Determinants of insulin secretion after renal transplantation

Metabolism. 2003 May;52(5):573-8. doi: 10.1053/meta.2003.50092.


The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associated with older age, family history of diabetes, immunosuppressive drugs, and antihypertensive therapy. However, the potential determinants of post-transplant beta-cell dysfunction are largely unknown. The objective of the present study was to address this issue in detail. A total of 167 previously nondiabetic renal transplant recipients underwent a 75-g oral glucose tolerance test (OGTT)10 weeks after transplantation. Serum glucose and insulin were measured at 0, 1, and 2 hours. Three insulin release indices (Secr(AUC), Secr(1.phase), and Secr(2.phase)) were calculated to assess the insulin secretory response as the dependent variable. To account for variations in insulin sensitivity (IS), beta-cell function was also estimated as the disposition index (DI); the product of the IS index (ISI(TX)) and Secr(1.phase). Increasing age was strongly and independently associated with a blunted insulin secretory response even after adjustment for IS (P =.001). An 80-year-old recipient had an approximately 50% lower insulin release than a 20-year-old individual, based on the linear regression model. Cytomegalovirus (CMV) disease and treatment with furosemide were both independently associated with beta-cell dysfunction (DI; P <.001 and P =.008). Patients treated with angiotensin-converting enzyme (ACE)-inhibitors had an enhanced absolute insulin release, but the DI was similar in both treated and untreated recipients. We conclude that older age is an important determinant of beta-cell dysfunction after renal transplantation. CMV disease and treatment with furosemide may also negatively influence pancreatic insulin release in renal transplant recipients.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use
  • Area Under Curve
  • Cyclosporine / blood
  • Cytomegalovirus Infections / metabolism
  • Diabetes Mellitus / etiology*
  • Diabetes Mellitus / metabolism*
  • Diuretics / therapeutic use
  • Female
  • Furosemide / therapeutic use
  • Glucose Tolerance Test
  • HLA-B27 Antigen / genetics
  • Humans
  • Immunosuppressive Agents / blood
  • Insulin / metabolism*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications / metabolism*
  • Regression Analysis
  • Risk Factors


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Diuretics
  • HLA-B27 Antigen
  • Immunosuppressive Agents
  • Insulin
  • Furosemide
  • Cyclosporine