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

作者：Calanna Salvatore; Scicali Roberto; Di Pino Antonino; Knop Filip Krag; Piro Salvatore; Rabuazzo Agata Maria; Purrello Francesco^*

来源：ACTA DIABETOLOGICA, 2014, 51(4): 567-575.

DOI：10.1007/s00592-014-0555-5

• Glucagon
• Incretin effect
• Insulin secretion
• Prediabetes
• Type 2 diabetes

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 a parts per thousand yen6.5 % (a parts per thousand yen48 mmol/mol)], and ten controls with HbA1c lower than 5.7 % (%26lt; 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 %26lt; 0.0001), and glucagon suppression compared with the controls. The incretin effect was significantly (P %26lt; 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.

• 出版日期2014-8