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Methods and findings
T2D, adiposity, Cancer
SECONDARY, ADIPOSITY, CANCER
We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised)...
PMC10138823
Conclusions
T2D
These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.
PMC10138823
Trial registration
TYPE 2 DIABETES
Australian New Zealand Clinical Trials Registry (ANZCTR) Jakub G Sobiecki and team aim to develop a biomarker score able to discriminate between Mediterranean diet and habitual diet, and test its association with incident type 2 diabetes in a European cohort.
PMC10138823
Author summary
PMC10138823
Why was this study done?
T2D, type 2 diabetes
DISEASE, TYPE 2 DIABETES
Epidemiological evidence has indicated that greater self-reported adherence to the Mediterranean diet may be associated with lower risk of new onset type 2 diabetes (T2D), but there has been uncertainty about the magnitude of association due to subjective reporting of diet.A combination of nutritional biomarkers could ...
PMC10138823
What did the researchers do and find?
BLOOD
Blood carotenoids and fatty acids can be used as an objective measure of adherence to the Mediterranean diet, as indicated by results from a trial (In a study across 8 European countries (
PMC10138823
What do these findings mean?
T2D
Adherence to the Mediterranean diet may be more beneficial for the primary prevention of T2D than previously estimated from observational dietary studies.Even small upward differences in objectively measured Mediterranean diet may be associated with a sizeable reduction of the risk of T2D at the population level.Causal...
PMC10138823
Data Availability
Data from the MedLey trial contains sensitive participant information. For data access, please contact the University of South Australia Human Research Ethics Committee at
PMC10138823
Introduction
T2D, Cancer
TYPE 2 DIABETES, DISEASES, CANCER
The Mediterranean diet is a dietary pattern typically characterised by high consumption of vegetables, legumes, fruit, nuts, grains, fish and seafood, virgin olive oil, and moderate intake of meat, dairy, and wine. It has been reported to be associated with decreased incidence of multiple noncommunicable diseases inclu...
PMC10138823
Methods
PMC10138823
Study designs and populations
T2D
The overall study design and participant flows are displayed in The MedLey trial is an RCT that tested effects of the Mediterranean diet on cardiovascular risk factors [We used the MedLey trial to derive a biomarker score of discrimination between the Mediterranean and habitual diet arms based on end-of-study nutrition...
PMC10138823
Nutritional and metabolic biomarkers
In the MedLey trial, venous blood samples were taken at baseline, 3 and 6 months post randomisation after 8 h of fasting, centrifuged and stored at −80°C. High-performance liquid chromatography (HPLC) with photo-diode array detection was used to assay carotenoids [In EPIC-InterAct, venous blood samples were collected a...
PMC10138823
Measurement of covariates and self-reported diet
In the MedLey trial, questionnaires and physical examination were used to collect data on baseline characteristics. Self-reported diet was measured with 3-day weighed food diaries. Intakes of energy and ethanol were estimated using a local nutrient database [In the EPIC study, questionnaires and physical examination we...
PMC10138823
Statistical analysis
Stata 16.1 and R 4.0.2 were used for statistical analysis.
PMC10138823
Derivation of the biomarker score
REGRESSION
We imputed values of fatty acids below the limit of detection using quantile regression imputation [We used logistic elastic net regression to derive the biomarker score in MedLey trial [
PMC10138823
Associations of the biomarker score with incident T2D
T2D, comorbidity, cancer, cardiovascular disease, T2D, smoking status (, adiposity
PAF, RECRUITMENT, HYPERLIPIDAEMIA, SECONDARY, ADIPOSITY, REGRESSION, HYPERTENSION
In EPIC-InterAct, individual nutritional biomarkers were Winsorised at 4 standard deviations (SDs) below or above the subcohort means and were then used to calculate the biomarker score with the scoring algorithm developed as described above. The biomarker score was standardised using the means and SD and categorised i...
PMC10138823
Sensitivity analyses
REGRESSION
We performed several sensitivity analyses to assess the robustness of the main findings. We repeated the derivation and assessment of discriminatory performance of the biomarker score in the MedLey trial with several alternative analytical decisions in the elastic net regression (
PMC10138823
Analyses conducted in response to peer review comments
We performed a graphical assessment of calibration of the biomarker score model for prediction of randomised assignment in the MedLey trial [
PMC10138823
Patient and public involvement
MINOR
The MedLey trial intervention was piloted in a group of volunteers that led to minor adjustments in its design and delivery [
PMC10138823
Results
T2D, hypertension, hyperlipidaemia
HYPERTENSION, HYPERLIPIDAEMIA
Compared to the MedLey trial participants, the EPIC-InterAct subcohort members were younger (mean age 52 years, EPIC-InterAct, versus 71 years, MedLey trial), had lower tertiary educational attainment (20% versus 53%), were less likely to have a family history of T2D (18% versus 30%), and had higher prevalence of hyper...
PMC10138823
Derivation of the biomarker score
The biomarker score consisted of a linear combination of 23 biomarkers in total (
PMC10138823
Nutritional biomarker score of the Mediterranean diet: study-specific distribution by the MedLey trial arms post-intervention and the EPIC-InterAct subcohort by country at baseline.
Cancer
CANCER
The biomarker score was derived as a discriminatory model between the Mediterranean and habitual diet in the MedLey randomised partial-feeding controlled trial. Circulating carotenoids and fatty acids were used to calculate the score as linear predictions from the discriminatory model. The score was standardised separ...
PMC10138823
The association of the biomarker score with incident T2D
T2D
The biomarker score of the Mediterranean diet was inversely associated with incident T2D (
PMC10138823
Association between the nutritional biomarker score of the Mediterranean diet and incidence of T2D in the EPIC-InterAct case-cohort study (
REGRESSION
The biomarker score was derived as a discriminatory model between the Mediterranean and habitual diet in the MedLey randomised partial-feeding controlled trial. Circulating carotenoids and fatty acids were used to calculate the score as linear predictions from the discriminatory model. Associations were assessed with t...
PMC10138823
Discussion
T2D
In the current research, we combined information from experimental and observational studies to investigate the association between a composite biomarker score of adherence to the Mediterranean diet and incident T2D. The key findings were that a biomarker score derived within the MedLey RCT had a high discriminatory pe...
PMC10138823
Comparison with previous studies
T2D, cardiovascular disease
DISEASE, CARDIOVASCULAR DISEASE
Attempts to derive biomarkers of the Mediterranean diet and other dietary patterns have previously been largely confined to metabolomic profiling using cross-sectional designs [Our work on derivation of the nutritional biomarker score of the Mediterranean diet adds to the previous literature by incorporating the streng...
PMC10138823
Strengths and limitations
T2D, weight loss
The major strength of the current research was the use of a novel analytical approach that combined the derivation of an objective measure of the Mediterranean diet in a partial-feeding study (the MedLey RCT) and its application in a large observational study (the EPIC-InterAct Study). The RCT compared the effects of t...
PMC10138823
Implications of this research
DISEASE
The analysis of dietary patterns aims to evaluate the cumulative impact of dietary exposures on disease risk to inform development of dietary guidelines [Our integrative approach of using a trial and an observational study with nutritional biomarkers strengthens the evidence for the utility of biomarkers in research on...
PMC10138823
Conclusions
T2D
The findings of the current study have demonstrated the utility of combining circulating carotenoids and fatty acids as a composite biomarker of the Mediterranean diet. The inverse association between a biomarker score of this dietary pattern and T2D was approximately 3-fold larger than for adherence to the Mediterrane...
PMC10138823
Supporting information
PMC10138823
STROBE Statement—Checklist of items that should be included in reports of cohort studies.
(DOCX)Click here for additional data file.
PMC10138823
CONSORT 2010 checklist of information to include when reporting a randomised trial.
(DOCX)Click here for additional data file.
PMC10138823
Supplementary methods.
(DOCX)Click here for additional data file.
PMC10138823
Medians (25th, 75th percentile) of circulating carotenoids and fatty acids: the MedLey trial post-intervention and the EPIC-InterAct subcohort at baseline.
Abbreviations: Hab, habitual; Med, Mediterranean.(DOCX)Click here for additional data file.
PMC10138823
Biomarker scores of discrimination between the Mediterranean and habitual diet in the MedLey trial.
Abbreviations: mol%, molar percent; RCT, randomised controlled trial; SD, standard deviation; wt%, weight percent; β-crypt., β-cryptoxanthin.(DOCX)Click here for additional data file.
PMC10138823
Percentages (numbers) of users of medications in the MedLey trial by randomised assignment at baseline (
(DOCX)Click here for additional data file.
PMC10138823
Medians (interquartile ranges) of the nutritional biomarker score of the Mediterranean diet in the MedLey trial post-intervention and in the EPIC-InterAct subcohort.
Abbreviations: Hab, habitual; Med, Mediterranean; (DOCX)Click here for additional data file.
PMC10138823
Nutritional biomarker score of the Mediterranean diet derived in the MedLey trial and incidence of type 2 diabetes in EPIC-InterAct: sensitivity analyses.
Cancer
MYOCARDIAL INFARCTION, CANCER
Abbreviations: CI, confidence interval; EPIC, European Prospective Investigation into Cancer and Nutrition; HR, hazard ratio; MI, myocardial infarction; RCT, randomised controlled trial; SD, standard deviation.(DOCX)Click here for additional data file.
PMC10138823
Nutritional biomarker score of the Mediterranean diet derived in the MedLey trial and incidence of type 2 diabetes in EPIC-InterAct: associations per 1 standard deviation by categories of covariates.
Cancer
CANCER
Abbreviations: CI, confidence interval; EPIC, European Prospective Investigation into Cancer and Nutrition; HR, hazard ratio; RCT, randomised controlled trial.(DOCX)Click here for additional data file.
PMC10138823
The score of self-reported Mediterranean diet.
(DOCX)Click here for additional data file.
PMC10138823
Designs of the MedLey trial and the EPIC-InterAct case-cohort study and numbers of participants included in the analysis.
(DOCX)Click here for additional data file.
PMC10138823
Differences in standardised means of nutritional biomarkers between the Mediterranean and habitual diet groups in the MedLey trial at 6 months.
Abbreviations: AA, arachidonic acid; ALA, α-linolenic acid; DGLA, dihomo-γ-linolenic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FAs, fatty acids; LA, linoleic acid. Mixed linear models were used to estimate standardised differences after 6 months of partial-feeding interven...
PMC10138823
Calibration plots of the nutritional biomarker score for prediction of randomised assignment to 6 months of the Mediterranean diet (
Abbreviations: AUC, area under the curve; CITL, calibration-in-the-large; E:O, ratio of expected and observed outcomes.(DOCX)Click here for additional data file.
PMC10138823
Study protocol.
RECRUITMENT
(DOCX)Click here for additional data file.We thank all the MedLey trial and EPIC participants and staff for their contribution to the study. The authors acknowledge the MedLey team for their support in the recruitment, data collection, and analysis during the trial. The authors acknowledge the following industry partne...
PMC10138823
Abbreviations
Cancer
DIABETES, CANCER
confidence intervalEuropean Prospective Investigation into Cancer and Nutritionhigh-performance liquid chromatographyhazard ratiointerquartile rangepopulation attributable fractionrandomised controlled trialstandard deviationtotal cholesteroltype 2 diabetes
PMC10138823
References
PMC10138823
Subject terms
infections
INFECTIONS
Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in a convenience sample of 1,411 patients receiving medical treatment in the...
PMC10199003
Introduction
infections
INFECTIONS
Population immunity against SARS-CoV-2 plays a key role in the course of the pandemic and determines morbidity and mortality of COVID-19At the beginning of 2022, a rapid surge of infections was detected worldwide and driven by the Omicron variant BA.1 that exhibited substantial immune evasion propertiesIn this multicen...
PMC10199003
Results
PMC10199003
Characteristics of study participants to determine SARS-CoV-2 humoral immunity
During the time of sample collection, 10,191 patients sought medical treatment in the emergency departments. Of those patients, 1411 (13.9%) were enrolled for study participation. There was no significant difference between the age and sex distributions of all emergency department patients and the study participants, i...
PMC10199003
High S-IgG seroprevalence in patients visiting emergency departments in North Rhine-Westphalia, Germany
To determine SARS-CoV-2 humoral immunity, we first measured seroprevalence and levels of S-IgG in all participants. S-IgG could be detected in 95.6% of the participants. Of the 4.4% S-IgG-negative participants, 27.9% reported drug immunosuppression at the time of sampling. Of those reporting no drug immunosuppression, ...
PMC10199003
NC-IgG seroprevalence and prediction of S-IgG levels
infections
REGRESSION, HAND INFECTION, INFECTIONS
Next, we determined seroprevalence and levels of NC-IgG in all participants. NC-IgG could be detected in 24.0% of all enrolled participants (Fig. Given the observed association between different clinical and serological features and S-IgG levels, we performed multivariable analysis including sex, height, weight, BMI, a...
PMC10199003
High S-IgG levels correlate with SARS-CoV-2 neutralizing activity
To determine serum neutralization against Wu01 and BA.4/5 variants, we first determined the fraction of participants that showed detectable serum neutralization indicated by serum ID
PMC10199003
S-IgG levels and S-antigen contacts contribute to serum neutralization against Wu01 and BA.4/5
infections
INFECTIONS
To explore predictive features for serum neutralization, we first characterized neutralizing activity against Wu01 and BA.4/5 stratified by sex, age, drug immunosuppression, pre-conditions, number of received vaccinations, number of previous infections, and NC-IgG serostatus (Fig. 
PMC10199003
Description of serum neutralizing activity.
REGRESSION, DISEASE
Dot plots depicting serum neutralization IDIn the following, we performed multivariable regression and Bayesian network analyses, as described above, to determine features that contribute to serum neutralization (serving as a correlate of immune protection and disease severity of COVID-19)
PMC10199003
Impaired serum neutralization activity against Omicron sub-lineage BQ.1.1
After completion of sample collection, a rapid spread of the Omicron variant BQ.1.1 exhibiting three additional mutations in the Spike-protein in comparison to BA.4/5 (R346T, K444T, and N460K) could be observed (Fig. 
PMC10199003
Discussion
infections
REGRESSION, INFECTIONS
Given the substantial immune escape of SARS-CoV-2 variants for the assessment of population immunity, completing S-IgG seroprevalence with serum neutralizing activity is essentialOur results demonstrate a high fraction of participants (95%) with detectable S-IgG but only moderate adherence to current recommendations on...
PMC10199003
Methods
PMC10199003
Ethical considerations
All samples and data were obtained under protocols approved by the ethics committees of the Medical Faculty of the University of Cologne (22_1262), of the Medical Faculty of the University of Bonn (314/22), of the Medical Faculty of the University of Düsseldorf (2022-2072), of the Medical Faculty of the University of E...
PMC10199003
Study design
infections, pain
RECRUITMENT, INFECTIONS
Recruitment of participants and sample collection were conducted at five study sites in North Rhine-Westphalia, Germany (University Hospital of Cologne, University Hospital of Düsseldorf, University Hospital of Essen, University Hospital of Bonn, and University Hospital of Münster). Participation was offered to patient...
PMC10199003
Processing of serum samples
HEAT
Serum samples were collected in serum-gel tubes (Sarstedt) by venipuncture. After that, the samples were transported at 4 °C and processed within 48 h. After centrifugation, the serum was transferred to 2 ml cryotubes and stored at −80 °C till use. For further analysis in serological assays, the samples were thawed at ...
PMC10199003
Serological assays
® SARS-CoV-2
Anti-SARS-CoV-2 antibodies were detected using commercial assays that use either SARS-CoV-2 Spike protein or SARS-CoV-2 Nucleocapsid antigens. All assays were used as per the manufacturer’s recommendations.For the main analysis of this study, S-IgG of all 1411 samples was measured using DiaSorin’s LIAISON® SARS-CoV-2 T...
PMC10199003
Cell lines
HEK293T cells and 293T-ACE2 cells (Cat#CRL-11268 and Cat#NR-52511, respectively) were maintained in DMEM (Gibco) containing 10% FBS, 1% Penicillin-Streptomycin, 1 mM
PMC10199003
Cloning of SARS-CoV-2 Omicron BA.4/5 and BQ.1.1 spike constructs
Cloning of Wu01- and BA.4/5 spike protein expression plasmids was previously described
PMC10199003
Pseudovirus neutralization assays
For pseudovirus particle production, HEK293T cells were co-transfected with plasmids encoding for the SARS-CoV-2 spike protein, HIV-1 Tat, HIV-1 Gag/Pol, HIV-1 Rev, and luciferase, followed by an internal ribosome entry site (IRES) and ZsGreen
PMC10199003
Quantification and statistical analysis
REGRESSION
We used stepwise forward regression to select features in a linear regression model. We distinguished between continuous features (age, height, weight, BMI, S-IgG, serum IDTesting for statistical significance of differences in sex distribution between the study population and the study sample was performed with the two...
PMC10199003
Additional software
Maps of Germany and North Rhine-Westphalia were designed with the iMapU tool provided by iExcelU. Data collection was performed using Microsoft Excel for Mac (v.14.7.3.). Data analysis and Figure preparation was performed using Prism 9.0 (GraphPad). Data analysis was performed using RStudio (lmtest: 0.9-40, bnlearn: 4....
PMC10199003
Reporting summary
Further information on research design is available in the 
PMC10199003
Supplementary information
Supplementary informationPeer review fileReporting Summary
PMC10199003
Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-38127-y.
PMC10199003
Acknowledgements
Claudia
We are grateful to all study participants for their dedication to our research. We thank all members of all involved institutes. In particular, we thank Andrea Klöckner, Christian Overath, Anna Lucia Petrucci, Flaurant Ramadani, Claudia Reddig, Jasmin Lange, and Monika Eschbach-Bludau for processing serum samples and s...
PMC10199003
Author contributions
P.K.
Conceptualization: F.D., F.K., J.T., S.L., H.S., C.E., M. Paluschinski, B.S., U.D.; J. Kü; Methodology: F.D., M. Pirkl., F.K.; Investigation: F.D., M. Paluschinski, F.K., E.A. B.M., V.D.C, V.B., H.G., F.T., M.B., M.M., M.L., M.A., M.T.H., W.H., M.M.M., P.K., J. Kü, M.S., G.O., J.K., C.E., C.K., D.E., I.G., M.K., W.O.M....
PMC10199003
Peer review
PMC10199003
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC10199003
Data availability
The generated data are available in the source data file. Raw data reported in this paper will be shared by the lead contact upon reasonable request. SARS-CoV-2 variant proportions were extrapolated from the bi-weekly. Our world in Data dashboard (
PMC10199003
Code availability
All original code has been deposited online
PMC10199003
Competing interests
The authors declare no competing interests.
PMC10199003
References
PMC10199003
Introduction
Endometriosis
ENDOMETRIOSIS, DYSMENORRHEA
Endometriosis is estimated to affect approximately 10% of women of reproductive age [Melatonin could be a treatment option due to its anti-inflammatory [We recently explored the analgesic effect of 10 mg melatonin daily in women suffering from severe dysmenorrhea, however we could not show this regimen to be superior t...
PMC10237656
Materials and methods
endometriosis, bleeding, Endometriosis, Pain, blood loss, dyspareunia, amenorrhea, pain, dysmenorrhea, dysuria, amenorrhoeic, Insomnia, liver or kidney disease, NRS
ENDOMETRIOSIS, BLEEDING, ENDOMETRIOSIS, BLOOD LOSS, DYSPAREUNIA, ADVERSE EVENTS, RECRUITMENT, DYSMENORRHEA, SECONDARY, CHRONIC PAIN
We conducted this randomized, double-blinded, parallel placebo-controlled trial at Södersjukhuset, a hospital in Stockholm, Sweden. Participants were recruited between August 2019 and March 2021. Prior to enrolment, a written informed consent was obtained from the participants. The principles expressed in the Declarati...
PMC10237656
Statistical analysis
NRS
To detect a clinically significant reduction of NRS of 1.3 units [
PMC10237656
CONSORT flow chart.
dyspareunia, pain, dysuria, insomnia, dyschezia
DYSPAREUNIA, DYSMENORRHEA
We used mixed models analysis to study if there were any differences between the groups over all time points for each of the five continuous outcomes recorded daily (EAPP, amount of ingested analgesic, dysuria, dyschezia and dyspareunia) [Covariance structure AR(1) with random intercept, without random slope proved to ...
PMC10237656
Results
We screened 120 volunteers to include 40 participants, 20 in each group (
PMC10237656
Treatment effect on the outcomes during the study period.
Analyzed with linear mixed models.Adjusting for weight or for hormonal therapy did not affect the results. A sensitivity analysis stratified by hormonal treatment showed no differences between the groups (
PMC10237656
Treatment effect of the outcomes analyzed at the end of the study.
pain
Independent t-test was used to evaluate sleep, quality of life and pain catastrophization. The participants answered to questionnaire on day 21 in the last treatment cycle.When assessing acceptability at the end of the study period 11 (61%) in the melatonin group had a good experience with the drug, 1 (6%) had a bad ex...
PMC10237656
Discussion
endometrial lesions, endometriosis, pelvic pain, pain
OXIDATIVE STRESS, ENDOMETRIOSIS
This randomized double-blinded placebo-controlled study could not show that 20 mg melatonin ingested at bedtime reduced endometriosis-associated pain, in contrast to a previous study [Studies have shown that melatonin inhibits the estrogen-driven epithelial cell migration, invasion and epithelial-mesenchymal transition...
PMC10237656
Conclusion
chronic pain, endometriosis-associated pain, pain
ADVERSE EFFECTS, CHRONIC PAIN
Our study could not show that 20 mg of melatonin given orally at bedtime during two menstrual cycles/ two months had better analgesic effect on endometriosis-associated pain as compared with placebo. We studied a higher dose melatonin than previously studied for EAPP, however no major adverse effects were observed. The...
PMC10237656
Supporting information
PMC10237656
CONSORT 2010 checklist of information to include when reporting a randomised trial*.
(DOC)Click here for additional data file.
PMC10237656
Sensitivity analysis.
Stratification by hormonal treatment end weight, respectively.(XLSX)Click here for additional data file.(DOCX)Click here for additional data file.(XLSX)Click here for additional data file.
PMC10237656
Background
T2DM
TYPE 2 DIABETES MELLITUS, SECONDARY
Type 2 diabetes mellitus (T2DM) is a major health problem in the western world. Despite a widespread implementation of integrated care programs there are still patients with poorly controlled T2DM. Shared goal setting within the process of Shared Decision Making (SDM) may increase patient’s compliance and adherence to ...
PMC10182591
Methods
T2DM
RECRUITMENT
In a German primary care setting, we collected data before intervention at baseline, 6, 12 and 24 months. Patients with T2DM with an HbA1c ≥ 8.0% (64 mmol/mol) at the time of recruitment and complete data at baseline and after 24 months were eligible for the presented analyses. Using a generalized estimating equation a...
PMC10182591
Results
From N = 833 recruited patients at baseline, n = 547 (65.7%) from 105 General Practitioners (GPs) were analysed. 53.4% patients were male, 33.1% without a partner, 64.4% had a low educational level, mean age was 64.6 (SD 10.6), 60.7% took insulin at baseline, mean baseline HbA1c was 9.1 (SD 1.0). For 287 patients (52.5...
PMC10182591
Conclusions
T2DM
Shared goal setting with T2DM patients targeting on HbA1c-levels had no significant impact on goal achievement. It may be assumed, that shared goal setting on patient-related clinical outcomes within the process of SDM has not been fully captured yet.
PMC10182591
Trial registration
The trial was registered at ISRCTN registry under the reference ISRCTN70713571.
PMC10182591
Supplementary Information
The online version contains supplementary material available at 10.1186/s12875-023-02067-9.
PMC10182591
Keywords
PMC10182591
Background
macrovascular complications, kidney failure, T2DM, diabetic complications, Diabetes, vision loss, diabetes
CARDIOVASCULAR DISEASE, SECONDARY, CHRONIC DISORDERS, KIDNEY FAILURE, DIABETIC COMPLICATIONS, DIABETES, TYPE 2 DIABETES, TYPE 2 DIABETES MELLITUS, DIABETES
Diabetes is one of the most common chronic disorders and a major public health problem in the western world which leads to an enormous economic burden; type 2 diabetes mellitus (T2DM) constitutes about 85–95% of all diabetes cases [Recent preventive therapeutic interventions and treatment concepts have been focusing to...
PMC10182591
Methods
SECONDARY
The presented secondary analyses are based on data of the cluster-randomized controlled DEBATE trial [Data was measured before randomization (baseline, T0), at 6–8 (T1), 12–14 (T2), 18–20 (T3) and 24–26 months (T4) after baseline. The DEBATE trial was not able to show a significant difference on the primary outcome (le...
PMC10182591
Measurement tools
Detailed information on data collection procedures in the DEBATE trial were published elsewhere [
PMC10182591