[show abstract][hide abstract] ABSTRACT: Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (>= 0.90 mm), in non-diabetic participants.
Nine hundred-sixty-one (range of age: 18-89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants.
Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of >= 2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness >= 0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P = 0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR = 1.12; 95% CI = 1.09-1.14), hypertension on pharmacologic treatment (OR = 1.81; 95% CI = 1.16-2.82), and pulse pressure (OR = 1.03; 95% CI = 1.01-1.04), while consuming >=2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR = 0.46; 95% CI = 0.26-0.80).
High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease.
[show abstract][hide abstract] ABSTRACT: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study is an ongoing observational survey that examines the role of estimated glomerular filtration rate (eGFR) as an independent predictor of cardiovascular and renal outcomes in 15,773 Italian subjects with type 2 diabetes. The analysis of data collected at the enrollment visit has provided a picture of chronic kidney disease (CKD) and its association with other complications, risk factors for cardiovascular disease (CVD) and treatments in a large contemporary cohort. Main results of this analysis were that (a) non-albuminuric renal impairment is the predominant clinical phenotype in patients, particularly women, with reduced eGFR; (b) concordance rate between CKD and diabetic retinopathy is low, with only a minority of patients with renal dysfunction presenting with any or advanced retinal lesions; (c) the non-albuminuric form is associated with a significant prevalence of CVD, especially at the level of coronary vascular bed; (d) CKD is associated with hemoglobin (Hb) A1c variability more than with average HbA1c, whereas retinopathy and CVD are not; (e) in elderly individuals with moderate-to-severe eGFR reduction, use of agents which are not recommended, such as sulphonylureas and metformin, is still frequent ; and (f) though complications are generally more prevalent in men (except non-albuminuric renal impairment) women show a less favourable CVD risk profile and achieve therapeutic targets to a lesser extent than men, despite the fact that treatment intensity is nor lower. These data update existing information on the natural history of CKD in patients with type 2 diabetes.
Trial registration number and date
Nutrition, Metabolism and Cardiovascular Diseases. 01/2014;
[show abstract][hide abstract] ABSTRACT: The use of diuretics for hypertension has been associated with unfavorable changes in cardiovascular risk factors, such as uric acid and glucose tolerance, though the findings in the literature are contradictory.
This study investigated whether diuretic use is associated with markers of metabolic and cardiovascular risk, such as insulin-resistance and uric acid, in a cohort of adults without known diabetes and/or atherosclerotic cardiovascular disease. Nine hundred sixty-nine randomly selected participants answered a questionnaire on clinical history and dietary habits. Laboratory blood measurements were obtained in 507 participants.
Previously undiagnosed type 2 diabetes was recognized in 4.2% of participants who were on diuretics (n = 71), and in 2% of those who were not (n = 890; P = 0.53). Pre-diabetes was diagnosed in 38% of patients who were on diuretics, and in 17.4% (P < 0.001) of those who were not. Multivariate analysis showed that insulin-resistance (HOMA-IR) was associated with the use of diuretics (P = 0.002) independent of other well-known predisposing factors, such as diet, physical activity, body mass index, and waist circumference. The use of diuretics was also independently associated with fasting plasma glucose concentrations (P = 0.001) and uric acid concentrations (P = 0.01).
The use of diuretics is associated with insulin-resistance and serum uric acid levels and may contribute to abnormal glucose tolerance.
Diabetology and Metabolic Syndrome 12/2013; 5(1):80. · 1.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Associazione Medici Diabetologi-annals initiative is a physician-led quality-of-care improvement scheme that has been shown to improve HbA1c concentration, blood pressure, lipid profiles and BMI in enrolled people with Type 2 diabetes. The present analysis investigated the long-term cost-effectiveness of enrolling people with Type 2 diabetes in the Associazione Medici Diabetologi-annals initiative when compared with conventional management.
Long-term projections of clinical outcomes and direct costs (in 2010 Euro) were made using a published and validated model of Type 2 diabetes in people with Type 2 diabetes who were either enrolled in the Associazione Medici Diabetologi-annals initiative or who were receiving conventional management. Treatment effects were based on mean changes from baseline seen at 5 years after enrolment in the scheme. Costs and clinical outcomes were discounted at 3% per annum.
The Associazione Medici Diabetologi-annals initiative was associated with improvements in mean discounted life expectancy and quality-adjusted life expectancy of 0.55 years (95% CI 0.54-0.57) years and 0.48 quality-adjusted life years (95% CI 0.46-0.49), respectively, compared with conventional management. Whilst treatment costs were higher in the Associazione Medici Diabetologi arm, this was offset by savings as a result of the reduced incidence and treatment of diabetes-related complications. The Associazione Medici Diabetologi-annals initiative was found to be cost-saving over patient lifetimes compared with conventional management [€ 37,289 (95% CI 37,205-37,372) vs € 41,075 (95% CI 40,956-41,155)].
Long-term projections indicate that the physician-led Associazione Medici Diabetologi-annals initiative represents a cost-saving method of improving long-term clinical outcomes compared with conventional management of people with Type 2 diabetes in Italy. This article is protected by copyright. All rights reserved.
[show abstract][hide abstract] ABSTRACT: To assess the predictive value of the risk factors (RF) for gestational diabetes (GDM) considered by the selective screening (SS), and to identify subgroups of women at higher risk for GDM.
Retrospective, single-center study.
Data of 1015 women, screened for GDM at 24-28 weeks gestation and diagnosed according to IADPSG criteria, were evaluated. Information on the RF considered by SS was also collected, and their association with GDM was tested. To identify distinct and homogeneous subgroups of patients at higher risk, the RECPAM (RECursive Partitioning and AMalgamation) method was used.
Overall, 113 (11.1%) women were diagnosed as having GDM. The application of SS would lead to the performance of an OGTT in 58.3% of women, and 26 (23.0%) cases of GDM would not be detected due to the absence of any RF. RECPAM analysis identified high risk subgroups characterized by fasting plasma glucose >5.1mmol/L (OR=26.5;95%CI 14.3-49.0) and pre-gestational BMI (OR=7.0;95%CI 3.9-12.8 for overweight women). In a final logistic model including RECPAM classes, previous macrosomia (OR=3.6;95%CI 1.1-11.6) and family history of diabetes (OR=1.8;95%CI 1.1-2.8), but not maternal age, were also associated with an increased risk of GDM. A screening approach based on the RECPAM model would reduce by over 50% (23.0% vs. 10.6%) the number of undiagnosed GDM cases as compared with the current SS approach, at the expense of 50 additional OGTTs needed.
A screening approach based on our RECPAM model allows a significant reduction of undetected GDM cases compared to current SS procedure.
European Journal of Endocrinology 10/2013; · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications.
Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model.
Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment. Trial Registration number and date: NCT01600924; 05.06.2012.
[show abstract][hide abstract] ABSTRACT: BACKGROUND/OBJECTIVES:Dietary habits are important determinants of individual cardiovascular and metabolic risk. This study investigated the association between dietary patterns and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness, and metabolic biomarkers of insulin resistance, including the homeostasis model assessment of insulin resistance (HOMA-IR) and the trygliceride/high-density lipoprotein (HDL)-cholesterol (Tg/HDL) ratio in a cohort of adults without known diabetes or atherosclerotic cardiovascular disease.SUBJECTS/METHODS:Nine hundred and twenty-nine randomly selected participants were cross-sectionally investigated. Each participant answered a food frequency questionnaire, and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Laboratory blood measurements were obtained in a subsample of 507 participants.RESULTS:A dietary pattern that could be defined as unhealthy (high consumption of soft drinks, fried foods, seed oils, cured meats, butter, red meat and sweets) was identified in 21% of the cohort, whereas 34% of the cohort exhibited a dietary pattern that resembled the Mediterranean diet (high intakes of fruit, milk and cheese, olive oil, vegetables, pasta and bread). Intermediate habits characterized the remaining 45%. After adjusting for age, body mass index (BMI), waist circumference, glycated hemoglobin (HbA1c) and hypertension on treatment, the Mediterranean dietary pattern was associated with significantly lower HOMA-IR (β-coefficient=-0.51; P=0.003). After adjusting for gender, BMI and HbA1c, the unhealthy dietary pattern was associated with a significantly higher Tg/HDL-cholesterol ratio (β-coefficient=0.43; P=0.006). No significant association was found between dietary patterns and carotid atherosclerosis.CONCLUSIONS:This study suggests that, independent of measures of adiposity, a Mediterranean dietary pattern is associated with lower insulin resistance.European Journal of Clinical Nutrition advance online publication, 18 September 2013; doi:10.1038/ejcn.2013.172.
European journal of clinical nutrition 09/2013; · 3.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Background: Telemedicine systems based on mobile phones represent new promising educational tools. The "Diabetes Interactive Diary" (DID) is a carbohydrate/bolus calculator promoting the patient-physician communication via short message service. This study aimed to compare the efficacy of the DID versus usual care on metabolic control, hypoglycemia, and quality of life. Patients and Methods: Patients with type 1 diabetes on a basal:bolus regimen with insulin glargine and insulin glulisine, not previously educated on carbohydrate (CHO) counting, were randomized to DID (Group A; n=63) or traditional education (Group B; n=64). Generalized hierarchical linear regression models for repeated measures were applied to compare changes between groups. Incidence of hypoglycemia was compared using Poisson regression models. Results: Of 127 patients (age, 36.9±10.5 years; diabetes duration, 16.3±9.3 years), 15 (11.8%) dropped out. After 6 months, hemoglobin A1c (HbA1c) levels decreased by -0.49±0.11 in Group A and -0.48±0.11 in Group B (P=0.73). Group A showed a 86% lower risk of grade 2 hypoglycemia than Group B. Compared with usual care, DID improved the "perceived frequency of hyperglycemic episodes" scale of the Diabetes Treatment Satisfaction Questionnaire and the "social relations" and the "fear of hypoglycemia" dimensions of the Diabetes Specific Quality of Life Scale. Results obtained with DID markedly differ among patients and centers. Conclusions: DID is no more effective than traditional CHO counting education in reducing HbA1c levels. DID reduces the risk of moderate/severe hypoglycemia and improves quality of life. A better understanding of patients' and healthcare professionals' attitudes associated with an effective care supported by technology is essential to avoid waste of resources.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Depression occurs relatively commonly in people with chronic kidney disease (CKD), but it is uncertain whether depression is a risk factor for premature death in this population. Interventions to reduce mortality in CKD consistently have been ineffective and new strategies are needed. STUDY DESIGN: Systematic review and meta-analysis of cohort studies. SETTING & POPULATION: Adults with CKD. SELECTION CRITERIA FOR STUDIES: Cohort studies identified in Ovid MEDLINE through week 3 December 2012 without language restriction. PREDICTOR: Depression status as determined by physician diagnosis, clinical coding, or self-reported scales. SELECTION CRITERIA FOR STUDIES: All-cause and cardiovascular mortality. Outcomes were summarized as relative risks (RRs) with 95% CIs using random-effects meta-analysis. RESULTS: 22 studies (83,381 participants) comprising 12,063 cases of depression (mean prevalence, 27.4%; 95% CI, 20.0%-36.3%) with a follow-up of 3 months to 6.5 years were included. Methodological quality generally was good or fair. Depression consistently increased the risk of death from any cause (RR, 1.59; 95% CI, 1.35-1.87), but had less certain effects on cardiovascular mortality (RR, 1.88; 95% CI, 0.84-4.19). Associations for mortality were similar regardless of the diagnostic method used for depression, but were weaker in analyses controlled for preexisting cardiovascular disease (RR, 1.36; 95% CI, 1.23-1.50). LIMITATIONS: Meta-analyses adjusting for antidepressant medication use were not possible, and data for kidney transplant recipients and individuals with earlier stages of CKD not treated with dialysis were limited. CONCLUSIONS: Depression is associated with a substantially increased risk of death in people with CKD. Effective treatment for depression in people with CKD may reduce mortality.
American Journal of Kidney Diseases 04/2013; · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: Poorer control of risk factors for cardiovascular disease (CVD) has been reported in diabetic women, as compared with diabetic men. It has been proposed that this finding is due to gender disparities in treatment intensity. We investigated this hypothesis in a large contemporary cohort of subjects with type 2 diabetes. DESIGN: Observational, cross-sectional study. SUBJECTS AND SETTING: Consecutive patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study (n=15,773), attending 19 hospital-based diabetes clinics in 2007-2008. MAIN OUTCOME MEASURES: Traditional CVD risk factors, macro- and microvascular complications, and current glucose-, lipid-, and blood pressure (BP)-lowering treatments were assessed. RESULTS: Though CVD was more prevalent in men, women showed a less favourable CVD risk profile and worse performance in achieving treatment targets for haemoglobin A1c , LDL, HDL and non-HDL cholesterol, systolic blood pressure (BP) and in particular obesity [body mass index (BMI) and waist circumference], but not for triglycerides and diastolic BP. However, women were more frequently receiving pharmacological treatment for hypertension and to a lesser extent hyperglycaemia and dyslipidaemia than men, and female gender remained an independent predictor of unmet therapeutic targets after adjustment for confounders such as treatments, BMI, duration of diabetes and, except for the systolic BP goal, age. CONCLUSIONS: In women with type 2 diabetes from the RIACE cohort, a more adverse CVD risk profile and a higher likelihood of failing treatment targets, compared with men, was not associated with treatment differences. This suggests that factors other than gender disparities in treatment intensity are responsible. This article is protected by copyright. All rights reserved.
Journal of Internal Medicine 04/2013; · 6.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE
To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.RESEARCH DESIGN AND METHODS
Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine.RESULTSMedian and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD.CONCLUSIONS
In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications.
[show abstract][hide abstract] ABSTRACT: Prevalence estimates of depression in chronic kidney disease (CKD) vary widely in existing studies. We conducted a systematic review and meta-analysis of observational studies to summarize the point prevalence of depressive symptoms in adults with CKD. We searched MEDLINE and Embase (through January 2012). Random-effects meta-analysis was used to estimate the prevalence of depressive symptoms. We also limited the analyses to studies using clinical interview and prespecified criteria for diagnosis. We included 249 populations (55,982 participants). Estimated prevalence of depression varied by stage of CKD and the tools used for diagnosis. Prevalence of interview-based depression in CKD stage 5D was 22.8% (confidence interval (CI), 18.6-27.6), but estimates were somewhat less precise for CKD stages 1-5 (21.4% (CI, 11.1-37.2)) and for kidney transplant recipients (25.7% (12.8-44.9)). Using self- or clinician-administered rating scales, the prevalence of depressive symptoms for CKD stage 5D was higher (39.3% (CI, 36.8-42.0)) relative to CKD stages 1-5 (26.5% (CI, 18.5-36.5)) and transplant recipients (26.6% (CI, 20.9-33.1)) and suggested that self-report scales may overestimate the presence of depression, particularly in the dialysis setting. Thus, interview-defined depression affects approximately one-quarter of adults with CKD. Given the potential prevalence of depression in the setting of CKD, randomized trials to evaluate effects of interventions for depression on patient-centered outcomes are needed.Kidney International advance online publication, 13 March 2013; doi:10.1038/ki.2013.77.
Kidney International 03/2013; · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: Besides its critical role in metabolic homeostasis, peroxisome proliferator-activated receptor (PPAR)-γ modulates several cellular responses involved in atherothrombosis. This multicenter, double-blind, randomized study investigated the effects of two oral hypoglycemic agents on markers of inflammation, platelet activation, thrombogenesis, and oxidative stress in patients with type 2 diabetes. METHODS AND RESULTS: The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin. Additionally, markers of vascular inflammatory response, platelet activation, thrombogenesis, oxidative stress, glucose, and lipid metabolism, as well as liver function, were measured. In total, 50 patients completed the study. Pioglitazonetreated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P = 0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P = 0.01), serum insulin (-2 vs. -1.9 mU/L; P = 0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P = 0.015), and E-selectin (-12.4 vs. +3.4 μg/mL; P = 0.01). Mean glycated hemoglobin (HbA(1c)) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P = 0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P = 0.05) and a decrease in liver enzyme levels. CONCLUSIONS: The favorable changes in markers of systemic and vascular inflammatory response with pioglitazone suggest that it may positively influence the atherothrombotic process in type 2 diabetes.
[show abstract][hide abstract] ABSTRACT: Background and aims
Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM.
Methods and Results
Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4±3.8 years; 53% males; diabetes duration 5.6±3.5 years; HbA1c 7.9±1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR=1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR=1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR=0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR=4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR=7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR=1.63; 95%CI 1.36-1.95). Mother’s age was inversely associated with the risk of both SH (IRR=0.95; 95%CI 0.92-0.98) and DKA (IRR=0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR=1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect.
The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.
[show abstract][hide abstract] ABSTRACT: No clinical trials have assessed the effects or cost-effectiveness of health check strategies to detect and manage vascular disease. We used a mathematical model to estimate the cost-effectiveness of several health check strategies in six European countries.
We used country-specific data from Denmark, France, Germany, Italy, Poland, and the United Kingdom to generate simulated populations of individuals aged 40-75 eligible for health checks in those countries (e.g. individuals without a previous diagnosis of diabetes, myocardial infarction, stroke, or serious chronic kidney disease). For each country, we used the Archimedes model to compare seven health check strategies consisting of assessments for diabetes, hypertension, lipids, and smoking. For patients diagnosed with vascular disease, treatment was simulated in a standard manner. We calculated the effects of each strategy on the incidence of type 2 diabetes, major adverse cardiovascular events (MACE), and microvascular complications in addition to quality of life, costs, and cost per quality-adjusted life-year (QALY).
Compared with current care, health checks reduced the incidence of MACE (6-17 events prevented per 1000 people screened) and diabetes related microvasular complications (5-11 events prevented per 1000 people screened), and increased QALYs (31-59 discounted QALYs) over 30 years, in all countries. The cost per QALY of offering a health check to all individuals in the study cohort ranged from €14903 (France) to cost saving (Poland). Pre-screening the population and offering health checks only to higher risk individuals lowered the cost per QALY. Pre-screening on the basis of obesity had a cost per QALY of €10200 (France) or less, and pre-screening with a non-invasive risk score was similar.
A vascular disease health check would likely be cost effective at 30 years in Denmark, France, Germany, Italy, Poland, and the United Kingdom.
PLoS ONE 01/2013; 8(7):e66454. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.
MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.
Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.
Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
PLoS ONE 01/2013; 8(8):e71583. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIMS: The Diabetes Attitudes Wishes and Needs 2 (DAWN2) study aims to provide a holistic assessment of diabetes care and management among people with diabetes (PWD), family members (FM), and healthcare professionals (HCPs) and explores potential drivers leading to active management. METHODS: DAWN2 survey over 16,000 individuals (∼9000 PWD, ∼2000 FM of PWD, and ∼5000 HCPs) in 17 countries across 4 continents. Respondents complete a group-specific questionnaire; items are designed to allow cross-group comparisons on common topics. The questionnaires comprise elements from the original DAWN study (2001), as well as psychometrically validated instruments and novel questions developed for this study to assess self-management, attitudes/beliefs, disease impact/burden, psychosocial distress, health-related quality of life, healthcare provision/receipt, social support and priorities for improvement in the future. The questionnaires are completed predominantly online or by telephone interview, supplemented by face-to-face interviews in countries with low internet access. In each country, recruitment ensures representation of the diabetes population in terms of geographical distribution, age, gender, education and disease status. DISCUSSION: DAWN2 aims to build on the original DAWN study to identify new avenues for improving diabetes care. This paper describes the study rationale, goals and methodology.
Diabetes research and clinical practice 12/2012; · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79-1·02] during years 5-9 and 0·75 [0·62-0·90] in later years; breast cancer mortality RR 0·97 [0·79-1·18] during years 5-9 and 0·71 [0·58-0·88] in later years). The cumulative risk of recurrence during years 5-14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5-14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89-1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13-3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83-1·36), ischaemic heart disease 0·76 (0·60-0·95, p=0·02), and endometrial cancer 1·74 (1·30-2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5-14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.