Recent Submissions

  • Normative wrist-worn accelerometer values for self-paced walking and running: a walk in the park

    Davies, Melanie (2022-01)
    This study aimed to a) determine whether wrist acceleration varies by accelerometer brand, wear location, and age for self-paced "slow", "normal" and "brisk" walking; b) develop normative acceleration values for self-paced walking and running for adults. One-hundred-and-three adults (40-79 years) completed self-paced "slow", "normal" and "brisk" walks, while wearing three accelerometers (GENEActiv, Axivity, ActiGraph) on each wrist. A sub-sample (n = 22) completed a self-paced run. Generalized estimating equations established differences by accelerometer brand, wrist, and age-group (walking only, 40-49, 50-59, 60-69, 70-79 years) for self-paced walking and running. Brand*wrist interactions showed ActiGraph dominant wrist values were ~10% lower than GENEActiv/Axivity values for walking and running, and non-dominant ActiGraph values were ~5% lower for running only (p < 0.001). Acceleration during brisk walking was lower in those aged 70-79 (p < 0.05). Normative acceleration values (non-dominant wrist, all brands; dominant wrist GENEActiv/Axivity) for slow and normal walking were 140 mg and 210 mg. Brisk walking, values were 350 mg in those aged 40-69 years, but 270 mg in those aged 70-79 years. Accelerations >600 mg approximated running. These values facilitate user-friendly interpretation of accelerometer-determined physical activity in large cohort and epidemiological datasets.
  • Prospective longitudinal characterization of the relationship between diabetes and cardiac structural and functional changes

    Athithan, Lavanya (2022)
    Objectives: In a cohort of type 2 diabetic (T2D) patients who underwent baseline cardiac magnetic resonance (CMR) and biomarker testing, during a median follow-up of 6 years, we aimed to determine longitudinal changes in the phenotypic expression of heart disease in diabetes, report clinical outcomes, and compare baseline clinical characteristics and CMR findings of patients who experienced major adverse cardiovascular events (MACE) to those remaining MACE free. Background: T2D increases the risk of heart failure (HF) and cardiovascular mortality. The long-term impact of T2D on cardiac phenotype in the absence of cardiovascular disease and other clinical events is unknown. Methods: Patients with T2D (n = 100) with no history of cardiovascular disease or hypertension were recruited at baseline. Biventricular volumes, function, and myocardial extracellular volume fraction (ECV) were assessed by CMR, and blood biomarkers were taken. Follow-up CMR was repeated in those without interim clinical events after 6 years. Results: Follow-up was successful in 83 participants. Of those, 29 experienced cardiovascular/clinical events (36%). Of the remaining 59, 32 patients who experienced no events received follow-up CMR. In this cohort, despite no significant changes in blood pressure, weight, or glycated hemoglobin, significant reductions in biventricular end-diastolic volumes and ejection fractions occurred over time. The mean ECV was unchanged. Baseline plasma high-sensitivity cardiac troponin T (hs-cTnT) was significantly associated with a change in left ventricular (LV) ejection fraction. Patients who experienced MACE had higher LV mass and greater LV concentricity than those who remained event free. Conclusions: T2D results in reductions in biventricular size and systolic function over time even in the absence of cardiovascular/clinical events.
  • Maternal hemodynamics and neonatal birth weight in pregnancies complicated by gestational diabetes: new insights from novel causal inference analysis modeling

    Anness, Abigail; Webb, David; Mousa, Hatem
    Objectives: Normal pregnancy is characterised by significant changes in maternal hemodynamics which correlate with fetal growth. Pregnancies complicated by gestational diabetes (GDM) are associated with large for gestational age (LGA) and macrosomia, but the relationship between maternal hemodynamic parameters and birthweight among women with GDM is yet to be established. Our objective was to investigate the influence of maternal hemodynamics on neonatal birthweight in healthy pregnancies and those complicated by GDM. Methods: We conducted a prospective cross-sectional case controlled study. GDM was defined as a fasting glucose ≥5.3mmol/L, and/or serum glucose of ≥7.8mmol/L 2 hours following a 75g oral glucose load. Data were collected on maternal characteristics and pregnancy outcomes, including body mass index (BMI) and birth weight centile, adjusted for gestation at delivery. Maternal hemodynamics were assessed using the Arteriograph® and bioreactance techniques at 34-42 weeks gestation. Graphical causal inference methodology was used to identify causational effects of the measured variables on neonatal birthweight centile. Results: 141 women with GDM and 136 normotensive non-diabetic controls were included in the analysis. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), pulse wave velocity (PWV) and BMI. Among controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal birthweight. Each standard deviation increase in BMI, CO and PWV produced an increase of 8.4 (p=0.002), 9.4 (p=0.008) and 7.1 (p=0.017) birth weight centiles, respectively. We found no significant relationship between MAP, TPR or aortic AIx and neonatal birthweight. Among the women with GDM, maternal hemodynamics influenced neonatal birth weight in a similar manner to the control group. Only the relationship between maternal BMI and neonatal birthweight reached statistical significance, with a 1 standard deviation increase in BMI producing a 6.1 centile increase in the birthweight (p=0.019). Conclusions: Maternal BMI, CO and PWV were determinants of birthweight in our control group. The relationship between maternal hemodynamics and neonatal birthweight is similar between women with GDM and healthy controls. Our findings demonstrate that FGR in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. The differences between our findings and that of previous work could be reconciled by a non-linear relationship between MAP and neonatal birthweight, which warrants further investigation. This article is protected by copyright. All rights reserved.
  • In-shoe pressure thresholds for people with diabetes and neuropathy at risk of ulceration: A systematic review

    Jones, Petra; Davies, Melanie; Webb, David (Elsevier Inc, 2021-03)
    Introduction: In-shoe pressure thresholds play an increasingly important role in the prevention of diabetes-related foot ulceration (DFU). The evidence of their effectiveness, methodological consistency and scope for refinement are the subject of this review. Methods: 1107 records were identified (after duplicate removal) based on a search of five databases for studies which applied a specific in-shoe pressure threshold to reduce the risk of ulceration. 37 full text studies were assessed for eligibility of which 21 were included. Results: Five in-shoe pressure thresholds were identified, which are employed to reduce the risk of diabetes-related foot ulceration: a mean peak pressure threshold of 200 kPa used in conjunction with a 25% baseline reduction target; a sustained pressure threshold of 35 mm Hg, a threshold matrix based on risk, shoe size and foot region, and a 40-80% baseline pressure reduction target. The effectiveness of the latter two thresholds have not been assessed yet and the evidence for the effectiveness of the other in-shoe pressure thresholds is limited, based only on two RCTs and two cohort studies. Conclusions: The heterogeneity of current measures precludes meta-analysis and further research and methodological standardisation is required to facilitate ready comparison and the further development of these pressure thresholds.
  • Evaluation of an 8-Week vegan diet on plasma trimethylamine-N-oxide and postchallenge glucose in adults with dysglycemia or obesity

    Davies, Melanie; Suzuki, Toru; Smith, Alice (Oxford University Press, 2021-07-01)
    Background: Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health. Objectives: We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia. Methods: This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight. Results: TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8. Conclusions: These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at as NCT03315988.
  • Impact of sodium-glucose co-transporter inhibitors on cardiac autonomic function and mortality: no time to die

    Ng, G Andre (2022)
    Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to improve cardiovascular outcomes not only in patients with diabetes but also in those with heart failure, irrespective of diabetic status. However, the mechanisms underlying the cardioprotective effects of these newer anti-diabetic drugs remain to be fully elucidated. One exciting avenue that has been recently explored in both preclinical and clinical studies is the modulation of the cardiovascular autonomic nervous system. A reduction in sympathetic nervous system activity by SGLT2 inhibitors may potentially translate into a reduction in arrhythmic risk and sudden arrhythmic death, which may explain, at least partly, the cardioprotection shown in the cardiovascular outcome trials with different SGLT2 inhibitors. Although some of the data from the preclinical and clinical studies are promising, overall the findings can be contradictory. This highlights the need for more studies to address gaps in our knowledge of these novel drugs. The present review offers an in depth overview of the existing literature regarding the role of SGLT2 inhibitors in modulating cardiovascular autonomic function as one of the possible pathways of their cardioprotective effects.
  • Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020)

    Gregory, Robert (Wiley, 2020-11-26)
    Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m(2) . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.
  • Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England

    Davies, Melanie; Seidu, Samuel; Webb, David; Zaccardi, Francesco
    OBJECTIVE: To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status. METHODS: Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated. RESULTS: 696,255 (mean 4.9 years [95% CI, 2.02-7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47-18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%. CONCLUSIONS: Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs.
  • Behavioural interventions to promote physical activity in a multiethnic population at high risk of diabetes: PROPELS three-arm RCT

    Davies, Melanie; Dallosso, Helen (NIHR Journals Library, 2022-01)
    BACKGROUND: Type 2 diabetes is a leading cause of mortality globally and accounts for significant health resource expenditure. Increased physical activity can reduce the risk of diabetes. However, the longer-term clinical effectiveness and cost-effectiveness of physical activity interventions in those at high risk of type 2 diabetes is unknown. OBJECTIVES: To investigate whether or not Walking Away from Diabetes (Walking Away) - a low-resource, 3-hour group-based behavioural intervention designed to promote physical activity through pedometer use in those with prediabetes - leads to sustained increases in physical activity when delivered with and without an integrated mobile health intervention compared with control. DESIGN: Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with follow-up conducted at 12 and 48 months. SETTING: Primary care and the community. PARTICIPANTS: Adults whose primary care record included a prediabetic blood glucose measurement recorded within the past 5 years [HbA(1c) ≥ 42 mmol/mol (6.0%), < 48 mmol/mol (6.5%) mmol/mol; fasting glucose ≥ 5.5 mmol/l, < 7.0 mmol/l; or 2-hour post-challenge glucose ≥ 7.8 mmol/l, < 11.1 mmol/l] were recruited between December 2013 and February 2015. Data collection was completed in July 2019. INTERVENTIONS: Participants were randomised (1 : 1 : 1) using a web-based tool to (1) control (information leaflet), (2) Walking Away with annual group-based support or (3) Walking Away Plus (comprising Walking Away, annual group-based support and a mobile health intervention that provided automated, individually tailored text messages to prompt pedometer use and goal-setting and provide feedback, in addition to biannual telephone calls). Participants and data collectors were not blinded; however, the staff who processed the accelerometer data were blinded to allocation. MAIN OUTCOME MEASURES: The primary outcome was accelerometer-measured ambulatory activity (steps per day) at 48 months. Other objective and self-reported measures of physical activity were also assessed. RESULTS: A total of 1366 individuals were randomised (median age 61 years, median body mass index 28.4 kg/m(2), median ambulatory activity 6638 steps per day, women 49%, black and minority ethnicity 28%). Accelerometer data were available for 1017 (74%) and 993 (73%) individuals at 12 and 48 months, respectively. The primary outcome assessment at 48 months found no differences in ambulatory activity compared with control in either group (Walking Away Plus: 121 steps per day, 97.5% confidence interval -290 to 532 steps per day; Walking Away: 91 steps per day, 97.5% confidence interval -282 to 463). This was consistent across ethnic groups. At the intermediate 12-month assessment, the Walking Away Plus group had increased their ambulatory activity by 547 (97.5% confidence interval 211 to 882) steps per day compared with control and were 1.61 (97.5% confidence interval 1.05 to 2.45) times more likely to achieve 150 minutes per week of objectively assessed unbouted moderate to vigorous physical activity. In the Walking Away group, there were no differences compared with control at 12 months. Secondary anthropometric, biomechanical and mental health outcomes were unaltered in either intervention study arm compared with control at 12 or 48 months, with the exception of small, but sustained, reductions in body weight in the Walking Away study arm (≈ 1 kg) at the 12- and 48-month follow-ups. Lifetime cost-effectiveness modelling suggested that usual care had the highest probability of being cost-effective at a threshold of £20,000 per quality-adjusted life-year. Of 50 serious adverse events, only one (myocardial infarction) was deemed possibly related to the intervention and led to the withdrawal of the participant from the study. LIMITATIONS: Loss to follow-up, although the results were unaltered when missing data were replaced using multiple imputation. CONCLUSIONS: Combining a physical activity intervention with text messaging and telephone support resulted in modest, but clinically meaningful, changes in physical activity at 12 months, but the changes were not sustained at 48 months. FUTURE WORK: Future research is needed to investigate which intervention types, components and features can help to maintain physical activity behaviour change over the longer term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83465245. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 77. See the NIHR Journals Library website for further project information.; When someone has type 2 diabetes, it means that their body no longer does a good job of controlling the sugar in their blood. This gives them a higher risk of other health problems. Fortunately, people can avoid getting type 2 diabetes if they can change their lifestyle. We wanted to know whether or not an education programme could help people at high risk of getting diabetes to become more physically active and, if so, whether or not they were still more active and healthier 4 years later. We also wanted to know whether it made a difference if we used text messages and telephone calls to support them and whether it worked better for some ethnic groups than others. We put 1366 people into one of three groups at random. The first group received an advice leaflet. The second group attended (in groups of up to 10 participants) a 3-hour education programme called ‘Walking Away from Type 2 Diabetes’ to help them to change their behaviour and then attended a group-based refresher session every year. The third group received the same education programme and the refresher sessions, but also received text messages and telephone calls to give them extra support. We measured how active the participants were at the start of the study, after 1 year and again 3 years after that (i.e. 4 years after the start). Then we looked at whether or not the Walking Away programme, with and without the extra support of text messages and telephone calls, did a better job of encouraging people to be more active than just giving them the advice leaflet. We found out that the Walking Away programme, when combined with text messages and telephone calls for support, did help participants to take over 500 more steps per day during the first year; however, when we checked again at 4 years, we found that the effects had worn off. Neither option proved to be good value for money.
  • Understanding the clinical implications of differences between GMI and HbA1c

    Choudhary, Pratik
    Laboratory measured glycosylated hemoglobin (HbA1c) is the gold standard for assessing glycemic control in people with diabetes and correlates with their risk of long-term complications. The emergence of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c (eA1c) that has been used as a substitute of laboratory HbA1c. However, it is evident that eA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short-term average glucose values, rather than long-term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and hemoglobinopathies. Recognising and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long term complications.