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Background: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.Methods: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR).Results: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p < 0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age.Conclusions: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria.Trial Registration: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008. [ABSTRACT FROM AUTHOR]

Background: New approaches to cope with clinical and psychosocial aspects of type 2 diabetes (T2DM) are needed; gender influences the complex interplay between clinical and non-clinical factors. We used data from the BENCH-D study to assess gender-differences in terms of clinical and person-centered measures in T2DM.Methods: Clinical quality of care indicators relative to control of HbA1c, lipid profile, blood pressure, and BMI were derived from electronic medical records. Ten self-administered validated questionnaires (SF-12 Health Survey; WHO-5 well-being index; Problem Areas in Diabetes (PAID) 5, Health Care Climate Questionnaire, Patients Assessment of Chronic Illness Care, Diabetes Empowerment Scale, Diabetes Self-care Activities, Global Satisfaction for Diabetes Treatment, Barriers to Taking Medications, Perceived Social Support) were adopted as person-centered outcomes indicators.Results: Overall, 26 diabetes clinics enrolled 2,335 people (men: 59.7%; women: 40.3%). Lower percentages of women reached HbA1c levels < =7.0% (23.2% vs. 27.8%; p = 0.03), LDL-cholesterol < 100 mg/dl (48.3 vs. 57.8%; p = 0.0005), and BMI <27 Kg/m2 (27.2 vs. 31.6%; p = 0.04) than men. Women had statistically significant poorer scores for physical functioning, psychological well-being, self-care activities dedicated to physical activities, empowerment, diabetes-related distress, satisfaction with treatment, barriers to medication taking, satisfaction with access to chronic care and healthcare communication, and perceived social support than men; 24.8% of women and 8.8% of men had WHO-5 < =28 (likely depression) (p < 0.0001); 67.7% of women and 55.1% of men had PAID-5 > 40 (high levels of diabetes-related distress) (p < 0.0001). At multivariate analysis, factors associated with an increased likelihood of having elevated HbA1c levels (≥8.0%) were different in men and women, e.g. having PAID-5 levels >40 was associated with a higher likelihood of HbA1c ≥8.0% in women (OR = 1.15; 95%CI 1.05-1.25) but not in men (OR = 1.00; 95%CI 0.93-1.08).Conclusions: In T2DM, women show poorer clinical and person-centered outcomes indicators than men. Diabetes-related distress plays a role as a correlate of metabolic control in women but not in men. The study provides new information about the interplay between clinical and person-centered indicators in men and women which may guide further improvements in diabetes education and support programs. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA)/exercise have become an integral part of the management of type 2 diabetes mellitus (T2DM). However, current guidelines are difficult to put into action in this population due to a number of barriers, especially the lack of acceptable, feasible, and validated behavioral intervention strategies. The present manuscript reports the rationale, study design and methods, and design considerations of the Italian Diabetes and Exercise Study (IDES)-2, a randomized controlled trial testing the efficacy of a behavior change strategy in increasing total daily PA and reducing sedentary time (SED-time) in patients with T2DM.Methods/design: Starting 7 January 2014, the IDES_2 began enrolling 300 patients with known T2DM of at least 1-year duration in three tertiary referral outpatient Diabetes Clinics in Rome. Additional requirements are age 40 to 80 years, body mass index 27 to 40 kg/m(2), sedentary lifestyle, and physically inactive for at least 6 months, ability to walk 1.6 km without assistance, and eligibility after cardiovascular evaluation. Patients are randomized by center and within each center, by age and type of diabetes treatment to either the intervention or the control group. Patients in the intervention (INT) group (n = 150) receive theoretical and practical exercise counseling consisting of aggregated behavior change techniques (one individual theoretical counseling session plus eight twice-a-week individual theoretical and practical exercise counseling sessions) once a year for 3 years. Patients in the control (CON) group (n = 150), receive standard care, including general physician recommendations for daily PA. The primary outcomes are total daily PA and SED-time, as measured objectively by the use of an accelerometer. Secondary outcomes include physical fitness, modifiable cardiovascular risk factors, musculoskeletal disturbances, well-being/depression, and health-related quality of life.Discussion: The behavioral intervention strategy tested in the IDES_2 is based on solid theoretical grounds and uses several behavioral change techniques, two factors which were found to improve effectiveness of behavioral intervention. In addition, physicians and exercise specialists have been specifically trained for counselling/prescribing and supervising PA/exercise, respectively, in subjects suffering from metabolic disorders. Finally, the large sample size, the long study duration, and the objective measurement of PA allow statistically significant and scientifically robust conclusions to be drawn on the feasibility and efficacy of this intervention in T2DM patients.Trial Registration: ClinicalTrials.gov; NCT01600937 ; 10 October 2012. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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). Multi vari ate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR =1.12; 95% CI = 1.09-1.14), hypertension on pharmacologie 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 offish weekly was protective compared with the condition of consumption of <1 serving offish weekly (OR = 0.46; 95% CI = 0.26-0.80). Conclusions High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role offish consumption in prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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). Conclusions The use of diuretics is associated with insulin-resistance and serum uric acid levels and may contribute to abnormal glucose tolerance. [ABSTRACT FROM AUTHOR]

Background: A genomic region on chromosome 9p21 has been identified as closely associated with increased susceptibility to coronary artery disease (CAD) and to type 2 diabetes (T2D) although the evidence suggests that the genetic variants within chromosome 9p21 that contribute to CAD are different from those that contribute to T2D. We carried out an association case-control study in an Italian population to test the association between two single nucleotide polymorphisms (SNPs) on the 9p21 locus, rs2891168 and rs10811661, previously reported by the PROCARDIS study, and respectively myocardial infarction (MI) and T2D. Our aim was to confirm the previous findings on a larger sample and to verify the independence of their susceptibility effects: rs2891168 associated with MI but not with T2D and rs10811661 associated with T2D but not with MI. Methods: Genomic DNA samples of 2407 Italians with T2D (602 patients), who had had a recent MI (600), or had both diseases (600) and healthy controls (605) were genotyped for the two SNPs. The genotypes were determined by allelic discrimination using a fluorescent-based TaqMan assay. Results: SNP rs2891168 was associated with MI, but not with T2D and the G-allele odds ratio (OR) was 1.20 (95% CI 1.02-1.41); SNP rs10811661 was associated with T2D, but not with MI, and the T-allele OR was 1.27 (95% CI 1.04-1.55). ORs estimates from the present study and the PROCARDIS study were pooled and confirmed the previous findings, with greater precision. Conclusions: Our replication study showed that rs2891168 and rs10811661 are independently associated respectively with MI and T2D in an Italian population. Pooling our results with those reported by the PROCARDIS group, we also obtained a significant result of association with diabetes for rs10811661 in the European population. [ABSTRACT FROM AUTHOR]

Background: Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors. Methods/Design: The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. Eligibility criteria: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, nonfatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transientischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners. Discussion: The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries. Methods: Patients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications. Results: The median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9–7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2–9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3–18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7–9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09–1.19), 1.30 (1.20–1.42), 1.03 (1.02–1.04) and 1.45 (1.25–1.69), respectively, and for macrovascular complications of 1.41 (1.34–1.48), 1.29 (1.16–1.45), 1.02 (1.01–1.02) and 1.24 (1.04–1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02–1.08]) but not macrovascular (1.00 [0.97–1.04]) complications. Conclusions: The global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications. Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762. ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822 [ABSTRACT FROM AUTHOR]