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Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetes (T2D) rat model was elucidated in this study. Type 2 diabetic rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5 weeks of treatment, and their blood and hearts were collected. Induction of T2D depleted the levels of reduced glutathione, glycogen, and HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase, and 5'nucleotidase. It simultaneously triggered increase in the levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, angiotensin converting enzyme (ACE), ATPase, glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase, and lipase. T2D induction further revealed an obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favorable comparison with the standard drug, metformin. Additionally, T2D induction led to the depletion of 40%, 75%, and 33% of fatty acids, fatty esters, and steroids, respectively, with concomitant generation of eicosenoic acid, gamolenic acid, and vitamin E. Ferulic acid treatment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-octadecenoic acid, (Z)-, cis-11-eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene. These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy., (© 2022 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Aims: To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis., Methods: Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models., Results: A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant., Conclusions: The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk., (© 2016 Diabetes UK.)

Aims: To assess the causes of death and cause-specific standardized mortality ratios in two nationwide, population-based cohorts diagnosed with Type 1 diabetes during the periods 1973-1982 and 1989-2012, and to evaluate changes in causes of death during the follow-up period., Methods: People with Type 1 diabetes who were aged < 15 years at diagnosis were identified in the Norwegian Childhood Diabetes Registry and followed from diagnosis until death, emigration or September 2013 (n = 7871). We assessed causes of death by linking data to the nationwide Cause of Death Registry and through a review committee that evaluated medical records, autopsy reports and death certificates., Results: During a mean (range) follow-up of 16.8 (0-40.7) years, 241 individuals (3.1%) died, representing 132 143 person-years. The leading cause of death before the age of 30 years was acute complications (41/119, 34.5%). After the age of 30 years cardiovascular disease was predominant (41/122, 33.6%), although death attributable to acute complications was still important in this age group (22/122, 18.0%). A total of 5% of deaths were caused by 'dead-in-bed' syndrome. The standardized mortality ratio was elevated for cardiovascular disease [11.9 (95% CI 8.6-16.4)] and violent death [1.7 (95% CI 1.3-2.1)] in both sexes combined, but was elevated for suicide only in women [2.5 (95% CI 1.2-5.3)]. The risk of death from acute complications was approximately half in women compared with men [hazard ratio 0.43 (95% CI 0.25-0.76)], and did not change with more recent year of diagnosis [hazard ratio 1.02 (0.98-1.05)]., Conclusions: There was no change in mortality attributable to acute complications during the study period. To reduce premature mortality in people with childhood-onset diabetes focus should be on prevention of acute complications. Male gender implied increased risk., (© 2016 Diabetes UK.)

Aims: Our aim was to investigate the proportional representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering drugs or strategies in Type 2 diabetes, noting that these are among the most significant pieces of evidence used to formulate the guidelines on which clinical practice is largely based., Methods: We searched for cardiovascular outcome trials in Type 2 diabetes published before January 2015, and extracted data on the ethnicity of participants. These were compared against expected values for proportional representation of South Asian individuals, based on population data from the USA, from the UK, and globally., Results: Twelve studies met our inclusion criteria and, of these, eight presented a sufficiently detailed breakdown of participant ethnicity to permit numerical analysis. In general, people of South Asian origin were found to be under-represented in trials compared with UK and global expectations and over-represented compared with US expectations. Among the eight trials for which South Asian representation could be reliably estimated, seven under-represented this group relative to the 11.2% of the UK diabetes population estimated to be South Asian, with the representation in these trials ranging from 0.0% to 10.0%., Conclusions: Clinicians should exercise caution when generalizing the results of trials to their own practice, with regard to the ethnicity of individuals. Efforts should be made to improve reporting of ethnicity and improve diversity in trial recruitment, although we acknowledge that there are challenges that must be overcome to make this a reality., (© 2016 Diabetes UK.)

Aims: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed., Methods: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores., Results: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28)., Conclusions: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure., (© 2015 Diabetes UK.)

Aims: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively., Methods: Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects., Results: Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred., Conclusions: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aims: To examine whether early endocrinologist care reduces the risk of cardiovascular complications among newly diagnosed patients with diabetes of differing complexity., Methods: We conducted a population-based propensity score-matched cohort study using provincial health data from Ontario, Canada. Adults (≥ 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who received endocrinologist care in the first year of diagnosis were matched to a comparison group receiving primary care alone (N = 79 020) based on propensity scores and medical complexity (assigned using information on chronic conditions). Individuals were followed for 3- and 5-year outcomes, including non-fatal acute myocardial infarction or coronary heart disease death (primary endpoint), major cardiovascular events (acute myocardial infarction, stroke) or all-cause death, amputation and end-stage renal disease., Results: Among medically complex patients, early endocrinologist care was associated with a lower 3-year incidence of the primary endpoint (hazard ratio 0.89, 95% CI 0.78-1.01) and major cardiovascular events or all-cause death (hazard ratio 0.91, 95% CI 0.85-0.97). These effects persisted after accounting for a higher incidence of end-stage renal disease on follow-up and were greatest in those with ≥ 3 visits to an endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56-0.86 and 0.61, 95% CI 0.45-0.82, for unadjusted and end-stage renal disease adjusted analyses, respectively). In contrast, no benefit was observed in the non-medically complex subgroup. Overall effects were similar at 5 years., Conclusions: Early endocrinologist care is associated with a lower incidence of cardiovascular events and death among newly diagnosed patients with diabetes who have comorbid medical conditions., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aims: To evaluate the effectiveness of a tailored, supportive intervention strategy in influencing diabetes-related distress, health status, well-being and clinical outcomes in people with Type 2 diabetes shortly after a first acute coronary event., Methods: People with Type 2 diabetes and a recent first acute coronary event (n = 201) were randomized to the intervention group (three home visits by a diabetes nurse) or the attention control group (one telephone consultation). Outcomes were measured after discharge (baseline) and at 5 months (follow-up) using validated questionnaires for diabetes-related distress (Problem Areas in Diabetes), well-being (WHO Well-Being Index) and health status (Euroqol 5 Dimensions; Euroqol Visual Analogue Scale). ancova was used to analyse change-over-time differences between groups., Results: Follow-up data were available for 81 participants in the intervention group (66.0 ± 9.3 years, 76% male) and 80 in the control group (65.6 ± 9.4 years, 75% male) participants. Mean diabetes-related distress was low after hospital discharge (intervention group: 8.2 ± 10.1; control group: 9.2 ± 12.4) and did not change after 5 months (intervention group: 9.2 ± 12.4; control group: 9.0 ± 11.2). Baseline well-being was less favourable but improved significantly in the intervention group (baseline: 58.5 ± 28.0; follow-up: 65.5 ± 23.7; P = 0.005), but not in the control group (baseline: 57.5 ± 25.2; follow-up: 59.6 ± 24.4; P = 0.481). Health status also improved in the intervention group (baseline: 69.9 ± 17.3; follow-up: 76.8 ± 15.6; P < 0.001) but not in the control group (baseline: 68.6 ± 15.9; follow-up: 69.9 ± 16.7; P = 0.470). A significant group effect was found for health status (F = 7.9; P = 0.006)., Conclusions: Although the intervention had no effect on diabetes-related distress, this might be at least partially attributable to very low levels of diabetes-related distress at baseline. Interestingly, health status scores and well-being, which were less favourable at baseline, both improved after the tailored support intervention., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aim: To compare the cardiovascular risks associated with second-line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study., Methods: We conducted a nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add-on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time., Results: In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20-0.75) and for the α-glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31-0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as-treated analyses, similar but less significant associations were found as compared with the primary intention-to-treat analyses for all treatment groups., Conclusion: There were no differences in overall cardiovascular risks among several add-on second-line oral antidiabetic agents; however, glinide plus metformin and α-glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aim: To describe the association between socio-economic position, health status and quality of diabetes care in people with Type 2 diabetes in France, where people may receive full healthcare coverage for chronic disease., Methods: Data from a national cross-sectional survey performed in people pharmacologically treated for diabetes were used. They combined data from medical claims, hospital discharge, questionnaires for patients (n = 3894 with Type 2 diabetes) and their physicians (n = 2485). Socio-economic position was assessed using educational level (low, intermediate, high) and ability to make ends meet (financial difficulties vs. financially comfortable)., Results: People with diabetes reporting financial difficulties were more likely to be smokers (adjusted odds ratio 1.4; 95% CI 1.1-1.6) and obese (adjusted odds ratio 1.3; 95% CI 1.2-1.6) and to have poorer glycaemic control (HbA1c > 64 mmol/mol (8%); adjusted odds ratio 1.4; 95% CI 1.1-1.8), than those who were financially comfortable. They were more likely to have their diabetes diagnosed because of complications (adjusted odds ratio 1.6; 95% CI 1.3-2.0). They were also more likely to have coronary and podiatric complications (adjusted odds ratios 1.3; 95% CI 1.1-1.6 and 1.7; 95% CI 1.4-2.2, respectively). They benefited more often from full coverage (adjusted odds ratio 1.3; 95% CI 1.1-1.6), visited general practitioners more often (ratio of estimated marginal means 1.2; 95% CI 1.1-1.2) but specialists less often (adjusted odds ratio 0.7; 95% CI 0.6-0.8 for a visit to private ophthalmologist). They also felt less well informed about their condition., Conclusions: Despite frequent access to full healthcare coverage, socio-economic position has an impact on the diagnosis of diabetes, health status and quality of diabetes care in France., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: Adding pharmacists to primary care teams significantly improved blood pressure control and reduced predicted 10-year cardiovascular risk in patients with Type 2 diabetes. This pre-specified sub-study evaluated the economic implications of this cardiovascular risk reduction strategy., Methods: One-year outcomes and healthcare utilization data from the trial were used to determine cost-effectiveness from the public payer perspective. Costs were expressed in 2014 Canadian dollars and effectiveness was based on annualized risk of cardiovascular events derived from the UKPDS Risk Engine., Results: The 123 evaluable trial patients included in this analysis had a mean age of 62 ( ± 11) years, 38% were men, and mean diabetes duration was 6 ( ± 7) years. Pharmacists provided 3.0 ( ± 1.9) hours of additional service to each intervention patient, which cost $226 ( ± $1143) per patient. The overall one-year per-patient costs for healthcare utilization were $190 lower in the intervention group compared with usual care [95% confidence interval (CI): -$1040, $668). Intervention patients had a significant 0.3% greater reduction in the annualized risk of a cardiovascular event (95% CI: 0.08%, 0.6%) compared with usual care. In the cost-effectiveness analysis, the intervention dominated usual care in 66% of 10,000 bootstrap replications. At a societal willingness-to-pay of $4000 per 1% reduction in annual cardiovascular risk, the probability that the intervention was cost-effective compared with usual care reached 95%. A sensitivity analysis using multiple imputation to replace missing data produced similar results., Conclusions: Within a randomized trial, adding pharmacists to primary care teams was a cost-effective strategy for reducing cardiovascular risk in patients with Type 2 diabetes. In most circumstances, this intervention may also be cost saving., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aims: To compare levels of diabetes distress in people with Type 2 diabetes treated in primary and secondary care and to examine demographic and clinical correlates that may explain potential differences in levels of distress between care settings., Methods: People with Type 2 diabetes from 24 primary care practices (n = 774) and three secondary care clinics (n = 526) completed the Problem Areas In Diabetes questionnaire. Data on HbA1c levels and diabetes complications were derived from medical charts. Hierarchical ordinal regression analysis was used to investigate which correlates could explain the potential differences in level of diabetes distress between care settings., Results: Diabetes distress levels and the prevalence of elevated diabetes distress were considerably lower in the participants treated in primary care (mean (SD) total diabetes distress score 8 (11); 4% of participants with a Problem Areas In Diabetes score ≥ 40) than in secondary care (mean (SD) total diabetes distress score 23 (21); 19% of participants with a Problem Areas In Diabetes score ≥ 40, P < 0.001). In addition to care setting, the following variables were also independently related to diabetes distress: younger age, ethnic minority status, using insulin, having a higher HbA1c level, having a higher BMI and the presence of neuropathy. Other diabetes complications were not independently associated with diabetes distress., Conclusions: In primary care, lower levels of diabetes distress were reported than in secondary care. The difference in diabetes distress between care settings can be largely, but not fully, explained by specific demographic and clinical characteristics. These results need to be interpreted with caution as they are based on two separate studies, but do call into question the need to screen for diabetes distress in people with Type 2 diabetes in primary care., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Aims: To synthesize evidence from randomized and non-randomized studies of physical activity interventions in children and young people with Type 1 diabetes so as to explore clinically relevant health outcomes and inform the promotion of physical activity., Method: We conducted a search of CINAHL Plus, the Cochrane Library, EMBASE, MEDLINE, PsycINFO, SCOPUS, SportDiscus and Web of Science between October and December 2012. Eligible articles included subjects aged ≤18 years with Type 1 diabetes and a physical activity intervention that was more than a one-off activity session. Physiological, psychological, behavioural or social outcomes were those of interest., Results: A total of 26 articles (10 randomized and 16 non-randomized studies), published in the period 1964-2012, were reviewed. Although there was heterogeneity in study design, methods and reporting, 23 articles reported at least one significant beneficial health outcome at follow-up. Meta-analyses of these studies showed potential benefits of physical activity on HbA1c (11 studies, 345 participants, standardized mean difference -0.52, 95% CI -0.97 to -0.07; P = 0.02), BMI (four studies, 195 participants, standardized mean difference -0.41, 95% CI -0.70 to -0.12; P = 0.006) and triglycerides (five studies, 206 participants, standardized mean difference -0.70, 95% CI -1.25 to -0.14; P = 0.01).The largest effect size was for total cholesterol (five studies, 206 participants, standardized mean difference -0.91, 95% CI -1.66 to -0.17; P = 0.02)., Conclusions: Physical activity is important for diabetes management and has the potential to delay cardiovascular disease, but there is a lack of studies that are underpinned by psychological behaviour change theory, promoting sustained physical activity and exploring psychological outcomes. There remains a lack of knowledge of how to promote physical activity in people with Type 1 diabetes., (© 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: To investigate the race-specific trend in attainment of the American Diabetes Association cardiovascular risk factor control goals (HbA1c <53 mmol/mol (7.0%), blood pressure <130/80 mmHg and LDL cholesterol <2.6mmol/l) by patients with Type 2 diabetes., Methods: The study sample included 14 946 African-American and 12 758 white patients who were newly diagnosed with Type 2 diabetes between 2001 and 2009 in the Louisiana State University Hospital system. The race-specific percentages of patients' attainment of American Diabetes Association goals were calculated using the baseline and follow-up measurements of HbA1c , blood pressure, and LDL cholesterol levels. Logistic regression was used to test the difference between African-American and white patients., Results: The percentage of patients who met all three American Diabetes Association goals increased from 8.2% in 2001 to 10.2% in 2009 (increased by 24.4%) in this cohort. Compared with African-American patients, white patients had better attainment of the following American Diabetes Association goals: HbA1c (61.4 vs. 55.1%), blood pressure (25.8 vs. 20.4%), LDL cholesterol (40.1 vs. 37.7%) and all three goals (7.3 vs. 5.1%). African-American and white patients generally had a better cardiovascular disease risk factor profile during follow-up when we assessed attainment of the American Diabetes Association goals by means of HbA1c , blood pressure and LDL cholesterol., Conclusions: During 2001-2009, the present low-income cohort of people with Type 2 diabetes generally experienced improved control of cardiovascular disease risk factors. White patients had better attainment of the American Diabetes Association cardiovascular risk factor control goals than their African-American counterparts., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Aim: To assess whether a 12-week participant-driven health education programme offered to individuals with screening-detected hyperglycaemia in Danish primary care would lead to improvements in cardiovascular risk factors, health behaviour and patient-reported outcomes after 3 years., Methods: We conducted a randomized controlled trial in 509 patients with screening-detected hyperglycaemia (impaired fasting glucose, impaired glucose tolerance or type 2 diabetes) from 33 general practices in Denmark. Individuals were pre-randomized to receive (i) routine care (n = 187), or (ii) an invitation to participate in the Ready to Act health education programme (n = 322). The programme was delivered over 12 weeks in primary care and focused on motivation, action experience, informed decision-making and social involvement to promote health behaviour change. The primary outcome was 10-year modelled cardiovascular risk., Results: Of 322 individuals, 123 (38%) received the intervention and 436/509 individuals (86%) returned for follow-up assessment. There was no difference between the trial groups in modelled cardiovascular risk at 3 years (relative difference: 1.01; 95% CI: 0.84 to 1.23). Total cholesterol was lower (-0.24mmol/l, 95% CI: -0.45 to -0.03, P = 0.027), and patient activation was higher in the intervention than in the control group (5.3, 95% CI: 0.97 to 9.7). No other between-group differences were observed for any cardiovascular risk factor, health behaviour or patient-reported outcome variables. Subgroup analyses suggested that the intervention was more beneficial in those with impaired fasting glucose/impaired glucose tolerance than in those with type 2 diabetes., Conclusion: For patients with screening-detected hyperglycaemia, a participant-driven health education programme was not associated with improvements in most clinical, behavioural and patient-reported outcomes after 3 years of follow-up., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)