Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes

Miura, Junnosuke; Yamagishi, Sho-ichi; Uchigata, Yasuko; Takeuchi, Masayoshi; Yamamoto, Hiroshi; Makita, Zenji; Iwamoto, Yasuhiko

« Previous Next »Journal of Diabetes and Its Complications
Volume 17, Issue 1 , Pages 16-21, January 2003

Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes

Junnosuke Miura
- Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
- Corresponding author. Tel.: +81-3-3353-8111x27011; fax: +81-3-3358-1941
Sho-ichi Yamagishi
- Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume 830-0011, Japan
Yasuko Uchigata
- Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
Masayoshi Takeuchi
- Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University, 3 Ho Kanagawa-machi, Kanazawa 920-1148, Japan
Hiroshi Yamamoto
- Department of Biochemistry, Kanazawa University School of Medicine, 13-1, Takaramachi, Kanazawa 920-8640, Japan
Zenji Makita
- Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume 830-0011, Japan
Yasuhiko Iwamoto
- Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

Received 1 November 2001; received in revised form 5 March 2002; accepted 15 April 2002.

Abstract

We investigated whether serum levels of N-(carboxymethyl)lysine (CML), non-CML advanced glycation endproducts (AGEs), or pentosidine are associated with severity of diabetic microvascular complications in patients with Type 1 diabetes. Serum levels of CML, non-CML AGE, and pentosidine were measured by an enzyme-linked immunosorbent assay in 38 males and 47 females aged 31±8 years (mean±S.D.) with Type 1 diabetes for 18.7±7.0 years. There was a significant correlation between serum levels of CML or non-CML AGE and current HbA_1c level (P<.01 and P<.05, respectively). The serum levels of non-CML AGE, but not CML or pentosidine, were significantly increased as normal renal status advanced to microalbuminuria, clinical nephropathy, and hemodialysis (P<.0001) and were positively correlated with urinary albumin excretion (UAE) in patients with Type 1 diabetes (P<.0001). A significant elevation of serum non-CML AGE was found in association with the severity of diabetic retinopathy (P<.0001). We found in the present study that CML levels were also increased in the stage of simple retinopathy, the early stage of clinically evident retinopathy (P<.05). Serum levels of non-CML AGE were significantly associated with the severity of diabetic nephropathy and retinopathy, suggesting a role of non-CML AGE in the progression of microvascular complications in patients with Type 1 diabetes. Since serum levels of CML were significantly increased in patients with simple retinopathy, CML may participate in the initiation of diabetic retinopathy.

Keywords: Serum AGE, Type 1 diabetes, Diabetic nephropathy, Diabetic retinopathy