Trading off dietary choices, physical exercise and cardiovascular disease risks

Despite several decades of decline, cardiovascular diseases are still the most common causes of death in Western societies. Sedentary living and high fat diets contribute to the prevalence of cardiovascular diseases. This paper analyses the trade-offs between lifestyle choices defined in terms of diet, physical activity, cost, and risk of cardiovascular disease that a representative sample of the population of Northern Ireland aged 40-65 are willing to make. Using computer assisted personal interviews, we survey 493 individuals at their homes using a Discrete Choice Experiment (DCE) questionnaire administered between February and July 2011 in Northern Ireland. Unlike most DCE studies for valuing public health programs, this questionnaire uses a tailored exercise, based on the individuals��� baseline choices. A ���fat screener��� module in the questionnaire links personal cardiovascular disease risk to each specific choice set in terms of dietary constituents. Individuals are informed about their real status quo risk of a fatal cardiovascular event, based on an initial set of health questions. Thus, actual risks, real diet and exercise choices are the elements that constitute the choice task. Our results show that our respondents are willing to pay for reducing mortality risk and, more importantly, are willing to change physical exercise and dietary behaviours. In particular, we find that to improve their lifestyles, overweight and obese people would be more likely to do more physical activity than to change their diets. Therefore, public policies aimed to target obesity and its related illnesses in Northern Ireland should invest public money in promoting physical activity rather than healthier diets.

High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes

To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes.

Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes

Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating IC containing modified lipoproteins in the progression of carotid intima-media thickness (IMT) in patients enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) Trial, a follow-up study of the Diabetes Control and Complications Trial (DCCT). This cohort includes 1229 patients with type 1 diabetes in whom B-mode ultrasonography of internal and common carotid arteries was performed in 1994-1996 and in 1998-2000. Conventional CHD risk factors, antibodies against modified forms of LDL and modified lipoprotein IC were determined in 1050 of these patients from blood collected in 1996-1998. Cholesterol and apolipoprotein B content of IC (surrogate markers of modified ApoB-rich lipoproteins) were significantly higher in patients who showed progression of the internal carotid IMT than in those showing no progression, regression or mild progression. Multivariate linear and logistic regression modeling using conventional and non-conventional risk factors showed that the cholesterol content of IC was a significant positive predictor of internal carotid IMT progression. In conclusion these data demonstrate that increased levels of modified ApoB-rich IC are associated with increased progression of internal carotid IMT in the DCCT/EDIC cohort of type 1 diabetes.

Impact of different health systems on the burden of type 2 diabetes in two populations

Objectives: Health policy directs the management of patients with chronic disease in a country, but evaluating nationwide policies is difficult, not least because of the absence of suitable comparators. This paper examines the management of patients with type 2 diabetes in two demographically comparable populations with different health care systems to see if this represents a viable approach to evaluation.<br/><br/>Methods: A secondary analysis of centralized prescribing databases for 2010 was undertaken to compare the levels and costs of care of patients with type 2 diabetes in Northern Ireland���s National Health Service (NHS) (NI, n���=���1.8 million) which has structured care, financial incentives related to diabetes care and an emphasis on generic prescribing, with that of the Republic of Ireland (ROI, n���=���4.3 million) where management of diabetes care is guided solely by clinical and other guidelines.<br/><br/>Results: The prevalence of treated type 2 diabetes was 3.59% in NI and 3.09% in ROI, but there were similar and high levels of prescribing of secondary cardiovascular medications. Medication costs per person for anti-diabetic, anti-obesity and cardiovascular medication were 46% higher in ROI than NI, due to differences in levels of generic prescribing.<br/><br/>Conclusions: These different health care systems appear to be producing similar levels of care for patients with type 2 diabetes, although at different levels of cost. The findings question the need for financial incentives in NI and highlight the large cost savings potentially accruing from a greater shift to generic prescribing in ROI. Cross-country comparison, though not without difficulties, may prove a useful adjunct to within-country analysis of policy impact.

Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients

Aim: To determine if serum pigment epithelium-derived factor (PEDF) levels in Type 2 diabetes are related to vascular risk factors and renal function. Methods: PEDF was quantified by ELISA in a cross-sectional study of 857 male Veterans Affairs Diabetes Trial (VADT) subjects, and associations with cardiovascular risk factors and renal function were determined. In a subset (n = 246) in whom serum was obtained early in the VADT (2.0 �� 0.3 years post-randomization), PEDF was related to longitudinal changes in renal function over 3.1 years. Results: Cross-sectional study: In multivariate regression models, PEDF was positively associated with serum triglycerides, waist-to-hip ratio, serum creatinine, use of ACE inhibitors or angiotensin receptor blockers, and use of lipid-lowering agents; it was negatively associated with HDL-C (all p &lt; 0.05). Longitudinal study: PEDF was not associated with changes in renal function over 3.1 years (p &gt; 0.09). Conclusions: Serum PEDF in Type 2 diabetic men was cross-sectionally associated with dyslipidemia, body habitus, use of common drugs for blood pressure and dyslipidemia, and indices of renal function; however, PEDF was not associated with renal decline over 3.1 years.

A Posteriori Dietary Patterns Are Related to Risk of Type 2 Diabetes: Findings from a Systematic Review and Meta-Analysis

Our review and meta-analysis examined the association between a posteriori���derived dietary patterns (DPs) and risk of type 2 diabetes mellitus. MEDLINE and EMBASE were searched for articles published up to July 2012 and data were extracted by two independent reviewers. Overall, 19 cross-sectional, 12 prospective cohort, and two nested case-control studies were eligible for inclusion. Results from cross-sectional studies reported an inconsistent association between DPs and measures of insulin resistance and/or glucose abnormalities, or prevalence of type 2 diabetes. A meta-analysis was carried out on nine prospective cohort studies that had examined DPs derived by principle component/factor analysis and incidence of type 2 diabetes risk (totaling 309,430 participants and 16,644 incident cases). Multivariate-adjusted odds ratios were combined using a random-effects meta-analysis. Two broad DPs (Healthy/Prudent and Unhealthy/Western) were identified based on food factor loadings published in original studies. Pooled results indicated a 15% lower type 2 diabetes risk for those in the highest category of Healthy/Prudent pattern compared with those in the lowest category (95% CI 0.80 to 0.91; P&lt;0.0001). Compared with the lowest category of Unhealthy/Western DP, those in the highest category had a 41% increased risk of type 2 diabetes (95% CI 1.32 to 1.52; P&lt;0.0001). These results provide evidence that DPs are consistently associated with risk of type 2 diabetes even when other lifestyle factors are controlled for. Thus, greater adherence to a DP characterized by high intakes of fruit, vegetables, and complex carbohydrate and low intakes of refined carbohydrate, processed meat, and fried food may be one strategy that could have a positive influence on the global public health burden of type 2 diabetes.

Multimodal functional and anatomical imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

Structural and functional change in the microcirculation in type 1 diabetes mellitus predicts future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track change in ocular hemodynamics in patients with this disease. 24 patients with uncomplicated type 1 diabetes mellitus, and 18 age-and-sex matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries and digital photography to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and following inhalation of 100% oxygen. Frequency data was compared between groups. No significant differences were found in the resistive index between groups at baseline or following inhaled oxygen. Frequency analysis of the Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and controls in data captured from the ophthalmic artery (p&lt;0.01 for each band). In response to inhaled oxygen, changes in the frequency band amplitudes were significantly greater in control subjects compared with patients (p&lt;0.05). Only control subjects demonstrated a positive correlation (R=0.61) between change in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical change in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

<p>Obesity has been linked with elevated levels of��C-reactive protein��(CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ���baseline��� measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50��years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95��% confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (���25���&lt;30��kg/m2) or moderately obese (���30���&lt;35) tended to be associated with a lower risk of mortality compared to normal (���18.5���&lt;25): ESTHER, HR (95��% CI) 0.69 (0.58���0.82) and 0.78 (0.63���0.97); Rotterdam, 0.86 (0.79���0.94) and 0.80 (0.72���0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95��% CI) 0.88 (0.76���1.02); and moderately obese in Troms��, HR (95��% CI) 0.79 (0.62���1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.</p>

A cross-sectional study demonstrating increased serum amyloid A-related inflammation in high density lipoproteins from subjects with type 1 diabetes mellitus and how this association was augmented by poor glycaemic control

Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins(HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this propertymay be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matchedcontrol subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-,and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly inserum (<i>P</i> = 0.088), and significantly in HDL2 (<i>P</i>����= 0.003) and HDL3 (<i>P</i>����= 0.005). When the T1DM group were separated accordingto mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ��� 8.34%, compared towhen HbA1c was &lt;8.34% (<i>P</i>����&lt; 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAAincreased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (<i>P</i>����&gt; 0.05).This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poorglycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increasedatherosclerosis risk.

Retinopathy in type 1 diabetes mellitus: Major differences between rural and urban dwellers in northwest Ethiopia

<p>Aim: To audit levels of diabetes-related eye disease in Type 1 diabetes mellitus (T1DM) patients in northwest Ethiopia. In particular to establish whether, despite identical clinical goals, major differences between the physically demanding life-style of rural subsistence farmers and the sedentary life-style of urban dwellers would influence the prevalence of diabetes-related eye complications.��</p><p>Methods: A robust infrastructure for chronic disease management that comprehensively includes all rural dwellers was a pre-requisite for the investigation. A total of 544 T1DM were examined, representing 80% of all T1DM patients under regular review at both the urban and rural clinics and representative of patient age and gender (62.1% male, 37.9% female) of T1DM patients from this region; all were supervised by the same clinical team. Eye examinations were performed for visual acuity, cataract and retinal changes (retinal photography). HbA1c levels and the presence or absence of hypertension were recorded.��</p><p>Results/conclusions: Urban and rural groups had similar prevalences of severe visual impairment/blindness (7.0% urban, 5.2% rural) and cataract (7.3% urban, 7.1% rural). By contrast, urban dwellers had a significantly higher prevalence of retinopathy compared to rural patients, 16.1% and 5.0%, respectively (OR 2.9, p &lt;. 0.02, after adjustment for duration, age, gender and hypertension). There was a 3-fold greater prevalence of hypertension in urban patients, whereas HbA1c levels were similar in the two groups. Since diabetic retinopathy is closely associated with microvascular disease and endothelial dysfunction, the possible influences of hypertension to increase and of sustained physical activity to reduce endothelial dysfunction are discussed.</p>

Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast

<p>BACKGROUND: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function.</p><p>OBJECTIVE: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food-style meal.</p><p>METHODS: Adults with T2D [n = 18; age (means �� SEs): 56 �� 3 y; BMI (in kg/m(2)): 35.3 �� 2.0; 14 women; 4 men) were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; &lt;0.1 mg flavanols) with a high-fat fast-food-style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10-12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment.</p><p>RESULTS: Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall ��: 1.5 �� 0.8 mg/dL; P ��� 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (��: 5.2 �� 3.2 mU/L; P &lt; 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P &lt; 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (��: -1.6 �� 0.7 mL/mm Hg; P &lt; 0.05), with the difference significant only at 2 h.</p><p>CONCLUSION: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food-style meal challenge. Although HDL cholesterol and insulin remained higher throughout the 6-h postprandial period, an overall decrease in large artery elasticity was found after cocoa consumption. This trial was registered at clinicaltrials.gov as NCT01886989.</p>

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

<p>BACKGROUND: Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women.</p><p>METHODS: We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n���=���79) or type 2 or gestational DM (DM-O; n���=���45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates.</p><p>RESULTS: DM-O were heavier at birth than Con-O (3.7 �� 0.6 vs. 3.4 �� 0.4 kg, p���=���0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 �� 14.9 vs. 9.5 �� 9.9 ng/ml in Con-O, p���&lt;���0.0001). Leptin was positively associated with birth weight (p���=���0.0007) and SSF (p���=���0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p���=���0.023; DM-O, p���=���0.006). PEDF was positively associated with birth weight in all infants (p���=���0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p���=���0.009). At 1-month, HMWA was positively associated with body weight (p���=���0.004), SSF (p���=���0.025) and % body fat (p���=���0.004) across the cohort.</p><p>CONCLUSIONS: Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.</p>

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies

<p><em>Aims/hypothesis</em>���The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.</p><p><em>Methods���</em>A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.</p><p><em>Results</em>���In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors��� adjustments for potential confounding made a substantial difference to the pooled ORs.</p><p><em>Conclusions/interpretation</em>���This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.</p>

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.<br/><br/>Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22���193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.<br/><br/>Results: There was a strong association between BMI and incident CHD (HR���=���1.20 per SD-increase of BMI, 95% CI, 1.12���1.28, P���=���1.9��10���7), heart failure (HR���=���1.47, 95% CI, 1.35���1.60, P���=���9��10���19) and ischaemic stroke (HR���=���1.15, 95% CI, 1.06���1.24, P���=���0.0008) in observational analyses. The genetic score was robustly associated with BMI (�����=���0.030 SD-increase of BMI per additional allele, 95% CI, 0.028���0.033, P���=���3��10���107). Analyses indicated a causal effect of adiposity on development of heart failure (HR���=���1.93 per SD-increase of BMI, 95% CI, 1.12���3.30, P���=���0.017) and ischaemic stroke (HR���=���1.83, 95% CI, 1.05���3.20, P���=���0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.<br/><br/>Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Systematic review of the use of behaviour change techniques (BCTs) in home-based cardiac rehabilitation programmes for patients with cardiovascular disease-protocol

<p>BACKGROUND: Cardiovascular diseases (CVDs), including myocardial infarction, heart failure, peripheral arterial disease and strokes, are highly prevalent conditions and are associated with high morbidity and mortality. Cardiac rehabilitation (CR) is an effective form of secondary prevention for CVD but there is a lack of information regarding which specific behaviour change techniques (BCTs) are included in programmes that are associated with improvements in cardiovascular risk factors. This systematic review will describe the BCTs which are utilised within home-based CR programmes that are effective at reducing a spectrum of CVD risk factors.</p><p>METHODS/DESIGN: The review will be reported in line with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidance. Randomised and quasi-randomised controlled trials of home-based CR initiated following a vascular event (myocardial infarction, heart failure, peripheral arterial disease and stroke patients) will be included. Articles will be identified through a comprehensive search of MEDLINE, Embase, PsycINFO, Web of Science and Cochrane Database guided by a medical librarian. Two review authors will independently screen articles retrieved from the search for eligibility and extract relevant data, identifying which specific BCTs are included in programmes that are associated with improvements in particular modifiable vascular risk factors.</p><p>DISCUSSION: This review will be of value to clinicians and healthcare professionals working with cardiovascular patients by identifying specific BCTs which are used within effective home-based CR. It will also inform the future design and evaluation of complex health service interventions aimed at secondary prevention in CVD.</p><p><br/></p>