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Investigating the Evidence of the Real-Life Impact of Acute Hyperglycaemia.

ABSTRACT:

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Poorly controlled diabetes mellitus (DM) is associated with the development of long-term micro- and macro-vascular complications. The predominant focus of anti-diabetic therapy has been on lowering glycosylated haemoglobin levels, with a strong emphasis on fasting plasma glucose (particularly in Type 2 DM). There is considerable evidence indicating that post-meal hyperglycaemic levels are independently associated with higher risks of macro-vascular disease. Although some have identified mechanisms which may account for these observations, interventions which have specifically targeted postprandial glucose rises showed little or no effect in reducing cardiovascular risk. Clinical experience and some recent studies suggest acute hyperglycaemia affects cognition and other indicators of performance, equivalent to impairment seen during hypoglycaemia. In this brief report, we evaluated the published studies and argue that acute hyperglycaemia is worth investigating in relation to the real-life implications. In summary, evidence exists suggesting that acute hyperglycaemia may lead to impaired cognitive performance and productivity, but the relationship between these effects and daily activities remains poorly understood. Further research is required to enhance our understanding of acute hyperglycaemia in daily life. A better appreciation of clinically relevant effects of acute hyperglycaemia will allow us to determine whether it needs to be addressed by specific treatment.

Funding

Novo Nordisk A/S Søborg, Denmark.

SUBMITTER: Heller S

PROVIDER: S-EPMC4575298 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveExposure to early-life adversity (ELA) can result in long-term changes to physiological systems, which predispose individuals to negative health outcomes. This biological embedding of stress-responsive systems may operate via dysregulation of physiological resources in response to common stressors. The present pilot study outlines a novel experimental design to test how young adults' exposure to ELA influences neuroendocrine and inflammatory responses to acute stress.Materials and methodsParticipants were 12 males (mean age = 21.25), half of whom endorsed at least three significant adverse events up to age 18 years ('ELA group'), and half who confirmed zero ('controls'). Using a randomized within-subjects, between-groups experimental design, we induced acute psychosocial stress (Trier Social Stress Test, TSST), and included a no-stress control condition one week apart. During these sessions, we obtained repeated measurements of physiological reactivity, gene expression of the glucocorticoid receptor (NR3C1), and plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) over a 4-hour window post-test.ResultsIn this pilot study, the ELA group evinced higher cortisol response and blunted NR3C1 gene expression in response to the TSST compared with controls, while no differences were observed in the no-stress condition. For pro-inflammatory cytokines, only IL-6 increased significantly in response to the TSST, with no differences between the two groups.ConclusionOverall, this pilot feasibility study provides a framework to investigate the biological embedding of early-adversity via dysregulation across physiological and genomic systems in response to acute psychosocial stress. ELA may program such systems in a maladaptive manner more likely to manifest during times of duress, predisposing individuals to the negative health consequences of everyday stressors. Future studies with larger sample size including both males and females are needed to replicate and expand upon these preliminary findings.

Project description:Background: Chemoradiotherapy (CRT) is a treatment standard in limited disease (LD) small cell lung cancer (SCLC). Currently, the timing of thoracic radiation therapy (TRT) remains the subject of randomised trials and meta-analyses. To investigate a correlation between CRT schedule parameters and overall survival (OS) in a real-life patient cohort, a temporal analysis was performed. Methods: 182 LD SCLC patients successfully treated with definitive CRT were retrospectively reviewed. TRT was applied concurrently or sequentially. Impact of the treatment mode and interval of simultaneous treatment (IST) (an interval in days when chemotherapy and TRT were applied simultaneously, including time between chemotherapy cycles and weekends) on OS was analysed. Results: 71 (39%) patients were treated with concurrent and 111 (61%) with sequential CRT. Median overall survival (MS) for the entire cohort was 534 days (95%CI 461 - 607) without any significant difference between the concurrent and sequential groups (589: 95%CI 358 - 820 vs. 533: 95%CI 446 - 620 days, p=0.746, log-rank test). IST was 0 days in 111 (61%) patients treated sequentially whereas in the concurrent group, 20 (11%) and 51 (28%) patients showed an IST < 35 and > 35 days, respectively. Patients with IST > 0 and < 35 days demonstrated a trend to improved overall survival (MS: IST 0 vs. > 35 vs. < 35 was 533 vs. 448 vs. 1169 days, p=0.109, log-rank test). When patients treated with sequential CRT (IST 0) were excluded from the analysis, statistical difference in overall survival according to the IST subgroups (IST > 35 vs. < 35) became significant (p=0.021, log-rank test). On multivariate analysis of patients treated with concurrent CRT, IST > 0 and < 35 days remained a variable that significantly correlated with better overall survival (p=0.039, HR 0.38). Conclusion: In this real-life LD SCLC patient cohort, improved overall survival was achieved in patients treated with CRT schedule according to the IST > 0 and < 35-day concept. By exceeding the 35-day interval, we have seen deterioration in survival.

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Investigating the Evidence of the Real-Life Impact of Acute Hyperglycaemia.

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