Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation

doi:10.2337/dc05-1247

Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation

A sign of impaired β-cell function?

¹Ludwig Boltzmann Institute of Metabolic Diseases and Nutrition, Vienna, Austria
²Department of Medical Genetics, Division of Genetic Epidemiology, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
³3rd Medical Department of Metabolic Diseases and Nephrology, Lainz Hospital, Vienna, Austria
⁴Department of Internal Medicine 3, Division of Endocrinology and Metabolism, Medical University Vienna, Vienna, Austria
⁵Metabolic Unit, Institute of Biomedical Engineering, Padova, Italy
⁶Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria

Address correspondence reprint requests to Marietta Stadler, MD, Lainz Hospital, 3rd Medical Department, Wolkersbergenstrasse 1, 1130 Vienna, Austria. E-mail: marietta.stadler{at}wienkav.at

Abstract

OBJECTIVE—In response to hyperglycemia, β-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all β-cell hormones.

RESEARCH DESIGN AND METHODS—Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, β-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 ± 1 kg/m², 47 ± 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 ± 1 kg/m², 50 ± 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 ± 1 kg/m², 47 ± 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT).

RESULTS—PKT patients had higher fasting amylin (19 ± 3 vs. control subjects: 7 ± 1 pmol/l) and insulin (20 ± 2 vs. control subjects: 10 ± 1 μU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9–31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin’s plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. β-Cell sensitivity to glucose was reduced in PKT patients (−64%, P < 0.009). Fasting plasma amylin was inversely associated with β-cell sensitivity to glucose (r = −0.543, P < 0.004).

CONCLUSIONS—After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post–glucose load plasma amylin, which appears to be linked to impaired β-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired β-cell function in type 1 diabetic patients after PKT.

Footnotes

M.S. and C.A. contributed equally to this work.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Accepted January 31, 2006.
- Received July 6, 2005.
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