제2형 당뇨병 환자에서 최종당화산물과 heme oxygenase-1의 상관성

Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress. 본 연구는 한국에서 최초로 시행되는 연구로서, 성인 제2형 당뇨환자에서 혈청 AGEs의 농도에 따라 두 군으로 나눈 뒤 신체계측 및 체조성, 영양소 섭취량, 생화학적 지표를 비교 분석한 연구이다. Low AGEs group과 High AGEs group의 평균 AGEs는 각각 0.4 ± 0.2, 3.4 ± 1.7 ng/mL로 나타났다. 항산화 효소인 HO-1은 High AGEs group이 Low AGEs group에 비해 유의적으로 높게 나타났다. 또한, 전체 연구참여자를 대상으로 연령과 성별을 보정한 후 상관관계를 분석한 결과, 혈청 HO-1 농도와 혈청 AGEs 농도 및 소변 8-OHdG 농도는 양의 상관관계를 가지는 것으로 나타났다. 본 연구를 통해 혈청 HO-1은 당뇨환자 특이적 지표인 AGEs와 더불어 DNA 손상 지표에도 예민하게 반응하는 것을 확인하였으며, 추후 한국 당뇨환자의 산화적 스트레스와 합병증 연구의 근거자료로 널리 사용될 수 있을