A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation

PLoS One. 2018 Mar 8;13(3):e0193569. doi: 10.1371/journal.pone.0193569. eCollection 2018.

Abstract

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

Publication types

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

MeSH terms

  • Algorithms*
  • Biomarkers / blood
  • Drug Administration Schedule
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / drug therapy*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Injections, Subcutaneous
  • Insulin Infusion Systems*
  • Insulin Lispro / administration & dosage*
  • Insulin Lispro / adverse effects
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Postoperative Period
  • Treatment Outcome

Substances

  • Biomarkers
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Lispro
  • hemoglobin A1c protein, human

Grants and funding

This work was supported by the Austrian Diabetes Association (ÖDG). The funder provided support in the form of an unrestricted grant for author M.H., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contribution’ section. This work was also supported by Astellas Pharma Europe. The funder provided support in the form of an unrestricted grant for author M.S., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contribution’ section. Lilly Österreich (Austria) provided support in the form of study medication (insulin) but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Medtronic Europe, Germany, provided support in the form of insulin pumps and consumables for these pumps as well as technical support by the author A.T., who is Medtronic employee, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contribution’ section.