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

Ravi Retnakaran (), Jiajie Pu, Alexandra Emery, Stewart B. Harris, Sonja M. Reichert, Hertzel C. Gerstein, Natalia McInnes, Caroline K. Kramer and Bernard Zinman
Additional contact information
Ravi Retnakaran: Leadership Sinai Centre for Diabetes, 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
Bernard Zinman: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: 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

Date: 2023
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DOI: 10.1038/s41467-023-40287-w

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