Accumulating data showed that the changes in metabolism of Trp and its active metabolites play essential roles in both the pathogenesis and complications of diabetes . The altered L-Trp metabolism may play a role in the pathogenesis of diabetes mellitus and developing the risk of complications. Some previous studies have suggested that Trp decreased and its metabolism up-regulates in diabetic patients [24,25]. Based on studies performed on the relationship between Trp and diabetes, the related studies on human and animal samples have been selected, the details of which are explained below:
In another study, L- Trp level was assessed in diabetic and normal serum samples in human using the reduced graphene oxide/gold nanoparticles/18-crown-6. Based on the square wave voltammetry (SWV) results, a low limit of detection (LOD) was calculated as about 0.48 μM and 0.61 μM for diabetic and normal samples, respectively. It seems that the nanocomposite could be known as a good choice for L-Trp determination in human serum . In another study, C-mannosyl tryptophan (C-Man-Trp) was measured in different tissues obtained from normal or diabetic mice. The increased excretion of C-Man-Trp level was also observed in urine and kidney tissue; however, C-Man-Trp levels reduced in the liver of diabetic mice. Correspondingly, these results suggested that C-Man-Trp metabolism is greatly affected by diabetes .
Chou et al. in their study evaluated serum levels of various metabolites among diabetic patients at various stages of chronic kidney disease. It was shown that Lower Trp levels are associated with a rapid drop in the estimated glomerular filtration rate (eGFR). Moreover, this study exhibited that Trp level might be considered as a potential biomarker for diabetic nephropathy .
In the Rebnord et al.’s study, the associations of the kynurenine (KYN): Trp ratio (KTR) to the occurrence of diabetes type 2, was considered. Thereafter, the plasma and urine samples of studied individuals with coronary artery disease were obtained, and the levels of KYN and Trp were then measured. Although the results showed no significant relationship between KTR and type 2 diabetes in Plasma samples, was a strong positive association was found between KTR and type 2 diabetes in urine samples .
Chen et al. in their study evaluated the role of Trp, as a predicting risk factor for T2D outcomes, in healthy and diabetic Chinese men. Accordingly, their results showed that serum Trp level was significantly higher among diabetic patients, and Trp biomarker was associated with DM onset risk positively and independently. It was indicated that the higher Trp levels in these patients can make higher levels of both insulin resistance and secretion. These findings revealed the potential of Trp as a new biomarker of diabetes risk in the Chinese population .
3.1 Determination of L-Trp as a biomarker of diabetes in old age
It was found that aging changes the composition and function of adipose tissue, and consequently leads to insulin resistance and fat storage in the ectopic body part . The cellular changes that converge during the aging process are dysfunction in mitochondria, antioxidant deficiency, inflammation, and the decreased immune response. Accordingly, these changes affect the KYN pathway (KP) (Fig. 3), which is known as a major pathway for Trp catabolism .
Some studies have previously reported that Trp metabolites play a key role as a potential biological mediator for T2D [29,32,33]. Trp metabolism is thought to be altered due to various physiological and psychological pressures such as self-care in diabetic patients . These findings exhibited the possible role of Trp in geriatric diabetic patients.
In a study, Trp metabolites were assessed in healthy and diabetic adult men. The results confirmed that 5-hydroxytryptophan (5-HTP) levels were higher in diabetic patients compared to healthy adult men .
Calvani et al. in their study determined the circulating amino acids in diabetic frail adults, in order to detect the concentrations of circulating 37 amino acids. They reported high Trp levels in serum samples of diabetic adults compared to their control participants . In another study, the measurement of Trp, KYN, and neopterin levels as immune activation markers in volunteers aged ≥ 65 and <65 years old, was performed. The geriatric groups had low Trp levels compared to the young groups. Conversely, Trp and KYN/Trp levels were found to be significantly higher than adults without DM .
In a research, Shimizu et al. evaluated the Trp metabolites in plasma samples obtained from both young and old participants with and without type 2 diabetes. Plasma Trp metabolites levels in young women and old men were found to be higher than young men and old women. Except the KYN and indole butyric acid, the plasma levels of Trp metabolites were higher in diabetic patients than adult men . Furthermore, Matsuoka et al. presented various Trp metabolites in diabetic and healthy men. Accordingly, their results showed that the plasma level of Trp in diabetic adults was lower than that of healthy subjects, but it was not statistically significant. As well, 5-HTP concentration and the other related Trp metabolites were statistically higher in diabetic adults .
As shown in most of the results, in human serum and plasma samples, the amount of Trp was higher in diabetic peoples compared to healthy ones. It seems that T2D is characterized by low-grade systemic inflammation, which consequently affects adipose tissue, the liver, pancreas, and kidneys . On the other hand, degradation of Trp also appears to be closely related to the immune system activation . Besides, KYN pathway activity significantly increased in chronic stress . Correspondingly, all these factors manifested themselves by growing the Trp degradation in a patient's serum. Altogether, our observations indicated that the Trp levels have been previously evaluated in different samples, participants, and disease stages in various studies. Unfortunately, there was a few studies on determining the role of Trp in diabetic patients; therefore, it is hard to speak about the exact changes of Trp levels and their metabolites in different study samples. More information on methodology and the obtained results are mentioned in Table 2.