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

    Research output: Contribution to journalArticle

    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 - Jan 1 2000

    Fingerprint

    Proinsulin
    Hyperglycemia
    Type 2 Diabetes Mellitus
    C-Peptide
    Fasting
    Therapeutics
    Multivariate Analysis
    Glucose
    Hypoglycemic Agents
    Healthy Volunteers
    Diet

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

    Cite this

    Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. / Inoguchi, Toyoshi; Umeda, Fumio; Kakimoto, Maiko; Sako, Yasuhiro; Ishii, Hidehiro; Noda, Katsumi; Kunisaki, Makoto; Imamura, Minako; Yu, Hai Yan; Etoh, Takashi; Yoshikawa, Hiroyasu; Aoki, Tsuyoshi; Hashimoto, Toshihiko; Nawata, Hajime.

    In: Endocrine Journal, Vol. 47, No. 6, 01.01.2000, p. 763-770.

    Research output: Contribution to journalArticle

    Inoguchi, T, Umeda, F, Kakimoto, M, Sako, Y, Ishii, H, Noda, K, Kunisaki, M, Imamura, M, Yu, HY, Etoh, T, Yoshikawa, H, Aoki, T, Hashimoto, T & Nawata, H 2000, 'Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes', Endocrine Journal, vol. 47, no. 6, pp. 763-770. https://doi.org/10.1507/endocrj.47.763
    Inoguchi, Toyoshi ; Umeda, Fumio ; Kakimoto, Maiko ; Sako, Yasuhiro ; Ishii, Hidehiro ; Noda, Katsumi ; Kunisaki, Makoto ; Imamura, Minako ; Yu, Hai Yan ; Etoh, Takashi ; Yoshikawa, Hiroyasu ; Aoki, Tsuyoshi ; Hashimoto, Toshihiko ; Nawata, Hajime. / Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes. In: Endocrine Journal. 2000 ; Vol. 47, No. 6. pp. 763-770.
    @article{52ef495247734adf8d148cd24c0535b8,
    title = "Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes",
    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.",
    author = "Toyoshi Inoguchi and Fumio Umeda and Maiko Kakimoto and Yasuhiro Sako and Hidehiro Ishii and Katsumi Noda and Makoto Kunisaki and Minako Imamura and Yu, {Hai Yan} and Takashi Etoh and Hiroyasu Yoshikawa and Tsuyoshi Aoki and Toshihiko Hashimoto and Hajime Nawata",
    year = "2000",
    month = "1",
    day = "1",
    doi = "10.1507/endocrj.47.763",
    language = "English",
    volume = "47",
    pages = "763--770",
    journal = "Endocrine Journal",
    issn = "0918-8959",
    publisher = "Japan Endocrine Society",
    number = "6",

    }

    TY - JOUR

    T1 - Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes

    AU - Inoguchi, Toyoshi

    AU - Umeda, Fumio

    AU - Kakimoto, Maiko

    AU - Sako, Yasuhiro

    AU - Ishii, Hidehiro

    AU - Noda, Katsumi

    AU - Kunisaki, Makoto

    AU - Imamura, Minako

    AU - Yu, Hai Yan

    AU - Etoh, Takashi

    AU - Yoshikawa, Hiroyasu

    AU - Aoki, Tsuyoshi

    AU - Hashimoto, Toshihiko

    AU - Nawata, Hajime

    PY - 2000/1/1

    Y1 - 2000/1/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=0034509382&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034509382&partnerID=8YFLogxK

    U2 - 10.1507/endocrj.47.763

    DO - 10.1507/endocrj.47.763

    M3 - Article

    C2 - 11228051

    AN - SCOPUS:0034509382

    VL - 47

    SP - 763

    EP - 770

    JO - Endocrine Journal

    JF - Endocrine Journal

    SN - 0918-8959

    IS - 6

    ER -