Chronic Sulfonylurea Treatment and Hyperglycemia Aggravate Disproportionately Elevated Plasma Proinsulin Levels in Patients with Type 2 Diabetes

TOYOSHI INOGUCHI; FUMIO UMEDA; MAIKO KAKIMOTO; YASUHIRO SAKO; HIDEHIRO ISHII; KATSUMI NODA; MAKOTO KUNISAKI; MINAKO IMAMURA; HM-YAN YU; TAKASHI ETOH; HIROYASU YOSHIKAWA; TSUYOSHI AOKI; TOSHIHIKO HASHIMOTO; HAJIME NAWATA

doi:10.1507/endocrj.47.763

TOYOSHI INOGUCHI, FUMIO UMEDA, MAIKO KAKIMOTO, YASUHIRO SAKO, HIDEHIRO ISHII, KATSUMI NODA, MAKOTO KUNISAKI, MINAKO IMAMURA, HM-YAN YU, TAKASHI ETOH, HIROYASU YOSHIKAWA, TSUYOSHI AOKI, TOSHIHIKO HASHIMOTO, HAJIME NAWATA

Author information

TOYOSHI INOGUCHI
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
FUMIO UMEDA
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
MAIKO KAKIMOTO
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
YASUHIRO SAKO
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
HIDEHIRO ISHII
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
KATSUMI NODA
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
MAKOTO KUNISAKI
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
MINAKO IMAMURA
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
HM-YAN YU
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
TAKASHI ETOH
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
HIROYASU YOSHIKAWA
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
TSUYOSHI AOKI
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
TOSHIHIKO HASHIMOTO
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
HAJIME NAWATA
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University

Keywords: Proinsulin, Type 2 diabetes, Hyperglycemia, Sulfonylurea

JOURNAL FREE ACCESS

2000 Volume 47 Issue 6 Pages 763-770

DOI https://doi.org/10.1507/endocrj.47.763

Details

Abstract

It is established that disproportionately elevated plasma proinsulin levels occur in patients with Type 2 diabetes. In the present study, multivariate analysis was performed to determine what factors contributed to the disproportionately elevated plasma proinsulin levels in Japanese patients with Type 2 diabetes (n=276). Results from univariate analysis showed that both fasting proinsulin/C-peptide ratio and proinsulin/IRI ratio were approximately 2-fold higher in patients with Type 2 diabetes than those in healthy nondiabetic subjects (n=45). In patients with Type 2 diabetes, both proinsulin/C-peptide ratio and proinsulin/IRI ratio were significantly positively correlated with fasting plasma glucose level (FPG) and HbA_1c. Neither proinsulin/C-peptide ratio nor proinsulin/IRI ratio was significantly correlated with BMI. Sulfonylurea-treated subjects had a significant elevation in both proinsulin/C-peptide ratio and proinsulin/IRI ratio compared with diet-treated subjects, whereas nonsulfonylurea hypoglycemic agent-treated subjects did not. Multivariate analysis confirmed that sulfonylurea treatment and FPG were significant determinants of both fasting proinsulin/C-peptide ratio (P=0.006 and P=0.030, respectively) and proinsulin/IRI ratio (P=0.003 and P=0.016, respectively) in patients with Type 2 diabetes. These results imply that disproportionate hyperproinsulinemia may reflect an excessive overwork of β cells under chronic sulfonylurea treatment as well as hyperglycemia.

Corresponding author

Register with J-STAGE for free!