The response to short‐term intensive insulin therapy in type 2 diabetes

TLDR

Short‑term intensive insulin therapy (IIT) improves beta‑cell function and glycaemic control in newly diagnosed type 2 diabetes, but its effect in patients with longer‑duration disease is unclear. The study aimed to assess the impact of short‑term IIT in patients with established type 2 diabetes. Thirty‑four patients (mean diabetes duration 5.9 ± 6.6 years) received 4–8 weeks of IIT and underwent a 4‑hour meal test at baseline and one day after therapy, with a positive response defined as fasting glucose < 7.0 mmol/L off all antidiabetic drugs, achieved by 68 % of participants. Responders exhibited lower post‑meal glucose and higher late‑phase C‑peptide secretion at baseline, and IIT markedly improved their beta‑cell function compared to non‑responders; baseline late‑phase insulin secretion predicted response, suggesting that preserved late‑phase secretion identifies patients likely to benefit from short‑term IIT.

Abstract

Although a short course of intensive insulin therapy (IIT) can improve beta-cell function and glycaemic control in most patients with newly diagnosed type 2 diabetes (T2DM), the impact of this intervention in diabetes of longer duration has not been carefully studied. Thus, we sought to evaluate the effect of short-term IIT in patients with established T2DM.Thirty-four patients, with diabetes of mean 5.9 +/- 6.6 years duration, underwent 4-8 weeks of IIT, with 4-h meal test administered at baseline and at 1 day post-IIT. A positive clinical response was defined as fasting glucose < 7.0 mmol/l off any antidiabetic therapy at the latter test.A positive response was achieved in 68% (n = 23) of the subjects. At baseline meal test, the responders had lower glucose levels than the non-responders from 120 to 240 min (all timepoints p < or = 0.0008) and higher late incremental area-under-the-C-peptide-curve (AUC(Cpep)), particularly from 60 to 150 min (all p < 0.005). Beta-cell function (ratio of AUC(Cpep) to AUC(gluc) divided by HOMA-IR) was similar between the groups at baseline (median 54.1 vs. 51.3, p = 0.62) but after IIT was significantly higher in the responders (109.3 vs. 57.4, p = 0.009). At baseline, the strongest predictors of the change in beta-cell function were glucose levels between 180 and 240 min (all r = -0.5, p = 0.005) and incremental AUC(Cpep) from 120 to 180 min (all r > or = 0.66, p < or = 0.0001), both reflecting late-phase insulin secretion.The clinical response to short-term IIT is variable, consistent with the heterogeneity of T2DM. However, preserved late-phase insulin secretion may identify those patients who can benefit from this intervention with improved beta-cell function.