title: Age-related increase in haemoglobin A1c and fasting plasma glucose is accompanied by a decrease in beta cell function without change in insulin sensitivity: evidence from a cross-sectional study of hospital personnel.
abstract: OBJECTIVE
  To examine the influence of age on glucose homeostasis in a population of healthy, non-diabetic hospital personnel.
  
  
  METHODS
  One hundred and twenty female and 71 male non-diabetic individuals (fasting plasma glucose < 7.0 mmol/l) were fasted overnight prior to blood sampling. Glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and fasting plasma insulin (FPI) were measured using a BioRad Diamat automated HPLC, a Hitachi 747 analyser and a sensitive in-house radioimmunoassay, respectively. Mathematical modelling of the fasting glucose and insulin pairs (homeostasis model assessment (HOMA)) generated indices of pancreatic beta cell function, HOMA-B and tissue insulin sensitivity HOMA-S.
  
  
  RESULTS
  Spearman rank correlation analysis showed that in the whole group there was a significant negative correlation between age and HOMA-B (rs = -0.218, P = 0.0022) and a significant positive correlation between age and both HbA1c (rs = 0.307, P = 0.0001) and FPG (rs = 0.26, P = 0.0003). There was no correlation between age and either FPI (rs = -0.08, P = 0.266) or HOMA-S (rs = 0.024, P = 0.75). Analysis by gender showed the above associations to be present in the females (rs = -0.243, P = 0.0076; rs = 0.304, P = 0.0007; rs = 0.32, P = 0.0004 for age vs. HOMA-B, HbA1c, and FPG, respectively). Again there was no correlation of age with FPI or insulin sensitivity. In the males there was a significant correlation of HbA1c with age (rs = 0.35, P = 0.002), but no significant correlation of age with any of the other parameters.
  
  
  CONCLUSIONS
  Glycaemic control deteriorates with age in healthy, non-diabetic individuals. Age-related rises in FPG and haemoglobin A1c result from a small but steady decline in pancreatic beta cell function.
authors.affiliation: Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester, UK. apyates@central.cmht.nwest.nhs.uk
authors.forename: A P
authors.initials: AP
authors.lastname: Yates
authors.forename: I
authors.initials: I
authors.lastname: Laing
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000254:growth & development / Q000502:physiology*; D008297:Male; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin