Introduction: This study examines the likelihood and evolution of overall and hypoglycemia-inducing variability of insulin sensitivity in ICU patients based on diagnosis and day of stay. Materials and Methods: An analysis of model-based insulin sensitivity for patients in a medical ICU (Christchurch, New Zealand). Two metrics are defined to measure the variability of a patient’s insulin sensitivity relative to predictions of a stochastic model created from the same data for all patients over all days of stay. The first selectively captures large increases related to the risk of hypoglycemia. The second captures overall variability. Distributions of per-patient variability scores were evaluated over different ICU days of stay and for different diagnosis groups based on APACHE III: operative and non-operative cardiac, gastric, all other. Linear and generalized linear mixed effects models assess the statistical significance of differences between groups and over days. Results: Variability defined by the two metrics was not substantially different. Variability was highest on day 1, and decreased over time () in every diagnosis group. There were significant differences between some diagnosis groups: non-operative gastric patients were the least variable, while cardiac (operative and non-operative) patients exhibited the highest variability. Conclusions: This study characterizes the variability and evolution of insulin sensitivity in critically ill patients, and may help inform the clinical management of metabolic dysfunction in critical care.