortality estimate (slope 0.129 [95% confidence interval −0.043; 0.302]) was observed. However, there was no sign of valid surrogacy. Conclusions Based on the results of more than 200 randomized trials, HbA1c is not a valid surrogate marker for all-cause mortality in people with type 2 diabetes.

Aims To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Materials and methods Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. Results A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Conclusions Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

The aim of this study was to analyze the incidence of type 1 diabetes in children and adolescents (20 years of age) during the COVID-19 pandemic (3/2020 to 12/2021) in Germany.The present study was based on the IQVIA longitudinal prescription database (LRx), All persons (age ≤ 20 years) with new insulin prescriptions from 2016 to 2021 (index date) were selected and stratified by age group. Weekly (age-specific) data were used to forecast the prescription incidence for the pandemic period based on pre-pandemic data and to explore the relationship between weekly reported age-specific COVID-19 incidences and type 1 diabetes incidence and rate ratios of observed vs. predicted diabetes incidence respectively.During the pre-pandemic period, there was a stable higher insulin prescription incidence during the winter period and a lower insulin prescription incidence during summer. During the pandemic period, there was less seasonal variation in incidence related to the finding that the observed incidence during summer in 2002 and 2021 was 44 % and 65 %, higher, respectively, than the expected incidence based on pre-pandemic year. We did not find any cross-correlations between the COVID-19 incidence and the type 1 diabetes incidence for any age group. Likewise, there were no cross-correlations between the COVID-19 incidence and the incidence rate ratios of observed incidences to predicted incidences.During the COVID-19 pandemic, there was less seasonal variation in the incidence of type 1 diabetes (defined by new insulin prescriptions), with higher observed than expected incidences during summer. We found no evidence that the increase in type 1 diabetes incidence during the COVID-19 pandemic relates to direct effects of COVID-19 pandemic.

Objective The aim of this study was to identify the occupational risk for a SARS-CoV-2 infection in a nationwide sample of German workers during the first wave of the COVID-19 pandemic (1 February–31 August 2020). Methods We used the data of 108 960 workers who participated in a COVID follow-up survey of the German National Cohort (NAKO). Occupational characteristics were derived from the German Classification of Occupations 2010 (Klassifikation der Berufe 2010). PCR-confirmed SARS-CoV-2 infections were assessed from self-reports. Incidence rates (IR) and incidence rate ratios (IRR) were estimated using robust Poisson regression, adjusted for person-time at risk, age, sex, migration background, study center, working hours, and employment relationship. Results The IR was 3.7 infections per 1000 workers [95% confidence interval (CI) 3.3–4.1]. IR differed by occupational sector, with the highest rates observed in personal (IR 4.8, 95% CI 4.0–5.6) and business adminis-tration (IR 3.4, 95% CI 2.8–3.9) services and the lowest rates in occupations related to the production of goods (IR 2.0, 95% CI 1.5–2.6). Infections were more frequent among essential workers compared with workers in non-essential occupations (IRR 1.95, 95% CI 1.59–2.40) and among highly skilled compared with skilled profes-sions (IRR 1.36, 95% CI 1.07–1.72). Conclusions The results emphasize higher infection risks in essential occupations and personal-related services, especially in the healthcare sector. Additionally, we found evidence that infections were more common in higher occupational status positions at the beginning of the pandemic. CA extern

Aim There is little evidence of the impact of diabetes risk scores on individual diabetes risk factors, motivation for behaviour changes and mental health. The aim of this study was to investigate the effect of applying a noninvasive diabetes risk score in primary care as component of routine health checks on physical activity and secondary outcomes. Methods Cluster randomised trial, in which primary care physicians (PCPs), randomised (1:1) by minimisation, enrolled participants with statutory health insurance without known diabetes, ≥ 35 years of age with a body mass index ≥ 27.0 kg/m2. The German Diabetes Risk Score was applied as add-on to the standard routine health check, conducted in the controls. Primary outcome was the difference in participants’ physical activity (International Physical Activity Questionnaire) after 12 months. Secondary outcomes included body mass index, perceived health, anxiety, depression, and motivation for lifestyle change. Analysis was by intention-to-treat principle using mixed models. Results 36 PCPs were randomised; remaining 30 PCPs (intervention: n = 16; control: n = 14) recruited 315 participants (intervention: n = 153; controls: n = 162). A slight increase in physical activity was observed in the intervention group with an adjusted mean change of 388 (95% confidence interval: − 235; 1011) metabolic equivalents minutes per week. There were no relevant changes in secondary outcomes. Conclusions The application of a noninvasive diabetes risk score alone is not effective in promoting physical activity in primary care. Clinical Trial Registration: ClinicalTrials.gov (NCT03234322, registration date: July 31, 2017).

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.

Regression models for continuous, binary, nominal, and ordinal outcomes almost completely rely on parametric models, whereas time-to-event outcomes are mainly analyzed by Cox’s Proportional Hazards model, an essentially non-parametric method. This is done despite a long list of disadvantages that have been reported for the hazard ratio, and also for the odds ratio, another effect measure sometimes used for time-to-event modelling. In this paper, we propose a parametric proportional risk model for time-to-event outcomes in a two-group situation. Modelling explicitly a risk instead of a hazard or an odds solves the current interpretational and technical problems of the latter two effect measures. The model further allows for computing absolute effect measures like risk differences or numbers needed to treat. As an additional benefit, results from the model can also be communicated on the original time scale, as an accelerated or a prolongated failure time thus facilitating interpretation for a non-technical audience. Parameter estimation by maximum likelihood, while properly accounting for censoring, is straightforward and can be implemented in each statistical package that allows coding and maximizing a univariate likelihood function. We illustrate the model with an example from a randomized controlled trial on efficacy of a new glucose-lowering drug for the treatment of type 2 diabetes mellitus and give the results of a small simulation study.

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.

Diagnostic accuracy studies often evaluate diagnostic tests at several threshold values, aiming to make recommendations on optimal thresholds for use in practice. Methods for meta-analysis of full receiver operating characteristic (ROC) curves have been proposed but still have deficiencies. We recently proposed a parametric approach that is based on bivariate time-to-event models for interval-censored data to this task. To increase the flexibility of that approach, to cover a wide range of distributions of diagnostic test values and to address the open point of model selection, we here suggest to use the generalized F family of distributions that includes previously used distributions for the bivariate time-to-event model as special cases. The results of a simulation study are given as well as an illustration by an example of population-based screening for type 2 diabetes mellitus.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19–74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

BACKGROUND: Numerous studies have reported an increase in mental disorders during the COVID-19 pandemic, but the exact reasons for this development are not well understood. In this study we investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. METHODS: We analyzed data from the German National Cohort (NAKO) Study. Between May and November 2020, 161 849 study participants answered questions on their mental state and social circumstances. Their responses were compared with data from the baseline survey before the pandemic (2014–2019). Linear fixed-effects models were used to determine whether individual changes in the severity of symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/ financial changes (controlling for various covariates). RESULTS: The prevalence of moderate or severe symptoms of depression and anxiety increased by 2.4% and 1.5%, respectively, during the COVID-19 pandemic compared with the preceding years. The mean severity of the symptoms rose slightly. A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91; 1.41], range 0–27). Increases were also seen for reduced working hours with no short-time allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. CONCLUSION: Depressive symptoms and anxiety disorders increased slightly in the study population during the first year of the COVID-19 pandemic. Occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures.

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.

It is unclear whether socio-economic status (SES) is associated with glycaemic control in people with recently diagnosed diabetes. The aim was to investigate whether SES is related to haemoglobin A1c (HbA1c) during the first year after diagnosis in people with type 1 and type 2 diabetes and if metabolic, quality of care or mental factors may explain the association.In the German Diabetes Study, people with type 1 (n = 274, median age 36 [25th; 75th percentile: 28; 48] years) and type 2 diabetes (n = 424, 54 [47; 60] years) underwent detailed metabolic characterisation within the first year after diagnosis. SES was documented using a standardised questionnaire. Associations between SES and HbA1c were assessed using multivariable linear regression and restricted cubic spline regression analyses. Additional covariables were patient characteristics, laboratory measurements, health behaviour, quality of care and depression variables. Models were separately fitted for diabetes type, SES and its dimensions (income, education, occupation).Higher SES score was associated with lower HbA1c (-0.7 mmol/mol per unit increase in SES, 95% CI: -1.1; -0.2 mmol/mol [-0.1%, 95% CI: -0.1; 0.0%]) in people with type 1 diabetes. Included covariates did not attenuate this association. In people with type 2 diabetes, effect estimates were close to zero indicating no relevant difference.Socio-economic inequalities in HbA1c already exist during the first year after diagnosis in people with type 1 diabetes. The absence of association between glycaemic control and SES in type 2 diabetes could be due to the lower complexity of diabetes therapy compared to type 1 diabetes.

Aims Treatment effects from the large cardiovascular outcome trials (CVOTs) of new antidiabetic drugs are almost exclusively communicated as hazard ratios, although reporting guidelines recommend to report treatment effects also on an absolute scale, e.g. as numbers needed to treat (NNT). We aimed to analyse NNTs in CVOTs comparing dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium–glucose cotransporter-2 (SGLT2) inhibitors to placebo. Methods We digitalized individual time-to-event information for the primary outcome and all-cause mortality from 19 CVOTs that compared DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors to placebo. We estimated Weibull models for each trial and outcome and derived monthly NNTs. NNTs were summarized across all trials and within drug classes by random effects meta-analysis methods. Results Treatment effects in the CVOTs appear smaller if they are reported as NNTs: Overall, 100 (95%-CI: 60, 303) patients have to be treated for 29 months (the median follow-up time across all trials) to avoid a single event of the primary outcome, and 128 (95%-CI: 85, 265) patients have to be treated for 39 months to avoid a single death. NNT time courses are very similar for GLP-1 receptor agonists and SGLT2 inhibitors, whereas treatment effects with DPP-4 inhibitors are smaller. Conclusions We found that the respective treatment effects look less impressive when communicated on an absolute scale, as numbers needed to treat. For a valid overall picture of the benefit of new antidiabetic drugs, trial authors should also report treatment effects on an absolute scale.

Aims/hypothesis The aim of this work was to investigate diabetes incidence after infection with coronavirus disease-2019 (Covid-19). Individuals with acute upper respiratory tract infections (AURI), which are frequently caused by viruses, were selected as a non-exposed control group. Methods We performed a retrospective cohort analysis of the Disease Analyzer, which comprises a representative panel of 1171 physicians’ practices throughout Germany (March 2020 to January 2021: 8.8 million patients). Newly diagnosed diabetes was defined based on ICD-10 codes (type 2 diabetes: E11; other forms of diabetes: E12–E14) during follow-up until July 2021 (median for Covid-19, 119 days; median for AURI 161 days). Propensity score matching (1:1) for sex, age, health insurance, index month for Covid-19/AURI and comorbidity (obesity, hypertension, hyperlipidaemia, myocardial infarction, stroke) was performed. Individuals using corticosteroids within 30 days after the index dates were excluded. Poisson regression models were fitted to obtain incidence rate ratios (IRRs) for diabetes. Results There were 35,865 individuals with documented Covid-19 in the study period. After propensity score matching, demographic and clinical characteristics were similar in 35,865 AURI controls (mean age 43 years; 46% female). Individuals with Covid-19 showed an increased type 2 diabetes incidence compared with AURI (15.8 vs 12.3 per 1000 person-years). Using marginal models to account for correlation of observations within matched pairs, an IRR for type 2 diabetes of 1.28 (95% CI 1.05, 1.57) was estimated. The IRR was not increased for other forms of diabetes. Conclusions/interpretation Covid-19 confers an increased risk for type 2 diabetes. If confirmed, these results support the active monitoring of glucose dysregulation after recovery from mild forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Graphical abstract

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.

BACKGROUND: The findings of observational studies can be distorted by a number of factors. So-called confounders are well known, but distortion by collider bias (CB) has received little attention in medical research to date. The goal of this article is to present the principle of CB, and measures that can be taken to avoid it, by way of a few illustrative examples. METHODS: The findings of a selective review of the literature on CB are explained with illustrative examples. RESULTS: The simplest case of a collider variable is one that is caused by at least two other variables. An example of CB is the observation that, among persons with diabetes, obesity is associated with lower mortality, even though it is associated with higher mortality in the general population. The false protective association between obesity and mortality arises from the restriction of the study population to persons with diabetes. CONCLUSION: CB is a distortion that arises through restriction on or stratification by a collider variable, or through statistical adjustment for a collider variable in a regression model. CB can arise in many ways. The graphic representation of causal structures helps to identify potential sources of CB. It is important to distinguish confounders from colliders, as methods that serve to correct for confounding can themselves cause bias when applied to colliders. There is no generally applicable method for correcting CB.

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.

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.

There is limited knowledge about mortality risk in persons with increased haemoglobin AWe 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).In both cohorts, participants with HbAHbA

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.

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.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.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.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.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.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 (18 Jahre) gestellt. Dabei waren 2,2 % der Frauen und 2,8 % der Männer von COA betroffen und 6,5 % der Frauen und 4,2 % der Männer von AOA. In den vorangegangenen 12 Monaten gaben 33 % der COA-Fälle und 60 % der AOA-Fälle an, ärztlich behandelt worden zu sein.Die Häufigkeit von Asthma in der NAKO Gesundheitsstudie in Abhängigkeit von Alter und Geschlecht entspricht weitgehend den Daten aus anderen Studien wie DEGS. Allerdings ist der AOA-Anteil höher als in der Literatur beschrieben. Der Anstieg der kumulativen Asthmadiagnosen ist bei den jüngeren Geburtsjahrgängen deutlich steiler, was für eine Zunahme über die Zeit spricht.

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.

In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks.The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example.The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements.On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health.The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

BACKGROUND: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far. OBJECTIVES: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test). METHODS: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents. RESULTS: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99). CONCLUSION: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.

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.

kein Abstract!

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.

IntroductionDiabetic sensorimotor polyneuropathy (DSPN) affects approximately 30% of people with diabetes, while around half of cases are symptomatic. Currently, there are only few pathogenetically oriented pharmacotherapies for DSPN, one of which is benfotiamine, a prodrug of thiamine with a high bioavailability and favourable safety profile. While benfotiamine has shown positive effects in preclinical and short-term clinical studies, no long-term clinical trials are available to demonstrate disease-modifying effects on DSPN using a comprehensive set of disease-related endpoints.Methods and analysisThe benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes trial is a randomised double-blind, placebo-controlled parallel group monocentric phase II clinical trial to assess the effects of treatment with benfotiamine compared with placebo in participants with type 2 diabetes and mild to moderate symptomatic DSPN. Sixty participants will be 1:1 randomised to treatment with benfotiamine 300 mg or placebo two times a day over 12 months. The primary endpoint will be the change in corneal nerve fibre length assessed by corneal confocal microscopy (CCM) after 12 months of benfotiamine treatment compared with placebo. Secondary endpoints will include other CCM measures, skin biopsy and function indices, variables from somatic and autonomic nerve function tests, clinical examination and questionnaires, general health, health-related quality of life, cost, safety and blood tests.Ethics and disseminationThe trial was approved by the competent authority and the local independent ethics committee. Trial results will be published in peer-reviewed journals, conference abstracts, and via online and print media.Trial registration numberDRKS00014832.

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.

Objectives The aim of the study was to identify the validity of effect estimates for serious rare adverse events in clinical study reports of antidepressants trials, across different meta-analysis methods. Study Design and Setting Four serious rare adverse events (all-cause mortality, suicidality, aggressive behavior, and akathisia) were meta-analyzed using different methods. The Yusuf-Peto odds ratio ignores studies with no events and was compared with the alternative approaches of generalized linear mixed models (GLMMs), conditional logistic regression, a Bayesian approach using Markov Chain Monte Carlo (MCMC), and a beta-binomial regression model. Results The estimates for the four outcomes did not change substantially across the different methods; the Yusuf-Peto method underestimated the treatment harm and overestimated its precision, especially when the estimated odds ratio deviated greatly from 1. For example, the odds ratio for suicidality for children and adolescents was 2.39 (95% confidence interval = 1.32–4.33), using the Yusuf-Peto method but increased to 2.64 (1.33–5.26) using conditional logistic regression, to 2.69 (1.19–6.09) using beta-binomial, to 2.73 (1.37–5.42) using the GLMM, and finally to 2.87 (1.42–5.98) using the MCMC approach. Conclusion The method used for meta-analysis of rare events data influences the estimates obtained, and the exclusion of double-zero event studies can give misleading results. To ensure reduction of bias and erroneous inferences, sensitivity analyses should be performed using different methods instead of the Yusuf-Peto approach, in particular the beta-binomial method, which was shown to be superior through a simulation study.

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.

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.

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

Meta-analysis of diagnostic studies is still a rapidly developing area of biostatistical research. Especially, there is an increasing interest in methods to compare different diagnostic tests to a common gold standard. Restricting to the case of two diagnostic tests, in these meta-analyses the parameters of interest are the differences of sensitivities and specificities (with their corresponding confidence intervals) between the two diagnostic tests while accounting for the various associations across single studies and between the two tests. We propose statistical models with a quadrivariate response (where sensitivity of test 1, specificity of test 1, sensitivity of test 2, and specificity of test 2 are the four responses) as a sensible approach to this task. Using a quadrivariate generalized linear mixed model naturally generalizes the common standard bivariate model of meta-analysis for a single diagnostic test. If information on several thresholds of the tests is available, the quadrivariate model can be further generalized to yield a comparison of full receiver operating characteristic (ROC) curves. We illustrate our model by an example where two screening methods for the diagnosis of type 2 diabetes are compared.

Diagnostic test accuracy studies frequently report on sensitivities and specificities for more than one threshold of the diagnostic test under study. Although it is obvious that the information from all thresholds should be used for a meta-analysis, in practice, frequently, only a single pair of sensitivity and specificity is selected. To overcome this disadvantage, we recently proposed a statistical model for the meta-analysis of such full receiver operating characteristic (ROC) curves that uses the relationship between a ROC curve and a bivariate model for interval-censored data. In this model, diagnostic tests values reported by the single studies were assumed to follow a parametric distribution. We propose a generalization of this model that allows for a flexible semiparametric modelling of the underlying distribution of the diagnostic test values by using the idea of piecewise constant hazard modelling. We show the results of a simulation study that indicates that the approach works reasonably well in practice. Finally, we illustrate the model by the example of population-based screening for type 2 diabetes mellitus.

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]

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.

Aims/hypothesis: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. Methods: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively. Results: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p