The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM). In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s′) and early diastolic (e′) longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12. T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05–0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e′ velocity (P < 0.005–0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = − 0.29 and − 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01–0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects. This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.

Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.

Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structural background for cardiovascular events. The present paper provides a critical overview of the clinical evidence linking diabetes-related metabolic abnormalities to cardiovascular risk, debates the pathophysiologic mechanisms through which insulin resistance and hyperglycemia may affect the arterial wall, and discusses the associations between vascular biomarkers, metabolic abnormalities and cardiovascular events.

Objective—: Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. Approach and Results—: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher ( P <0.05) in the lowest M/I tertile, whereas in women CCA-IMT was higher ( P <0.0005) in the highest fasting plasma glucose tertile (after adjustment for established risk factors). In multiple regression models, with CCA-IMT as the dependent variable and with risk factors and univariate metabolic correlates as independent variables, circulating free fatty acids and the leptin:adiponectin ratio replaced M/I as independent metabolic determinants of CCA-IMT in men. The strongest metabolic determinant of CCA-IMT in women was fasting plasma glucose. Three-year CCA-IMT changes were not associated with any cardio-metabolic risk factor. Conclusions—: In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.

Poor glycemic control is associated with impaired left ventricular (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM). Inappropriate LV mass increase and accelerated aortic stiffening were suggested to participate on deterioration of diastolic function. The present study investigated the inter-relationships between glycemic control, early diastolic and systolic longitudinal velocity of mitral annulus, LV mass and aortic stiffness in T2DM patients free of cardiovascular disease and with preserved LV ejection fraction, and compared them with those observed in healthy volunteers of similar age and sex distribution. 125 T2DM patients and 101 healthy volunteers underwent noninvasive measurement of systolic (s′) and early diastolic (e′) velocities of mitral annulus, LV mass, carotid-femoral pulse wave velocity (cfPWV) and local carotid blood pressure (BP). Forty-four (35.2%) T2DM patients had e′ velocity lower than that expected for age (against 7.9% in healthy volunteers; P < 0.0001), 34 (27.2%) had cfPWV higher than that expected for age and mean BP (against 5.9% in healthy volunteers; P < 0.0001), and 71 (56.8%) had LV mass higher than that expected for body size and stroke work (against 17.6% in healthy volunteers; P < 0.0001). Carotid systolic BP was higher in T2DM patients (124 ± 14 vs 111 ± 11 mmHg; P < 0.0001). In multivariate analysis, e′ velocity was independently related to age, carotid BP and s′ velocity in healthy volunteers, and to male sex, age, carotid BP, heart rate and LV mass in T2DM. Glycosylated hemoglobin (HbA1c) was independently related to cfPWV and LV mass in T2DM patients. T2DM patients with HbA1c ≥6.5% (N = 85) had higher cfPWV (P < 0.05), central BP (P = 0.01), prevalence of LV hypertrophy (P = 0.01) and lower e′ and s′ velocity (P = 0.001 and <0.05, respectively) as compared to those with HbA1c <6.5%. One-third of T2DM patients with preserved LV ejection fraction has sign of subclinical LV diastolic dysfunction. HbA1c levels are positively associated with LV mass and aortic stiffness, both of which show a negative independent impact on early diastolic velocity e′, the latter through an increase in afterload. T2DM patients with suboptimal glycemic control (HbA1c ≥ 6.5%) have lower diastolic and systolic LV longitudinal performance, together with increased aortic stiffness and a higher prevalence of LV hypertrophy.

Context: An independent association between obesity and preclinical carotid atherosclerosis has been demonstrated, however, the pathophysiological links were not clearly established. Body composition (BC) influences systemic hemodynamics and may participate in the remodeling of common carotid artery (CCA), independently of risk factors. Objective: This study evaluated the association between CCA structure and BC in a large population of healthy subjects. Design: This was a cross-sectional study. Settings: The study was conducted at 19 European centers. Subjects: The study included 627 healthy subjects (252 men, age 30–60 yr, body mass index 17–40 kg/m²). Main Outcome Measures: CCA luminal diameter and intima-media thickness were measured on digitized ultrasound images. Acoustic properties of CCA wall were evaluated by digital densitometric analysis and described in terms of mean gray level. BC was assessed by electrical bioimpedance. Insulin sensitivity (euglycemic hyperinsulinemic clamp) and plasma adiponectin levels were measured. Associations between CCA structure, age, BC, and metabolic and atherosclerotic risk factors were analyzed by multivariate regression models. Results: Independent factors affecting CCA diameter were fat-free mass and waist girth (standardized r = 0.44 and 0.12; P < 0.01 and < 0.0001; R² = 0.35); independent correlates of intima-media thickness were age, CCA diameter, systolic blood pressure, and low-density lipoprotein-cholesterol (standardized r = 0.39, 0.25, 0.10, and 0.14; P < 0.005–0.0001; R² = 0.40). The mean gray level of carotid wall was independently associated with age and waist girth (standardized r = 0.23 and 0.12; P < 0.0001 and = 0.001; R² = 0.30). Conclusions: Findings of this cross-sectional study suggest that BC modulates CCA diameter, and may induce adaptive changes in carotid wall thickness, independently of metabolic and atherosclerotic factors. Central adiposity modifies the acoustic properties of carotid wall.