Colestimide lowers plasma glucose levels and increases plasma glucagon-like PEPTIDE-1 (7-36) levels in patients with type 2 diabetes mellitus complicated by hypercholesterolemia.
BACKGROUND
Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia.


OBJECTIVE
To examine the mechanism by which colestimide decreases plasma glucose levels in the above patients.


METHODS
A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared.


RESULTS
Preprandial plasma glucose levels (baseline: 132 +/- 33 mg/dL vs. completion: 118 +/- 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 +/- 49 mg/dL vs. completion: 166 +/- 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 +/- 56 mg/dL vs. completion: 178 +/- 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels.


CONCLUSIONS
The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.
Suzuki
Tatsuya
T
Department of Functional Pathophysiology for Human Organs, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. t.suzuki@nms.ac.jp
Oba
Kenzo
K
Igari
Yoshimasa
Y
Matsumura
Noriaki
N
Watanabe
Kentaro
K
Futami-Suda
Shoko
S
Yasuoka
Hiroko
H
Ouchi
Motoshi
M
Suzuki
Kazunari
K
Kigawa
Yoshiaki
Y
Nakano
Hiroshi
H
D000837:Anion Exchange Resins; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D004811:Epichlorohydrin / Q000008:administration & dosage*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D012117:Resins, Synthetic / Q000008:administration & dosage*
D000837:Anion Exchange Resins; D001786:Blood Glucose; D007093:Imidazoles; D008055:Lipids; D012117:Resins, Synthetic; C417427:colestimide; D004811:Epichlorohydrin; D052216:Glucagon-Like Peptide 1