Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.

Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.

Experiences that matter in bipolar disorder: a qualitative study using the capability, comfort and calm framework.

BACKGROUND: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective. METHODS: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families. RESULTS: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens. CONCLUSIONS: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

An investigation of factors affecting changes in health behaviours during the COVID-19 pandemic in a UK population-based cohort study.

OBJECTIVES: The COVID-19 pandemic has led to changes in behaviours, which may have different health effects in population subgroups. We investigated whether within-individual changes in health behaviours from before to during the pandemic differ by socio-economic deprivation, age or sex. STUDY DESIGN: Prospective cohort study. METHODS: Participants were recruited from the existing UK Fenland cohort study with measurements of health behaviours twice prepandemic (2005 to February 2020) and three times during the pandemic (July 2020 to April 2021). Health behaviours included daily servings of fruit and vegetables, units of alcohol consumed per week, smoking status, sleep duration and total and domain-specific physical activity energy expenditure. Sociodemographic information (English indices of multiple deprivation, education, occupation and ethnicity) and COVID-19 antibody status were also collected. Participants were grouped into three categories based on their English indices of multiple deprivation score: most, middle and least deprived. RESULTS: Participants were included if they had completed at least one measurement during the pandemic and one prepandemic (n = 3212). Fruit and vegetable consumption, total physical activity energy expenditure and smoking prevalence decreased during the pandemic compared with prepandemic, whereas average sleep duration increased and alcohol consumption did not change. Decreases in fruit and vegetable intake and physical activity energy expenditure were most pronounced in the most deprived group compared with the least deprived group and were greater in women than men. CONCLUSIONS: Socio-economic inequalities in health behaviours have worsened during the pandemic. As the country emerges from the COVID-19 pandemic, strategies to reduce health inequalities need to be put at the forefront of recovery plans.

Induced Pluripotent Stem Cell (iPSC)-Derived Endothelial Cells to Study Bacterial-Brain Endothelial Cell Interactions.

Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs when blood-borne bacteria are able to exit the cerebral vasculature and cause inflammation. The blood-brain barrier (BBB) and the meningeal blood-CSF barrier (mBCSFB) are composed of highly specialized brain endothelial cells (BECs) that possess unique phenotypes when compared to their peripheral endothelial counterparts. To cause meningitis, bacterial pathogens must be able to interact and penetrate these specialized BECs to gain access to the CNS. In vitro models have been employed to study bacterial-BEC interactions; however, many lack BEC phenotypes. Induced pluripotent stem cell (iPSC) technologies have enabled the derivation of brain endothelial-like cells that phenocopy BECs in culture. Recently, these iPSC-BECs have been employed to examine the host-pathogen interaction at the endothelial brain barriers. Using two clinically relevant human meningeal pathogens, this chapter describes the use of iPSC-BECs to study various aspects of BEC-bacterial interaction.

Validity and severity thresholds for the depression subscale of the affective self rating scale: An equipercentile equating study using classical test theory.

BACKGROUND: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16). METHODS: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9. RESULTS: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5. LIMITATIONS: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting. CONCLUSIONS: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.

Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes.

AIMS: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. METHODS: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). RESULTS: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. CONCLUSIONS: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.

Correction: External validation of risk prediction models for incident colorectal cancer using UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Elevated prevalence of nodal positivity in carcinoid tumours of the appendix smaller than 2 cm has a negative impact on overall survival.

AIM: The current standard of care for clinically node-negative carcinoid tumours of the appendix < 2.0 cm in size is appendectomy alone. The aim of this analysis was to evaluate the prevalence of pathological nodal positivity in clinically node-negative appendiceal tumour specimens < 2.0 cm and quantify the impact of occult pathological nodal positivity on overall survival following resection. METHOD: A retrospective database review of the 2019 US National Cancer Database for appendiceal cancer identified 2007 cases of clinically node-negative appendiceal carcinoid tumours based on SEER histology codes 8240, 8241, 8242, 8243, 8243, 8244, 8245, 8246 and 8249. Kaplan-Meier with log-rank testing and multivariate Cox regression analysis evaluated the impact of occult nodal positivity on overall survival following resection for clinically node-negative appendiceal carcinoma. RESULTS: The prevalence of occult nodal positivity increased from 1.9% for sub-centimetre tumours to 7% for tumours between 1.0 and 1.5 cm, 16.5% for tumours between 1.5 and 2.0 cm and to >29.5% for tumours > 2.0 cm. Rates of metastatic spread were similar for tumours < 2.0 cm but increased for larger tumours. Over two-thirds of patients received a segmental colectomy as definitive surgical therapy. After controlling for differences in cohorts, multivariate analysis showed an increased hazard ratio for mortality of 162% (HR 2.62, CI 1.884-3.541) for patients with pathological node-positive disease. CONCLUSION: Clinically node-negative carcinoid tumours of the appendix bigger than 1.5 cm have an increased rate of occult nodal spread which has a negative impact on overall survival.

Racial disparities after stoma construction in colorectal surgery.

AIM: Racial disparities are under-recognized among patients undergoing colorectal surgery. The purpose of this study was to determine the complication rates and surgical outcomes stratified by race and ethnicity among patients undergoing colorectal surgery with intestinal stoma creation. METHOD: The ACS NSQIP database from 2013 to 2016 was used. Colon, rectum and small bowel cases requiring intestinal stoma creation were selected. Both African-American and other groups of minority patients were compared with Caucasian patients using a complex multivariable analysis model. Primary outcomes of interest were complication rates, mortality and extended hospital length of stay. RESULTS: The study included 38 088 admissions. After multivariable analysis, African-American patients still had a prolonged length of hospital stay and higher complication rates. Other minorities also had a prolonged length of hospital stay and higher complication rates. CONCLUSIONS: Both African-American and other groups of minority patients requiring an ostomy suffer significantly higher postoperative complication rates and a prolonged hospital length of stay, even after comorbidity adjustment. Access to care, socioeconomic status and comorbid disease management are all important factors for minority patients who undergo colorectal surgery requiring intestinal stoma construction.

Gross and histopathologic diagnoses from North Atlantic right whale Eubalaena glacialis mortalities between 2003 and 2018.

Seventy mortalities of North Atlantic right whales Eubalaena glacialis (NARW) were documented between 2003 and 2018 from Florida, USA, to the Gulf of St. Lawrence, Canada. These included 29 adults, 14 juveniles, 10 calves, and 17 of unknown age class. Females represented 65.5% (19/29) of known-sex adults. Fourteen cases had photos only; 56 carcasses received external examinations, 44 of which were also necropsied. Cause of death was determined in 43 cases, of which 38 (88.4%) were due to anthropogenic trauma: 22 (57.9%) from entanglement, and 16 (42.1%) from vessel strike. Gross and histopathologic lesions associated with entanglement were often severe and included deep lacerations caused by constricting line wraps around the flippers, flukes, and head/mouth; baleen plate mutilation; chronic extensive bone lesions from impinging line, and traumatic scoliosis resulting in compromised mobility in a calf. Chronically entangled whales were often in poor body condition and had increased cyamid burden, reflecting compromised health. Vessel strike blunt force injuries included skull and vertebral fractures, blubber and muscle contusions, and large blood clots. Propeller-induced wounds often caused extensive damage to blubber, muscle, viscera, and bone. Overall prevalence of NARW entanglement mortalities increased from 21% (1970-2002) to 51% during this study period. This demonstrates that despite mitigation efforts, entanglements and vessel strikes continue to inflict profound physical trauma and suffering on individual NARWs. These cumulative mortalities are also unsustainable at the population level, so urgent and aggressive intervention is needed to end anthropogenic mortality in this critically endangered species.

Rare variant analysis in multiply affected families, association studies and functional analysis suggest a role for the ITGΒ4 gene in schizophrenia and bipolar disorder.

Recent results imply that rare variants contribute to the risk of schizophrenia. Exome sequence data from the UK10K project was used to identify three rare, amino acid changing variants in the ITGB4 gene which segregated with schizophrenia in two families: rs750367954, rs147480547 and rs145976111. Association analysis was carried out in the exome-sequenced Swedish schizophrenia study and in UCL schizophrenia and bipolar cases and controls genotyped for these variants. A gene-wise weighted burden test was performed on a trio sample of schizophrenia cases and their parents. rs750367954 was seen in two Swedish cases and in no controls. The other two variants were commoner in cases than controls in both Swedish and UCL cohort samples and an overall burden test was significant at p=0.0000031. The variants were not observed in the trio sample but ITGB4 was most highly ranked out of 14,960 autosomal genes in a gene-wise weighted burden test. The effect of rs147480547 and rs145976111 was studied in human neuroblastoma SH-SY5Y cells. Cells transfected with both variants had increased proliferation at both 24 and 48h (p=0.013 and p=0.05 respectively) compared to those with wild-type ITGB4. Taken together, these results suggest that rare variants in ITGB4 which affect function may contribute to the aetiology of schizophrenia and bipolar disorder.

Head imaging in suspected non accidental injury in the paediatric population. In the advent of volumetric CT imaging, has the skull X-ray become redundant?

AIM: To assess whether the inclusion of skull radiography, as part of the skeletal survey performed in suspected non-accidental injury (NAI), is still justified when volume computed tomography (CT) of the head has also been performed. MATERIALS AND METHODS: This was a retrospective study which included 94 patients aged between 24 days and 23 months who presented to the Emergency Department between August 2014 to July 2016 and had subsequent investigations for suspected NAI. Patients were identified from the local radiology systems (Carestream PACS and CRIS) using strict inclusion and exclusion criteria. Inclusion criteria were any suspected NAI patient who had both unenhanced volume CT head and skull radiography during the same episode of presentation. Any child with suspected NAI who only had one of either CT or radiographs of the skull (and not both) were excluded. RESULTS: None of the cases reviewed demonstrated additional findings on skull X-rays that were not demonstrated on the CT head. Due to the starkness of this result, the confidence interval is 0-3.9%. In two cases, additional bony findings were demonstrated on the CT head which were not evident on the skull X-rays. CONCLUSION: Skull X-rays could be excluded from the NAI skeletal survey without missing intracranial injuries or skull fractures in cases where a contemporaneous volumetric CT head is also performed.

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.

A two-step method for variable selection in the analysis of a case-cohort study.

Background: Accurate detection and estimation of true exposure-outcome associations is important in aetiological analysis; when there are multiple potential exposure variables of interest, methods for detecting the subset of variables most likely to have true associations with the outcome of interest are required. Case-cohort studies often collect data on a large number of variables which have not been measured in the entire cohort (e.g. panels of biomarkers). There is a lack of guidance on methods for variable selection in case-cohort studies. Methods: We describe and explore the application of three variable selection methods to data from a case-cohort study. These are: (i) selecting variables based on their level of significance in univariable (i.e. one-at-a-time) Prentice-weighted Cox regression models; (ii) stepwise selection applied to Prentice-weighted Cox regression; and (iii) a two-step method which applies a Bayesian variable selection algorithm to obtain posterior probabilities of selection for each variable using multivariable logistic regression followed by effect estimation using Prentice-weighted Cox regression. Results: Across nine different simulation scenarios, the two-step method demonstrated higher sensitivity and lower false discovery rate than the one-at-a-time and stepwise methods. In an application of the methods to data from the EPIC-InterAct case-cohort study, the two-step method identified an additional two fatty acids as being associated with incident type 2 diabetes, compared with the one-at-a-time and stepwise methods. Conclusions: The two-step method enables more powerful and accurate detection of exposure-outcome associations in case-cohort studies. An R package is available to enable researchers to apply this method.

Adiposity and grip strength as long-term predictors of objectively measured physical activity in 93 015 adults: the UK Biobank study.

BACKGROUND/OBJECTIVES: Fatness and fitness are associated with physical activity (PA) but less is known about the prospective associations of adiposity and muscle strength with PA. This study aimed to determine longitudinal associations of body mass index (BMI), waist circumference (WC) and grip strength (GS) with objectively measured PA. SUBJECTS/METHODS: Data are from the UK Biobank study. At baseline (2006-2010), BMI, WC and GS were objectively measured. At follow-up (2013-2015), a sub-sample of 93 015 participants (52 161 women) wore a tri-axial accelerometer on the dominant wrist for 7 days. Linear regression was performed to investigate longitudinal associations of standardised BMI, WC and GS at baseline with moderate-to-vigorous PA (MVPA) and acceleration after a median 5.7-years follow-up (interquartile range: 4.9-6.5 years). RESULTS: Linear regression revealed strong inverse associations for BMI and WC, and positive associations for GS with follow-up PA; in women, MVPA ranges from lowest to highest quintiles of GS were 42-48 min day-1 in severely obese (BMI⩾35 kg m-2), 52-57 min day-1 in obese (30⩽BMI<35 kg m-2), 61-65 min day-1 in overweight (25⩽BMI<30 kg m-2) and 69-75 min day-1 in normal weight (18.5⩽BMI<25 kg m-2). Follow-up MVPA was also lower in the lowest GS quintile (42-69 min day-1) compared with the highest GS quintile (48-75 min day-1) across BMI categories in women. The pattern of these associations was generally consistent for men, and in analyses using WC and mean acceleration as exposure and outcome, respectively. CONCLUSIONS: More pronounced obesity and poor strength at baseline independently predict lower activity levels at follow-up. Interventions and policies should aim to improve body composition and muscle strength to promote active living.

Increased food availability raises eviction rate in a cooperative breeding mammal.

In group-living mammals, the eviction of subordinate females from breeding groups by dominants may serve to reduce feeding competition or to reduce breeding competition. Here, we combined both correlational and experimental approaches to investigate whether increases in food intake by dominant females reduces their tendency to evict subordinate females in wild meerkats (Suricata suricatta). We used 20 years of long-term data to examine the association between foraging success and eviction rate, and provisioned dominant females during the second half of their pregnancy, when they most commonly evict subordinates. We show that rather than reducing the tendency for dominants to evict subordinates, foraging success of dominant females is positively associated with the probability that pregnant dominant females will evict subordinate females and that experimental feeding increased their rates of eviction. Our results suggest that it is unlikely that the eviction of subordinate females serves to reduce feeding competition and that its principal function may be to reduce reproductive competition. The increase in eviction rates following experimental feeding also suggests that rather than feeding competition, energetic constraints may normally constrain eviction rates.

Bidirectional association between physical activity and muscular strength in older adults: Results from the UK Biobank study.

Background: The relationship between physical activity and muscular strength has not been examined in detail among older adults. The objective of this study was to examine the associations between physical activity and hand grip strength among adults aged ≥ 60 years. Methods: Using data from the UK Biobank study, we included 66 582 men and women with complete baseline data and 6599 with 4.5 years of follow-up data. We used multiple linear regression models to examine the cross-sectional, longitudinal and bidirectional associations between moderate-to-vigorous physical activity (MVPA) and grip strength, adjusting for potential confounding by age, sex, height, weight, health status, education level, smoking status, Townsend deprivation index and retirement status. Results: In cross-sectional analyses, grip strength and MVPA were linearly and positively associated with each other. Longitudinally, baseline MVPA was not associated with grip strength at follow-up {difference between quintile [Q] 5 and Q1 = 0.40 [95% confidence interval (CI): -0.14, 0.94]kg}, whereas baseline grip strength was associated with MVPA at follow-up [Q5 vs Q1 = 7.15 (1.18, 13.12) min/day]. People who maintained/increased time spent in MVPA did not experience any benefit in grip strength [0.08 (-0.20, 0.37) kg] whereas those who increased their grip strength spent 3.69 (0.20, 7.17) min/day extra in MVPA. Conclusion: Promotion of strength-training activities may enable and maintain participation in regular physical activity among older adults.

Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

BACKGROUND: Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. OBJECTIVES: To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. SEARCH STRATEGY: Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. SELECTION CRITERIA: Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. MAIN RESULTS: Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. CONCLUSIONS: The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. TWEETABLE ABSTRACT: Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy.

Fruit and vegetable intake and cardiovascular risk factors in people with newly diagnosed type 2 diabetes.

BACKGROUND/OBJECTIVES: The cardiovascular benefit of increasing fruit and vegetable (F&V) intake following diagnosis of diabetes remains unknown. We aimed to describe how quantity and variety of F&V intake, and plasma vitamin C, change after diagnosis of type 2 diabetes and examine whether these changes are associated with improvements in cardiovascular risk factors. SUBJECTS/METHODS: A total of 401 individuals with screen-detected diabetes from the ADDITION-Cambridge study were followed up over 5 years. F&V intake was assessed by food frequency questionnaire and plasma vitamin C at baseline, at 1 year and at 5 years. Linear mixed models were used to estimate associations of changes in quantity and variety of F&V intake, and plasma vitamin C, with cardiovascular risk factors and a clustered cardiometabolic risk score (CCMR), where a higher score indicates higher risk. RESULTS: F&V intake increased in year 1 but decreased by year 5, whereas variety remained unchanged. Plasma vitamin C increased at 1 year and at 5 years. Each s.d. increase (250g between baseline and 1 year and 270g between 1 and 5 years) in F&V intake was associated with lower waist circumference (-0.92 (95% CI: -1.57, -0.27) cm), HbA1c (-0.11 (-0.20, -0.03) %) and CCMR (-0.04 (-0.08, -0.01)) at 1 year and higher high-density lipoprotein (HDL)-cholesterol (0.04 (0.01, 0.06) mmol/l) at 5 years. Increased plasma vitamin C (per s.d., 22.5 µmol/l) was associated with higher HDL-cholesterol (0.04 (0.01, 0.06) mmol/l) and lower CCMR (-0.07 (-0.12, -0.03)) between 1 and 5 years. CONCLUSIONS: Increases in F&V quantity following diagnosis of diabetes are associated with lower cardiovascular risk factors. Health promotion interventions might highlight the importance of increasing, and maintaining increases in, F&V intake for improved cardiometabolic health in patients with diabetes.