Arterial stiffness and microvascular disease in type 2 diabetes.

BACKGROUND: The clustering of arterial stiffness with microvascular disease (MD) and their effects on the clinical outcome of patients with type 2 diabetes (T2D) remains not fully clarified. METHODS: In a prospective study of 414 patients with T2D, we investigated the prognostic value of arterial stiffness and MD for clinical outcomes. Participants were assessed for the presence of MD (ie diabetic retinopathy, nephropathy and neuropathy) and arterial stiffness by pulse wave velocity (PWV) and followed-up for a median of 30 (range 1-60) months. The primary endpoint of the study was the composite endpoint of major adverse cardiovascular events, that is, cardiovascular and non-cardiovascular mortality and non-fatal myocardial infarction/stroke. RESULTS: A total of 146 (35.3%) patients had evidence of MD at baseline. In cox regression models, MD and PWV were independently associated with the composite clinical endpoint; for MD hazard ratio (HR), 3.24, 95%CI, 1.10-9.54, P=.032, and for PWV HR, 1.20, 95%CI, 1.06-1.36, P=.004) after adjustment for traditional risk factors, and enhanced risk discrimination and reclassification. The subgroup of patients with MD and high PWV was associated with increased incidence of the composite clinical endpoint (20.9% vs 1.8% in those with no MD & low PWV, P=.001). Importantly, absence of MD at baseline was associated with no mortality events during the follow-up period. PWV at baseline was not associated with MD progression during follow-up. CONCLUSIONS: These findings support that screening for arterial stiffness and MD in the routine clinical assessment of patients with T2D may enhance prognostication and cardiovascular risk reclassification.

Polymorphism analysis of ADIPOQ gene in Greek patients with diabetic retinopathy.

BACKGROUND: Several genetic polymorphisms have been identified as risk factors for diabetic retinopathy (DR) onset. The purpose of our study was to determine whether ADIPOQ rs1501299 and rs2241766 gene polymorphisms are associated with DR in a cohort of Greek diabetic patients. MATERIALS AND METHODS: 218 patients with type-2 diabetes mellitus (T2DM) were included in the study; 109 suffered from DR and 109 not. All the participants underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. RESULTS: Between the studied groups, no significant differences were detected regarding the demographic and clinical data (p > .05 for all), except for hemoglobin A1c levels and frequency of insulin treatment (higher in DR patients). We detected that the frequency of rs1501299 GT genotype was significantly elevated in DR patients (53% vs. 34%, p = .004) and was associated with a higher risk of developing retinopathy (OR 2.31, 95% CI 1.30-4.11). Furthermore, we demonstrated that the rs1501299 GT genotype was significantly and independently associated with increased odds for DR development in diabetic subjects (OR 2.68, 95% CI 1.38-5.21, p = .004), regardless of the impact of other known risk factors. CONCLUSIONS: We documented that rs1501299 GT genotype could be recognized as an independent risk factor of retinopathy in T2DM Greek patients, while no role for rs2241766 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk of DR development.

The association of T786C and G894T polymorphisms of eNOS gene with diabetic retinopathy in Greece.

PURPOSE: To investigate whether eNOS T786C (rs2070744) and G894T (rs1799983) gene polymorphisms are associated with diabetic retinopathy in Greek diabetic patients. MATERIALS: 271 patients with type-2 diabetes mellitus participated in our study; 130 suffered from diabetic retinopathy and 141 not. All the patients underwent a complete ophthalmological examination, while clinical and demographic data were assessed. Furthermore, they were genotyped for rs2070744 and rs1799983 single nucleotide polymorphisms of eNOS gene. RESULTS: Regarding the clinical and demographic data, no significant differences were detected between the studied groups, except for hemoglobin A1c levels and the frequency of insulin treatment (higher in patients with diabetic retinopathy). The frequency of rs1799983 GT genotype was significantly elevated in patients with diabetic retinopathy (55% vs. 40%, P = 0.011) and was associated with a 2-fold increased risk of developing retinopathy (OR 1.92, 95% CI 1.16-3.17). Furthermore, we demonstrated that the aforementioned genotype was significantly and independently associated with increased odds for retinopathy onset in diabetic subjects (OR 2.23, 95% CI 1.28-3.90, P = 0.005), regardless of the impact of other confounders. CONCLUSIONS: We documented that rs1799983 GT genotype could be recognized as an independent risk factor of retinopathy in Greek patients with type-2 diabetes mellitus, while no role for rs2070744 polymorphism was identified. Further research in different ethnic groups will clarify the exact association of these polymorphisms with the risk for diabetic retinopathy development.

Associations between Adiponectin Gene Variability, Proinflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND: Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE: To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS: Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS: Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION: Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

Novel biomarkers in heart failure: usefulness in clinical practice.

Biomarkers have become an increasingly important tool in clinical practice, helping to improve patient care. In heart failure (HF), brain natriuretic peptide and N-terminal prohormone of the brain natriuretic peptide have been widely applied in prognosis, clinical diagnosis and treatment. Recently, several novel biomarkers have been examined on their efficacy to improve diagnosis, determine the pathophysiologic state of HF, improve clinical decision making, clinical outcome, guide treatment and assess prognosis of HF patients. In this special report, the authors summarize the usefulness and significance of the most promising novel biomarkers in patients with HF.

MicroRNAs: Biomarkers for cardiovascular disease in patients with diabetes mellitus.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by low insulin production/secretion by pancreatic beta cells and/or low responsiveness by insulin target tissues MicroRNAs have been associated with DM, but it is not clear whether this is a cause or an effect of metabolic abnormalities related to DM. In the hyperglycemic environment miRNAs are in involved in multiple stages of cardiovascular disease development and progression. In diabetic patients with cardiovascular disease miRNAs could potentially serve as early biomarkers for diagnosis and as therapeutic agents. The current review focuses on the involvement of miRNAs in molecular mechanisms underlying the pathogenesis of DM and its cardiovascular complications.