Improved Prandial Glucose Control With Lower Risk of Hypoglycemia With Nateglinide Than With Glibenclamide in Patients With Maturity-Onset Diabetes of the Young Type 3
- Tiinamaija Tuomi, MD, PHD12,
- Elina H. Honkanen, MD12,
- Bo Isomaa, MD23,
- Leena Sarelin, RN3 and
- Leif C. Groop, MD, PHD4
- 1Department of Medicine, Helsinki University Hospital, Helsinki, Finland
- 2Folkhälsan Genetic Institute, Folkhalsan Research Center and Research Program for Molecular Medicine, Helsinki University, Helsinki, Finland
- 3Folkhalsan Ostanlid and Malmska Municipal Health Care Center and Hospital, Jakobstad, Finland
- 4Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmö, Sweden
- Address correspondence and reprint requests to Tiinamaija Tuomi, Department of Medicine/Diabetology, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. E-mail: tiinamaija.tuomi{at}hus.fi
Abstract
OBJECTIVE—To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas.
RESEARCH DESIGN AND METHODS—We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug.
RESULTS—Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test.
CONCLUSIONS—A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.
Footnotes
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L.C.G. has been a paid consultant of and has received honoraria for serving on advisory boards for Aventis-Sanofi, Bristol-Myers Squibb, Kowa, and Roche.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted October 31, 2005.
- Received July 14, 2005.
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