Relationship between serum bilirubin levels, urinary biopyrrin levels, and retinopathy in patients with diabetes

Kudo, Kana; Inoue, Tomoaki; Sonoda, Noriyuki; Ogawa, Yoshihiro; Inoguchi, Toyoshi

doi:10.1371/journal.pone.0243407

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…Bilirubin is a strong endogenous antioxidant [6]. Accumulating evidence has shown the relationship between serum bilirubin levels and oxidative stress-related diseases such as diabetes, diabetic nephropathy, and cardiovascular diseases [7][8][9][10][11][12]. In addition, in the previous report, we showed that serum levels of bilirubin is a strong predictive biomarker for ADL disability in older patients with diabetes (aged 70 years and over) [13].…”

Section: Introductionmentioning

confidence: 60%

“…Bilirubin is a strong endogenous antioxidant. Many epidemiological and animal studies have shown that serum bilirubin levels are inversely associated with the onset and development of oxidative stress-related diseases including diabetes, diabetic vascular complications, chronic kidney disease (CKD), and cardiovascular diseases [7][8][9][10][11][12]. Therefore, it is most likely that the negative relationship between serum indirect bilirubin levels and the skeletal muscle mass in male old-old patients with type 2 diabetes is due to the decreased antioxidative activity and subsequent increased oxidative stress.…”

Section: Plos Onementioning

confidence: 99%

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Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes

Inoguchi

Inoguchi²,

Eto³

et al. 2022

PLoS ONE

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Objective We previously showed that low serum bilirubin levels are associated with disability in quality of daily living in older patients with diabetes. However, the underlying mechanism is not fully understood. The aim of this study is to assess the relationship between serum bilirubin levels and skeletal muscle mass in older patients with type2 diabetes. Methods A total of 272 older patients with type2 diabetes (152 male and 120 female) aged 60 years and over were continuously recruited from April 2020 to July 2020. Body composition was evaluated by bioelectrical impedance analysis. The skeletal muscle mass index (SMI) was calculated as appendicular muscle mass divided by height squared (m2). Results The SMI was markedly lower in old-old patients (aged 75 years and over) than in young-old patients (aged 60–74 years) in both male and female (7.1 ± 0.8 kg/m2 vs 7.6 ± 0.9 kg/m2, P<0.001; 5.5 ± 0.9 kg/m2 vs 6.3 ± 0.8 kg/m2, P<0.001, respectively). Multivariate regression analysis showed that the SMI was associated with body mass index (BMI) (p<0.001) and age (p = 0.048) in male young-old patients, while it was associated with BMI (p<0.001), age (p = 0.008), and serum indirect bilirubin levels (p = 0.038) in male old-old patients. In female, the SMI was associated with BMI (p<0.001) and age (p = 0.042) in young-old patients and associated with BMI alone (p<0.001) in old-old patients. Conclusion Serum indirect bilirubin levels may be associated with the decreased skeletal muscle mass in male older patients (aged 75 years and over) with type 2 diabetes.

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Section: Introductionmentioning

confidence: 60%

Section: Plos Onementioning

confidence: 99%

Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes

Inoguchi

Inoguchi²,

Eto³

et al. 2022

PLoS ONE

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“…Biopyrrins served as markers of oxidative stress in various studies. − The inherent biological activity of these oxidation products is still not understood. Structurally related tripyrrindiones also suggest interesting chemical properties for this class of molecules .…”

Section: Resultsmentioning

confidence: 99%

A Platform for the Synthesis of Oxidation Products of Bilirubin

Mujawar,

Sevelda,

Madea

et al. 2024

J. Am. Chem. Soc.

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Bilirubin is the principal product of heme catabolism. High concentrations of the pigment are neurotoxic, yet slightly elevated levels are beneficial. Being a potent antioxidant, oxidative transformations of bilirubin occur in vivo and lead to various oxidized fragments. The mechanisms of their formation, intrinsic biological activities, and potential roles in human pathophysiology are poorly understood. Degradation methods have been used to obtain samples of bilirubin oxidation products for research. Here, we report a complementary, fully synthetic method of preparation. Our strategy leverages repeating substitution patterns in the parent tetracyclic pigment. Functionalized ready-to-couple γ-lactone, γ-lactam, and pyrrole monocyclic building blocks were designed and efficiently synthesized. Subsequent modular combinations, supported by metal-catalyzed borylation and cross-coupling chemistries, translated into the concise assembly of the structurally diverse bilirubin oxidation products (BOXes, propentdyopents, and biopyrrins). The discovery of a new photoisomer of biopyrrin A named lumipyrrin is reported. Synthetic bilirubin oxidation products made available in sufficient purity and quantity will support future in vitro and in vivo investigations.

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“…Similar to our ndings, a study including 336 patients with T2DM demonstrated that serum bilirubin was dramatically higher in the patients without DR than in those with PDR (p < 0.05)(18). Additionally, Kudo et al found that serum bilirubin levels decreased as the severity of retinopathy increased (39). Therefore, it is suggested that serum bilirubin not only was a simple indicator to evaluate the risk of DR, but also might be a reliable indicator of DR progression in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

High-normal serum bilirubin is a useful indicator to assess the risk of diabetic retinopathy in type 2 diabetes: A real-world study

Xu²,

Wang³

et al. 2023

Preprint

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Objective To investigate the association of serum bilirubin within normal range, especially unconjugated bilirubin (UCB), with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods In this cross-sectional, real-world study, 7617 T2DM patients were stratified into quartiles based on serum UCB levels. DR was determined by digital fundus photography and further classified into non-proliferative diabetic retinopathy (NPDR) and PDR. The associations of serum bilirubin levels and UCB quartiles with DR were investigated by logistic regression analysis.Results After controlling for age, sex, and diabetes duration, the DR prevalence was significantly decreased across the serum UCB quartiles (40.4%, 33.4%, 29.7%, 26.6% for each quartile, respectively, p < 0.001 for trend). The subjects with DR had lower serum total bilirubin (TB) and UCB, rather than conjugated bilirubin (CB), compared with those without DR (p = 0.003 for TB, p < 0.001 for UCB, and p = 0.528 for CB, respectively), while all three types of serum bilirubin in the subjects with PDR were obviously lower than those with NPDR (p = 0.006 for TB, and p < 0.001 for UCB and CB, respectively). After adjustment for confounding factors, logistic regression demonstrated negative associations of serum TB and UCB levels, rather than CB, with the presence of DR (OR: 0.844, 95%CI: 0.774–0.920, p < 0.001 for TB; OR: 0.828, 95%CI: 0.763–0.899, p < 0.001 for UCB; and OR: 0.984, 95%CI: 0.900-1.074, p = 0.713 for CB, respectively). Additionally, a fully-adjusted analysis revealed a negative correlation between UCB quartiles and DR (p < 0.001).Conclusions High-normal serum TB and UCB were closely associated with the decreased risk of DR, while all types of serum bilirubin were negatively correlated with the severity of DR in T2DM. Serum bilirubin may be used as a potential indicator to assess the risk and severity of DR in T2DM.

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Relationship between serum bilirubin levels, urinary biopyrrin levels, and retinopathy in patients with diabetes

Cited by 8 publications

References 39 publications

Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes

Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes

A Platform for the Synthesis of Oxidation Products of Bilirubin

High-normal serum bilirubin is a useful indicator to assess the risk of diabetic retinopathy in type 2 diabetes: A real-world study

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