Establishment of Tacrolimus-Induced Diabetes in Rat Model and Assessment of Clinical Treatments for Post-Transplant Diabetes Mellitus in Liver Transplant Recipients

Clin Lab. 2013;59(7-8):869-74. doi: 10.7754/clin.lab.2012.120913.

Abstract

Background: To establish a tacrolimus-induced diabetes rat model and assess efficacy and safety of insulin glargine combined with repaglinide in Chinese patients with diabetes after liver transplantation.

Methods: Animal experiments and clinical trial were conducted. Animal experiments: Male SD rats were randomly divided into tacrolimus (4 mg/kg daily) and control group (saline). Rats were sacrificed after five months of treatment and blood was collected through heart puncture. Patients who underwent liver transplantation were selected and followed up regularly. If HbA1c was < 9%, repaglinide was administered; if HbA1c was > or = 9%, glargine plus repaglinide was administered.

Results: For rat model studies, in the tacrolimus group, fasting blood glucose (FBG) levels were increased after three months (p < 0.01). After five months, the insulin secretion index and the sensitivity index in the tacrolimus group was significantly lower than in the control group (p < 0.01). For studies of post-transplant diabetes mellitus (PTDM), eighty-six liver transplant recipients were enrolled. 51 were given repaglinide and 35 were given repaglinide combined with glargine. After treatment for 1, 6, and 12 months, FBG, post-prandial blood glucose (PPBG), and HbA1c levels decreased (p < 0.05) in both groups, and no statistically significant changes were observed in the liver and kidney function indicators (p > 0.05). No severe hypoglycemia episodes were reported.

Conclusions: Tacrolimus caused islet cell necrosis, reduced insulin secretion, increased insulin resistance, and increased blood glucose in the model. The blood glucose levels increased in a time-dependent manner. Combination of glargine and repaglinide was effective and safe for Chinese patients with post liver transplant diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus / etiology*
  • Immunosuppressive Agents / adverse effects*
  • Liver Transplantation / adverse effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tacrolimus / adverse effects*

Substances

  • Blood Glucose
  • Immunosuppressive Agents
  • Tacrolimus