Intensive Insulin Therapy for Type 2 Diabetes

Early intervention, particularly within the first two years after diagnosis of type 2 diabetes mellitus (T2DM), is the key factor in inducing sustained drug-free diabetes remission with short-term intensive insulin therapy (ITT), according to a new study.

In early T2DM, short-term IIT for 2–4 weeks has been shown to decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to one year in some patients, state researchers led by Caroline K. Kramer of Mount Sinai Hospital, Toronto, Ontario, Canada.

“There is a need for identification of the predictors of a sustained positive response to identify those patients who are most likely to benefit from this therapy, and serial assessment of metabolic function in the months after stopping IIT may provide relevant mechanistic insight,” they state.

Previously, lower baseline fasting glucose, higher body mass index (BMI), better early-phase insulin secretion, and lower exogenous insulin requirements have been suggested as possible predictors of diabetes remission in newly diagnosed patients treated with short-term IIT.

The Canadian researchers evaluated data from the placebo arm of a double-blind, randomized controlled trial of 25 patients with early T2DM with less than 7 years duration. The patients had 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks. They had an oral glucose tolerance test every 12 weeks, which enabled a serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as hemoglobin A1c of less than 6.5% on no medication.

The results show that at 48 weeks post-IIT, more than half (56%) of the participants remained in remission. There were no differences in waist, BMI, insulin sensitivity, or glucagon profile, either at baseline or over 48 weeks, between those who achieved remission and those who did not. The remission group had lower baseline A1c and better baseline β-cell function that was then sustained across 48 weeks post-IIT as compared to the non-remission group.

A regression analysis found that shorter duration of diabetes supplanted baseline A1c and β-cell function as an independent predictor of remission. “In particular, diabetes duration of less than 2 years predicted persistence of remission,” they state.

The first 12 weeks after stopping IIT is “a critical window during which those destined not to achieve sustained remission may experience a loss of the beneficial effects on insulin sensitivity, glucagon regulation, and β-cell function that were seen immediately post-IIT,” they state.

The researchers also note that short-term IIT improves insulin sensitivity and glucagonemia, but the effects do not differ from remitters and non-remitters over 48 weeks. Also, those who attain sustained drug-free remission have better β-cell function at baseline that is preserved over 48 weeks, whereas non-remitters have post-IIT deterioration of endogenous insulin secretion over time.

Taken together with sustained remission is early intervention, “these data suggest that, early in the course of type 2 DM, there may be sufficient reversibility in the disease process to stabilize progressive β-cell deterioration and induce sustained drug-free remission with short-term IIT,” they state.

Reference: Kramer CK, et al. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes. BMJ Open Diabetes Res Care. 2016 Aug 1;4(1):e000270.