A chronic disease with an elevated blood glucose level, diabetes mellitus (DM), is one of the oldest and most prevalent in the world, with 285 million adults worldwide suffering from it according to the WHO. By 2030, the prevalence is estimated to reach 7.7% (439 million adults) by a 3.96 million mortality rate (1, 2). Based on the WHO's classification system, diabetes can generally be categorized into four main types: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes, and other types (3). Usually, T1DM results from an autoimmunity mediated by T cells that destroys pancreatic beta-cells, leading to an inability to produce insulin (4). It accounts for 5–10% of all diabetic cases worldwide, and its incidence and prevalence are increasing by approximately 2–3% every year (5, 6). However, T1DM is the most common diabetes type among children and adolescents, causing severe growth problems for them. Since T1DM and its complications are more prevalent and severe in children than in adults, it is important to conduct research to prevent the development of diabetes and its complications (7, 8).
T1DM is diagnosed through a combination of symptoms, blood sugar tests, and other laboratory tests. fasting blood sugar level higher than 126 mg/dL and random blood sugar level higher than 200 mg/dL along with symptoms of diabetes, indicates diabetes (9). T1DM can also be diagnosed based on the concentration of sugar-based hemoglobin (HBA1C) above 48 mmol/mol (6.5%) that measures the average blood sugar level over the past 1–3 months while being controlled and influenced by many other factors (10, 11). For children with T1DM, long-term use of blood collection to detect blood sugar is indeed an unacceptable process, Therefore, is it necessary to use long-term and non-invasive tools for diagnosis and monitoring blood glucose levels of T1DM.
Advanced glycation end products (AGEs) are a group of compounds formed when sugars react with proteins and lipids that accumulate in various tissues in the body. It is well known that AGEs can cause damage to blood vessels as well as other tissues in the body, resulting in complications such as diabetic neuropathy, nephropathy, and retinopathy (12). Furthermore, AGEs can increase inflammation and oxidative stress in the body, which can further damage tissues and exacerbate diabetes complications (13). AGEs play an important role in the development and progression of T1DM, so they can reflect a patient's blood sugar over a longer period of time (14). It has been found that the generation of AGEs is faster in T1DM patients than the eradication of AGEs, leading to an accumulation of AGEs in the patient's body (15). Thus, the increase or decrease in AGEs in the body is an important criterion for measuring the severity of diabetes and its complications (15).
A subset of AGEs called sAGEs (soluble advanced glycation end products) are found in the circulation and can be determined by testing blood or urine samples. In comparison, sAGEs are rapidly metabolized in serum, whereas AGEs have long half-life in tissues, resulting in more stability and representativeness, which is more reliable for evaluating AGEs accumulation in tissues (16). For the detection of AGEs in the human body, liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent assays (ELISA) are currently used. There are, however, many disadvantages to these methods, such as: high price, high infection risk, high discomfort for patients, and invasiveness, making them not suitable for long-term use in clinical fields (17, 18).
A wide range of clinical trials have been promoted in recent years for measuring skin AGEs levels using autofluorescence (19). The ability of certain molecules to emit light when excited by a specific wavelength of light is known as autofluorescence. AGEs accumulate in the tissue, causing an increase in autofluorescence, which can be measured using specialized imaging techniques in T1DM (20, 21). As the traditional method for measuring AGE levels in tissues is biochemical determination in skin biopsies, skin autofluorescence (SAF) has emerged as an accurate, non-invasive, and practical method to measure AGEs levels in skin (22). Recently, recent reviews have indicated that SAF levels may serve as new biomarkers for complications associated with diabetes mellitus (23). In this way, The AGE Reader® allows the assessment of AGEs accumulation without invasive procedures. Currently, there is limited evidence regarding the relationship between the levels of AGEs measured by SAF and T1DM, and no meta-analysis has been conducted. In this systematic review and meta-analysis, we present the first study that provides clinical verification for SAF application. The purpose of this investigation was to determine whether SAF was associated with both status and development, as well as whether it was useful as a tool for detecting T1DM and its complications in children.