Summary of clinical investigation plan for The DIATEC trial: in-hospital diabetes management by a diabetes team and continuous glucose monitoring or point of care glucose testing - a randomised controlled trial.

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

EU-LIFE charter of independent life science research institutes.

The diverse range of organizations contributing to the global research ecosystem is believed to enhance the overall quality and resilience of its output. Mid-sized autonomous research institutes, distinct from universities, play a crucial role in this landscape. They often lead the way in new research fields and experimental methods, including those in social and organizational domains, which are vital for driving innovation. The EU-LIFE alliance was established with the goal of fostering excellence by developing and disseminating best practices among European biomedical research institutes. As directors of the 15 EU-LIFE institutes, we have spent a decade comparing and refining our processes. Now, we are eager to share the insights we've gained. To this end, we have crafted this Charter, outlining 10 principles we deem essential for research institutes to flourish and achieve ground-breaking discoveries. These principles, detailed in the Charter, encompass excellence, independence, training, internationality and inclusivity, mission focus, technological advancement, administrative innovation, cooperation, societal impact, and public engagement. Our aim is to inspire the establishment of new institutes that adhere to these principles and to raise awareness about their significance. We are convinced that they should be viewed a crucial component of any national and international innovation strategies.

Identification of a CTX-M-255 ß-lactamase containing a G239S substitution selectively conferring resistance to penicillin/ß-lactamase inhibitor combinations.

OBJECTIVES: An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized ß-lactamase, CTX-M-255, as the only acquired ß-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported ß-lactamase, CTX-M-178, also containing a G239S substitution and compare it to their respective parental enzymes, CTX-M-27 and CTX-M-15. METHODS: All ß-lactamase genes were expressed in E. coli TOP10 and MICs to representative ß-lactam-antibiotics were determined. Furthermore, blaCTX-M-15,  blaCTX-M-27, blaCTX-M-178 and blaCTX-M-255 with C-terminal His-tag fusions were affinity purified for enzyme kinetic assays determining Michaelis-Menten kinetic parameters against representative ß-lactam-antibiotics and IC50s of clavulanate, sulbactam, tazobactam and avibactam. RESULTS: TOP10-transformants expressing blaCTX-M-178 and blaCTX-M-255 showed resistance to penicillin/ß-lactamase combinations and susceptibility to cephalothin and cefotaxime in contrast to transformants expressing blaCTX-M-15 and blaCTX-M-27. Determination of enzyme kinetic parameters showed that CTX-M-178 and CTX-M-255 both lacked hydrolytic activity against cephalosporins and showed impaired hydrolytic efficiency against penicillin antibiotics compared to their parental enzymes. Both enzymes appeared more active against piperacillin compared to benzylpenicillin and ampicillin. Compared to their parental enzymes, IC50s of ß-lactamase-inhibitors were increased more than 1000-fold for CTX-M-178 and CTX-M-255. CONCLUSIONS: CTX-M-178 and CTX-M-255, both containing a G239S substitution, conferred resistance to piperacillin/tazobactam and may be characterized as inhibitor-resistant CTX-M ß-lactamases. Inhibitor resistance was accompanied by loss of activity against cephalosporins and monobactams. These findings add to the necessary knowledge base for predicting antibiotic susceptibility from genotypic data.

Statistical Packages and Algorithms for the Analysis of Continuous Glucose Monitoring Data: A Systematic Review.

BACKGROUND: Continuous glucose monitoring (CGM) measures glucose levels every 1 to 15 minutes and is widely used in clinical and research contexts. Statistical packages and algorithms reduce the time-consuming and error-prone process of manually calculating CGM metrics and contribute to standardizing CGM metrics defined by international consensus. The aim of this systematic review is to summarize existing data on (1) statistical packages for retrospective CGM data analysis and (2) statistical algorithms for retrospective CGM analysis not available in these statistical packages. METHODS: A systematic literature search in PubMed and EMBASE was conducted on September 19, 2023. We also searched Google Scholar and Google Search until October 12, 2023 as sources of gray literature and performed reference checks of the included literature. Articles in English and Danish were included. This systematic review is registered with PROSPERO (CRD42022378163). RESULTS: A total of 8731 references were screened and 46 references were included. We identified 23 statistical packages for the analysis of CGM data. The statistical packages could calculate many metrics of the 2022 CGM consensus and non-consensus CGM metrics, and 22/23 (96%) statistical packages were freely available. Also, 23 statistical algorithms were identified. The statistical algorithms could be divided into three groups based on content: (1) CGM data reduction (eg, clustering of CGM data), (2) composite CGM outcomes, and (3) other CGM metrics. CONCLUSION: This systematic review provides detailed tabular and textual up-to-date descriptions of the contents of statistical packages and statistical algorithms for retrospective analysis of CGM data.

Predicting the primary infection source of Escherichia coli bacteremia using virulence-associated genes.

PURPOSE: To investigate the role of E. coli virulence-associated genes (VAGs) in predicting urinary tract infection (UTI) as the source of bacteremia in two distinct hospital populations, one with a large general catchment area and one dominated by referrals. METHODS: E. coli bacteremias identified at Department of Clinical Microbiology (DCM), Hvidovre Hospital and DCM, Rigshospitalet in the Capital Region of Denmark from October to December 2018. Using whole genome sequencing (WGS), we identified 358 VAGs from 224 E. coli bacteremia. For predictive analysis, VAGs were paired with clinical source of UTI from local bacteremia databases. RESULTS: VAGs strongly predicting of UTI as primary infection source of bacteremia were primarily found within the pap gene family. papX (PPV 96%, sensitivity 54%) and papGII (PPV 93%, sensitivity 56%) were found highly predictive, but showed low sensitivities. The strength of VAG predictions of UTI as source varied significantly between the two hospital populations. VAGs had weaker predictions in the tertiary referral center (Rigshospitalet), a disparity likely stemming from differences in patient population and department specialization. CONCLUSION: WGS data was used to predict the primary source of E. coli bacteremia and is an attempt on a new and different type of infection source identification. Genomic data showed potential to be utilized to predict the primary source of infection; however, discrepancy between the best performing profile of VAGs between acute care hospitals and tertiary hospitals makes it difficult to implement in clinical practice.

Response of Arctic benthic foraminiferal traits to past environmental changes.

The Arctic is subjected to all-encompassing disruptions in marine ecosystems caused by anthropogenic warming. To provide reliable estimates of how future changes will affect the ecosystems, knowledge of Arctic marine ecosystem responses to past environmental variability beyond the instrumental era is essential. Here, we present a novel approach on how to evaluate the state of benthic marine biotic conditions during the deglacial and Holocene period on the Northeast Greenland shelf. Benthic foraminiferal species were assigned traits (e.g., oxygen tolerance, food preferences) aiming to identify past faunal changes as a response to external forcing mechanisms. This approach was applied on sediment cores from offshore Northeast Greenland. We performed numerical rate-of-change detection to determine significant changes in the benthic foraminiferal traits. That way, the significant abrupt trait changes can be assessed across sites, providing a better understanding of the impact of climate drivers on the traits. Our results demonstrate that during the last ~ 14,000 years, bottom water oxygen is the main factor affecting the variability in the benthic foraminiferal faunas in this area. Our results show that significant changes in the traits correspond to drastic climate perturbations. Specifically, the deglacial-Holocene transition and mid-Holocene warm period exhibited significant change, with several trait turnovers.

The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial.

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes.

Association between childhood trauma, cognition, and psychosocial function in a large sample of partially or fully remitted patients with bipolar disorder and healthy participants.

BACKGROUND: Childhood trauma (CT) are frequently reported by patients with bipolar disorder (BD), but it is unclear whether and how CT contribute to patients' cognitive and psychosocial impairments. We aimed to examine the impact of CT on cognition and psychosocial functioning in a large sample of 345 patients with BD and 183 healthy control participants (HC) using the Childhood Trauma Questionnaire, neurocognitive tests and ratings of mood symptoms and functioning. RESULTS: Patients showed broad cognitive impairments across memory, attention and executive function and functional disability despite being in partial or full remission and had higher levels of CT than HC. Higher levels of CT correlated with impairments across almost all cognitive domains and lower psychosocial functioning across BD patients and HC. Of these, the associations between CT and poorer working memory and lower psychosocial functioning, respectively, prevailed after adjusting for clinical and demographical variables. Diagnosis of BD and estimated verbal intelligence did not moderate these associations. Analysis of CT sub-categories showed that working memory impairments were related particularly to childhood physical and emotional abuse, while psychosocial difficulties were related to physical and emotional neglect. CONCLUSIONS: CT may have negative implications for working memory and psychosocial functioning across both BD and healthy populations. If the findings are replicated, this would suggest that early interventions that reduce the frequency of CT in vulnerable families may aid children's cognitive and psychosocial development.

Low-level expression of human Epidermal growth Factor Receptor-2 (HER2) in High-Grade Mullerian Tumors: Implications for therapy decision making.

Introduction: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas. Methods: We reviewed all high-grade Mullerian cancers between 2016 and 2021, where HER2 by IHC and/or FISH tests were available. Additional clinical information was recorded, and statistical analysis was performed using SPSS (version 27). Results: Forty (49.4%) tumors were endometrial, 20 (24.7%) ovarian, 16 (19.8%) fallopian tubal, and 5 (6.2%) primarily peritoneal. Overall, 17 (21.0%) were HER2 positive (IHC 3+/IHC 2+/FISH amplified), 31 (38.3%) HER2 low (IHC 1+/2+/FISH non-amplified), and 30 (37.0%) were HER2 negative (IHC = 0). HER2 low expression was noted in 15% ovarian, 25% fallopian tubal, 53% endometrial, and 60% peritoneal tumors; 34% and 21% of serous carcinomas, 63% and 13% of carcinosarcomas, and 67% and 33% of endometrioid carcinomas were HER2 low and HER2 positive respectively. HER2 negative and HER2 low expression had a significant association with primary tumor location (p = 0.001); endometrium and peritoneal tumors were more likely to be HER2 low and HER2 negative. During a mean follow-up of 13.2 months (range: 1-34), 5% of the patients were deceased. Conclusions: Based on the current HER2-low recommendations in the breast, about one-third of patients with high-grade Mullerian carcinomas might qualify for anti-HER2 therapy with a potential for improved progression-free and overall survival.

Why is measuring and predicting fitness under genomic conflict so hard?

Genomic conflict between the sexes is caused by differences in the optimal male and female reproductive strategies, and is a major contributor to genetic, phenotypic, and life history variation. While early experimental work appeared to strongly support the sexual conflict paradigm, recent work has produced more ambiguous results. Recent advances in experimental evolution studies combined with theoretical arguments can shed light on why measuring fitness under a conflict is so challenging, including the incidental alteration of mating dynamics, demographic effects, and inherent complexity in what quantity selection maximizes. We stress that non-intuitive results do not necessarily mean the absence of conflict, and follow-up experiments to determine why a priori predictions failed can ultimately teach us more than if they had been confirmed.

Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach.

AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

No effect of the turmeric root phenol curcumin on prednisolone-induced glucometabolic perturbations in men with overweight or obesity.

Objectives: Preclinically, curcumin has been shown to protect against glucocorticoid-induced insulin resistance. We evaluated the effect of curcumin administered with prednisolone in healthy overweight or obese men. Methods: In a double-blind, parallel-group trial, 24 overweight/obese non-diabetic men were randomised to one of three intervention groups (A) prednisolone placebo+curcumin placebo, (B) prednisolone (50 mg/day)+curcumin placebo or (C) prednisolone and curcumin (400 mg/day). Curcumin or curcumin placebo treatment started 1 day prior to 10-day prednisolone or prednisolone placebo treatment. The primary endpoint was change in prednisolone-induced insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA2-IR). Other endpoints included anthropometric measurements, magnetic resonance spectroscopy-assessed hepatic fat content, blood pressure, circulating metabolic markers and continuous glucose monitoring measures. Results: Baseline characteristics (mean ± s.d): age 44.2 ± 13.7 years, BMI 30.1 ± 3.5 kg/m2, HbAlc 33.3 ± 3.2 mmol/mol, HOMA2-IR 1.10 ± 0.45 and fasting plasma glucose 5.2 ± 0.4 mmol/L. Prednisolone significantly increased HOMA2-IR (estimated treatment difference 0.36 (95% CI 0.16; 0.57)). Co-treatment with curcumin had no effect on HOMA2-IR (estimated treatment difference 0.08 (95% CI -0.13; 0.39)). Prednisolone increased HbAlc, insulin, C-peptide, glucagon, blood pressure, mean interstitial glucose, time spent in hyperglycaemia and glucose variability, but no protective effect of curcumin on any of these measures was observed. Conclusions: In this double-blind, placebo-controlled parallel-group study involving 24 overweight or obese men randomised to one of three treatment arms, curcumin treatment had no protective effect on prednisolone-induced insulin resistance or other glucometabolic perturbations.

Management of diabetes and hyperglycaemia in non-intensive care units.

Diabetes and hyperglycaemia are frequent diagnoses in the hospital, and in-hospital hyperglycaemia is associated with adverse clinical outcomes. Insulin is the preferred treatment for in-hospital hyperglycaemia. This review summarises the management of hyperglycaemia in Danish hospitals. In Denmark, sliding-scale insulin is often applied with the addition of basal insulin after 1-2 days with hyperglycaemia which differs from international guidelines recommending a basal-bolus regimen. The optimal non-intensive care unit glucose targets, the safety and efficacy level of non-insulin antidiabetic agents, and continuous glucose monitoring are subjects of further research.

Creativity as an antidote to research becoming too predictable.

In this commentary, Sonne-Hansen and colleagues argue that research leaders and organizations should encourage more "theory-guessing" by budding young scientists, rather than incentivizing safe mainstream research.

Female-limited X chromosome evolution reveals that lifespan is mainly modulated by interlocus rather than intralocus sexual conflict.

Abstract: Sexual dimorphism in somatic investment may be shaped by two distinct forms of sexual conflict; under intralocus sexual conflict (IASC), males and females have different optimal levels of somatic investment but are constrained from reaching their respective optima by their shared genome, while under interlocus sexual conflict (IRSC), males and females have different optimal sexual strategies, which could have direct or indirect effects on levels of somatic investment. We investigated effects of IASC and IRSC on two aspects of somatic investment, immune defence strategies and longevity, using previously established female-limited experimental evolution lines in Drosophila melanogaster. We found little evidence for any effect of either type of sexual conflict on investment in the immune defence resistance or tolerance. Nor did we find convincing evidence that longevity is subject to IASC in this species. However, we did find evidence that increased female control over mating rate had important and opposite effects on longevity between the sexes. Specifically, females that had adapted to high levels of female control over mating had a longer lifespan when kept in mixed-sex groups, while males had shorter longevity, perhaps due to increased investment in post-copulatory sexual selection. These novel results show that female control over mating rates may have important and unexpected effects on patterns of somatic investment. Significance statement: Sexual conflict occurs between the two sexes over numerous life history traits, and it is complex to disentangle how these traits interact and affect each other. Here we use a long-term evolution experiment to investigate sexual dimorphism in somatic maintenance. We found no effect of feminising the X chromosome on female immune defence. However, we did find that increased female control over mating rate resulted in longer female lifespan, but reduced male lifespan, and that these effects were dependent on social context (isolated or in mixed-sex groups). Unlike previous studies on the effect of sexual conflict on longevity, our experiment did not manipulate environmental conditions nor the adult sex ratio, which is likely to reduce both pre- and post-copulatory sexual selection. Supplementary Information: The online version contains supplementary material available at 10.1007/s00265-022-03231-4.

Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE.

Stratified mucin-producing intraepithelial lesion (SMILE) is a histologic subtype of HPV-associated endocervical adenocarcinoma in situ. We have observed benign endocervical changes resembling SMILE. We aim to characterize this pattern and explore its potential association with dysplasia. We retrospectively retrieved all 296 consecutive cases accessioned as endocervical biopsies. Some included multiple specimens, totaling 483 biopsies and 219 endocervical curettages (ECC), n = 702. We included cases showing endocervical epithelial stratification often with pencillate (triangular-shaped) nuclei. We rejected cases in which layering represented tangential sectioning, metaplasia, microglandular hyperplasia, gastric type epithelial changes, and dysplasia. We found benign stratified intraepithelial mucinous proliferation in 51 patients, either with a multilayered (n = 27) or a two-layered appearance (n = 24). Overall, multilayered proliferation occurred in 6 % (29/483) of biopsies and in 0.9 % of ECCs (2/219). Two-layering was identified in 4 % of all biopsies (20/482) and was not seen in ECCs. Histologic findings included stratification, intracytoplasmic mucin, paler cytoplasm, low nuclear-to-cytoplasmic ratio, often pencillate nuclei, rare mitoses, and no apoptotic bodies. P16 immunohistochemistry (n = 12) was negative, suggesting absence of underlying high-risk HPV infection. HSIL was concomitant in 29.6 % (8/27) of patients with multilayered proliferation. Concurrent SMILE was not observed. We also reviewed 13 SMILE cases. Concurrent multilayered benign proliferation was identified in 54 % (7/13) of cases. We describe benign stratified intraepithelial mucinous proliferation of the cervix, which morphologically may overlap with SMILE. Its presence in most SMILE cases suggests a potential relationship. The multilayered form represents a diagnostic pitfall when mitotically active. Because of the often-coexistent HSIL, we propose that its presence should prompt scrutiny to rule out any associated dysplasia.

Detection of SARS-CoV-2 in exhaled breath from non-hospitalized COVID-19-infected individuals.

The diagnosis of COVID-19 is based on detection of SARS-CoV-2 in oro-/nasopharyngel swabs, but due to discomfort and minor risk during the swab procedure, detection of SARS-CoV-2 has been investigated in other biological matrixes. In this proof-of-concept study, individuals with confirmed SARS-CoV-2 infection performed a daily air sample for five days. Air samples were obtained through a non-invasive electrostatic air sampler. Detection of SARS-CoV-2 RNA was determined with qRT-PCR. The association of positive samples with different exposures was evaluated through mixed-effect models. We obtained 665 air samples from 111 included participants with confirmed SARS-CoV-2 infection. Overall, 52 individuals (46.8%) had at least one positive air sample, and 129 (19.4%) air samples were positive for SARS-CoV-2. Participants with symptoms or a symptom duration ≤ four days had significantly higher odds of having a positive air sample. Cycle threshold values were significantly lower in samples obtained ≤ 4 days from symptom onset. Neither variant of SARS-CoV-2 nor method of air sampling were associated with a positive air sample. We demonstrate that SARS-CoV-2 is detectable in human breath by electrostatic air sampling with the highest detection rate closest to symptom onset. We suggest further evaluation of the air sampling technique to increase sensitivity.

Effects of an exercise-based lifestyle intervention on systemic markers of oxidative stress and advanced glycation endproducts in persons with type 2 diabetes: Secondary analysis of a randomised clinical trial.

AIMS/HYPOTHESIS: This secondary analysis aimed to investigate the effects of a 12 months intensive exercise-based lifestyle intervention on systemic markers of oxidative stress in persons with type 2 diabetes. We hypothesized lifestyle intervention to be superior to standard care in decreasing levels of oxidative stress. METHODS: The study was based on the single-centre, assessor-blinded, randomised, controlled U-turn trial (ClinicalTrial.gov NCT02417012). Persons with type 2 diabetes ˂ 10 years, ˂ 3 glucose lowering medications, no use of insulin, BMI 25-40 kg/m2 and no severe diabetic complications were included. Participants were randomised (2:1) to either intensive exercise-based lifestyle intervention and standard (n = 64) or standard care alone (n = 34). Standard care included individual education in diabetes management, advice on a healthy lifestyle and regulation of medication by a blinded endocrinologist. The lifestyle intervention included five to six aerobic exercise sessions per week, combined with resistance training two to three times per week and an adjunct dietary intervention aiming at reduction of ∼500 kcal/day (month 0-4). The diet was isocaloric from months 5-12. The primary outcome of this secondary analysis was change in oxidative stress measured by 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and secondarily in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), as markers of RNA and DNA oxidation, respectively, from baseline to 12-months follow-up. RESULTS: A total of 77 participants, 21 participants receiving standard care and 56 participants receiving the lifestyle intervention, were included in the analysis. Mean age at baseline was 54.1 years (SD 9.1), 41% were women and mean duration of type 2 diabetes was 5.0 years (SD 2.8). From baseline to follow-up the lifestyle group experienced a 7% decrease in 8-oxoGuo (-0.15 nmol/mmol creatinine [95% CI -0.27, -0.03]), whereas standard care conversely was associated with a 8.5% increase in 8-oxoGuo (0.19 nmol/mmol creatinine [95% CI 0.00, 0.40]). The between group difference in 8-oxoGuo was -0.35 nmol/mmol creatinine [95% CI -0.58, -0.12,], p = 0.003. No between group difference was observed in 8-oxodG. CONCLUSION/INTERPRETATION: A 12 months intensive exercise-based lifestyle intervention was associated with a decrease in RNA, but not DNA, oxidation in persons with type 2 diabetes.