What Makes Tight Glycemic Control Tight? The Impact of Variability and Nutrition in Two Clinical Studies

Abstract

Tight glycemic control (TGC) remains controversial, and successful, consistent and effective protocols elusive. This research analyses data from 2 TGC trials for root causes of the differences achieved in control and thus potentially in glycemic and other outcomes. The goal is to uncover aspects of successful TGC and delineate the impact of differences in cohorts. Protocols that dose insulin blind to carbohydrate administration can suffer greater outcome glycemic variability, even if average cohort glycemic targets are met. While the cohorts varied significantly in model-assessed insulin resistance, their variability was similar. Such significant intra- and inter- patient variability is a further significant cause and marker of glycemic variability in TGC. The results strongly recommended that TGC protocols be explicitly designed to account for significant intra- and inter- patient variability in insulin resistance, as well as specifying or having knowledge of carbohydrate administration to minimise variability in glycemic outcomes across diverse cohorts and/or centres.