Effectiveness of lifestyle counseling by certified expert nurse of Japan for non-insulin-treated diabetic outpatients: a 1-year randomized controlled trial.

We examine whether one-to-one lifestyle counseling for non-insulin-treated diabetic outpatients by a Certified Expert Nurse (CEN) can improve patients' health outcomes. Participants were randomly assigned to a 1-year lifestyle intervention (n=67) or to a usual care group (n=67). Main outcome measures were changes from baseline in: HbA(1C) and score of health related quality of life scales (SF-36 and Problem Areas in Diabetes Scale). Cognitive/behavioral modification for 1 year and satisfaction in CEN counseling was also measured by self-produced items. We found no significant differences in HbA(1C), BMI, blood pressure, serum lipids, or health related quality of life over 1 year between the two groups. Patients in the intervention group, however, showed modest but more favorable modification of cognition (p=0.004) and behavior (p<0.001) than subjects in usual care group. The low attrition rate (9%), more frequent hospital visit (12+/-2 times versus 11+/-3 times; p=0.03) and high degree of satisfaction (95%) in the intervention group indicate feasibility of the monthly CEN counseling in the outpatient settings of Japanese hospitals. Future research should confirm the long-term effectiveness of the CEN counseling on clinical outcomes and the cost effectiveness of a possibly time-consuming intervention.

Sphingosine 1-phosphate acts as a signal molecule in ceramide signal transduction of TNF-alpha-induced activator protein-1 in osteoblastic cell line MC3T3-E1 cells.

We previously demonstrated that tumor necrosis factor (TNF)-alpha stimulated the production of activation protein (AP)-1, a transcriptional factor, in mouse osteoblastic MC3T3-E1 cells. Recent studies have shown the importance of ceramide and its metabolites as signal molecules for TNF-alpha-induced gene expression in several cell types. Therefore, our interest was to investigate whether sphingosine metabolites are involved in TNF-alpha-induced signaling in MC3T3-E1 cells. DL-threo-1-phenyl-2-hexadecanoyl-amino-3-pyrrolidino-1-propanol (PPPP), which causes accumulation of intracellular ceramide, stimulated the TNF-alpha-induced expression of the c-fos and c-jun genes. Gel shift assay clearly showed that PPPP increased the cytokine-induced specific binding of nuclear proteins to the 12-tetra-decanoyl phorbol 13-acetate-responsive element (TRE), a consensus sequence for AP-1. In addition, cell-permeable ceramide (N-acetylsphingosine, N-hexanoylsphingosine or N-octanoylsphingosine) stimulated expression of the c-fos and c-jun genes and nuclear protein binding to TRE. Interestingly, DL-threo-dihydrosphingosine (DHS), an inhibitor of sphingosine kinase, clearly blocked the ceramide analogue-induced stimulation. Sphingosine 1-phosphate (SPP) actually induced expression of these oncogenes and activated AP-1. Although TNF-alpha stimulated the AP-1-mediated expression of the monocyte chemoattractant JE/MCP-1, this stimulation was inhibited by DHS. SPP also stimulated JE/MCP-1 gene expression. The present study thus suggests that SPP acts as a signal molecule in ceramide-dependent signal transduction in TNF-alpha-induced AP-1 in osteoblastic MC3T3-E1 cells.