The Pre-diabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE) programme study: are improvements in glucose regulation sustained at 2 years?

OBJECTIVE: To determine whether improvements in glucose regulation following the PREPARE structured education programme were sustained at 24 months. PATIENTS AND METHODS: Ninety-eight overweight or obese individuals with impaired glucose tolerance were randomized to receive: (1) advice leaflet, (2) 3-h structured education programme aimed at promoting physical activity, (iii) 3-h structured education with personalized pedometer use. The primary outcome was change in 2-h post-challenge plasma glucose. RESULTS: Seventy-three (74%) individuals were included for analysis at 24 months; age 65 ± 8 years, BMI 29.3 ± 4.8 kg/m(2), South Asian ethnicity 21%. A statistically significant reduction in 2-h glucose of -1.6 mmol/l (-0.4 to -2.7) was seen in the education-with-pedometer group compared with the control group. There is no significant difference in the education-only group. CONCLUSION: Improvements in glucose regulation following a pragmatic group-based structured education with pedometer use were sustained at 24 months.

Modulation of hippocampal excitability by 5-HT4 receptor agonists persists in a transgenic model of Alzheimer's disease.

5-HT(4) receptors are widely distributed in both peripheral and central nervous systems where they couple, via a G-protein, to the activation of adenylate cyclase. In the brain, the highest 5-HT(4) receptor densities are found in the limbic system, including the hippocampus and frontal cortex. It has been suggested that activation of these receptors may be of therapeutic benefit in diseases that produce cognitive deficits such as Alzheimer's disease (AD). Previous electrophysiological studies have shown that the 5-HT(4) agonist, Zacopride, can increase population spike amplitude recorded in region CA1 of rat hippocampal slices in a cyclic AMP (cAMP)/cAMP-dependent protein kinase A-dependent manner. We report here that the 5-HT(4) agonist, Prucalopride, and the 5-HT(4) partial agonist, SL65.0155, produce a similar effect in rat hippocampal slices and that the specific 5-HT(4) antagonist, GR113808, blocks these effects. To investigate the potential use of 5-HT(4) agonists in the treatment of AD, Prucalopride was applied to hippocampal slices from a transgenic mouse line that overexpresses the Abeta peptide. Despite the deficit in synaptic transmission present in these mice, the percentage increase of the CA1 population spike induced by Prucalopride was the same as that observed in wild-type mice. These data support 5-HT(4) receptors as a target for cognitive enhancement and suggest that a partial agonist would be sufficient to produce benefits, while reducing potential peripheral side effects. In addition, we show that 5-HT(4) receptors remain functional in the presence of excess Abeta peptide and may therefore be a useful target in AD.