Wolfgang Rathmann

• Dr. med. MSPH
• Managing Director at Deutsches Diabetes-Zentrum e.V.

Background To date, various epigenetic clocks have been constructed to estimate biological age, most commonly using DNA methylation (DNAm). These include “first-generation” clocks such as DNAmAgeHorvath and “second-generation” clocks such as DNAmPhenoAge and DNAmGrimAge. The divergence of one’s predicted DNAm age from chronological age, termed DNAm...

The impact of different drinking solutions used for an oral glucose tolerance test (oGTT) on 2-h glucose values and gastrointestinal side effects are not clear. This study compared a commercially produced solution (Accu-Chek Roche solution) and a standardized pharmacy solution (NRF 13.8. oGTT solution) within the German National Cohort (NAKO), incl...

Background Using a data-driven approach, six clusters with different risk profiles and burden of complications were recently identified in middle-aged people before the diagnosis of type 2 diabetes (T2D). We aimed to investigate whether these clusters could be generalised to older people and if subclinical inflammation was related to their cardiome...

Depression is associated with diabetes, but the underlying causes remain unclear. To better understand depression in diabetes, this study investigated associations between 135 inflammatory and neurological protein biomarkers and depressive symptoms in individuals with diabetes. This cross-sectional study included 430 adults with a known diabetes du...

In this review, we discuss how partnership and marriage influence cardiometabolic risk factors and risk of type 2 diabetes, and how couple-based approaches to type 2 diabetes prevention might complement individual-focused prevention efforts. There is some evidence that being married per se has a small positive effect on type 2 diabetes risk. Moreov...

Background Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multip...

Aims There is a lack of studies on the impact of diabetes risk scores on diabetes prevention. The aim of this study was to investigate the effect of applying a non-invasive diabetes risk score as component of routine health checks on counselling intensity and shared decision-making (SDM) in primary care. Methods Cluster randomised trial, in which p...

Background Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet. Methods Here, we developed the Interpretable Multimodal Machine Lear...

STUDY IMPORTANCE QUESTIONS What is already known about this subject? Osteosarcopenic adiposity (OSA) is defined as the hazardous triad of osteopenia, sarcopenia, and adiposity causing impaired functionality and metabolic dysregulation. Ectopic adipogenesis and fat redistribution into the viscera, bone, and muscle tissue have been described as the k...

Background Diabetic sensorimotor polyneuropathy (DSPN) is often asymptomatic and remains undiagnosed. The ability of clinical and anthropometric variables to identify individuals likely to have DSPN might be limited. Here, we aimed to integrate protein biomarkers for reliably predicting present DSPN. Methods Using the proximity extension assay, we...

Aims A data‐driven cluster analysis in a cohort of European individuals with type 2 diabetes (T2D) has previously identified four subgroups based on clinical characteristics. In the current study, we performed a comprehensive statistical assessment to (1) replicate the above‐mentioned original clusters; (2) derive de novo T2D subphenotypes in the K...

Background Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality in middle-aged and older adults. Purpose Given the distinctive impact of type 2 diabetes (T2D) on mortality rates and protein levels, this study aimed to explore the association of proteins with all-cause and cause-specific mortality...

Background Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause...

Introduction/objectives Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation. Methods We analyze...

Denosumab initiation is related to a lower risk of type 2 diabetes than alendronate in anti-osteoporotic treatment-naïve users in primary care practices. Links have been suggested between bone metabolism and glucose tolerance. Downregulation of the receptor activator of nuclear factor κ B ligand (RANKL) signaling improves glucose metabolism. Denosu...

Background Obesity is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Effects of glucocorticoids on adipose tissues appear to depend on the specific adipose depot, in which they take place. In this study, we aimed to investigate the role of MRI-based adrenal gland volume as an imaging marker in association with differe...

Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 s...

Aims: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study. Materials and methods: I...

Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic–pituitary–adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular diseas...

Aims The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN). Materials and Methods Cross‐sectional analyses were based on 1032 participants aged 61–82 years from the population‐based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. P...

Background Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effe...

Background and aims Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with...

Accurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA coh...

Background Multiple risk factors contribute jointly to the development and progression of cardiometabolic diseases. Therefore, joint longitudinal trajectories of multiple risk factors might represent different degrees of cardiometabolic risk. Methods We analyzed population-based data comprising three examinations (Exam 1: 1999–2001, Exam 2: 2006–2...

Introduction Circulating omentin levels have been positively associated with insulin sensitivity. Although a role for adiponectin in this relationship has been suggested, underlying mechanisms remain elusive. In order to reveal the relationship between omentin and systemic metabolism, this study aimed to investigate associations of serum concentrat...

Background Metformin and sodium-glucose-cotransporter-2 inhibitor (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes, yet their nuanced impacts on metabolic processes, particularly in the citric acid (TCA) cycle and its anaplerotic pathways, are not fully delineated. This study aims to investigate the tissue-specific metaboli...

Background Coronary heart disease (CHD) is a major global health concern, especially among individuals with type 2 diabetes (T2D). Given the crucial role of proteins in various biological processes, this study aimed to elucidate the aetiological role and predictive performance of protein biomarkers on incident CHD in individuals with and without T2...

Aim Diabetes is a global health challenge, and many individuals are undiagnosed and not aware of their increased risk of morbidity/mortality although dedicated tests are available, which indicates the need for novel population-wide screening approaches. Here, we developed a deep learning pipeline for opportunistic screening of impaired glucose meta...

Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet. In order to address this, we developed the Interpretable Multimodal Machine Lear...

OBJECTIVE Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes. RESEARCH DESIGN AND METHODS Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (...

Background: Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. Methods: We used observational data from the German popul...

Background and aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels wit...

Objective: We investigated whether COVID-19 vaccination had an impact on diabetes risk. Methods: We used data of 6,198 patients (mean age 64.3 years) from the nationwide Disease Analyzer database, a representative panel of physicians' practices in Germany. Patients received their first COVID-19 vaccination between 1 April 2021 and 31 March 2022,...

Background Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS...

Aims/hypothesis This study aimed to elucidate the aetiological role of plasma proteins in glucose metabolism and type 2 diabetes development. Methods We measured 233 proteins at baseline in 1653 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort study (median follow-up time: 13.5 years). We used logistic r...

Background: Non-alcoholic fatty liver disease (NAFLD) represents a major disease burden in the population. While the bidirectional association between NAFLD and diabetes is established, little is known about the association of hepatic iron content and glycaemia. Moreover, analyses of sex-specific effects and of dynamic changes in glycaemia are sca...

Aim: To investigate whether the SARS-CoV-2 pandemic affected care for people with newly diagnosed type 2 diabetes in Germany. Methods: The Disease Analyzer database (IQVIA, Germany) contains routine data on diagnoses and treatments (ICD-10 and ATC codes) from patients followed in selected physician practices across Germany. We compared 21,747 in...

Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D i...

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, 2...

Background Metabolic syndrome (MetS) consists of risk factors (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL–C), hypertension, hyperglycemia) for cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its risk factors to better understand the complex...

Background: Intervertebral disc degeneration (IVDD) may be linked to dysregulations of skeletal muscle glucose metabolism and fatty alterations of muscle composition (Myosteatosis). Our aim was to evaluate the different associations of magnetic resonance imaging (MRI)-based paravertebral myosteatosis with lumbar disc degeneration in individuals wi...

Introduction: Aldosterone excess is linked to cardiovascular events and mortality as well as to low-grade inflammation in the context of metabolic diseases. Whether mildly elevated aldosterone levels in the general population promote cardiovascular risk is still under debate. We analyzed the association of plasma aldosterone concentrations with in...

Obesity plays an important role in the development of insulin resistance and diabetes, but the molecular mechanism that links obesity and diabetes is still not completely understood. Here, we used 146 targeted metabolomic profiles from the German KORA FF4 cohort consisting of 1715 participants and associated them with obesity and type 2 diabetes. I...

Background Many persons with diabetes do not achieve optimal glycemic control. An improvement of therapy could be achieved by using genetic information. It is unclear whether there are enough studies on the pharmacogenetics of the new glucose-lowering drugs glucagon-like peptide 1 receptor agonists (GLP-1 RA), DPP‑4 inhibitors (DPP4i) and sodium–gl...

Introduction The role of endogenous androgens in kidney function and disease has not been extensively explored in men and women. Research design and methods We analyzed data from the observational KORA F4 study and its follow-up examination KORA FF4 (median follow-up time 6.5 years) including 1293 men and 650 peri- and postmenopausal women, not us...

Aims/hypothesis No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL level...

Distal sensorimotor polyneuropathy (DSPN) is a common condition in older populations with high prevalence of obesity and type 2 diabetes. We hypothesised that the risk of DSPN is increased by multiple ubiquitous environmental risk factors, particularly in people with obesity. This study was based on 423 individuals aged 62–81 years without DSPN who...

Aims /hypothesis 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. Methods The present study was based on the IQVIA longitudinal prescription database (LRx), All persons (age ≤ 20 years) with new insulin prescriptions fro...

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors...

Background: We aimed to evaluate the relationship of fatty liver, estimated by fatty liver index (FLI), with kidney function and chronic kidney disease (CKD) in a German cohort study, given the lack of prospective evidence in Europeans. Methods: We included 2920 participants (51.6% women, mean age 56.1 years) from the KORA study, of which 1991 w...

The aim of metabotyping is to categorize individuals into metabolically similar groups. Earlier studies that explored metabotyping used numerous parameters, which made it less transferable to apply. Therefore, this study aimed to identify metabotypes based on a set of standard laboratory parameters that are regularly determined in clinical practice...

Background The best definition of the metabolic syndrome (MetSyn) remains controversial. The aim was to develop a latent variable measurement model for the MetSyn using primary care data. Methods This retrospective case-control study was based on the data from the IQVIA Disease Analyzer (DA) database including a representative panel of general and...

Purpose: In Germany, record linkage of claims and cancer registry data is cost- and time-consuming, since up until recently no unique personal identifier was available in both data sources. The aim of this study was to evaluate the feasibility and performance of a deterministic linkage procedure based on indirect personal identifiers included in t...

Objectives: To analyze whether prescription use of GLP-1RA and SGLT2i in individuals with type 2 diabetes with cardiovascular disease (CVD) has increased after the ADA/EASD consensus guidelines (2018) in a German Real-World setting, and which clinical characteristics are associated with prescription use of these drugs. Methods: The Disease Analy...

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effec...

Background/objectives The association between vitamin D and DSPN has been investigated in cross-sectional studies in individuals with diabetes. However, evidence from prospective and population-based studies is still lacking. Also, the potential modifying effect of obesity and glucose tolerance has not been investigated. Therefore, we examined the...

Background: The neurofilament light chain (NFL) is a polypeptide abundant in neuronal axons, reflecting ongoing neuroaxonal degeneration when detected in the blood. However, no previous study has explored NFL as a potential biomarker for diabetic sensorimotor polyneuropathy (DSPN) , a neurodegenerative disease of the peripheral nervous system commo...

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 outcome...

Aims: Diabetes management requires cognitive abilities. Unfortunately, diabetes is a risk factor for cognitive decline. However, the effects of diabetes in persons with reduced cognitive reserves are unclear. We aimed to examine whether the effects of diabetes and education on cognitive skills simply add up or deviate from simple additivity. Meth...

Introduction Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early ath...

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are...

Aims/hypothesis Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by com...

Background Despite strong evidence of benefit, uptake of newer glucose-lowering medications that reduce cardiovascular risk has been low. We sought to examine global trends and predictors of use of SGLT2i and GLP-1 RA in patients with type 2 diabetes. Methods DISCOVER is a global, prospective, observational study of patients with diabetes enrolled...

DISCOVER is a 3-year observational study program of 15,983 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. We investigated the association between socioeconomic status and both the availability of a baseline glycated hemoglobin (HbA1c) measurement and poor glycemic control (HbA1c level ≥ 9.0%) in partici...

Aims: To examine whether the incidence rates of diagnosed depression, anxiety disorders and stress reactions, as well as prescription rates of antidepressants and anxiolytics were higher during the COVID-19 pandemic than before in persons with type 2 diabetes in Germany. Contrary to earlier studies, clinical diagnoses of psychiatric disorders (ICD...

The original cohorts The Study of Health in Pomerania (SHIP) comprises the two independent cohorts SHIP-START (recruited between 1997 and 2001) and SHIP-TREND (recruited between 2008 to 2012), which were established to examine the health and disease status of the general adult population in Northeast Germany given that this region had the lowest li...

Background and aims: It is unclear whether socioeconomic 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 ment...

Aims/hypothesis In men with diabetes, the prevalence of erectile dysfunction increases with advanced age and longer diabetes duration and is substantially higher in men with type 2 diabetes than those with type 1 diabetes. This study aimed to evaluate the prevalence of erectile dysfunction among the five novel subgroups of recent-onset diabetes and...

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 Dise...

Objectives: The aim of this study was to asses adrenal gland volume by magnetic resonance imaging (MRI) and to study its role as an indirect marker of impaired glucose metabolism and hypothalamic-pituitary-adrenal (HPA) axis activation in a population-based cohort. Methods: Asymptomatic participants were enrolled in a nested case-control study a...

Obesity increases the risk of cardiovascular diseases (CVD), however, whether adipose tissue relates to dyslipidemia, and consequently to cardiovascular events remains unknown. Thus, we investigated the association of adipose tissue with circulating lipoproteins and triglycerides (TG) in subjects without CVD. 384 participants from the KORA-MRI stud...

Aims/hypothesis The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA 1c levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic ‘diabetes-related’ complications. This umbrella review aimed to provide a systematic overview of...

Background The renal tubular glycoprotein uromodulin is associated with obesity and type 2 diabetes, but the underlying mechanisms are elusive. We investigated the association of serum uromodulin with adipokines and tested the effect modification by diabetes status. Methods The associations of serum uromodulin with eight adipokines were assessed i...

Background and Aim While there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states...

Introduction Primary aldosteronism is associated with impaired glucose tolerance. Whether plasma aldosterone and/or renin concentrations are associated with type 2 diabetes and continuous measures of glucose metabolism in the general population is still under debate. Research design and methods The analyses included 2931 participants of the KORA F...

Background Skeletal muscle mass is subjected to constant changes and is considered a good predictor for outcome in various diseases. Bioelectrical‐impedance analysis (BIA) and magnetic resonance imaging (MRI) are approved methodologies for its assessment. However, muscle mass estimations by BIA may be influenced by excess intramuscular lipids and a...

Background and aim Despite its vasodilatory effect, adrenomedullin and its surrogate mid-regional pro-adrenomedullin (MR-proADM) have been found to be positively associated with all-cause and cardiovascular mortality. However, the underlying mechanisms thereof remain unclear and the associations were mostly shown in geriatric cohorts or in patients...

We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP–CpG associations (methylation quantitative trait loci (meQTL), P < 10⁻¹⁴), including 467,915 meQTL that operate in trans. The meQTL are enriched for functionally relevant char...