The relationship between adipokines and the onset of type 2 diabetes in middle-aged men: The PRIME study.

AIMS: Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men. METHODS: Baseline serum levels of leptin and adiponectin were measured in 1839 non-diabetic men aged 50-60years who were participating in the prospective population-based PRIME study. Over a mean follow-up of 14.7years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners. RESULTS: 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67-6.83) and men in the top third of the adiponectin distribution at reduced risk (HR 0.24, 95% CI 0.14-0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin. CONCLUSIONS: This study provides evidence that adipokines are associated with men's future type 2 diabetes risk but not independently of other risk factors.

Myxofibrosarcomas contain large numbers of infiltrating immature dendritic cells.

Myxofibrosarcoma is a malignant tumor with distinctive histologic features and is believed to be derived from fibroblasts. The function of infiltrating myeloid cells in myxofibrosarcoma is poorly understood. It previously has been shown that a combination of dendritic morphologic features and expression of the C-type lectin, dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), is useful for identifying DC populations in tissue sections. In the present study, we found that 3% to 61% (median, 22%) of cells in myxofibrosarcomas express DC-SIGN and have dendritic morphologic features. These DC-SIGN--positive cells are not in cell cycle and are consistent with infiltrating DCs. The percentage of DCs in myxofibrosarcomas is independent of tumor grade. It previously has been shown that DC-SIGN--positive cells are either immature DCs or DCs that predominantly activate TH2 cells, both subsets likely to give rise to ineffective antitumor responses. The DC-SIGN--positive DCs that we have identified in myxofibrosarcoma may, therefore, be involved in the induction of ineffective immune responses or even tolerance to tumor antigens.