Objective: Although clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).Design and methods: To investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.Results: All three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97±0.22) and SHO (1.99±0.13) versus EU (1.27±0.16, P<0.05), while Matsuda index was decreased in HO (3.89±0.36) and SHO (4.26±0.48) versus EU (7.76±0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 μU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215±19 mean fluorescence intensity, MFI) and SHO (218±24 MFI) versus EU (270±25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481±30 MFI) and SHO (462±19 MFI) were decreased versus EU (571±15 MFI, P=0.04 and 0.004 respectively).Conclusions: In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.

There is a growing body of evidence suggesting that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Indeed, changes in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression, including detachment of tumor cells from the primary site, intravasation into the blood stream, extravasation into distant target organs, and formation of the secondary lesions. This review presents recent data regarding the role of cell adhesion molecules in tumor development and progress with concern to their clinical exploitation as potential biomarkers in neoplastic diseases.

Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06–1.91]; P =0.02), masked hypertension (1.55; 95% CI [1.12–2.14]; P <0.01) and sustained hypertension (2.13; 95% CI [1.66–2.73]; P <0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79–1.72]; P =0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23–2.53]; P =0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02–1.94]; P =0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.

Accumulating evidence suggests that central blood pressure (BP) may reflect the hemodynamic stress on target organs more accurately than brachial BP. A systematic review assessing the relationship of central versus brachial BP with preclinical target-organ damage was performed. Meta-analysis of cross-sectional data showed that central compared with brachial systolic BP was more closely associated with (1) left ventricular mass index (12 studies, n=6431; weighted age [SD], 49.9 [13.1] years; 51% hypertensives): pooled correlation coefficients r =0.30; 95% confidence interval (CI), 0.23–0.37 versus r =0.26; 95% CI, 0.19–0.33, respectively; P <0.01 for difference; (2) carotid intima-media thickness (7 studies, n=6136; weighted age, 55.6 [13.2] years; 48% hypertensives): r =0.27; 95% CI, 0.19–0.34 versus r =0.23; 95% CI, 0.16–0.30, respectively; P <0.01 for difference; (3) pulse-wave velocity (14 studies, n=3699; weighted age, 53.9 [13.3] years; 53% hypertensives): r =0.42; 95% CI, 0.37–0.47 versus r =0.39; 95% CI, 0.33–0.45, respectively; P <0.01 for difference. Four studies assessing urine albumin excretion (n=3718; weighted age, 56.4 [5] years; 69% hypertensives) reported similar correlations ( P =not significant) with central ( r =0.22; 95% CI, 0.14–0.29) and brachial systolic BP ( r =0.22; 95% CI, 0.12–0.32). Similar findings were observed for central compared with brachial pulse pressure in terms of relationship with target-organ damage. Metaregression analyses did not reveal any significant effect of age. In conclusion, central compared with brachial BP seems to be more strongly associated with most of the investigated indices of preclinical organ damage.