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

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• 作者：Salvatore Calanna (1)
  Roberto Scicali (1)
  Antonino Di Pino (1)
  Filip Krag Knop (2) (3)
  Salvatore Piro (1)
  Agata Maria Rabuazzo (1)
  Francesco Purrello (1)
  
• 关键词：Glucagon ; Incretin effect ; Insulin secretion ; Prediabetes ; Type 2 diabetes
• 刊名：Acta Diabetologica
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：51
• 期：4
• 页码：567-575
• 全文大小：530 KB
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• 作者单位：Salvatore Calanna (1)
  Roberto Scicali (1)
  Antonino Di Pino (1)
  Filip Krag Knop (2) (3)
  Salvatore Piro (1)
  Agata Maria Rabuazzo (1)
  Francesco Purrello (1)
  
  1. Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy
  2. Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
  3. Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  
• ISSN：1432-5233

文摘

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?% (39-6?mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes [HbA1c??.5?% (?8?mmol/mol)], and ten controls with HbA1c lower than 5.7?% (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?P?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.