Growing evidence suggests that glycaemic variability increases diabetic complications. However, the significance of glycaemic variability in critically ill patients remains unclear. We evaluated the predictors of glycaemic fluctuation and its association with critical care outcomes. This is a nested-cohort study within a clinical trial in which 523 patients at a medical surgical intensive care unit were randomised to either intensive insulin therapy (target glycaemic control: 4.4 to 6.1 mmol/l) or conventional insulin therapy (target control: 10.0 to 11.1 mmol/l). Glycaemic fluctuation was defined as the mean difference between the highest and lowest daily blood glucose. Patients were divided into wide and narrow fluctuation groups according to the median glycaemic fluctuation (6.0 mmol/l). The association between glycaemic fluctuation and different intensive care unit outcomes was studied. Predictors of glycaemic fluctuation were age (odds ratio for each year increment 1.03, 95% confidence interval 1.02 to 1.05), diabetes mellitus (odds ratio 3.00, 95% confidence interval 1.74 to 5.17), and daily insulin dose (odds ratio for each unit increment 1.04, 95% confidence interval 1.03 to 1.05). Similar levels of glucose fluctuation were observed in intensive insulin therapy and conventional insulin therapy patients. Wide glycaemic fluctuation was associated with higher mortality (22.2 vs 8.4%, P <0.001). Glycaemic fluctuation was identified as an independent predictor of intensive care unit mortality (odds ratio per mmol 1.08, 95% confidence interval 1.00 to 1.18) and hospital mortality (odds ratio per mmol 1.09, 95% confidence interval 1.02 to 1.17) using multivariate logistic regression analysis. In conclusion, wide glycaemic fluctuation is an independent predictor of mortality in critically ill patients. Whether reducing glycaemic fluctuation would lead to better outcomes needs further evaluation.

Although the association between antidepressant drug use and risk of cancer has received considerable attention in the past years, no work has been done specifically on prostate cancer. We carried out a population-based case -control study to assess the risk of prostate cancer in association with exposure to tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). 7767 prostate cancer cases diagnosed between 1981 and 2000 were accrued through the Saskatchewan Cancer Agency. Saskatchewan Health identified a total of 31 068 male controls who were matched on age and calendar time. Data on exposure to TCAs and SSRIs were compiled from the Saskatchewan outpatient prescription drug database, and covered a period upto 24 years. A positive significant association was found between TCA use and risk of prostate cancer, when exposure took place 2-5 years before diagnosis, with rate ratios of 1.31, 1.58, and 2.42 at the low, medium and high average daily dose levels, respectively. Exposure to SSRIs was not found to be significantly associated with the risk of prostate cancer. TCA use 2-5 years in the past was associated with a small dose-dependent increase in the risk of prostate cancer. Nevertheless, detection bias could have contributed to the observed association.