title: Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys.
abstract: BACKGROUND
  Rhesus monkeys have a high prevalence of obesity and spontaneous type 2 diabetes mellitus after the age of 10 years. These monkeys go through a defined, sequential set of metabolic phases, including fasting hyperinsulinemia, impaired glucose tolerance, and fasting hyperglycemia. Using these monkeys, we addressed the hypothesis that renal structural features characteristic of diabetic nephropathy might precede the appearance of overt diabetes.
  
  
  METHODS
  We carried out a quantitative analysis of renal tissue, using light microscopy and electron microscopy, from 6 metabolically normal young monkeys, 7 metabolically normal aged monkeys, 7 hyperinsulinemic monkeys, and 18 diabetic monkeys.
  
  
  RESULTS
  Glomerular volume was increased significantly in hyperinsulinemic monkeys and diabetic monkeys compared with aged normal monkeys. In the normal monkey, glomerular basement membrane (GBM) width rises with age but reaches a plateau at about 20 years of age; the presence of diabetes was associated with markedly increased GBM width. Glomerular tuft volume and GBM width were correlated most closely with age and with glucose tolerance.
  
  
  CONCLUSIONS
  Diabetic monkey kidneys are characterized by glomerular enlargement, glomerulosclerosis, and thickening of the GBM. Glomerular hypertrophy begins in the prediabetic hyperinsulinemic phase. This finding suggests that early intervention may be required in human patients to preserve normal glomerular structure.
authors.affiliation: CEMIC, Section of Nephrology, and Department of Pathology, Center of Medical Education and Clinical Investigation, Buenos Aires, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cusumano
authors.forename: Noni L
authors.initials: NL
authors.lastname: Bodkin
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Hansen
authors.forename: Roberto
authors.initials: R
authors.lastname: Iotti
authors.forename: Jennie
authors.initials: J
authors.lastname: Owens
authors.forename: Paul E
authors.initials: PE
authors.lastname: Klotman
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D021461:Animals, Outbred Strains; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D003928:Diabetic Nephropathies / Q000473:pathology; D005260:Female; D006946:Hyperinsulinism / Q000150:complications* / Q000473:pathology; D006984:Hypertrophy / Q000150:complications / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D012044:Regression Analysis