Adjusted hazard ratios for selected cause-specific mortality by fresh fruit consumption among 30,300 participants with diabetes at baseline.

<p>Mortality from (A) diabetes, (B) cardiovascular disease, and (C) other causes. Conventions as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002279#pmed.1002279.g001" target="_blank">Fig 1</a>. Baseline status for cardiovascular disease, diabetes, and anti-diabetic treatment were also adjusted for. HR, hazard ratio.</p

Number of events and adjusted hazard ratios (95% CIs) for diabetic complications according to five categories of fresh fruit consumption.

<p>Number of events and adjusted hazard ratios (95% CIs) for diabetic complications according to five categories of fresh fruit consumption.</p

Adjusted hazard ratios for macro- and microvascular complications of diabetes by fresh fruit consumption among 30,300 participants with diabetes at baseline.

<p>(A) Microvascular complications; (B) macrovascular complications. Conventions as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002279#pmed.1002279.g001" target="_blank">Fig 1</a>. HR, hazard ratio.</p

Fresh fruit consumption in relation to incident diabetes and diabetic vascular complications: A 7-y prospective study of 0.5 million Chinese adults

BACKGROUND: Despite the well-recognised health benefits of fresh fruit consumption, substantial uncertainties remain about its potential effects on incident diabetes and, among those with diabetes, on risks of death and major vascular complications. METHODS AND FINDINGS: Between June 2004 and July 2008, the nationwide China Kadoorie Biobank study recruited 0.5 million adults aged 30-79 (mean 51) y from ten diverse localities across China. During ~7 y of follow-up, 9,504 new diabetes cases were recorded among 482,591 participants without prevalent (previously diagnosed or screen-detected) diabetes at baseline, with an overall incidence rate of 2.8 per 1,000 person-years. Among 30,300 (5.9%) participants who had diabetes at baseline, 3,389 deaths occurred (overall mortality rate 16.5 per 1,000), along with 9,746 cases of macrovascular disease and 1,345 cases of microvascular disease. Cox regression yielded adjusted hazard ratios (HRs) associating each disease outcome with self-reported fresh fruit consumption, adjusting for potential confounders such as age, sex, region, socio-economic status, other lifestyle factors, body mass index, and family history of diabetes. Overall, 18.8% of participants reported consuming fresh fruit daily, and 6.4% never/rarely (non-consumers), with the proportion of non-consumers about three times higher in individuals with previously diagnosed diabetes (18.9%) than in those with screen-detected diabetes (6.7%) or no diabetes (6.0%). Among those without diabetes at baseline, higher fruit consumption was associated with significantly lower risk of developing diabetes (adjusted HR = 0.88 [95% CI 0.83-0.93] for daily versus non-consumers, p andlt; 0.001, corresponding to a 0.2% difference in 5-y absolute risk), with a clear dose-response relationship. Among those with baseline diabetes, higher fruit consumption was associated with lower risks of all-cause mortality (adjusted HR = 0.83 [95% CI 0.74-0.93] per 100 g/d) and microvascular (0.72 [0.61-0.87]) and macrovascular (0.87 [0.82-0.93]) complications (p andlt; 0.001), with similar HRs in individuals with previously diagnosed and screen-detected diabetes; estimated differences in 5-y absolute risk between daily and non-consumers were 1.9%, 1.1%, and 5.4%, respectively. The main limitation of this study was that, owing to its observational nature, we could not fully exclude the effects of residual confounding. CONCLUSION: In this large epidemiological study in Chinese adults, higher fresh fruit consumption was associated with significantly lower risk of diabetes and, among diabetic individuals, lower risks of death and development of major vascular complications

The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways

Few things can be considered to be more important to a cell than its threshold for apoptotic cell death, which can be modulated up or down, but rarely in both directions, by a single enzyme. Therefore, it came as quite a surprise to find that one enzyme, glycogen synthase kinase-3 (GSK3), has the perplexing capacity to either increase or decrease the apoptotic threshold. These apparently paradoxical effects now are known to be due to GSK3 oppositely regulating the two major apoptotic signaling pathways. GSK3 promotes cell death caused by the mitochondrial intrinsic apoptotic pathway, but inhibits the death receptor-mediated extrinsic apoptotic signaling pathway. Intrinsic apoptotic signaling, activated by cell damage, is promoted by GSK3 by facilitation of signals that cause disruption of mitochondria and by regulation of transcription factors that control the expression of anti- or pro-apoptotic proteins. The extrinsic apoptotic pathway entails extracellular ligands stimulating cell-surface death receptors that initiate apoptosis by activating caspase-8, and this early step in extrinsic apoptotic signaling is inhibited by GSK3. Thus, GSK3 modulates key steps in each of the two major pathways of apoptosis, but in opposite directions. Consequently, inhibitors of GSK3 provide protection from intrinsic apoptosis signaling but potentiate extrinsic apoptosis signaling. Studies of this eccentric ability of GSK3 to oppositely influence two types of apoptotic signaling have shed light on important regulatory mechanisms in apoptosis and provide the foundation for designing the rational use of GSK3 inhibitors for therapeutic interventions