Background and objective Serum uric acid may predict the onset and progression of kidney disease, but it is unclear whether uric acid is an independent risk factor for diabetic nephropathy. Our aim was to study the relationship between uric acid levels and the development of CKD components in patients with type 2 diabetes. Design, setting, participants, & measurements Longitudinal study of a cohort of patients with type 2 diabetes from the database of the Italian Association of Clinical Diabetologists network. From a total of 62,830 patients attending the diabetes centers between January 1, 2004, and June 30, 2008, we considered those with baseline eGFR values ≥60 ml/min per 1.73 m² and normal albumin excretion (n=20,142). Urinary albumin excretion, GFR, and serum uric acid were available in 13,964 patients. We assessed the association of serum uric acid quintiles with onset of CKD components by multinomial logistic regression model adjusting for potential confounders. We calculated the relative risk ratios (RRRs) for eGFR <60 ml/min per 1.73 m², albuminuria, and their combination at 4 years. Results At 4-year follow-up, 1109 (7.9%) patients developed GFR <60 ml/min per 1.73 m² with normoalbuminuria, 1968 (14.1%) had albuminuria with eGFR ≥60 ml/min per 1.73 m², and 286 (2.0%) had albuminuria with eGFR <60 ml/min per 1.73 m². The incidence of eGFR <60 ml/min per 1.73 m² increased in parallel with uric acid quintiles: Compared with the lowest quintile, RRRs were 1.46 (95% confidence interval [CI], 1.14 to 1.88; P=0.003), 1.44 (95% CI, 1.11 to 1.87; P=0.006), 1.95 (95% CI, 1.48 to 2.58; P<0.001), and 2.61 (95% CI, 1.98 to 3.42; P<0.001) for second, third, fourth, and fifth quintiles, respectively. Serum uric acid was significantly associated with albuminuria only in presence of eGFR <60 ml/min per 1.73 m². Conclusions Mild hyperuricemia is strongly associated with the risk of CKD in patients with type 2 diabetes.

OBJECTIVE: Despite the achievement of blood glucose, blood pressure, and LDL cholesterol (LDL-C) targets, the risk for diabetic kidney disease (DKD) remains high among patients with type 2 diabetes. This observational retrospective study investigated whether diabetic dyslipidemia—that is, high triglyceride (TG) and/or low HDL cholesterol (HDL-C) levels—contributes to this high residual risk for DKD. RESEARCH DESIGN AND METHODS: Among a total of 47,177 patients attending Italian diabetes centers, 15,362 patients with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, normoalbuminuria, and LDL-C ≤130 mg/dL completing a 4-year follow-up were analyzed. The primary outcome was the incidence of DKD, defined as either low eGFR (30% and/or albuminuria. RESULTS: Overall, 12.8% developed low eGFR, 7.6% an eGFR reduction >30%, 23.2% albuminuria, and 4% albuminuria and either eGFR 30%. TG ≥150 mg/dL increased the risk of low eGFR by 26%, of an eGFR reduction >30% by 29%, of albuminuria by 19%, and of developing one abnormality by 35%. HDL-C <40 mg/dL in men and 30%, with a 24% higher risk of developing albuminuria and a 44% risk of developing one abnormality. These associations remained significant when TG and HDL-C concentrations were examined as continuous variables and were only attenuated by multivariate adjustment for numerous confounders. CONCLUSIONS: In a large population of outpatients with diabetes, low HDL-C and high TG levels were independent risk factors for the development of DKD over 4 years.

OBJECTIVE—Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease (CHD) event in CVD-free type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics, was followed up for 4 years. Baseline assessment included retinopathy, nephropathy, and foot ulcers. First CHD events (myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and electrocardiogram-proven angina) were analyzed for 29,069 person-years. RESULTS—The age-standardized incidence rate (per 1,000 person-years) of first CHD event (n = 881) was 28.8 (95% CI 5.4–32.2) in men and 23.3 (20.2–26.4) in women. Major CHD (myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) was less frequent in women (5.8 [4.3–7.2]) than in men (13.1 [10.9–15.4]; a sex ratio of 0.5 [0.4–0.6]). Incidence rates of all outcomes were higher in patients with microvascular complications (for major CHD, age-adjusted rate ratios were 1.6 [1.2–2.21] in men and 1.5 [1.0–2.2] in women). By multivariate Cox analysis, age and diabetes duration were risk predictors common in both sexes. In men, glycemic control and treated hypertension were additional independent risk factors, but residing in the south was associated with a significant 29% risk reduction. In women, higher triglycerides/lower HDL cholesterol and microvascular complications were independent risk factors. CONCLUSIONS—In CVD-free patients with type 2 diabetes, risk of first CHD event depends on sex, geographic location, and presence of microvascular disease. Hyperglycemia and hypertension, particularly in men, and diabetic dyslipidemia, especially in women, are risk factors amenable to more aggressive treatment.

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, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic 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. Trial registration: Current Controlled Trials ISRCTN48110081.

OBJECTIVE: To investigate the quality of type 2 diabetes care according to sex. RESEARCH DESIGN AND METHODS: Clinical data collected during the year 2009 were extracted from electronic medical records; quality-of-care indicators were evaluated. Multilevel logistic regression analysis was applied to estimate the likelihood of women versus men to be monitored for selected parameters, to reach clinical outcomes, and to be treated with specific classes of drugs. The intercenter variability in the proportion of men and women achieving the targets was also investigated. RESULTS: Overall, 415,294 patients from 236 diabetes outpatient centers were evaluated, of whom 188,125 (45.3%) were women and 227,169 (54.7%) were men. Women were 14% more likely than men to have HbA1c >9.0% in spite of insulin treatment (odds ratio 1.14 [95% CI 1.10–1.17]), 42% more likely to have LDL cholesterol (LDL-C) ≥130 mg/dL (1.42 [1.38–1.46]) in spite of lipid-lowering treatment, and 50% more likely to have BMI ≥30 kg/m2 (1.50 [1.50–1.54]). Women were less likely to be monitored for foot and eye complications. In 99% of centers, the percentage of men reaching the LDL-C target was higher than in women, the proportion of patients reaching the HbA1c target was in favor of men in 80% of the centers, and no differences emerged for blood pressure. CONCLUSIONS: Women show a poorer quality of diabetes care than men. The attainment of the LDL-C target seems to be mainly related to pathophysiological factors, whereas patient and physician attitudes can play an important role in other process measures and outcomes.