Associations between serum total bilirubin, obesity and type 2 diabetes

Yuan, Wei; Liu, Chaoqun; Lai, Fangfang; Dong, Shan; Chen, Haiyan; Chen, Li; Shi, Liping; Zhu, Fengcai; Zhang, Chuangbiao; Lv, Xiuxiu; Peng, Shuang; Hao, Guang

doi:10.1186/s13098-021-00762-0

Cited by 16 publications

(9 citation statements)

References 35 publications

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“…The top locus included an eQTL for UGT1A3 , which is directly involved in bilirubin metabolism. Although the cluster suggests a positive association between bilirubin levels and T2D risk, previous studies have demonstrated a negative association 22 . In addition, bile acid sequestrants may be used for treatment of T2D 23 ; however, the link between bile acid sequestrants and serum bilirubin levels is uncertain.…”

Section: Discussionmentioning

confidence: 68%

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity

Smith,

Deutsch,

McGrail

et al. 2023

Preprint

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We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg/m2in the European subpopulation and 24.2 (22.9- 25.5) kg/m2in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg/m2in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.

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Section: Discussionmentioning

confidence: 68%

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity

Smith,

Deutsch,

McGrail

et al. 2023

Preprint

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“…Recently, many investigations have shown that bilirubin is a regulator with multiple biological functions [ 17 , 18 ]. Slightly elevated bilirubin has been connected to a reduced incidence of cardiovascular events, diabetes, and metabolic syndrome [ 19 – 21 ]. In contrast to these studies, the subjects included in the current study were healthy patients, and the direct interaction between bilirubin levels and CVDs, diabetes, and metabolic syndrome cannot be derived from the present research, but some differences were observed.…”

Section: Discussionmentioning

confidence: 99%

Mildly elevated serum bilirubin and its correlations with lipid levels among male patients undergoing health checkups

Bai,

Qiao,

Zhang

2023

Lipids Health Dis

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Background Bilirubin’s ability to lower lipid levels was confirmed by several studies, but those studies mainly focused on total bilirubin (TBil). The present study aimed to elucidate the correlations of the two subtypes of bilirubin with lipid levels. Methods A total of 1732 male patients undergoing health checkups were categorized into three groups according to the levels of direct bilirubin (DBil) and indirect bilirubin (IBil). The differences in medical characteristics among the three groups were analysed. Results Subjects in the elevated DBil group had the lowest serum alanine aminotransferase (ALT), total cholesterol (TC), blood urea nitrogen (BUN), γ-glutamyl transpeptidase (γ-GT), fasting blood glucose (FBG), haemoglobin (HGB), and triglyceride (TG) levels in contrast to the other groups (P < 0.01), while subjects in the elevated IBil group had the highest ALT, γ-GT, BUN, serum creatinine (SCR), HGB, TC, and TG levels among the three groups (P < 0.01). DBil levels exhibited a significant negative correlation with TC (r = -0.777, P < 0.01) and TG (r = -0.397, P < 0.01) levels, while IBil levels exhibited a significant positive correlation with TC (r = 0.790, P < 0.01) and TG (r = 0.302, P < 0.01) levels. The frequencies of abnormal TC, TG, HGB and BUN levels were the lowest in the elevated DBil group, while the levels of these four variables were the highest in the elevated IBil group. Mildly elevated DBil levels were related to lower TG (OR = 0.112, 95% CI = 0.027–0.458) and TC (OR = 0.097, 95% CI = 0.013–0.700), and mildly elevated IBil levels were connected with increased TC (OR = 3.436, 95% CI = 2.398–4.924) and TG (OR = 1.636, 95% CI = 1.163–2.303). DBil was an independent protective factor against increased TC (OR = 0.702, 95% CI = 0.602–0.817, P < 0.01) and TG (OR = 0.632, 95% CI = 0.541–0.739, P < 0.01) levels, and IBil was an independent risk factors for increased TC (OR = 1.251, 95% CI = 1.176–1.331, P < 0.01). Conclusions DBil was an independent protective factor against high TC and TG levels. IBil was an independent risk factors for elevated TC levels. The prognostic value of IBil levels warrants further attention.

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“…In fact, this association with abnormal glucose tolerance tests was reported as early as 1996 [ 10 ]. Numerous clinical studies reporting lower serum/plasma bilirubin concentrations with the risk of diabetes (and its complications) were published in the following decade, as summarized in 2012 [ 11 ], as well as being confirmed in more recent studies [ 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 92%

Association of Low Serum Bilirubin Concentrations and Promoter Variations in the UGT1A1 and HMOX1 Genes with Type 2 Diabetes Mellitus in the Czech Population

Jirásková

Škrha

Vı́tek

2023

IJMS

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Bilirubin has potent biological beneficial effects, protecting against atherosclerosis, obesity, and metabolic syndrome. The aim of this study was to assess serum bilirubin concentrations and (TA)n and (GT)n microsatellite variations in the promoter regions of the UGT1A1 and HMOX1 genes, respectively, in patients with type 2 diabetes mellitus (T2DM). The study was carried out in 220 patients with T2DM and 231 healthy control subjects, in whom standard biochemical tests were performed. The (TA)n and (GT)n dinucleotide variations were determined by means of fragment (size-based) analysis using an automated capillary DNA sequencer. Compared to controls, both male and female patients with T2DM had lower serum bilirubin concentrations (9.9 vs. 12.9 μmol/L, and 9.0 vs. 10.6 μmol/L, in men and women, respectively, p < 0.001). Phenotypic Gilbert syndrome was much less prevalent in T2DM patients, as was the frequency of the (TA)7/7UGT1A1 genotype in male T2DM patients. (GT)nHMOX1 genetic variations did not differ between diabetic patients and controls. Our results demonstrate that the manifestation of T2DM is associated with lower serum bilirubin concentrations. Consumption of bilirubin due to increased oxidative stress associated with T2DM seems to be the main explanation, although (TA)n repeat variations in UGT1A1 partially contribute to this phenomenon.

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Associations between serum total bilirubin, obesity and type 2 diabetes

Cited by 16 publications

References 35 publications

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity

Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity

Mildly elevated serum bilirubin and its correlations with lipid levels among male patients undergoing health checkups

Association of Low Serum Bilirubin Concentrations and Promoter Variations in the UGT1A1 and HMOX1 Genes with Type 2 Diabetes Mellitus in the Czech Population

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