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Aim: To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine‐Westphalia. Methods: Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population‐based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics. Area deprivation was assessed in five groups based on quintiles of an index of multiple deprivation and its seven deprivation domains. Poisson regression accounting for spatial dependence was applied to investigate associations of area deprivation and urban/rural traits with type 1 diabetes incidence. Results: Between 2007 and 2014, 6143 incident cases were reported (99% completeness); the crude incidence was 22.3 cases per 100 000 person‐years. The incidence decreased with increasing employment and environmental deprivation (relative risk of the most vs. the least deprived municipalities: 0.905 [95% CI: 0.813, 1.007] and 0.839 [0.752, 0.937], respectively) but was not associated with the composite deprivation index. The incidence was higher in more peripheral, rural, smaller and less densely populated municipalities, and the strongest association was estimated for the location trait (relative risk of peripheral/very peripheral compared with very central location: 1.231 [1.044, 1.452]). Conclusions: The results suggest that the type 1 diabetes risk is higher in more remote, more rural, less densely populated and less deprived areas. Urban/rural traits were stronger predictors of type 1 diabetes risk than area deprivation indicators. What's new?: Socio‐economic and environmental variables are suggested to influence the risk of type 1 diabetes.For the first time, an Index of Multiple Deprivation and urban/rural traits were associated with the geographical variation in type 1 diabetes incidence in children and adolescents at the municipality level in Germany.Children and adolescents aged 0–19 years living in more remote, less densely populated or less deprived areas were at a higher risk of developing type 1 diabetes.Urban/rural traits were stronger predictors of type 1 diabetes risk than indicators of area deprivation. [ABSTRACT FROM AUTHOR]

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. What's new?: In Europe, estimates of age at Type 2 diabetes diagnosis are rarely available and are often not representative of the general population.A high proportion of newly diagnosed Type 2 diabetes cases occur in the age group of 60–80 years.The present study found that the mean age at Type 2 diabetes diagnosis was 61.0 ± 13.4 years in men [median (interquartile range) 62 (53–72) years] and 63.4 ± 14.9 years in women [median (interquartile range) 65 (54–76) years].As a result of increasing life expectancy, a mean age at diagnosis in the early 60s indicates a long diabetes duration, which increases the risk of complications. [ABSTRACT FROM AUTHOR]

Aim: To identify groups of heterogeneous HbA1c trajectories over time in newly diagnosed Type 2 diabetes. Methods: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m2) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA1c measurements during follow‐up. Latent class growth modelling was used to determine distinct subgroups that followed similar longitudinal HbA1c patterns (SAS: Proc Traj). Multinomial logistic regression models were used to investigate which variables were associated with the respective HbA1c trajectory groups. Results: Four distinct longitudinal HbA1c trajectory (glycaemic control) groups were found. The largest group (56% of participants) maintained stable good glycaemic control (HbA1c 42–45 mmol/mol). Twenty‐six percent maintained stable moderate glycaemic control (HbA1c 57–62 mmol/mol). A third group (12%) initially showed severe hyperglycaemia (HbA1c 97 mmol/mol) but reached good glycaemic control within 1 year. The smallest group (6%) showed stable poor glycaemic control (HbA1c 79–88 mmol/mol). Younger age at diabetes diagnosis, male sex, and higher BMI were associated with the stable moderate or poor glycaemic control groups. Insulin therapy was strongly associated with the highly improved glycaemic control group. Conclusions: Four subgroups with distinct HbA1c trajectories were determined in newly diagnosed Type 2 diabetes using a group‐based modelling approach. Approximately one‐third of people with newly diagnosed Type 2 diabetes need either better medication adherence or earlier intensification of glucose‐lowering therapy. What's new?: Currently, data on HbA1c trajectories in newly diagnosed Type 2 diabetes are limited.This longitudinal study identified four distinct HbA1c trajectories during the first 5 years after Type 2 diabetes diagnosis. The largest group (56%) showed persistent good glycaemic control, whereas two smaller groups exhibited either stable moderate (26%) or poor (6%) glycaemic control, respectively. Twelve percent of people with Type 2 diabetes showed initial poor glycaemic control, which highly improved during the first year after diabetes diagnosis.A personalized medicine approach in the treatment of newly diagnosed Type 2 diabetes could be supported by identification of subgroups with specific HbA1c trajectories in response to glucose‐lowering therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim To describe for the first time the direct costs of Type 2 diabetes treatment by analysing nationwide routine data from statutory health insurance in Germany. Methods This cost-of-illness-study was based on a 6.8% random sample of all German people with statutory health insurance (4.3 out of 70 million people). The healthcare expenses show direct per capita costs from the payer perspective. Healthcare expenses for physicians, dentists, pharmacies, hospitals, sick benefits and other healthcare costs were considered. Per capita costs, cost ratios for people with Type 2 diabetes and without diabetes as well as diabetes-attributable costs were calculated. Results Per capita costs for people with Type 2 diabetes amounted to €4,957 in 2009 and €5,146 in 2010. People with Type 2 diabetes had 1.7-fold higher health expenses than people without diabetes. The largest differences in health expenses were found for prescribed medication from pharmacies (cost ratio diabetes/no diabetes: 2.2) and inpatient treatment (1.8). Ten percent of the total statutory health insurance expense, in total €16.1 billion, was attributable to the medical care of people with Type 2 diabetes. Conclusions This nationwide study indicates that one in 10 Euros of healthcare expenses is spent on people with Type 2 diabetes in Germany. In the future, national statutory health insurance data can be used to quantify time trends of costs in the healthcare system. [ABSTRACT FROM AUTHOR]

In real life and somewhat contrary to biostatistical textbook knowledge, sensitivity and specificity (and not only predictive values) of diagnostic tests can vary with the underlying prevalence of disease. In meta-analysis of diagnostic studies, accounting for this fact naturally leads to a trivariate expansion of the traditional bivariate logistic regression model with random study effects. In this paper, a new model is proposed using trivariate copulas and beta-binomial marginal distributions for sensitivity, specificity, and prevalence as an expansion of the bivariate model. Two different copulas are used, the trivariate Gaussian copula and a trivariate vine copula based on the bivariate Plackett copula. This model has a closed-form likelihood, so standard software (e.g., sas proc nlmixed) can be used. The results of a simulation study have shown that the copulamodels perform at least as good but frequently better than the standard model. The methods are illustrated by two examples. [ABSTRACT FROM AUTHOR]

Meta-analyses with rare events, especially those that include studies with no event in one ('single-zero') or even both ('double-zero') treatment arms, are still a statistical challenge. In the case of double-zero studies, researchers in general delete these studies or use continuity corrections to avoid them. A number of arguments against both options has been given, and statistical methods that use the information from double-zero studies without using continuity corrections have been proposed. In this paper, we collect them and compare them by simulation. This simulation study tries to mirror real-life situations as completely as possible by deriving true underlying parameters from empirical data on actually performed meta-analyses. It is shown that for each of the commonly encountered effect estimators valid statistical methods are available that use the information from double-zero studies without using continuity corrections. Interestingly, all of them are truly random effects models, and so also the current standard method for very sparse data as recommended from the Cochrane collaboration, the Yusuf-Peto odds ratio, can be improved on. For actual analysis, we recommend to use beta-binomial regression methods to arrive at summary estimates for the odds ratio, the relative risk, or the risk difference. Methods that ignore information from double-zero studies or use continuity corrections should no longer be used. We illustrate the situation with an example where the original analysis ignores 35 double-zero studies, and a superior analysis discovers a clinically relevant advantage of off-pump surgery in coronary artery bypass grafting. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle ( CARLA) study. Methods The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. Results We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10-12). The area under the receiver-operator characteristic curve ( AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration ( AUC 0.81; 95% CI 0.76-0.86) or HbA1c concentration ( AUC 0.84; 95% CI 0.80-0.91) was found to peform better. Conclusions Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition ( EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes. [ABSTRACT FROM AUTHOR]

Leisure-time physical activity is associated with better health and a reduced risk of all-cause mortality. It is unclear if this association is also present with a high level of physical activity as it is found in professional athletes. In a population-based retrospective cohort study, we compared the survival experience of all soccer players participating for Germany in international matches between 1908 and 2006 to that of the general population. To summarize survival experience, we calculated cumulative relative survival ratios (RSRs) from a life table. We included data of 812 international players, of which 428 (=52.7%) died during follow-up. In all 13 intervals, cumulative observed survival was smaller than cumulative expected survival, resulting in cumulative RSRs being <1. The cumulative RSRs are statistically significantly different from 1 in all but the last interval. This impaired survival experience of the internationals translates into a loss of median residual lifetime of 1.9 years [95% confidence interval: 0.6, 3.2] years at the entry time into the cohort. This loss is mainly driven by the mortality of internationals from the earlier half of the observation period. Reasons for this might be poorer medical care in former times, internationals being killed in action during World War II, and a changing distribution of causes of death during the 20th century. [ABSTRACT FROM AUTHOR]

Background Tape stripping the skin prior to patch testing (strip patch test, SPT) may enhance percutaneous penetration of test substances and increase skin reactivity to test substances. Objective To evaluate the test sensitivity of SPT in compliance with our recently presented practical method vs. conventional patch test (PT) in nickel- and dichromate-sensitive subjects. Methods Thirty subjects participated in the prospective, randomized, controlled, investigator-blind study. Serial dilution tests of nickel sulphate (10 000–50 ppm aq.) and potassium dichromate (1000–5 ppm aq.) were used. Tests were applied in duplicate to both sides of the upper back of the subject, where one, randomly chosen side was tape stripped. Results According to the estimated test sensitivities, SPT is more sensitive than PT in nickel- and dichromate-sensitive subjects, regardless of the interindividual different numbers of tape strips. The superiority of the SPT grows with diminishing concentrations of the allergens. Conclusion Test sensitivity of SPT vs. PT is increased. If no positive results are obtained by PT, the SPT could help to detect hidden allergens in case of weak sensitization or low concentration and poor percutaneous penetration of the test substances. Conflict of Interest None declared. [ABSTRACT FROM AUTHOR]

We have recently engineered recombinant derivatives of the major birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly reduced allergenic activity. The aim of this study was the in vivo characterization of potential allergy vaccines based on Al(OH)3-adsorbed genetically modified rBet v 1 derivatives in mice. BALB/c mice were immunized either with courses of nine injections of increasing doses of Al(OH)3-adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone in weekly intervals or with three high-dose injections applied in intervals of 3 weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant allergens were measured by ELISA and Western blotting, and the ability of mouse antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied by ELISA competition experiments. In both schemes, hypoallergenic rBet v 1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type. The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross-reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic patients' IgE to Bet v 1 wild-type. Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies. [ABSTRACT FROM AUTHOR]

Reports on the incidence of occupational skin diseases (OSD) in northern Bavaria from 1990 to 1999. Formation of the register of OSD in northern Bavaria with help from the Bavarian State Department of Occupational Medicine and the Department of Dermatology at the University of Erlangen; One-year incidence rate of OSD in 24 occupational groups; Incidence rate.

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short-time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2× a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5-day protocol. Furthermore, in spite of the expected inter-centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter-instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres. [ABSTRACT FROM AUTHOR]

The volar forearm is the favored location for bioengineering studies. However, transepidermal water loss (TEWL), which is an important indicator of the function of the epidermal barrier, shows regional variations, and for the evaluation of cosmetic formulations, facial skin would be more suitable. In this study, we have compared 10 facial locations with 1 test site on the volar forearm for absolute TEWL values, reproducibility, and correlation. Measurements were performed over 3 consecutive days. The TEWL values of the facial test sites were higher compared to forearm values and did not correlate with the forearm. On the face, there was a good correlation between the values of the right compared to the left side of the face. The sites superior to the nervus supraorbitalis, the medial borders of the musculus masseter, and the center of the chin proved to be locations with relatively stable TEWL values. There was a greater variability at the center of the forehead and at the center of the cheeks. It is recommended that TEWL measurements on facial locations with stable TEWL values are used for the evaluation of cosmetic formulations. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Comparative study of patch test using traditional method vs. prior skin abrading," by M.F.M. Fernandes and colleagues in the 2007 issue.

Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors. Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors. Methods In an observational birth cohort study 1314 infants born in 1990 were followed-up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)-models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustment Results Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01–1.09 for each year), with each additional month of breastfeeding (1.03; 1.00–1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38–3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25–1.88), and asthma (1.41; 1.07–1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk. Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes., Methods: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis., Results: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm 3 ). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm 3 ) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes., Conclusions: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR., (© 2024 John Wiley & Sons Ltd.)

Aims: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability., Methods: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta-regression analyses were performed with respect to variability of body weight after treatment and potential predictors., Results: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta-regression model, the difference in body weight log(SD) was -0.026 (95% confidence interval -0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo)., Conclusions: We found no major treatment response heterogeneity in RCTs of glucose-lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To identify distinct HbA1c trajectories in people with type 2 diabetes (T2D) starting second-line glucose-lowering therapy., Materials and Methods: DISCOVER was a 3-year observational study of individuals with T2D beginning second-line glucose-lowering therapy. Data were collected at initiation of second-line treatment (baseline) and at 6, 12, 24 and 36 months. Latent class growth modelling was used to identify groups with distinct HbA1c trajectories., Results: After exclusions, 9295 participants were assessed. Four distinct HbA1c trajectories were identified. Mean HbA1c levels decreased between baseline and 6 months in all groups; 72.4% of participants showed stable good levels of glycaemic control over the remainder of follow-up, 18.0% showed stable moderate levels of glycaemic control and 2.9% showed stable poor levels of glycaemic control. Only 6.7% of participants showed highly improved glycaemic control at month 6 and stable control over the rest of follow-up. For all groups, dual oral therapy use decreased over time, compensated for by the increasing use of other treatment regimens. Use of injectable agents increased over time in groups with moderate and poor glycaemic control. Logistic regression models suggested that participants from high-income countries were more probable to be in the stable good trajectory group., Conclusions: Most people receiving second-line glucose-lowering treatment in this global cohort achieved stable good or highly improved long-term glycaemic control. One-fifth of participants showed moderate or poor glycaemic control during follow-up. Further large-scale studies are required to characterize possible factors associated with patterns of glycaemic control to inform personalized diabetes treatment., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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., (© 2020 John Wiley & Sons Ltd.)

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., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: The aim of this study was to investigate whether insulin sensitivity, beta-cell function or glycaemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes., Research Design and Methods: Type 2 diabetes patients (n = 138) undergoing initial metformin monotherapy (age [mean ± SD], 52 ± 10 years; 67% males; BMI, 32 ± 6 kg/m 2 ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under care of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp, M value; i.v. glucose tolerance test, incremental C-peptide area under the curve 0-60 minutes, CP iAUC). The associations of baseline M value, CP iAUC, fasting glucose and HbA1c with time to second-line therapy were assessed using parametric survival analysis, accounting for interval-censoring., Results: Second-line treatment was initiated in 26% of newly diagnosed type 2 diabetes patients within the first 3.3 years after diagnosis, using mostly DPP-4 inhibitors or GLP-1 receptor agonists (64%). In age-, sex- and BMI-adjusted survival models, higher baseline HbA1c and fasting glucose values were associated with earlier treatment intensification. Lower baseline M value and C-peptide secretion (CP iAUC) were also related to an earlier initiation of second-line treatment. In the best multivariable model, baseline HbA1c ≥ 7% (hazard ratio, HR; 95% CI: 3.18; 1.35-7.50) and fasting glucose ≥140 mg/dL (HR, 2.45; 95% CI, 1.04-5.78) were associated with shorter time to second-line therapy, adjusting for age, sex and BMI., Conclusions: Baseline hyperglycaemia is a strong predictor of requirement of early intensification of glucose-lowering therapy in newly diagnosed type 2 diabetes., (© 2017 John Wiley & Sons Ltd.)

Aim: The sleep disturbing effect of many drugs is derived from clinical trials with highly selected patient collectives. However, the generalizability of such findings to the general population is questionable. Our aim was to assess the association between intake of drugs labelled as sleep disturbing and self-reported nocturnal sleep disturbances in a population-based study., Methods: We used data of 4221 participants (50.0% male) aged 45 to 75 years from the baseline examination of the Heinz Nixdorf Recall Study in Germany. The interview provided information on difficulties falling asleep, difficulties maintaining sleep and early morning arousal. We used the summary of product characteristics (SPC) for each drug taken and assigned the probability of sleep disturbances. Thereafter, we calculated cumulative probabilities of sleep disturbances per subject to account for polypharmacy. We estimated prevalence ratios (PR) using log Poisson regression models with robust variance., Results: The adjusted PRs of any regular nocturnal sleep disorder per additional sleep disturbing drug were 1.01 (95% confidence interval (CI) 0.97, 1.06) and 1.03 (95% CI 1.00, 1.07) for men and women, respectively. Estimates for each regular nocturnal sleep disturbance were similarly close to 1. PRs for regular nocturnal sleep disturbances did not increase with rising cumulative probability for drug-related sleep disturbances., Conclusions: SPC-based probabilities of drug-related sleep disturbances showed barely any association with self-reported regular nocturnal sleep disturbances. We conclude that SPC-based probability information may lack generalizability to the general population or may be of limited data quality., (© 2016 The British Pharmacological Society.)