SINGLE ORAL CHALLENGE BY ADVANCED GLYCATION END PRODUCTS ACUTELY IMPAIRS ENDOTHELIAL FUNCTION IN DIABETIC AND NONDIABETIC SUBJECTS

  1. Jaime Uribarri, MD (jaime.uribarri{at}mssm.edu)&,
  2. Alin Stirban, MD#,
  3. Denise Sander, MS†,
  4. Weijing Cai, MD*,
  5. Monica Negrean, MS#,
  6. Cristina E. Buenting, MS†,
  7. Theodore Koschinsky, MD† and
  8. Helen Vlassara, MD*
  1. *Division of Diabetes and Aging Research, The Brookdale Department of Geriatrics and
  2. &Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY.
  3. †German Diabetes Center at the Heinrich-Heine-University, Duesseldorf, Germany and
  4. #Heart and Diabetes Center NRW, Ruhr-University of Bochum, Bad Oeynhausen, Germany.

    Abstract

    Objective: The current study was designed to test the acute effects of dietary advanced glycation end products (AGEs) on endothelial function of diabetic and non-diabetic subjects.

    Research Design and Methods: Flow-mediated dilatation (FMD) of the brachial artery and serum levels of AGEs, plasminogen activator inhibitor (PAI-1), vascular cell adhesion molecule (VCAM-1) and glucose were assessed before and after a single oral AGE challenge (∼1.8x106 AGE U) in 44 diabetic and 10 non-diabetic subjects.

    Results: The diabetic patients had higher baseline levels of serum AGEs (p=0.020), PAI-1 (p=NS) and VCAM-1 (p=0.033) and lower baseline values of FMD compared with non-diabetic subjects (p=0.032). Ninety minutes after a single oral AGE challenge, serum AGEs and PAI-1 levels increased and FMD decreased significantly in both healthy (AGEs: 7.2±0.5 to 9.3±1 U/ml, p=0.014; PAI-1: 5.4±0.4 to 6.8±0.4 ng/ml, p=0.007; and FMD: 9.9±0.7 to 7.4±0.9 %, p=0.019) and diabetic subjects (AGEs: 10.5±0.7 to 14.2±1 U/ml, p=0.020; PAI-1: 6.5±1 to 10±2 ng/ml, p=0.030 and FMD: 5.4±0.4 to 4.0±0.3 %, p=0.032). Serum glucose and VCAM-1 levels remained unchanged.

    Conclusions: Significant increases in serum AGEs can occur together with altered clinical measures of endothelial dysfunction in diabetic and non-diabetic subjects following a single modest AGE-rich meal. Thus, repeated or chronic exposure to high AGE diets could over time lead to, and/or accelerate vascular disease.

    Footnotes

      • Received February 15, 2007.
      • Accepted April 29, 2007.

    This Article

    1. Published online before print May 11, 2007, doi: 10.2337/dc07-0320
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