Objective: Chronic hyperglycemia increases glycation as well as oxidization, and, thus, facilitates production of advanced glycation end products (AGEs), whose accumulation is involved in the pathophysiology of diabetic complications. Although association between AGE and insulin resistance has been reported thoroughly, association between AGE and insulin secretion has not been well examined, especially in relation with age.

Research Design: Among participants of the population-based Iwaki study of Japanese held in 2014, those who attended the Iwaki study consecutively in 2014 and 2015 were enrolled in this study (n=518; model A), and we excluded fasting blood glucose levels <63 and >140 to calculate HOMA-β and IR (n=489; model B). We used skin autofluorescence as AGE, and also measured blood levels of Pentosidine and urine albumin-to-creatinine ratio.

Results: 1. AGE levels significantly increased from 1.93±0.52 to 1.97±0.44 (p=0.014) in the 1 year period.

2. Regression analysis showed correlations between ∆AGE (change in AGE in the 1 year period) and age, BUN, FPG and log10uACR in model A, and, age, log10uACR, and log10HOMA-ß in model B. However, these correlations became none-significant after adjustment for multiple factors mentioned above as well as factors representing glucose control levels such as HbA1c, except for age in models A and B, respectively.

3. Subjects were stratified into tertiles (mildly, moderately, rapidly progress) based on their ∆AGE, Logistic analysis revealed the aging is a significant risk for the accumulation of AGE (rapidly progress) (OR: 1.02. 95%CI: 1.01-1.03). ROC analysis showed the age of 60 as an optimal cut-off value for determining the risk subjects for the increase in AGE (OR: 1.74, 95%CI: 1.20-2.51).

Conclusions: The accumulation of AGEs may increase with increasing speed, which becomes rapid over the age of 60 independent of glycemic levels, uACR and HOMA-ß, indicating that not glycemic control levels but aging per se is a major contributor for AGE accumulation.


S. Mizushiri: None. M. Daimon: None. H. Murakami: None. A. Kamba: None. M. Murabayashi: None. Y. Nishiya: None.

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