Exp Clin Endocrinol Diabetes 2001; 109(8): 397-401
DOI: 10.1055/s-2001-18992

© Johann Ambrosius Barth

Modified hyperinsulinaemic, eu- and hypoglycaemic clamp technique using lispro-insulin for insulinoma diagnostic

N. Roudovitch 1 , M. A. Nauck 2 , H. Schatz 3 , A. F. H. Pfeiffer 1
  • 1 Division of Endocrinology Department of Medicine, Clinic B. Franklin, Free University of Berlin, Germany and
  • Department for Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Germany
  • 2 Diabetes-Centre Bad Lauterberg, Bad Lauterberg, Germany
  • 3 Division of Endocrinology, Department of Internal Medicine, Clinic Bergmannsheil, Ruhr-University, Bochum, Germany
Further Information

Publication History

Publication Date:
13 December 2001 (online)


Characterization of metabolically inadequate insulin secretion is essential for insulinoma diagnostics. Hyperinsulinaemic, eu- and hypoglycaemic clamp procedures have been used to suppress endogenous insulin secretion in healthy subjects. The use of exogenous insulin precluded the use of insulin as a parameter to be measured. We now suggest to use exogenous insulin lispro and an insulin-specific ELISA not cross reacting with insulin lispro. Thus, determination of insulin by ELISA in this experimental setting reflects endogenous insulin. A 39-year-old man with a surgically confirmed pancreatic insulinoma was studied under hyperinsulinaemic [lispro insulin 40 mU · m-2 body surface ·min-1] clamp conditions. Euglycaemia was achieved (3.8 ± 0.5 mmol/L) for 1 h and hypoglycaemia (2.36 ± 0.49 mmol/L) was achieved for another 30 min. Insulin was evaluated by ELISA (cross-reaction with lispro insulin < 0.006%, C-peptide < 0.01%, proinsulin < 0.001%) and by a nonselective RIA (cross-reaction with proinsulin 40%). In control subjects the euglycaemic hyperinsulinaemia suppressed C-peptide to 0.36 ± 0.03 ng/ml and hypoglycaemic hyperinsulinaemia to 0.29 ± 0.03 ng/ml. Endogenous insulin was suppressed to 2.8 ± 0.03 mU/L under euglycaemia and to 2.6 ± 0.03 mU/L under hypoglycaemia in control subjects. In the insulinoma patient apparently irregular but small changes in both C-peptide (1.43 ± 0.1 ng/ml) and more pronounced changes in endogenous insulin concentrations 4.41 ± 0.1 mU/l under euglycaemia and 5.35 ± 0.3 mU/l under hypoglycaemic conditions, were observed. The basal level of insulin (ELISA insulin 4.6 mU/L) and C-peptide (1.7 ng/ml) were not markedly elevated. Determination of insulin allowed better characterization of irregular pulses because of the shorter half-life of insulin relative to C-peptide. The new modification of sequential eu- and hypoglycaemic clamp procedures should also be useful in pharmacological studies of insulinotropic substances. Direct measurement of peripheral insulin may be more sensitive than C-peptide to detect low levels of autonomous insulin secretion in small insulinomas.


Prof. Dr. A. F. H. Pfeiffer

Universitätsklinikum Benjamin Franklin

Abteilung Ernährungsmedizin, Endokrinologie und Stoffwechsel

Hindenburgdamm 30

D-12200 Berlin


Phone: + 49-30-8445 2114

Fax: + 49-30-8445 4204

Email: pfeifa@medizin.fu-berlin.de

Deutsches Institut für Ernährungsforschung

Abteilung Klinische Ernährung

Arthur-Scheunert-Allee 114-116

D-14558 Bergholz-Rehbrücke


Phone: + 49-33-2008 8505

Fax: + 49-33-2008 8555

Email: afhp@www.dife.de