Glucose variability measures and their effect on mortality: a systematic review

OBJECTIVE: To systematically review the medical literature on the association between glucose variability measures and mortality in critically ill patients. METHODS: Studies assessing the association between a measure of glucose variability and mortality that reported original data from a clinical trial or observational study on critically ill adult patients were searched in Ovid MEDLINE(®) and Ovid EMBASE(®). Data on patient populations, study designs, glucose regulations, statistical approaches, outcome measures, and glucose variability indicators (their definition and applicability) were extracted. RESULT: Twelve studies met the inclusion criteria; 13 different indicators were used to measure glucose variability. Standard deviation and the presence of both hypo- and hyperglycemia were the most common indicators. All studies reported a statistically significant association between mortality and at least one glucose variability indicator. In four studies both blood glucose levels and severity of illness were considered as confounders, but only one of them checked model assumptions to assert inference validity. CONCLUSIONS: Glucose variability has been quantified in many different ways, and in each study at least one of them appeared to be associated with mortality. Because of methodological limitations and the possibility of reporting bias, it is still unsettled whether and in which quantification this association is independent of other confounders. Future research will benefit from using an indicator reference subset for glucose variability, metrics that are linked more directly to negative physiological effects, more methodological rigor, and/or better reporting.