Tissue Accumulation of Advanced Glycation end Products Profile in Diabetic Subjects During Ramadan Fasting: New Clinical Value for Diabetes Management

To date no data about the profile of tissue accumulation of advanced glycation end products (AGEs) in diabetic subjects during Ramadan fasting. This short communication shows the effect of Ramadan fasting on AGEs profile in Tunisian diabetic subjects measured rapidly and non-invasively by The AGE reader device (Diagnoptics, Netherlands). The device has been developed to assess skin autofluorescence (SAF) using the fluorescent properties of several of AGEs.  Ramadan month on 2021 to Ramadan month on 2023, we have included 73 diabetic subjects from the Monastir region in Tunisia and all participants provided written informed consent. This first report shows 30% of diabetic subjects have a significant increase of SAF in Ramadan fasting (P<0.001) and the increased AGEs profile is still significantly higher after Ramadan (P<0.01). These data highlighted new clinical practical values to optimize diabetes management during Ramadan fasting to prevent cardiovascular events and requested other studies with a large cohort.

Advanced glycation end products (AGEs) are heterogeneous compounds issues by chronic hyperglycemia [1,2] and by diet-derived AGEs [3]. Diabetes, kidney and cardiovascular diseases have been related to increased levels of AGEs [4]. Skin autofluorescence (SAF) has been used as a rapid and non-invasive to measure tissue accumulation of AGEs and to assess the risk of cardiovascular in diabetic patients [5,6]. A high level of SAF is a predictor of diseases and mortality [7]. Ramadan fasting has been shown to be associated with metabolic dysfonction related to glycemic control and serum lipids levels [8,9]. However, to date, there are no studies about the effect of Ramadan fasting on tissue accumulation of AGEs in diabetic subjects. The aim of this study is to show the role of the AGE Reader as a non-invasive and rapid tool to measure AGEs profile in diabetic subjects in Ramadan fasting, that it can add a new clinical value for diabetes management to prevent cardiovascular events. 

Ramadan 2021 to Ramadan 2023, we have included 73 diabetic subjects from the Monastir region in Tunisia and all participants provided written informed consent. SAF was performed before Ramadan (Pre-R), at the last of week of Ramadan (R) and four weeks after Ramadan (Post-R). SAF was measured with the AGE Reader (Diagnoptics, Groningen, The Netherlands) as described previously [5]. The device, a non-invasive tool, evaluates AGEs in skin using the principle that several AGEs emit autofluorescence when excited by UV light. Excitation light source which wavelength is between 300 and 420 nm and the peak intensity is at ~ 370 nm. This light source is projected approximately onto 4 cm2 on the volar side of the forearm skin surface, and the intensity of any light (420-600 nm) emitted is measured with an internal spectrometer. SAF was expressed in arbitrary units (AU) and was calculated from the mean value of the emitted light intensity divided by the excitation light intensity and multiplying by 100. The subject with Fitzpatrick phototypes V and VI were not included due their skin pigmentation, which had ultraviolet reflectance of less than 6 Percentage. The reproducibility of SAF is indicated by a mean coefficient of variance ~ 5 Percentage [10]. For every participant, SAF was measured three times on normal skin without scars, tattoos, or other skin abnormalities. For every participant, mean SAF was calculated from the three consecutive measurements on skin at each period of Pre-R, R and Post-R.

For all diabetic subjects (n=73) we collected clinical characteristics one week before Ramadan and we measured SAF (Table 1).

Table 1: Clinical and skin autofluorescence (SAF) levels in diabetic subjects before Ramadan

Data are shown as the median (interquartile range), mean ± SD or number (percentage).

Ramadan fasting have shown a significant increase of SAF in 30% diabetic subjects and this increasing is still significantly higher in after Ramadan (Table 2) with P  less than 0.001 and P  less than 0.01 respectively. Also, the profile of SAF was represented by box plot before, in Ramadan and after Ramadan as shown in figure 1.

Table 2: SAF profile in diabetic patients before Ramadan, in Ramadan and after Ramadan.

a No significant; b Significant compared to Pre-R; P less than 0.001 (Student's t-test); c Significant compared to Pre-R; P less than 0.01(Student's t-test); Pre-R: before Ramadan; R: Ramadan; Post-R: after Ramadan

Figure 1: SAF levels before Ramadan (Pre-R), in Ramadan (R) and after Ramadan (Post-R) in diabetic subjects (n=22).

Increased SAF raise the risk of cardiovascular disease on these subjects and this new study needs to follow up each Ramadan to optimize diabetes management in Ramadan fasting for screening, monitoring and treatment to avoid any complications related to diabetes [11,12]. Several pathways remain unclear to explain the raise of SAF in some diabetic subjects on Ramadan fasting, the first way may be by increased oxidative stress, glucose metabolic imbalance and treatment effects specially medications type use for anti-diabetes [13,14], and the second way may be by the nature of food consummations at each post fasting day in Ramadan [15, 16]. Some limitations of this case report should be noted. The number of diabetic subjects was small, and we had limited information on medication use, long-term glycaemic control of diabetes and biochemical parameters. Future research should incorporate SAF, as a rapid tool and non-invasive for monitoring and cardiovascular risk assessment to manage diabetes and its complications in order to further investigate the effect of Ramadan fasting on tissue accumulation of AGEs.

During Ramadan, diabetes subjects may face challenges with hyperglycemia during fasting. It's essential to monitor blood glucose levels regularly, measure tissue accumulation of advanced glycation end products by skin autofluorescence and adjust medication and meal timings accordingly to prevent complications. Consulting with your healthcare provider for personalized guidance is key to managing. 

The author would like to thank Professor Bruce H R Wolffenbuttel Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands for giving us the AGE Reader device as a gift to make clinical studies in Tunisia.