Determinants of insulin secretion after renal transplantation.
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.
Hjelmesaeth
Jøran
J
Department of Medicine, Section of Nephrology, Rikshospitalet, University of Oslo, Oslo, Norway.
Jenssen
Trond
T
Hagen
Monica
M
Egeland
Thore
T
Hartmann
Anders
A
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000378:metabolism; D003920:Diabetes Mellitus / Q000209:etiology* / Q000378:metabolism*; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D015796:HLA-B27 Antigen; D007166:Immunosuppressive Agents; D007328:Insulin; D005665:Furosemide; D016572:Cyclosporine