Sex and ethnic differences in the cardiovascular complications of type 2 diabetes

Diabetes mellitus represents a global health concern affecting 463 million adults and is projected to rapidly rise to 700 million people by 2045. Amongst those with type 2 diabetes (T2D), there are recognised differences in the impact of the disease on different sex and ethnic groups. The relative risk of cardiovascular complications between individuals with and without T2D is higher in females than males. People of South Asian heritage are two to four times more likely to develop T2D than white people, but conversely not more likely to experience cardiovascular complications. Differences in the pathophysiological responses in these groups may identify potential areas for intervention beyond glycaemic control. In this review, we highlight key differences of diabetes-associated cardiovascular complications by sex and ethnic background, with a particular emphasis on South Asians. Evidence assessing therapeutic efficacy of new glucose lowering drugs in minority groups is limited and many major cardiovascular outcomes trials do not report ethnic specific data. Conversely, lifestyle intervention and bariatric surgery appear to have similar benefits regardless of sex and ethnic groups. We encourage future studies with better representation of women and ethnic minorities that will provide valuable data to allow better risk stratification and tailored prevention and management strategies to improve cardiovascular outcomes in T2D

Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis

Aim: To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. Methods: Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models. Results: A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I[superscript: 2] = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (−1.81 kg, 95% CI −2.91, −0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001). Conclusions: The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines

Evaluating the impact of an enhanced primary care diabetes service on diabetes outcomes: A before-after study

Diabetes is an ambulatory care-sensitive condition and a high quality primary care or risk factor control can lead to a decrease in the risk of non-elective hospitalisations while ensuring continuity of care with usual primary care teams. Aims and methods In this before and after study, eight primary care practices providing a newer enhanced diabetes model of care in Leicester UK, were compared with matched neighbouring practices with comparable demographic features providing a more expensive integrated specialist—community care diabetes service. The primary outcome at twelve months was to demonstrate equivalence in non-elective bed days. The enhanced practices had primary care physicians and nurses with an interest in diabetes who attended monthly diabetes education meetings and provided care plans and audits. The control practices provided an integrated primary-specialist care service. Results The difference between the mean change in the non-elective bed days from baseline and at follow up in core and enhanced practices was not statistically significant (mean = 2.20 per 100 patients, 95% CI = −0.92 to 5.31 per 100 patients, p = 0.14). The analogous change for first outpatients’ attendance were 0.23 per 100 patients (95% CI = −0.47 to 0.52 per 100 patients p = 0.92) and for diabetes related complications admissions was 0.30 per 100 patients (95% CI = −0.85 to 1.45 per 100 patients p = 0.55). Conclusion A model of enhanced primary care based diabetes care appears unlikely to increase hospitalisations, outpatients’ attendance or admissions for diabetes related complications

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. 131â .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

Device-measured physical activity behaviours, and physical function, in people with type 2 diabetes mellitus and peripheral artery disease: A cross-sectional study

Aim: To quantify differences in device-measured physical activity (PA) behaviours, and physical function (PF), in people with type 2 diabetes mellitus (T2DM) with and without peripheral artery disease (PAD). Materials and methods: Participants from the Chronotype of Patients with T2DM and Effect on Glycaemic Control cross-sectional study wore accelerometers on their non-dominant wrist for up to 8-days to quantify: volume and intensity distribution of PA, time spent inactive, time in light PA, moderate-to-vigorous PA in at least 1-minute bouts (MVPA1min), and the average intensity achieved during the most active continuous 2, 5, 10, 30, and 60-minute periods of the 24-h day. PF was assessed using the short physical performance battery (SPPB), the Duke Activity Status Index (DASI), sit-to-stand repetitions in 60 s (STS-60); hand-grip strength was also assessed. Differences between subjects with and without PAD were estimated using regressions adjusted for possible confounders. Results: 736 participants with T2DM (without diabetic foot ulcers) were included in the analysis, 689 had no PAD. People with T2DM and PAD undertake less PA (MVPA1min: −9.2 min [95 % CI: −15.3 to −3.0; p = 0.004]) (light intensity PA: −18.7 min [−36.4 to −1.0; p = 0.039]), spend more time inactive (49.2 min [12.1 to 86.2; p = 0.009]), and have reduced PF (SPPB score: −1.6 [−2.5 to −0.8; p = 0.001]) (DASI score: −14.8 [−19.8 to −9.8; p = 0.001]) (STS-60 repetitions: −7.1 [−10.5 to −3.8; p = 0.001]) compared to people without; some differences in PA were attenuated by confounders. Reduced intensity of activity for the most active continuous 2–30 min in the 24-h day, and reduced PF, persisted after accounting for confounders. There were no significant differences in hand-grip strength. Conclusions: Findings from this cross-sectional study suggest that, the presence of PAD in T2DM may have been associated with lower PA levels and PF.</p

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.</p

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

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 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.</p

Impact of remission of type 2 diabetes on cardiovascular structure and function, exercise capacity and risk profile: a propensity matched analysis

Background and aims: Type 2 diabetes (T2D) confers high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The aim of this work was to describe the impact of remission of T2D, beyond weight-loss and glycaemia, on cardiovascular structure and function and exercise capacity. Materials and methods: Obese adults with T2D without cardiovascular disease were recruited into the "Prevalence and determinants of subclinical cardiovascular dysfunction in adults with type 2 diabetes" study (PREDICT). PREDICT is a prospective cross-sectional, case-control study. All participants underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing, and cardiometabolic profiling. T2D-remission cases (HbA1c Results: The average exposure to T2D was less than six years across both groups and the duration of remission was 4.2±2.5 years. The variance between groups for demographic, anthropometry and metabolic profile was expected based on the study design. T2D-remission was associated with lower leptin-adiponectin ratio (0.75 (0.37,1.50) vs. 2.24 (1.43,4.10)), hepatic steatosis (3.20% (2.20,7.33) vs. 9.40 (4.80,15.20)) and triglycerides (1.45mmol/l (0.96,1.74) vs. 1.69 (1.3,2.2)), a trend towards greater exercise capacity and significantly lower VE/VCO2 slope vs. active-T2D (27.74 ± 3.95 vs. 30.52 ± 5.46) all p Conclusion: T2D-remission is associated with improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.</p

Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study).

INTRODUCTION: Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established. METHODS AND ANALYSIS: Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18-65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control. ETHICS AND DISSEMINATION: The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER: NCT02590822; Pre-results