Clinical predictors and time course of the improvement in β-cell function with short-term intensive insulin therapy in patients with Type 2 diabetes.

Abstract

In patients with Type2 diabetes, a short course of intensive insulin therapy can improve β-cell function and even induce transient remission of diabetes. However, not all patients respond to this therapy. Although the achievement of fasting glucose <7.0mmol/l oneday after stopping intensive insulin therapy can identify patients in whom β-cell function has improved, we sought to determine clinical predictors for the early identification of such responders and the time course of response. We pooled data from two studies in which 97 patients with Type2 diabetes mellitus (median 3years duration) and HbA1c 51±8.7mmol/mol (6.8±0.8%) underwent 4-8weeks of intensive insulin therapy, consisting of basal detemir and pre-meal insulin aspart. They were classified as responders (n=74) or non-responders (n=23), defined by the achievement of fasting glucose <7.0mmol/l after stopping intensive insulin therapy. On logistic regression analyses, duration of diabetes (odds ratio [OR]=0.72, 95% confidence interval [CI] 0.56-0.92, P=0.009) and baseline fasting glucose (OR=0.40, 95% CI 0.24-0.68, P=0.001) emerged as predictors of the likelihood of responding. Ninety percent of patients with duration≤4years and fasting glucose≤8.0mmol/l responded to intensive insulin therapy. Despite having lower glucose levels during intensive insulin therapy, responders had less hypoglycaemia than non-responders (median 0.3 vs. 1.6 episodes/week, P<0.0001), with rates of hypoglycaemia diverging sharply from the third week onwards. At baseline, shorter duration of diabetes and lower fasting glucose can identify patients most likely to benefit from short-term intensive insulin therapy. Most importantly, during therapy, responders had less hypoglycaemia from the third week onwards, despite lower glycaemia, suggesting that 2weeks of intensive insulin therapy may be needed to improve endogenous islet function.