Prevention of Diabetic Nephropathy in Mice by a Diet Low in Glycoxidation Products

Diabetes Metab Res Rev. May-Jun 2002;18(3):224-37. doi: 10.1002/dmrr.283.

Abstract

Background: Reactive advanced glycation end products (AGEs), known to promote diabetic tissue damage, occur endogenously as well as in heated foods and are orally absorbed. The relative contribution of diet-derived AGEs to diabetic nephropathy (DN) remains unclear.

Methods: We tested a standard mouse food (AIN-93G) found to be rich in AGEs (H-AGE diet) in parallel with a similar diet that contained six-fold lower AGE content (L-AGE), but equal calories, macronutrients, and micronutrients. Non-obese diabetic mice (NOD) with type 1 diabetes (T1D) and db/db mice with type 2 diabetes (T2D) were randomly assigned to each formula for either 4 or 11 months, during which time renal parameters and AGE levels were assessed.

Results: Compared to the progressive DN and short survival seen in NOD mice exposed to long-term H-AGE feeding, L-AGE-fed NOD mice developed minimal glomerular pathology and a modest increase in urinary albumin:creatinine ratio (p<0.005), and a significantly extended survival (p<0.0001), consistent with lower serum (p<0.025) and kidney AGEs (p<0.01). Also, in the 4-month study, and in contrast to the H-AGE-fed mice, L-AGE-fed NOD and db/db mice exhibited low levels of renal cortex TGF beta-1 (p<0.05), laminin B1 mRNA (p<0.01) and alpha 1 IV collagen mRNA (p<0.05) and protein, in concert with reduced serum and kidney AGEs (p<0.05, respectively).

Conclusion: Intake of high-level, food-derived AGEs is a major contributor to DN in T1D and T2D mice. Avoidance of dietary AGEs provides sustained protection against DN in mice; providing the rationale for similar studies in human diabetic patients.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albuminuria
  • Animals
  • Diabetes Mellitus, Type 1 / diet therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Nephropathies / prevention & control*
  • Diet, Diabetic*
  • Dietary Carbohydrates / administration & dosage*
  • Disease Models, Animal
  • Glycation End Products, Advanced / administration & dosage*
  • Glycation End Products, Advanced / blood
  • Glycation End Products, Advanced / urine
  • Kidney / pathology
  • Kidney Glomerulus / pathology*
  • Mice
  • Mice, Inbred NOD
  • Polymerase Chain Reaction

Substances

  • Dietary Carbohydrates
  • Glycation End Products, Advanced