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

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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.

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Acknowledgments

S.C. contributed to study design, researched data, contributed to discussion, and wrote the manuscript. R.S. researched data, contributed to discussion, and reviewed and edited the manuscript. A.D.P. contributed to study design, researched data, contributed to discussion, and reviewed and edited the manuscript. F.K.K., S.P. and A.M.R. contributed to study design and discussion, and reviewed and edited the manuscript. F.P. designed the study, researched data, contributed to discussion, and reviewed and edited the manuscript. F.P. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version. This study was supported by the Department of Clinical and Molecular Biomedicine, University of Catania. S.C. is a Novo Nordisk employee now in the Pharmaceutical Medicine Programme.

Conflict of interest

Salvatore Calanna, Roberto Scicali, Antonino Di Pino, Filip Krag Knop, Salvatore Piro, Agata Maria Rabuazzo and Francesco Purrello declare they have no conflict of interest.

Human and Animal Rights disclosure

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent disclosure

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy

    Salvatore Calanna, Roberto Scicali, Antonino Di Pino, Salvatore Piro, Agata Maria Rabuazzo & Francesco Purrello

  2. Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

    Filip Krag Knop

  3. Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Filip Krag Knop

Authors
  1. Salvatore Calanna
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  2. Roberto Scicali
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  3. Antonino Di Pino
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  4. Filip Krag Knop
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  5. Salvatore Piro
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  6. Agata Maria Rabuazzo
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  7. Francesco Purrello
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Corresponding author

Correspondence to Francesco Purrello.

Additional information

Communicated by Antonio Secchi.

Salvatore Calanna and Roberto Scicali have contributed equally to this work.

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Calanna, S., Scicali, R., Di Pino, A. et al. Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes. Acta Diabetol 51, 567–575 (2014). https://doi.org/10.1007/s00592-014-0555-5

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  • DOI: https://doi.org/10.1007/s00592-014-0555-5

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