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, Hai Yan Yu, Takashi Etoh, Hiroyasu Yoshikawa, Tsuyoshi Aoki, Toshihiko Hashimoto, Hajime Nawata

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    22 Citations (Scopus)

    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 HbA1c. 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.

    Original languageEnglish
    Pages (from-to)763-770
    Number of pages8
    JournalEndocrine Journal
    Volume47
    Issue number6
    DOIs
    Publication statusPublished - 2000

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

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