Transmitral E/A ratio decreases in association with abdominal fat accumulation in patients with impaired glucose tolerance or mild diabetes without left ventricular hypertrophy.

An abnormal left ventricular (LV) diastolic function is an early sign of diabetic cardiomyopathy, which is characterized by an impaired diastolic and/or systolic function of the left ventricle in the absence of ischemic, valvular, or hypertensive heart disease, and serves as a marker of cardiovascular risk. However, it is unclear whether LV diastolic abnormalities can be detected in patients with impaired glucose tolerance (IGT) or mild diabetes without LV hypertrophy (LVH). We examined echocardiographic data from 92 consecutive Japanese patients aged 45-79 years with or without IGT or mild diabetes in the absence of LVH. Impaired glucose tolerance or mild diabetes was defined as the presence of one or more of the following criteria: fasting plasma glucose >110 mg/dl, hemoglobin A1c >5.6%, homeostasis model assessment ratio >1.73, or the taking of oral antihyperglycemic drugs. Left ventricular hypertrophy was defined as an LV mass index (LVMI) >116 g/m(2) in men and >104 g/m(2) in women. Patients with ischemic, valvular, or hypertensive heart disease were excluded. The age, blood pressure, heart rate, and LVMI were similar between patients with (IGT/DM group, n = 43) and without IGT or mild diabetes (non-IGT/DM group, n = 49), whereas the body mass index and waist circumference (WC) were greater in the IGT/DM compared to the non-IGT/DM group (P < 0.05 and P < 0.001, respectively). The transmitral E/A ratio was lower and the deceleration time longer in the IGT/DM than in the non-IGT/DM group (both P < 0.05). Stepwise regression analysis revealed that age and WC were independent determinants of the E/A ratio. In conclusion, diastolic abnormalities without LVH can be detected in Japanese patients with IGT or mild diabetes. The E/A ratio decreases in association with abdominal fat accumulation.

Soluble VEGF receptor-2 is increased in sera of subjects with metabolic syndrome in association with insulin resistance.

OBJECTIVE: Metabolic syndrome (MetS) is associated with impaired angiogenesis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptor, VEGF receptor-2 (VEGFR-2), whereas the expression of VEGF and VEGFR-2 in the myocardium of insulin-resistant rats is down-regulated. Soluble VEGF receptor-1 (sVEGFR-1) and -2 (sVEGFR-2) have been reported to inhibit angiogenesis both in vitro and in vivo. However, the balance between circulating levels of VEGF and its soluble receptors, which may reflect and/or affect cardiovascular VEGF signaling, in subjects with MetS is unknown. METHODS AND RESULTS: We carried out a cross-sectional study including 272 consecutive, apparently healthy subjects who were not receiving any drugs. Plasma levels of VEGF and serum levels of its soluble receptors were determined using enzyme-linked immunosorbent assays. VEGF and sVEGFR-1 levels did not differ between subjects with and those without MetS. However, sVEGFR-2 levels were significantly increased in MetS compared with non-MetS subjects. Stepwise regression analysis revealed that HOMA-IR was the strongest independent determinant of the sVEGFR-2 level. Accordingly, the mean sVEGFR-2 levels increased in proportion to both the accumulation of components of MetS and quartile of HOMA-IR. Interestingly, multiple regression analyses revealed that independent determinants of VEGF were the body mass index and blood pressure, whereas, in contrast, those of sVEGFR-2 were HOMA-IR and high-sensitivity C-reactive protein. CONCLUSIONS: The correlation of sVEGFR-2 with insulin resistance supports the need for further investigations to define the clinical utility and predictive value of serum sVEGFR-2 levels in cardiovascular dysfunction in MetS.

Small dense LDL-cholesterol relative to LDL-cholesterol is a strong independent determinant of hypoadiponectinemia in metabolic syndrome.

BACKGROUND: Small dense low-density lipoprotein (sd-LDL) is an atherogenic lipoprotein closely associated with an increased risk of cardiovascular diseases. However, a precise analysis of the actual amount of sd-LDL-cholesterol (sd-LDL-C) in patients with metabolic syndrome (MS) has not been performed. METHODS AND RESULTS: Among 214 patients enrolled in the present study, 101 patients (47%) met the Japanese MS criteria. The serum levels of sd-LDL-C determined with a dual detection HPLC system were higher in MS than non-MS patients, while total cholesterol and low-density lipoprotein-cholesterol (LDL-C) were similar between MS and non-MS patients. Compared with the sd-LDL-C and LDL-C level, the ratio sd-LDL-C/LDL-C was more closely correlated with various parameters associated with MS. A multivariate regression analysis revealed that the ratio sd-LDL-C/LDL-C is the strongest independent determinant of hypoadiponectinemia. Furthermore, weight reduction therapy through diet and exercise rapidly decreased LDL-C but slowly decreased sd-LDL-C. At 12 months after the therapy, weight reduction led to a significant decrease in the ratio sd-LDL-C/LDL-C in tandem with increasing adiponectin levels. CONCLUSIONS: These findings demonstrate that the ratio sd-LDL-C/LDL-C is tightly connected with hypoadiponectinemia and provides a useful clinical indicator for MS. The results also suggest that the elevation of this ratio can be modulated by long-term lifestyle changes.