Related Experiment Videos
Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy
T Koschinsky1, C J He, T Mitsuhashi
1Diabetes Research Institute, auf Hennekamp 65, Dusseldorf, Germany.
Abstract:
Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum ( approximately 10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only approximately 30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis.
Insights
Dietary advanced glycation endproducts (AGEs) are absorbed and can be excreted by the kidneys. In diabetic kidney disease, AGE excretion is reduced, increasing risk for vascular and kidney injury.
Area of Science:
- Biochemistry
- Nephrology
- Endocrinology
Background:
- Advanced glycation endproducts (AGEs) are linked to vascular and renal complications in diabetes mellitus (DM).
- Kidney disease (KD) impairs the renal excretion of AGEs, both endogenous and exogenous.
- Dietary AGEs may contribute to the accumulation of harmful glycotoxins.
Purpose of the Study:
- To investigate the oral absorption and renal clearance of dietary AGEs in individuals with diabetes and kidney disease.
- To determine if circulating AGEs derived from the diet contain active glycotoxins.
Main Methods:
- A controlled dietary study involving a single meal of egg white cooked with or without fructose.
- Serum and urine samples were collected over 48 hours from diabetic (DM) and healthy (NL) subjects.
- AGEs were quantified using ELISA, and crosslinking activity was assessed using 125I-labeled fibronectin.
Main Results:
- Consuming the AGE-rich diet significantly increased serum AGE levels, proportional to intake.
- Serum AGE levels correlated with the severity of kidney disease.
- Renal excretion of absorbed AGEs was reduced in diabetic patients, especially those with renal failure, and inversely correlated with albuminuria.
Conclusions:
- Renal excretion of orally absorbed AGEs is significantly reduced in patients with diabetic nephropathy.
- Dietary AGEs, including active glycotoxins, represent a potential chronic risk factor for renal and vascular injury in diabetes.
- Restricting dietary AGE intake may mitigate the AGE burden and improve outcomes for diabetic patients.