Impact of weight loss and weight gain trajectories on body composition in a population at high risk of type 2 diabetes: A prospective cohort analysis.

AIM: In a primary care population at high risk of type 2 diabetes, 24-month weight change trajectories were used to investigate the impact of weight cycling on fat mass (FM) and fat-free mass (FFM). MATERIALS AND METHODS: Cohort data from the Walking Away from Type 2 Diabetes trial was used, which recruited adults at-risk of type 2 diabetes from primary care in 2009/10. Annual weight change trajectories based on weight loss/gain of ≥5% were assessed over two 24-month periods. Body composition was measured by bioelectrical impedance analysis. Repeated measures were analysed using generalized estimating equations with participants contributing up to two 24-month observation periods. RESULTS: In total, 622 participants were included (average age = 63.6 years, body mass index = 32.0 kg/m2 , 35.4% women), contributing 1163 observations. Most observations (69.2%) were from those that maintained their body weight, with no change to FM or FFM. A minority (4.6% of observations) lost over 5% of body weight between baseline and 12 months, which was then regained between 12 and 24 months. These individuals regained FM to baseline levels, but lost 1.50 (0.66, 2.35) kg FFM, adjusted for confounders. In contrast, those that gained weight between baseline and 12 months but lost weight between 12 and 24 months (5.5% of observations) had a net gain in FM of 1.70 (0.27, 3.12) kg with no change to FFM. CONCLUSION: Weight cycling may be associated with a progressive loss in FFM and/or gain in FM in those with overweight and obesity at-risk of type 2 diabetes.

Moderate-intensity stepping in older adults: insights from treadmill walking and daily living.

BACKGROUND: A step cadence of 100 steps/minute is widely used to define moderate-intensity walking. However, the generalizability of this threshold to different populations needs further research. We investigate moderate-intensity step cadence values during treadmill walking and daily living in older adults. METHODS: Older adults (≥ 60 years) were recruited from urban community venues. Data collection included 7 days of physical activity measured by an activPAL3™ thigh worn device, followed by a laboratory visit involving a 60-min assessment of resting metabolic rate, then a treadmill assessment with expired gas measured using a breath-by-breath analyser and steps measured by an activPAL3™. Treadmill stages were undertaken in a random order and lasted 5 min each at speeds of 1, 2, 3, 4 and 5 km/h. Metabolic equivalent values were determined for each stage as standardised values (METSstandard) and as multiples of resting metabolic rate (METSrelative). A value of 3 METSstandard defined moderate-intensity stepping. Segmented generalised estimating equations modelled the association between step cadence and MET values. RESULTS: The study included 53 participants (median age = 75, years, BMI = 28.0 kg/m2, 45.3% women). At 2 km/h, the median METSstandard and METSrelative values were above 3 with a median cadence of 81.00 (IQR 72.00, 88.67) steps/minute. The predicted cadence at 3 METSstandard was 70.3 (95% CI 61.4, 75.8) steps/minute. During free-living, participants undertook median (IQR) of 6988 (5933, 9211) steps/day, of which 2554 (1297, 4456) steps/day were undertaken in continuous stepping bouts lasting ≥ 1 min. For bouted daily steps, 96.4% (90.7%, 98.9%) were undertaken at ≥ 70 steps/minute. CONCLUSION: A threshold as low as 70 steps/minute may be reflective of moderate-intensity stepping in older adults, with the vast majority of all bouted free-living stepping occurring above this threshold.

Calcium requests in a primary care; An observational audit of biochemical requests and frequency of abnormal results.

BACKGROUND/AIMS: This aim of this audit was to assess the extent of serum calcium testing and the frequency of hypercalcaemia in the primary care setting. We also assessed the appropriateness of subsequent investigations with repeat serum calcium and PTH testing if hypercalcaemia was identified. METHODS: All laboratory requests for adjusted calcium and PTH samples sent from primary care in Glasgow were analysed over a 12 month period. This covered approximately 125 GP practices and a patient population of over 590,000. RESULTS: There were 78,845 requests for adjusted calcium and 2053 PTH requests from 62,745 patients aged 16-105 years (median age 57, IQ range 30 years). Of these requests 1423 (2.3%) of patients had biochemical evidence of hypercalcaemia (adjusted calcium ≥ 2.61 mmol/L). Of the 1423 patients with hypercalcaemia, 368 patients (45.8%) had a single raised calcium level that was within the normal range on repeat testing. Of the 400 patients with persistent hypercalcaemia on 2 or more samples, 210 (52.5%) had a PTH measured. Eight patients had a PTH < 2.0 pmol/L, whilst 202 (96.1%) had a PTH ≥ 2.0 pmol/L (range 2.1-106.1 pmol/L). CONCLUSIONS: Serum calcium was checked in 10.6% of the population per year within primary care. In the 2.4% with a raised calcium on initial testing, approximately half (45.8%) will normalise on repeat testing. Of those who remained persistently hypercalcaemic, only half (52.5%) had a PTH measured and the majority (96.1%) were in keeping with primary hyperparathyroidism being the most common cause of hypercalcaemia.

Self-reported walking pace, polygenic risk scores and risk of coronary artery disease in UK biobank.

BACKGROUND AND AIMS: Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. METHODS AND RESULTS: We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006-Feb/2021. In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30-3.13) in women; 9.60% (8.62-10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81-1.71) in women; 3.63% (2.58-4.67) in men] than lower [0.76% (0.59-0.93) and 2.37% (1.96-2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793-0.808) in women; 0.732 (0.728-0.737) in men. CONCLUSION: Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.

Creation and evaluation of full-text literature-derived, feature-weighted disease models of genetically determined developmental disorders.

There are >2500 different genetically determined developmental disorders (DD), which, as a group, show very high levels of both locus and allelic heterogeneity. This has led to the wide-spread use of evidence-based filtering of genome-wide sequence data as a diagnostic tool in DD. Determining whether the association of a filtered variant at a specific locus is a plausible explanation of the phenotype in the proband is crucial and commonly requires extensive manual literature review by both clinical scientists and clinicians. Access to a database of weighted clinical features extracted from rigorously curated literature would increase the efficiency of this process and facilitate the development of robust phenotypic similarity metrics. However, given the large and rapidly increasing volume of published information, conventional biocuration approaches are becoming impractical. Here, we present a scalable, automated method for the extraction of categorical phenotypic descriptors from the full-text literature. Papers identified through literature review were downloaded and parsed using the Cadmus custom retrieval package. Human Phenotype Ontology terms were extracted using MetaMap, with 76-84% precision and 65-73% recall. Mean terms per paper increased from 9 in title + abstract, to 68 using full text. We demonstrate that these literature-derived disease models plausibly reflect true disease expressivity more accurately than widely used manually curated models, through comparison with prospectively gathered data from the Deciphering Developmental Disorders study. The area under the curve for receiver operating characteristic (ROC) curves increased by 5-10% through the use of literature-derived models. This work shows that scalable automated literature curation increases performance and adds weight to the need for this strategy to be integrated into informatic variant analysis pipelines. Database URL: https://doi.org/10.1093/database/baac038.

Views of the public about Snacktivity™: a small changes approach to promoting physical activity and reducing sedentary behaviour.

BACKGROUND: Many people do not meet the recommended health guidance of participation in a minimum of 150-300 min of moderate intensity physical activity per week, often promoted as at least 30 min of physical activity on 5 days of the week. This is concerning and highlights the importance of finding innovative ways to help people to be physically active each day. Snacktivity™ is a novel approach that aims to encourage people to do small, 2-5 min bouts of physical activity 'snacks' throughout the whole day, such that they achieve at least 150 min of moderate intensity activity per week. However, before it can be recommended, there is a need to explore whether the concept is acceptable to the public. METHODS: A survey to assess the views of the public about Snacktivity™ was distributed to adult patients registered at six general practices in the West Midlands, UK and to health care employees in the same region. RESULTS: A total of 5989 surveys were sent to patients, of which 558 were returned (9.3%). A further 166 surveys were completed by health care employees. A total of 85% of respondents liked the Snacktivity™ concept. The flexibility of the approach was highly rated. A high proportion of participants (61%) reported that the ability to self-monitor their behaviour would help them to do Snacktivity™ throughout their day. Physically inactive participants perceived that Snacktivity™ would help to increase their physical activity, more than those who were physically active (OR = 0.41, 95% CI: 0.25-0.67). Approximately 90% of respondents perceived that Snacktivity™ was easy to do on a non-working day compared to 60% on a working day. Aerobic activity 'snacks' were preferred to those which were strength based. CONCLUSIONS: The Snacktivity™ approach to promoting physical activity was viewed positively by the public and interventions to test the merits of such an approach now need to be developed and tested in a variety of everyday contexts.

ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder.

ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype-phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype-phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.

Association of working shifts, inside and outside of healthcare, with severe COVID-19: an observational study.

BACKGROUND: Health and key workers have elevated odds of developing severe COVID-19; it is not known, however, if this is exacerbated in those with irregular work patterns. We aimed to investigate the odds of developing severe COVID-19 in health and shift workers. METHODS: We included UK Biobank participants in employment or self-employed at baseline (2006-2010) and with linked COVID-19 data to 31st August 2020. Participants were grouped as neither a health worker nor shift worker (reference category) at baseline, health worker only, shift worker only, or both, and associations with severe COVID-19 investigated in logistic regressions. RESULTS: Of 235,685 participants (81·5% neither health nor shift worker, 1·4% health worker only, 16·9% shift worker only, and 0·3% both), there were 580 (0·25%) cases of severe COVID-19. The odds of severe COVID-19 was higher in health workers (adjusted odds ratio: 2·32 [95% CI: 1·33, 4·05]; shift workers (2·06 [1·72, 2·47]); and in health workers who worked shifts (7·56 [3·86, 14·79]). Being both a health worker and a shift worker had a possible greater impact on the odds of severe COVID-19 in South Asian and Black and African Caribbean ethnicities compared to White individuals. CONCLUSIONS: Both health and shift work (measured at baseline, 2006-2010) were independently associated with over twice the odds of severe COVID-19 in 2020; the odds were over seven times higher in health workers who work shifts. Vaccinations, therapeutic and preventative options should take into consideration not only health and key worker status but also shift worker status.

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study.

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).

Device-measured physical activity and its association with physical function in adults with type 2 diabetes mellitus.

AIM: To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function. METHODS: This analysis included participants' data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10). Hand-grip strength, sit-to-stand 60 (STS-60) and the Duke Activity Status Index (DASI) score were used to assess functional capacity, while physical activity metrics were measured with a wrist-worn accelerometer. The associations between physical activity metrics and measures of functional capacity were analysed using generalized linear modelling. RESULTS: Some 635 adults (median age 66 years, 34% female) were included in this analysis. Overall, 29% of the cohort scored < 10 in the SPPB test indicating impaired physical function. This group spent more time in prolonged sedentary behaviour (600.7 vs. 572.5 min) and undertook less-intense physical activity. Each sd increase in physical activity volume and intensity gradients for those with impaired physical function was associated with 17% more repetitions for STS-60 with similar associations seen for DASI score. Each sd in sedentary time was associated with 15% fewer repetitions in STS-60 and 16% lower DASI score in those with impaired physical function, whereas in normal physical function group it was 2% and 1%, respectively. CONCLUSIONS: The strength of the associations for physical activity measures and functional capacity were modified by physical function status, with the strongest association seen in those with impaired physical function.

Re-imagining fMRI for awake behaving infants.

Thousands of functional magnetic resonance imaging (fMRI) studies have provided important insight into the human brain. However, only a handful of these studies tested infants while they were awake, because of the significant and unique methodological challenges involved. We report our efforts to address these challenges, with the goal of creating methods for awake infant fMRI that can reveal the inner workings of the developing, preverbal mind. We use these methods to collect and analyze two fMRI datasets obtained from infants during cognitive tasks, released publicly with this paper. In these datasets, we explore and evaluate data quantity and quality, task-evoked activity, and preprocessing decisions. We disseminate these methods by sharing two software packages that integrate infant-friendly cognitive tasks and eye-gaze monitoring with fMRI acquisition and analysis. These resources make fMRI a feasible and accessible technique for cognitive neuroscience in awake and behaving human infants.

Tuberculosis from transmission in clinics in high HIV settings may be far higher than contact data suggest.

BACKGROUND: In South Africa, it is generally estimated that only 0.5-0.6% of people's contacts occur in clinics. Both people with infectious tuberculosis and people with increased susceptibility to disease progression may spend more time in clinics, however, increasing the importance of clinic-based transmission to overall disease incidence.METHODS: We developed an illustrative mathematical model of Mycobacterium tuberculosis transmission in clinics and other settings. We assumed that 1% of contact time occurs in clinics. We varied the ratio of clinic contact time of human immunodeficiency virus (HIV) positive people compared to HIV-negative people, and of people with infectious TB compared to people without TB, while keeping the overall proportion of contact time occurring in clinics, and each person's total contact time, constant.RESULTS: With clinic contact rates respectively 10 and 5 times higher in HIV-positive people and people with TB, 10.7% (plausible range 8.5-13.4%) of TB resulted from transmission in clinics. With contact rates in HIV-positive people and people with TB respectively 5 and 2 times higher, 5.3% (plausible range 4.3-6.3%) of all TB was due to transmission in clinics.CONCLUSION: The small amount of contact time that generally occurs in clinics may greatly underestimate their contribution to TB disease in high TB-HIV burden settings.

Leisure-time physical activity and life expectancy in people with cardiometabolic multimorbidity and depression.

BACKGROUND: Whether and to what extent leisure-time physical activity at the recommended levels of 150-min moderate activity is associated with survival in people with cardiometabolic multimorbidity and depression is unknown. METHODS: UK Biobank participants were classified into groups: (i) no disease; (ii) diabetes; (iii) cardiovascular disease (CVD); (iv) depression; (v) diabetes and CVD; (vi) diabetes and depression; (vii) CVD and depression; (viii) diabetes, CVD and depression. Leisure-time physical activity was categorized as active (meeting recommendations) or inactive. Survival models were applied to estimate life expectancy. RESULTS: A total of 480 940 participants were included (median age, 58 years; 46% men; 95% white), of whom 74% with cardiometabolic multimorbidity and depression were inactive. During a mean follow-up of 7 years, 11 006 deaths occurred. At age of 45 years, being physically active was associated with 2.34 (95% confidence interval: 0.93, 3.54) additional years of life compared with being inactive in participants with diabetes; corresponding estimates were 2.28 (1.40, 3.16) for CVD; 2.15 (0.05, 4.26) for diabetes and CVD; and 1.58 (1.27, 1.89) for no disease. Participants with a combination of diabetes, CVD and depression, being active was associated with 6.81 (-1.50, 15.31) additional years compared with being inactive; corresponding estimates were 3.07 (-2.46, 8.59) for diabetes and depression; 2.34 (-1.24, 5.91) for CVD and depression; and 0.80 (-0.46, 2.05) for depression. A similar pattern was found at 65 years. CONCLUSIONS: Meeting the recommended level of physical activity was associated with a longer life expectancy in people with cardiometabolic multimorbidity but not in those with depression.

Association of depression and anxiety with clinical, sociodemographic, lifestyle and environmental factors in South Asian and white European individuals at high risk of diabetes.

AIM: To investigate the prevalence and correlates of depressive and anxiety symptoms within South Asian and white European populations at high risk of developing Type 2 diabetes. METHODS: Data were collected at baseline, and at 12, 24 and 36 months from 1429 white European individuals (age 64±7 years, 35.8% women) and 160 South Asian individuals (age 59±9 years, 30.6% women) who were at high risk of Type 2 diabetes and who took part in two Type 2 diabetes prevention trials in Leicestershire, UK. The Hospital Anxiety and Depression Scale was administered during each study visit. Clinical, sociodemographic, lifestyle and environmental data were collected. RESULTS: At baseline, the burden of depressive symptoms varied by ethnic group and gender, with 9.9% of white European men, 14.9% of white European women, 23.6% of South Asian men and 29.2% of South Asian women exceeding the cut-off score for mild-to-severe depression. During the course of the study and after adjustment for clinical, sociodemographic, lifestyle and environmental factors, depressive symptoms remained higher in the South Asian compared to the white European participants [score higher by 1.5, 95% CI 0.9-2.1]. Levels of anxiety were also higher in the South Asian participants, although associations were attenuated after adjustment. Social deprivation, BMI, proximity to fast-food outlets and physical activity were correlates for depression in both the South Asian and white European participants. CONCLUSIONS: A higher burden of depressive symptoms was consistently evident among the South Asian individuals, even after adjustment for multiple covariates. It is important to understand both the reasons why these differences are present, to help reduce health inequalities, and whether higher levels of depressive symptoms affect the uptake of and retention rates in diabetes prevention programmes in South Asian communities.

Multimorbidity and lifestyle factors among adults with intellectual disabilities: a cross-sectional analysis of a UK cohort.

BACKGROUND: Multimorbidity [two or more conditions in addition to intellectual disability (ID)] is known to be more common among people with ID. However, the relationship between multimorbidity and lifestyle factors is currently unknown. The aim of this study was to determine the prevalence of multimorbidity in a population of adults with ID. We also aimed to identify risk factors, including lifestyle factors, for multimorbidity in this population. METHODS: This was a cross-sectional analysis using data from a diabetes screening study of 920 adults aged 18-74 years with ID living in Leicestershire, UK. We described comorbidities and the prevalence of multimorbidity in this population. We explored the relationship between multimorbidity and age, gender, ethnicity, severity of ID, socio-economic status, physical activity, sedentary behaviour, fruit and vegetable consumption and smoking status using multiple logistic regression. RESULTS: The prevalence of multimorbidity was 61.2% (95% CI 57.7-64.7). Multimorbidity was independently associated with being female (P < 0.001) and severe/profound ID (P = 0.004). Increasing age was of borderline significance (P = 0.06). Individuals who were physically inactive or sedentary were more likely to be multimorbid, independent of ability to walk, age, gender, severity of ID, ethnicity and socio-economic status (adjusted OR = 1.91; 95% CI 1.23-2.97; P = 0.004 and OR = 1.98; 95% CI 1.42-2.77; P < 0.001). After excluding probable life-long conditions (autism spectrum conditions, attention deficit hyperactivity disorders, epilepsy, cerebral palsy and other paralytic syndromes) as contributing comorbidities, the effect of sedentary behaviour, but not physical activity, remained (P = 0.004). We did not observe a relationship between multimorbidity, fruit and vegetable consumption and smoking status. CONCLUSIONS: Multimorbidity presents a significant burden to people with ID. Individuals who were physically inactive or sedentary were more likely to be multimorbid, but further work is recommended to explore the relationship between multimorbidity and lifestyle factors using standardised objective measures.

Moderate increases in daily step count are associated with reduced IL6 and CRP in women with PCOS.

Aims Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS. Subjects and Methods Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM. Results Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (ß: -0.81 ng/L; 95% CI, -1.37, -0.25, P = 0.005) and a 13% reduction in CRP (ß: -0.68 mg/L; 95% CI, -1.30, -0.06, P = 0.033). Additionally, there was a modest decrease in BMI (ß: 0.20 kg/m2; 95% CI, -0.38, -0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count. Conclusions Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.