INS and Hypoglycemia: These negative and inconclusive outcomes could be largely due to the studies having a significant increase in the risk of hypoglycemia (17–29 % <2.2 mmol/L), which is associated with increased mortality [21–23], and can be associated with large changes in patient response to insulin over short periods [13, 24, 25], particularly in the first 48 h [26], where many hypoglycemic events occur and there is a strong association with mortality [22].