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

Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin
  • Insulin Resistance*
  • Metformin* / therapeutic use

Substances

  • Insulin
  • Hypoglycemic Agents
  • Glycated Hemoglobin
  • Metformin
  • Blood Glucose

Associated data

  • ClinicalTrials.gov/NCT02192424

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