Short-term treatment with insulin can induce remission of type 2 diabetes (T2DM) in some patients but not others. We thus sought to identify baseline predictors of diabetes remission in response to short-term insulin-based therapy. In this study, adult patients with T2DM of <7 years duration were randomized to 8-weeks treatment with (i) insulin glargine, (ii) glargine + thrice-daily lispro, or (iii) glargine + twice-daily exenatide, followed by 12-weeks washout that enabled assessment of remission (defined as A1c<6.5% after ≥3 months without glucose-lowering therapy). At baseline, 8-weeks, and washout, beta-cell function was assessed with 4 measures: Insulin Secretion-Sensitivity Index-2 (ISSI-2), insulinogenic index/HOMA-IR, ΔCpeptide0-120/Δglucose0-120×Matsuda, and ΔISR0-120/Δgluc0-120×Matsuda. Diabetes remission was achieved in 31 of 90 participants (34.4%). Compared to their peers, those who went on to remission had lower A1c (p<0.001) and better beta-cell function at baseline (all 4 measures p≤0.01). The non-remission and remission groups did not otherwise differ in baseline insulin sensitivity/resistance (Matsuda, HOMA-IR), BMI, duration of diabetes, pre-trial 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 ΔCpeptide0-120/Δglucose0-120×Matsuda: 1.62 (1.00-2.64); log ΔISR0-120/Δgluc0-120×Matsuda: 1.87 (1.09-3.23). Similarly, higher baseline ISSI-2 tertile predicted longer time to glycemic relapse after cessation of the insulin-based therapy (log-rank P=0.029). In conclusion, beta-cell function is the dominant baseline determinant of the likelihood of achieving remission of diabetes in response to short-term insulin-based therapy.

Disclosure

R.Retnakaran: Other Relationship; Sanofi, Eli Lilly and Company, Research Support; Boehringer Ingelheim/Mount Sinai Hospital, Novo Nordisk. J.Pu: None. A.Emery: None. C.K.Kramer: Research Support; Boehringer Ingelheim Inc. B.Zinman: Consultant; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk A/S, Novo Nordisk Canada Inc., Boehringer Ingelheim Inc., Merck & Co., Inc.

Funding

Canadian Institutes of Health Research (MOP136938)

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