The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study.
BACKGROUND
An elevated PI/I ratio is attributable to increased secretory demand on β-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT).


METHODS
MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride.


RESULTS
Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders.


CONCLUSIONS
Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired β-cell function from the viewpoint of the PI/I ratio.
UMIN000010467.
Division of Cardiovascular Medicine, Endocrinology and Metabolism, Department of Molecular Medicine and Therapeutics, Tottori University Faculty of Medicine, Yonago, Tottori, Japan. ohkura@med.tottori-u.ac.jp.
Tsuyoshi
T
Ohkura
Kazuoki
K
Inoue
Youhei
Y
Fujioka
Risa
R
Nakanishi
Hideki
H
Shiochi
Keisuke
K
Sumi
Naoya
N
Yamamoto
Kazuhiko
K
Matsuzawa
Shoichiro
S
Izawa
Hiroko
H
Ohkura
Masahiko
M
Kato
Kazuhiro
K
Yamamoto
Shin-ichi
S
Taniguchi
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D054833:Isoindoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D019518:Postprandial Period; D011384:Proinsulin / Q000097:blood*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D054833:Isoindoles; D013453:Sulfonylurea Compounds; D014280:Triglycerides; C057619:glimepiride; D011384:Proinsulin; C087255:mitiglinide