Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products.
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).


CONCLUSIONS
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.
Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Feng
F
Zheng
Cijiang
C
He
Weijing
W
Cai
Masakazu
M
Hattori
Michael
M
Steffes
Helen
H
Vlassara
D000419:Albuminuria; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D003927:Diet, Diabetic; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016133:Polymerase Chain Reaction
D004040:Dietary Carbohydrates; D017127:Glycation End Products, Advanced