Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial.

AIMS: To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D. METHODS: Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D. RESULTS: At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training. CONCLUSIONS: Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

Relative protein intake and associations with markers of physical function in those with type 2 diabetes.

AIMS: To examine the independent associations between relative protein intake (g kg-1  day 1 ) and markers of physical function in those with type 2 diabetes, while also comparing with current guidelines for protein intake. METHODS: This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) study. Functional assessments included: Short Physical Performance Battery (SPPB), 60 s sit-to-stand (STS-60), 4-m gait speed, time to rise from a chair (×5) and handgrip strength. Participants also completed a self-reported 4 day diet diary. Regression analyses assessed whether relative protein intake was associated with markers of physical function. Interaction terms assessed whether the associations were modified by sex, age, HbA1c or body mass index (BMI). RESULTS: 413 participants were included (mean ± SD:age = 65.0 ± 7.7 years, 33% female, BMI = 30.6 ± 5.1 kg/m2 ). The average total protein intake was 0.88 ± 0.31 g kg-1  day-1 . 33% of individuals failed to meet the reference nutrient intake for the United Kingdom (≥0.75 g kg-1  day-1 ), and 87% for European recommendations (≥1.2 g kg-1  day-1 ). After adjustment, each 0.5 g/kg of protein intake was associated with an 18.9% (95% CI: 2.3, 35.5) higher SPPB score, 22.7% (1.1, 44.3) more repetitions in STS-60, 21.1% (4.5, 37.7) faster gait speed and 33.2% (16.9, 49.5) lower chair rise time. There were no associations with handgrip strength or any interactions. CONCLUSIONS: Relative protein intake was positively associated with physical function outcomes, even after consideration of total energy intake. As a number of individuals were below the current guidelines, protein intake may be a modifiable factor of importance for people with type 2 diabetes.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

AIM: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. MATERIALS AND METHODS: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. RESULTS: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. CONCLUSIONS: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. CLINICAL TRIALS REGISTRATION: NCT02798744, www. CLINICALTRIALS: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

The potential blunting effect of metformin and/or statin therapy on physical activity-induced associations with HbA1c in type 2 diabetes.

Highlights Our analysis indicates a potential blunting effect of metformin and/or statin therapy on physical activity-induced associations with HbA1c. The benefit of daily physical activity on glycemic control in people with type 2 diabetes is potentially more apparent in those prescribed neither metformin nor statin therapy. As physical activity is rarely prescribed in isolation of other background medications used to manage type 2 diabetes, the results of this analysis may help to maximize interventions delivered through routine clinical care, while allowing for personalization in prescribed physical activity and pharmacotherapy.

Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans.

Background: South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. Objectives: The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Methods: Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Results: Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Conclusions: Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. Trail registration: NCT02590822.

Age at Diagnosis of Type 2 Diabetes and Depressive Symptoms, Diabetes-Specific Distress, and Self-Compassion.

OBJECTIVE: To investigate the association between age at diagnosis of type 2 diabetes and depressive symptoms, diabetes-specific distress, and self-compassion among adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: This analysis used data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycemic Control (CODEC) cross-sectional study. Information was collected on depressive symptoms, diabetes-specific distress, and self-compassion, measured using validated self-report questionnaires, in addition to sociodemographic and clinical data. Multivariable regression models, adjusted for diabetes duration, sex, ethnicity, deprivation status, prescription of antidepressants (selective serotonin reuptake inhibitors), and BMI were used to investigate the association between age at diagnosis of type 2 diabetes and each of the three psychological outcomes. RESULTS: A total of 706 participants were included; 64 (9.1%) were diagnosed with type 2 diabetes at <40 years, 422 (59.8%) between 40 and 59 years, and 220 (31.2%) at ≥60 years of age. After adjustment for key confounders, including diabetes duration, younger age at diagnosis was significantly associated with higher levels of depressive symptoms (ßadj: -0.18 [95% CI -0.25 to -0.10]; P < 0.01) and diabetes-specific distress (ßadj: -0.03 [95% CI -0.04 to -0.02]; P < 0.01) and lower levels of self-compassion (ßadj: 0.01 [95% CI 0.00 to 0.02]; P < 0.01). CONCLUSIONS: Diagnosis of type 2 diabetes at a younger age is associated with lower psychological well-being, suggesting the need for clinical vigilance and the availability of age-appropriate psychosocial support.

Differences in Dietary Intake, Eating Occasion Timings and Eating Windows between Chronotypes in Adults Living with Type 2 Diabetes Mellitus.

Chronotype studies investigating dietary intake, eating occasions (EO) and eating windows (EW) are sparse in people with type 2 Diabetes mellitus (T2DM). This analysis reports data from the CODEC study. The Morningness-Eveningness questionnaire (MEQ) assessed chronotype preference. Diet diaries assessed dietary intake and temporal distribution. Regression analysis assessed whether dietary intake, EW, or EO differed by chronotype. 411 participants were included in this analysis. There were no differences in energy, macronutrient intake or EW between chronotypes. Compared to evening chronotypes, morning and intermediate chronotypes consumed 36.8 (95% CI: 11.1, 62.5) and 20.9 (95% CI: -2.1, 44.1) fewer milligrams of caffeine per day, respectively. Evening chronotypes woke up over an hour and a half later than morning (01:36 95% CI: 01:09, 02:03) and over half an hour later than intermediate chronotypes (00:45 95% CI: 00:21; 01:09. Evening chronotypes went to sleep over an hour and a half later than morning (01:48 95% CI: 01:23; 02:13) and an hour later than intermediate chronotypes (01:07 95% CI: 00:45; 01:30). Evening chronotypes' EOs and last caffeine intake occurred later but relative to their sleep timings. Future research should investigate the impact of chronotype and dietary temporal distribution on glucose control to optimise T2DM interventions.

The Effects of Omega-3 Supplementation on Depression in Adults with Cardiometabolic Disease: A Systematic Review of Randomised Control Trials.

Background: Omega-3 polyunsaturated fatty acids' concurrent benefits for cardiometabolic and mental health are equivocal. Despite lack of evidence, up to a third of adults consume Omega-3 supplements. No review has yet been published to report effect on depression in this cardiometabolic population. Methods: We conducted a systematic review of double-blinded, controlled randomised trials to investigate the safety and effect of Omega-3 supplementation on depression scores in people with cardiometabolic diseases. Primary outcome was change in depression scores versus placebo. Secondary outcomes were side-effects, concurrent medication and adherence. Results: Seven trials reporting on 2575 (672 female) adults aged 39−73 were included. Omega-3 dosages ranged from 1−3 g with an intervention duration of 10−48 weeks. Six out of seven trials found no statistically or clinically significant change to depression scores compared to placebo. One trial favoured intervention (Relative Risk Reduction: 47.93%, 95% CI: 24.89−63.98%, p < 0.001). Sub-analyses showed clinically meaningful reductions in depression scores for those on antidepressants (Intervention: 20.9 (SD: 7.1), Placebo: 24.9 (SD: 8.5) p < 0.05) or with severe depression (−1.74; 95% CI −3.04 to −0.05, p < 0.05) in two separate trials. Side effects were comparable between treatment arms. Conclusions: Omega-3 supplementation is safe to use but not superior to placebo for depression in adults with concurrent cardiometabolic disease.

The impact of lifestyle intervention on left atrial function in type 2 diabetes: results from the DIASTOLIC study.

Aerobic exercise training and low energy diets have been shown to improve left ventricular remodelling and diastolic function in adults with type 2 diabetes (T2D), albeit with differential effects. The impact of these lifestyle interventions on left atrial (LA) function, however, has not previously been reported. The DIASTOLIC study was a prospective, randomised, open-label, blind endpoint trial, in which 90 people with obesity and T2D and no prevalent cardiovascular disease were randomised to a 12-week intervention of: (i) routine care, (ii) aerobic exercise training, or (iii) low energy (≈ 810 kcal/day) meal replacement plan (MRP). Cardiac magnetic resonance (CMR) imaging was performed pre- and post-intervention. Image analysis included LA volumes (LAV), emptying fraction (LAEF), and LA strain (LAS) corresponding to LA reservoir (LAS-r), conduit (LAS-cd), and booster pump (LAS-bp) function. 73 participants with T2D (mean age 50 ± 6 years, 62% male, body mass index (BMI) 36.1 ± 5.3 kg/m2) completed the trial and had analysable LA images. There was no significant change in CMR measured LA volumetric function (LAV/LAEF) in any group. The routine care group showed no significant change in BMI or LAS. In the MRP group, there were significant reductions in BMI (4.5 kg/m2) and a significant increase in LAS-r and LAS-bp (29.9 ± 7.0 to 32.3 ± 7.0%, p = 0.036 and 14.6 ± 5.3 to 17.2 ± 3.7%, p = 0.034). The exercise group showed a small reduction in BMI (0.49 kg/m2), with no significant change in LAS. Compared to routine care, weight loss via a 12-week MRP, led to improvements in LA filling and contractile function in adults with T2D and obesity. However, these within-group changes were not statistically significant on between-group comparison. ClinicalTrials.gov Identifier: NCT02590822.

Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS: We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity. RESULTS: Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity. CONCLUSIONS: The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile: A pooled analysis.

BACKGROUND: The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age. AIM: To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D. METHODS: A pooled dataset was used, comprised of data from five previous studies of adults with T2D, including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years. Anthropometric and blood biomarker measurements included body weight, body mass index (BMI), waist circumference, body fat percentage, glycaemic control (HbA1c), lipid profile and blood pressure. Univariable and multivariable linear regression models, adjusted for diabetes duration, sex, ethnicity and smoking status, were used to investigate the association between age at diagnosis and each cardiovascular risk factor. RESULTS: A higher proportion of participants diagnosed with T2D under the age of 40 were female, current smokers and treated with glucose-lowering medications, compared to participants diagnosed later in life. Participants diagnosed with T2D under the age of 40 also had higher body weight, BMI, waist circumference and body fat percentage, in addition to a more adverse lipid profile, compared to participants diagnosed at an older age. Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight [95% confidence interval (CI): 0.52-0.82 kg], 0.18 kg/m2 higher BMI (95%CI: 0.10-0.25) and 0.32 cm higher waist circumference (95%CI: 0.14-0.49), after adjustment for duration of diabetes and other confounders. Younger age at diagnosis was also significantly associated with higher HbA1c, total cholesterol, low-density lipoprotein cholesterol and triglycerides. CONCLUSION: The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile, compared to those diagnosed later in life.

Remission of type 2 diabetes and improved diastolic function by combining structured exercise with meal replacement and food reintroduction among young adults: the RESET for REMISSION randomised controlled trial protocol.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome. METHODS AND ANALYSIS: This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18-45 years of age within 6 years' T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800-900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher's exact test statistics. ETHICS AND DISSEMINATION: The trial is approved in Leicester (East Midlands - Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial. TRIAL REGISTRATION NUMBER: ISRCTN15487120.

Supporting people to implement a reduced carbohydrate diet: a qualitative study in family practice.

INTRODUCTION: Much of the science behind dietary guidelines for risk reduction and chronic disease management is equivocal, and there are well-accepted uncertainties and complexities relating to diet in everyday life, as well as physiological processes. Guidelines have therefore stopped short of aligning with one particular approach, instead highlighting several evidence-based options. However, reduced carbohydrate, or 'low-carb', diets have increasing traction in the media and with patients, practitioners and the general public. This qualitative study examines healthcare practitioner (HCP) experiences of implementing a reduced carbohydrate diet. METHODS: Semistructured, qualitative interviews were conducted with 19 HCPs in the UK family practice (including general practitioners, practice nurses and non-medical practitioners), recruited through a special interest forum, and social media. Data analysis employed social science theory and methods to produce key themes. RESULTS: All participants self-identified as 'low-carb practitioners' who, over time, had introduced a specific focus around carbohydrate reduction into their work. They reported transformations in patients' metabolic markers, patient enthusiasm for the approach and renewed job satisfaction. Key themes highlight experiences of: (1) discovering low-carb as a new 'tool-in-the-box'; (2) promoting and supporting incremental low-carb experimentation; and (3) diverging from established dietary guidelines. CONCLUSIONS: This study provides important experience-based evidence on a topical dietary intervention. Participants strongly advocated for the use of low-carb diets. The successes described draw attention to the need for pragmatic, formative evaluation of low-carb advice and support as a 'complex intervention' (alongside physiological research), to justify, challenge and/or shape low-carb intervention in clinical practice. The findings raise important questions about the contribution of particular care practices to the apparent success of low-carb. Social science analyses can elucidate how dietary intervention is carried out across different healthcare settings (eg, dietetics, endocrinology) and patient groups, how healthcare practices intersect with people's everyday self-management and how different forms of evidence are invoked and prioritised.

Promoting physical activity with self-management support for those with multimorbidity: a randomised controlled trial.

BACKGROUND: Targeted self-management programmes may improve health and increase physical activity (PA) in people with multimorbidity. AIM: To investigate the impact of a structured, theoretically driven, self-management group education programme on habitual PA levels in people with multimorbidity. DESIGN AND SETTING: Individually randomised controlled trial with 12-month follow-up, involving nine primary care practices in Leicestershire, UK. METHOD: In total, 353 adults with multimorbidity (age 67.8 years [±9 years], 161 male sex) were randomised to intervention (n = 180) or control (n = 173) groups. Intervention participants were invited to attend four group-based self-management sessions, centred primarily on increasing PA, and received motivational text-message support. The primary outcome measure was change in overall volume (time and intensity) of daily PA at 12 months, as measured by the GENEActiv wrist-worn accelerometer device. RESULTS: At baseline, the total sample achieved 22 min of moderate-vigorous intensity PA per day (mean/participant). At 12 months, in the complete-case analysis, a reduction in daily mean PA volume was seen in the intervention group relative to control (-0.80 milligravity [m g]; 95% confidence interval [CI] = -1.57 to -0.03; P = 0.04). Reductions were also seen in the intervention group in time spent in moderate-vigorous PA (-3.86 min per day; 95% CI= -6.70 to -1.03; P = 0.008) and time spent at an intensity equivalent to a slow walk (-4.66 min per day; 95% CI = -8.82 to -0.51; P = 0.028). However, the per-protocol analysis (excluding participants who did not attend at least one education session) found no between-group differences in overall daily PA at 12 months (-0.65 mg; 95% CI = -1.46 to 0.15; P = 0.11). CONCLUSION: The self-management programme elicited a slight reduction in PA levels in people with multimorbidity. Future research should identify and target subgroups of those with multimorbidity in greatest need of PA promotion in order to maximise potential capacity for benefit, and also focus on refining the intervention in order to increase efficacy in increasing PA.

Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes.

Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case-control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148⋅9 v. 131⋅7; P 0⋅01) and B6 lower (37⋅3 v. 52⋅9; P 0⋅01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.