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Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes

Author

Listed:
  • Ravi Retnakaran

    (Leadership Sinai Centre for Diabetes, Mount Sinai Hospital
    University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

  • Jiajie Pu

    (Leadership Sinai Centre for Diabetes, Mount Sinai Hospital)

  • Alexandra Emery

    (Leadership Sinai Centre for Diabetes, Mount Sinai Hospital)

  • Stewart B. Harris

    (Western University)

  • Sonja M. Reichert

    (Western University)

  • Hertzel C. Gerstein

    (McMaster University)

  • Natalia McInnes

    (McMaster University)

  • Caroline K. Kramer

    (Leadership Sinai Centre for Diabetes, Mount Sinai Hospital
    University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

  • Bernard Zinman

    (Leadership Sinai Centre for Diabetes, Mount Sinai Hospital
    University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

Abstract

In early type 2 diabetes, the strategy of “induction” with short-term intensive insulin therapy followed by “maintenance” with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this secondary analysis of ClinicalTrials.Gov NCT02192424, adults with ≤5-years diabetes duration were randomized to 3-weeks induction insulin therapy (glargine/lispro) followed by metformin maintenance either with or without intermittent 2-week courses of insulin every 3-months for 2-years. Sustained stabilization (higher beta-cell function at 2-years than at baseline) was achieved in 55 of 99 participants. Independent predictors of sustained stabilization were the change in beta-cell function during induction and changes in hepatic insulin resistance and alanine aminotransferase during maintenance. Thus, initial reversibility of beta-cell dysfunction during induction and subsequent preservation of hepatic insulin sensitivity during maintenance are associated with sustained stabilization of beta-cell function following short-term insulin and metformin. ClinicalTrials.Gov NCT02192424

Suggested Citation

  • Ravi Retnakaran & Jiajie Pu & Alexandra Emery & Stewart B. Harris & Sonja M. Reichert & Hertzel C. Gerstein & Natalia McInnes & Caroline K. Kramer & Bernard Zinman, 2023. "Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40287-w
    DOI: 10.1038/s41467-023-40287-w
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    References listed on IDEAS

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    1. Ravi Retnakaran & Chang Ye & Alexandra Emery & Caroline K. Kramer & Bernard Zinman, 2022. "The metabolic effects of adding exenatide to basal insulin therapy when targeting remission in early type 2 diabetes in a randomized clinical trial," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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