Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.).

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR Ͼ300 mg/g and eGFR Ͻ60 ml/min per 1.73 m 2 at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

Objectives To determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular (CVD) events beyond conventional risk factors. Background Several studies have shown that aPWV may be a useful risk factor for predicting CVD but have been underpowered to examine whether this is true for different sub-groups. Methods We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with cardiovascular outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Results Of 17,635 participants, 1,785 (10%) had a cardiovascular (CVD) event. The pooled age- and sex-adjusted hazard ratio [95% CI] per SD change in loge aPWV was 1.35 [1.22, 1.50, p<0.001] for coronary heart disease (CHD), 1.54 [1.34, 1.78, p<0.001] for stroke, and 1.45 [1.30, 1.61, p<0.001) for CVD. Associations stratified by sex, diabetes and hypertension were similar, but decreased with age (1.89, 1.77, 1.36 and 1.23 for ≤50, 51–60, 61–70 and >70 years respectively, pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor: CHD 1.23, [1.11, 1.35 p<0.001]; stroke 1.28, [1.16, 1.42 p<0.001]; cardiovascular events 1.30 [1.18, 1.43, p<0.001]. Reclassification indices showed the addition of aPWV improved risk prediction (13% for 10 year CVD risk for intermediate risk) for some sub-groups. Conclusions Consideration of aPWV improves model fit and reclassifies risk for future cardiovascular events in models that include standard risk factors. aPWV may enable better identification of high-risk populations who may benefit from more aggressive cardiovascular risk factor management.

Background The aims of this study were to investigate the effects of age, gender, body mass index (BMI), glycaemic control, socioeconomic status, dyslipidaemia, hypertension, ischaemic heart disease (IHD) and smoking status in type 2 diabetes in a population-based analysis. Methods Data were collected from 46 General Practice databases in 2009 and 2014. Cox regressions were run in the non-diabetes population plus type 2 diabetes patients. Results People with type 2 diabetes (n=16,643) had higher mortality rates than non-diabetes subjects. Ranked in order of Hazard Ratio (HR), increasing age (HR 2.31), smoking (HR 1.79), IHD (HR 1.65), deprivation (HR 1.36), hypertension (HR 1.23) and male gender (HR 1.20) all increased mortality risk (p<0.01). Statin therapy was associated with better outcome (HR 0.65, p<0.01). Abnormal lipid levels whilst not on a statin signi cantly increased mortality risk for raised total-cholesterol (HR 1.74) and low HDL-cholesterol (HR 1.48) but not for triglycerides (HR 0.67) (all p<0.01). Conclusions This large study con rmed that the all-cause mortality risk in people with type 2 diabetes remains elevated. In the study we demonstrated that a man with type 2 diabetes of 5-10 years duration who smoked, had hypertension and IHD plus lived in the most deprived area had a HR of 6.2 compared with a non-smoking, normotensive, non-diabetes subject without IHD living in the least deprived area.. Further research is required to understand the gender risk difference in all-cause mortality in type 1 compared with type 2 diabetes and why obesity plus raised triglycerides appear to be protective. Highlights Ranked in order of Hazard Ratio (HR), increasing age (HR 2.31), smoking (HR 1.79), Ischaemic Heart Disease (IHD) (HR 1.65), deprivation (HR 1.36), hypertension (HR 1.23) and male gender (HR 1.20) all increased mortality risk (p<0.01). This study demonstrated that a man with type 2 diabetes of 5-10 years duration who smoked, had hypertension and IHD plus lived in the most deprived area had a HR of 6.2 compared with a nonsmoking, normotensive, non-diabetes subject without IHD living in the least deprived area. Smoking prevalence decreased with duration falling from 26.8% for diabetes <5 yrs to 17.7% for diabetes >10 yrs. Body Mass Index > 30kg/m 2 appeared to reduce mortality risk (HR 0.77, p<0.01).

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Aims/hypothesis Data are inconsistent regarding the associations between age, age at diagnosis of diabetes, diabetes duration and subsequent vascular complications.

OBJECTIVEThere is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA 1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. RESEARCH DESIGN AND METHODSADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA 1c and glucose taken 3-24 months after randomization. Outcomes were combined macro-and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group. RESULTSAmong 4,399 patients in the intensive group, an increase in VVV of HbA 1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05-2.55) and 3.31 (1.57-6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 [1.65-4.42]). HbA 1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro-and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results. CONCLUSIONSConsistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.

None.