Search

Aims/hypothesis: Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up., Methods: We used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE [SUivi Rénal, DIAbète de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors., Results: We monitored 1321 individuals (58% men, mean age 64 ± 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly., Conclusions/interpretation: In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.

Objective: Sodium intake is associated with cardiovascular outcomes. However, no study has specifically reported an association between cardiovascular mortality and urinary sodium concentration (U Na ). We examined the association of U Na with mortality in a cohort of type 2 diabetes (T2D) patients., Methods: Patients were followed for all-cause death and cardiovascular death. Baseline U Na was measured from second morning spot urinary sample. We used Cox proportional hazard models to identify independent predictors of mortality. Improvement in prediction of mortality by the addition of U Na to a model including known risk factors was assessed by the relative integrated discrimination improvement (rIDI) index., Results: Participants ( n = 1,439) were followed for a median of 5.7 years, during which 254 cardiovascular deaths and 429 all-cause deaths were recorded. U Na independently predicted all-cause and cardiovascular mortality. An increase of one standard deviation of U Na was associated with a decrease of 21% of all-cause mortality and 22% of cardiovascular mortality. U Na improved all-cause and cardiovascular mortality prediction beyond identified risk factors (rIDI = 2.8%, P = 0.04 and rIDI = 4.6%, P = 0.02, resp.)., Conclusions: In T2D, U Na was an independent predictor of mortality (low concentration is associated with increased risk) and improved modestly its prediction in addition to traditional risk factors., Competing Interests: No competing interests were known or perceived.

Objective: Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown., Research Design and Methods: Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease)., Results: Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure., Conclusions: AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77-7.74; P = 0.0012) and of 4.29 (95% CI, 2.79-6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.

Background: Left ventricular hypertrophy (LVH) and kidney damage (abnormal urinary albumin-to-creatinine ratio [uACR] or estimated glomerular filtration rate [eGFR]) are predictive of major cardiovascular events (MACE) in patients with type 2 diabetes (T2D) but are rarely used in cardiovascular score calculators. Our study aimed to assess their respective prognostic values for MACE and the additive information they provide to score calculators., Methods: A total of 1298 T2D (43% women) aged 65 (SD 11) years were followed up for a median of 65 months, with MACE as a primary composite end point: cardiovascular death, nonfatal myocardial infarction, or stroke. Electrocardiogram (ECG)-derived LVH was defined using Sokolow, Gubner, and Cornell product indexes; uACR was considered as abnormal if >2.5 mg/mmol in men or >3.5 mg/mmol in women and eGFR if <60 mL/min per 1.73 m(2)., Results: Urinary albumin-to-creatinine ratio was higher in subjects with electrocardiographic LVH (ECG-LVH) than in subjects without (median [interquartile range] 7.61 [43.48] and 2.56 [10.53], respectively; P < .0001). After adjustment for age, history of myocardial infarction, and peripheral artery disease, ECG-LVH and kidney damage were strong predictors for MACE (adjusted hazard ratio [1.64; 95% CI 1.23-2.20], [1.90; 95% CI 1.43-2.53], and [1.85; 95% CI 1.42-2.41] for ECG-LVH, uACR, and eGFR, respectively). Net reclassification improvement was higher with the model including both ECG-LVH and uACR than models with ECG-LVH alone (P < .0001) or uACR alone (P < .0001). In addition, using cardiovascular risk calculators (Framingham score and others), we observed an additional prognostic value of ECG-LVH for each one of them., Conclusions: Electrocardiographic LVH is complementary to kidney damage for MACE prediction in T2D., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Epidemiological studies and randomized clinical trials have demonstrated in various populations that resting heart rate (RHR) was an independent predictor of cardiovascular (CV) risk and all-cause mortality. However, few data specifically evaluated the relationship between RHR and long-term CV and renal complications in a large population of type 2 diabetic (T2D) patients., Research Design and Methods: We performed a single-center, prospective analysis in 1,088 T2D patients. RHR was determined at baseline by electrocardiogram. The primary outcome was a composite criterion of CV and renal morbi-mortality (CV death, nonfatal myocardial infarction and/or stroke, hospitalization for heart failure, renal replacement therapy), which was adjusted for death from non-CV cause as a competing event. The secondary outcome was a renal composite criterion (renal replacement therapy or doubling of baseline serum creatinine) adjusted for all-cause death as a competing event., Results: During median follow-up of 4.2 years, 253 patients (23%) and 62 patients (6%) experienced the primary and secondary outcomes, respectively. In the subgroup of patients with CV disease history at baseline (n = 336), RHR was found to be associated with the incidence of primary outcome (P = 0.0002) but also with renal risk alone, adjusted for all-cause death as a competing event (secondary outcome; P < 0.0001). In patients without history of CV disease, no relation was found between RHR and the incidence of CV and/or renal events., Conclusions: In the real-life setting, RHR constitutes an easy and less time-consuming factor that would permit identification of CV disease diabetic patients with an increased risk for long-term CV and renal complications.

Objective: To assess the impact of genetic susceptibility on evolution toward type 2 diabetes (T2D) by analyzing time trajectories of fasting glucose, glycated hemoglobin (HbA(1c)), insulin sensitivity (homeostasis model assessment [HOMA2%S]), and β-cell secretion (HOMA2%B) in a large nondiabetic cohort. We also examined whether baseline HbA(1c) modified the effect of genetic predisposition on the time trajectories., Research Design and Methods: Time trajectories were drawn in 4,744 participants from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort based on samples collected every 3 years over a 9-year follow-up. Trajectories were analyzed according to the TCF7L2 common variant, a family history of T2D, and a combination of at-risk alleles from nine T2D-associated genes., Results: There was a marked decrease in HOMA2%B in parallel to a steep increase in HbA(1c) over the 3 years before incident diabetes, which was not influenced by genetic predisposition when considered alone. However, after the onset of T2D, the TCF7L2 at-risk variant was associated with a greater decrease in HOMA2%B. There was a joint effect of a family history of T2D with the presence of the TCF7L2 risk allele with a greater rise in HbA(1c) conferred by the coexistence of a family history and the T risk allele. An HbA(1c) ≥5.7% at baseline was associated with a greater increase in both glycemia and HbA(1c) levels in the presence of a combination of diabetes at-risk alleles., Conclusions: After incident T2D, TCF7L2 at-risk variants were associated with a faster decrease in β-cell function compared with those with the CC genotype. There was a joint effect of family history of T2D and TCF7L2 risk variant on the rise in glycemia and the decrease in insulin secretion at the end of follow-up, suggesting the joint influence of the combination of diabetes genetic predisposition with familial factors on the evolution of glycemia over time.