Baseline determinants of remission of type 2 diabetes in response to short-term insulin-based therapy: The pivotal role of beta-cell function

Aim: To identify baseline determinants of diabetes remission in response to short-term insulin-based therapy. Methods: In this study, adult patients with type 2 diabetes (T2D) of less than 7 years duration were randomized to 8 weeks of treatment with (a) insulin glargine, (b) glargine + thrice-daily lispro, or (c) glargine + twice-daily exenatide, followed by 12 weeks of washout that enabled assessment of remission (defined as HbA1c < 6.5% after >= 3 months without glucose-lowering therapy). At baseline, 8 weeks and washout, betacell function was assessed with four measures: Insulin Secretion-Sensitivity Index-2 (ISSI-2), insulinogenic index/Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Delta C-peptide(0-120)/Delta glucose(0-120) x Matsuda and Delta insulin secretion rate (ISR)(0-120)/Delta gluc(0-120) x Matsuda. Results: Diabetes remission was achieved in 31 of 90 participants (34.4%). Compared with their peers, those who went on to remission had lower HbA1c (P <.001) and better beta-cell function at baseline (all four measures P <=.01). The non-remission and remission groups did not otherwise differ in baseline insulin sensitivity/resistance (Matsuda, HOMA-IR), body mass index, duration of diabetes, pretrial diabetes medications or allocated insulin-based therapy during the trial. On logistic regression analyses, each baseline measure of beta-cell function emerged as a significant predictor of remission (log ISSI-2: adjusted OR 4.41 [95% CI: 1.71-11.34]; log insulinogenic index/HOMA-IR: 2.21 [1.26-3.89]; log Delta C-peptide(0-120)/Delta glucose(0-120) x Matsuda: 1.62 [1.00-2.64]; log Delta ISR0-120/Delta gluc(0-120) x Matsuda: 1.87 [1.09-3.23]). Similarly, higher baseline ISSI-2 tertile predicted longer time to glycaemic relapse after cessation of the insulin-based therapy (log-rank P =.029). Conclusion: Beta-cell function is the dominant baseline pathophysiological determinant of the likelihood of achieving remission of diabetes in response to short-term insulin-based therapy.

Automated summary

The aim of this study was to identify baseline determinants of diabetes remission in response to short-term insulin-based therapy. The study found that beta-cell function plays a dominant role in achieving remission of diabetes.