Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE
    • Publication Information:
      Publication: Berlin : Springer Verlag
      Original Publication: Berlin : Springer International, c1991-
    • Subject Terms:
      Diabetes Mellitus, Type 2/*blood ; Glucagon-Secreting Cells/*metabolism ; Glycated Hemoglobin/*metabolism ; Insulin-Secreting Cells/*metabolism ; Prediabetic State/*blood; Blood Glucose/metabolism ; C-Peptide/blood ; Diabetes Mellitus, Type 2/diagnosis ; Female ; Glucagon/blood ; Humans ; Incretins/blood ; Insulin/blood ; Male ; Middle Aged ; Prediabetic State/diagnosis
    • Abstract:
      New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten subjects with HbA1c-defined prediabetes, i.e. HbA1c from 5.7 to 6.4 % (39-46 mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes [HbA1c ≥6.5 % (≥48 mmol/mol)], and ten controls with HbA1c lower than 5.7 % (<39 mmol/mol), were studied. Blood was sampled over 4 h on two separate days after a 75 g-oral glucose tolerance test and an isoglycaemic intravenous glucose infusion, respectively. Blood was analysed for glucose, insulin, C-peptide, glucagon, and incretin hormones. Insulinogenic index, disposition index, glucagon suppression, and incretin effect were evaluated. Subjects with HbA1c-defined prediabetes showed significantly lower insulinogenic index (P = 0.02), disposition index (P = 0.001), and glucagon suppression compared with controls; and similar (P = NS) insulinogenic index and glucagon suppression and higher disposition index (P = 0.02) compared to HbA1c-diagnosed type 2 diabetic patients. The patients with type 2 diabetes showed lower insulinogenic index (P = 0.0003), disposition index (P < 0.0001), and glucagon suppression compared with the controls. The incretin effect was significantly (P < 0.05) reduced in patients with HbA1c-defined type 2 diabetes compared to subjects with HbA1c-defined prediabetes and controls. Plasma levels of incretin hormones were similar across the three groups. HbA1c associated negatively with insulinogenic index, disposition index, and incretin effect. Our findings show clear alpha- and beta-cell dysfunction in HbA1c-defined type 2 diabetes compatible with the previously described pathophysiology of plasma glucose-defined type 2 diabetes. Furthermore, in HbA1c-defined prediabetes, we show defective insulin response in combination with inappropriate suppression of glucagon, which may constitute new targets for pharmacological interventions.
    • Accession Number:
      0 (Blood Glucose)
      0 (C-Peptide)
      0 (Glycated Hemoglobin A)
      0 (Incretins)
      0 (Insulin)
      9007-92-5 (Glucagon)
    • Publication Date:
      Date Created: 20140121 Date Completed: 20150420 Latest Revision: 20221207
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00592-014-0555-5
    • Accession Number:
      24442427