Liver fat accumulation is associated with reduced hepatic insulin extraction and beta cell dysfunction in healthy older individuals

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• 作者：Francis M Finucane (23) (24)
  Stephen J Sharp (23)
  Mensud Hatunic (25)
  Alison Sleigh (26)
  Ema De Lucia Rolfe (23)
  Avan Aihie Sayer (27)
  Cyrus Cooper (27)
  Simon J Griffin (23)
  Nicholas J Wareham (23)
  
• 关键词：Adaptation index ; Beta cell dysfunction ; C ; peptide ; genic index ; Disposition index ; Hepatic insulin extraction ; Insulinogenic index ; Intrahepatic lipid ; Non ; alcoholic fatty liver disease
• 刊名：Diabetology and Metabolic Syndrome
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：6
• 期：1
• 全文大小：289 KB
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• 作者单位：Francis M Finucane (23) (24)
  Stephen J Sharp (23)
  Mensud Hatunic (25)
  Alison Sleigh (26)
  Ema De Lucia Rolfe (23)
  Avan Aihie Sayer (27)
  Cyrus Cooper (27)
  Simon J Griffin (23)
  Nicholas J Wareham (23)
  
  23. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Hospital, Box 285, Hills Road, Cambridge, CB20QQ, UK
  24. Galway Diabetes Research Centre, HRB Clinical Research Facility, School of Medicine, NUI Galway, Galway, Ireland
  25. Institute of Metabolic Science, University of Cambridge Metabolic Research Laboratories, Cambridge, CB20QQ, UK
  26. Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, CB20QQ, UK
  27. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO166YD, UK
  
• ISSN：1758-5996

文摘

Background There is a well-established association between type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of intrahepatic lipid (IHL), but the mechanistic basis for this association is unclear. Emerging evidence suggests that in addition to being associated with insulin resistance, NAFLD may be associated with relative beta-cell dysfunction. We sought to determine the influence of liver fat on hepatic insulin extraction and indices of beta-cell function in a cohort of apparently healthy older white adults. Methods We performed a cross-sectional analysis of 70 healthy participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3?±-.4?years) who underwent oral glucose tolerance testing with glucose, insulin and C-Peptide levels measured every 30?minutes over two hours. The areas under the concentration curve for glucose, insulin and C-Peptide were used to quantify hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral fat was quantified with magnetic resonance (MR) imaging and IHL with MR spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin Sensitivity (OGIS) model. Results 29 of 70 participants (41%) exceeded our arbitrary threshold for NAFLD, i.e. IHL >5.5%. Compared to those with normal IHL, those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age, HbA1c and alanine aminotransferase (ALT) levels were similar in both groups. Insulin and C-Peptide excursions after oral glucose loading were higher in the NAFLD group, but the CGI and AI were significantly lower, indicating a relative defect in beta-cell function that is only apparent when C-Peptide is measured and when dynamic changes in glucose levels and also insulin sensitivity are taken into account. There was no difference in IGI or DI between the groups. Conclusions Although increased IHL was associated with greater insulin secretion, modelled parameters suggested relative beta-cell dysfunction with NAFLD in apparently healthy older adults, which may be obscured by reduced hepatic insulin extraction. Further studies quantifying pancreatic fat content directly and its influence on beta cell function are warranted. Trial registration ISRCTN60986572