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

Abstract 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, beta‐cell function was assessed with four measures: Insulin Secretion‐Sensitivity Index‐2 (ISSI‐2), insulinogenic index/Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR), ΔC‐peptide 0‐120 /Δglucose 0‐120 × Matsuda and Δinsulin secretion rate (ISR) 0‐120 /Δgluc 0‐120 × 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 ΔC‐peptide 0‐120 /Δglucose 0‐120 × Matsuda: 1.62 [1.00‐2.64]; log ΔISR 0‐120 /Δgluc 0‐120 × 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.