Yin TT, Lin HY, Zhou M, Li JW, Mo QL, Wang HJ, Chen J, Zhu HL, Li YT, Zheng MY, Yang JH. Lean type 2 diabetes mellitus is an independent predictor of mortality in primary biliary cholangitis. World J Gastroenterol 2026; 32(13): 115649 [DOI: 10.3748/wjg.v32.i13.115649]
Corresponding Author of This Article
Jin-Hui Yang, Chief Physician, Full Professor, Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dianmian Avenue, Wuhua District, Kunming 650101, Yunnan Province, China. yangjinhui@kmmu.edu.cn
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Gastroenterology & Hepatology
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Retrospective Cohort Study
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Apr 7, 2026 (publication date) through Mar 27, 2026
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World Journal of Gastroenterology
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1007-9327
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Yin TT, Lin HY, Zhou M, Li JW, Mo QL, Wang HJ, Chen J, Zhu HL, Li YT, Zheng MY, Yang JH. Lean type 2 diabetes mellitus is an independent predictor of mortality in primary biliary cholangitis. World J Gastroenterol 2026; 32(13): 115649 [DOI: 10.3748/wjg.v32.i13.115649]
Ting-Ting Yin, Hui-Ying Lin, Min Zhou, Jian-Wei Li, Qiu-Lan Mo, Hong-Jing Wang, Jie Chen, Hui-Ling Zhu, Yu-Ting Li, Meng-Yao Zheng, Jin-Hui Yang, Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
Co-corresponding authors: Meng-Yao Zheng and Jin-Hui Yang.
Author contributions: Yin TT and Lin HY made equal contributions as co-first authors; Yin TT, Lin HY, and Zhou M contributed to the study design and manuscript preparation; Li JW, Mo QL, Wang HJ, Chen J, Zhu HL, and Li YT collected the clinical data; Zheng MY and Yang JH reviewed the data and revised the manuscript, contributed equally as co-corresponding authors. All authors approved the final version.
Supported by National Natural Science Foundation of China, No. 82160106; Yunnan Provincial Department of Education Scientific Research Fund Project, No. 2025J0270; and Yunnan Provincial Science and Technology Department Science and Technology Program Project, No. 202501AY070001-088.
Institutional review board statement: The present study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Kunming Medical University, No. YJ-2023-96.
Informed consent statement: The requirement for informed consent was waived by Ethics Committee of the Second Affiliated Hospital of Kunming Medical University due to retrospective nature of study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to ethical restrictions.
Corresponding author: Jin-Hui Yang, Chief Physician, Full Professor, Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, No. 374 Dianmian Avenue, Wuhua District, Kunming 650101, Yunnan Province, China. yangjinhui@kmmu.edu.cn
Received: October 22, 2025 Revised: December 16, 2025 Accepted: January 28, 2026 Published online: April 7, 2026 Processing time: 156 Days and 18.4 Hours
Abstract
BACKGROUND
The impact of lean type 2 diabetes mellitus (T2DM) on the prognosis of patients with primary biliary cholangitis (PBC) remains unclear.
AIM
To explore the adverse prognostic impact of lean T2DM on liver-related mortality risk in patients with PBC.
METHODS
This retrospective cohort study of 877 PBC patients stratified by T2DM status and lean phenotype used Cox regression models to analyze liver-related outcomes. Interaction effect models investigated T2DM and lean phenotype synergy. Propensity score matching (1:1) controlled for confounders between lean T2DM and non-T2DM non-lean groups, with sensitivity analyses validating results.
RESULTS
The median age of patients was 57 years (50-66), with 716 (81.64%) being female, and median follow-up was 45 months (25-48), during which 234 deaths (26.68%) occurred. After fully adjusting for confounding factors, lean T2DM remained an independent mortality risk factor in PBC patients [hazard ratio (HR) = 1.845, 95% confidence interval: 1.219-2.793, P = 0.004]. Interaction effect analysis confirmed a significant synergistic effect of T2DM and lean phenotype on mortality risk (interaction term HR = 2.546, 95% confidence interval: 1.342-4.831, P = 0.004). Stratified analysis further substantiated that T2DM significantly increased mortality risk only in lean patients (HR = 2.331, P < 0.001), while lean phenotype elevated risk only among T2DM patients (HR = 2.165, P = 0.0078). Propensity score matching validated this association (HR = 1.63, P = 0.008), with sensitivity analyses confirming the robustness of the conclusions.
CONCLUSION
Lean T2DM is an independent risk factor for liver-related adverse outcomes in PBC patients, and the coexistence of T2DM and lean phenotype exhibits a significant synergistic effect on mortality risk.
Core Tip: Although the adverse prognostic implications of lean diabetes have been documented in various disease contexts, its specific impact on clinical outcomes and underlying mechanisms in primary biliary cholangitis patients remain largely unexplored. This study represents the first comprehensive investigation that systematically evaluates the detrimental effects of lean diabetes on primary biliary cholangitis patient prognosis and critically examines the synergistic interaction and cooperative enhancement mechanisms between diabetes and lean phenotype.
Citation: Yin TT, Lin HY, Zhou M, Li JW, Mo QL, Wang HJ, Chen J, Zhu HL, Li YT, Zheng MY, Yang JH. Lean type 2 diabetes mellitus is an independent predictor of mortality in primary biliary cholangitis. World J Gastroenterol 2026; 32(13): 115649
Primary biliary cholangitis (PBC) is an autoimmune-mediated chronic liver disease characterized by progressive intrahepatic bile duct injury and cholestasis, ultimately leading to liver cirrhosis, hepatic failure, and potential mortality[1]. Predominantly affecting middle-aged women, the disease demonstrates a remarkably high serum anti-mitochondrial antibody positivity rate of up to 95%[1,2]. Currently, ursodeoxycholic acid remains the first-line treatment for PBC, effectively improving bile flow, protecting hepatocytes, and retarding disease progression[3]. However, patients with PBC frequently experience multiple metabolic abnormalities during disease progression, which may significantly impact patient outcomes.
Metabolic abnormalities have gained increasing recognition for their critical role in chronic liver diseases. Extensive research has confirmed that glucose metabolism disorders and insulin resistance significantly promote hepatic inflammation and fibrosis progression. These metabolic factors markedly increase the risk of adverse clinical outcomes, including cirrhosis, liver failure, and death[4]. The global burden of metabolic diseases has grown explosively due to accelerated urbanization and modern lifestyle changes. Diabetes prevalence shows particularly striking trends. The number of diabetic adults aged ≥ 18 years worldwide has surged from approximately 200 million in 1990 to 828 million[5]. Lean diabetes[6,7], characterized by normal or low body mass index (BMI), differs from traditional overweight/obese diabetes. These patients exhibit more severe pancreatic β-cell dysfunction, higher cardiovascular event risks, and increased all-cause mortality[8-10]. Additionally, lean diabetic patients frequently present with sarcopenia, malnutrition, and chronic low-grade inflammation[11-13]. This pattern represents a metabolic-immune system interactive disorder that may influence the natural course and prognosis of chronic liver diseases through unique pathophysiological mechanisms.
Patients with PBC commonly develop fat-soluble vitamin deficiencies, protein-energy malnutrition, and immune-metabolic dysregulation as a consequence of chronic cholestasis[14,15]. They may also experience secondary glucose metabolism abnormalities. When PBC coexists with lean diabetes, patients face multiple pathophysiological insults: “Cholestasis-metabolic disorder-malnutrition-immune dysregulation”. This combination may perpetuate hepatic inflammation, accelerate fibrosis progression, and ultimately impact disease prognosis. Although lean diabetes has been reported to worsen outcomes in cardiovascular disease, metabolic dysfunction-associated fatty liver disease, and sarcopenia[11-13], its specific impact on PBC patients remains unexplored. The potential mechanisms underlying this relationship also require investigation. This study aims to systematically evaluate the association between lean diabetes and liver-related adverse outcomes in PBC patients and investigate its relationship with nutritional status. These findings will provide new scientific evidence for risk stratification and personalized management of PBC patients.
MATERIALS AND METHODS
Study design and population
This is a single-center, retrospective cohort study that included patients with PBC who visited the Second Affiliated Hospital of Kunming Medical University from January 2013 to December 2023. Patients were initially screened using International Classification of Diseases codes, followed by manual chart review based on predefined inclusion and exclusion criteria (Figure 1).
Figure 1 Study flow chart of patient selection.
PBC: Primary biliary cholangitis; T2DM: Type 2 diabetes mellitus.
Inclusion criteria: PBC diagnosis based on the European Association for the Study of the Liver guidelines[16].
Exclusion criteria: (1) Concurrent viral hepatitis, alcoholic liver disease, or autoimmune hepatitis-PBC overlap syndrome; (2) Coexistent malignancy; (3) Incomplete follow-up data; (4) Patients receiving corticosteroid or immunosuppressive therapy; and (5) Patients with non-liver-related causes of death.
Definitions
Patients were stratified by the presence of type 2 diabetes mellitus (T2DM) and lean phenotype into four groups: Lean T2DM, non-lean T2DM, lean non-T2DM, and non-lean non-T2DM. The adopted criteria for T2DM used in this study were defined by the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III[6]: Fasting glucose ≥ 6.11 mmol/L (110 mg/dL); postprandial glucose ≥ 7.77 mmol/L (140 mg/dL); previously diagnosed T2DM; and/or on treatment for T2DM.
Lean status was defined by a BMI < 23 kg/m2 according to World Health Organization Asian standards[7], which classify overweight as 23 kg/m2 ≤ BMI < 25 kg/m2 and obesity as BMI ≥ 25 kg/m2. Lean type 2 diabetes was defined as the coexistence of lean status (BMI < 23 kg/m2) and diabetes.
Data collection and definitions
Baseline clinical data of PBC patients were retrospectively collected through electronic medical record systems, including demographic characteristics, medical history of underlying diseases, laboratory parameters, treatment regimens, and complications. Corrected BMI was calculated using the “dry weight” method, current weight reduced by 5%, 10%, or 15% for patients with mild, moderate, or severe ascites, respectively; an additional 5% reduction for patients with peripheral edema[17]. All laboratory tests were completed within 24 hours of admission.
Follow-up and outcomes
Follow-up was conducted through outpatient visits and hospitalization records. The outcome was liver-related mortality. Survival time was defined as the time interval from PBC diagnosis to death or last follow-up.
Statistical analysis
Statistical analyses were performed using SPSS version 29.0 and R version 4.5.1 software. Non-normally distributed continuous variables were expressed as medians (interquartile range) and compared between groups using the Mann-Whitney U test. Categorical data were reported as n (%) and analyzed using χ2 tests or Fisher’s exact tests. The Kaplan-Meier method was used to plot survival curves, and Log-rank tests were applied to compare survival differences between groups. To clarify whether lean diabetes is an independent risk factor for prognosis in PBC patients, we conducted a Cox proportional hazards model analysis and established multiple models to adjust for potential confounders. Model assumptions were verified using Schoenfeld residual tests for proportional hazards assumptions and variance inflation factors (> 5) for multicollinearity assessment. Interaction effect Cox regression models were constructed to assess the synergistic effect of diabetes and lean phenotype, followed by stratified analyses to explore the applicability and independence of the interaction in different subgroups. To further control for confounding bias, propensity score matching (PSM) was used to perform 1:1 nearest neighbor matching between the lean T2DM group and the non-T2DM non-lean group. The matching process employed sampling without replacement, with caliper width set at 0.2 times the standard deviation of propensity scores (standardized mean difference < 0.1 was considered adequate matching). Rosenbaum bounds sensitivity analysis was conducted to examine the robustness of main effect estimates under different sensitivity parameters gamma (1.0-2.0). Sensitivity analyses were conducted by excluding specific comorbidities to validate the robustness of the main conclusions. A two-tailed P value < 0.05 was considered statistically significant. This study focused on data with no missing values.
RESULTS
Baseline characteristics of the study population
A total of 877 patients with PBC were included in this study, with a median age of 57 years, and females accounted for 81.64% (n = 716). Among these, 77.42% (n = 679) were diagnosed through serological markers, while 22.58% (n = 198) were diagnosed via liver tissue pathology. During a median follow-up of 45 months (interquartile range: 25-84 months), there were 234 deaths (26.68%) in the cohort. Patients were divided into four groups based on diabetes and nutritional status (lean defined as BMI < 23 kg/m2): Lean T2DM group (14.7%), non-lean T2DM (8.6%), lean non-T2DM (47.3%), and non-lean non-T2DM (29.4%). Detailed baseline characteristics of the patients are presented in Table 1. Patients with lean T2DM were generally older, had a higher proportion of metabolic complications (such as hypertension, fatty liver, and coronary heart disease) (P < 0.001), and exhibited the highest mortality rate (51.2%). Additionally, they showed particularly severe liver dysfunction, indicated by significantly elevated serum total bilirubin (TBil) and total bile acid (TBA) levels (35.2 μmol/L vs 29.8 μmol/L vs 25.9 μmol/L vs 20.55 μmol/L, P < 0.001; 44.9 μmol/L vs 30.8 μmol/L vs 38.5 μmol/L vs 17.45 μmol/L, P < 0.001), and a marked decrease in albumin levels (39 g/L vs 48 g/L vs 52 g/L vs 53 g/L, P < 0.001). Notable reductions in platelets and increases in international normalized ratio (INR) related to portal hypertension were also observed. There were no statistically significant differences in gender distribution, gamma-glutamyltransferase levels, or the distribution of major autoimmune antibodies (anti-sp100, anti-gp210) among the groups (P > 0.05).
Table 1 Baseline characteristics of primary biliary cholangitis with different diabetes status and lean phenotype status, median (interquartile range)/n (%).
Lean diabetes as a prognostic factor for adverse outcomes in PBC: Cox survival analysis
Univariate Cox regression analysis revealed that age, TBil, TBA, alkaline phosphatase, elevated INR, and positivity for anti-gp210 antibodies significantly increased the risk of mortality, whereas liver steatosis, albumin, alanine aminotransferase, and elevated platelet counts had protective effects (P < 0.05). Using the non-T2DM non-lean group as a reference, both T2DM and lean phenotype were significantly associated with adverse prognosis, with significant differences among the four groups (P < 0.05).
Multivariable Cox regression constructed model A (adjusting for age and sex), model B (further adjusting for comorbidities), and fully adjusted model C (including laboratory parameters): In model C, after full adjustment, lean T2DM remained an independent risk factor for mortality [hazard ratio (HR) = 1.845, 95% confidence interval (CI): 1.219-2.793, P = 0.004], while the associations for the other groups were no longer significant. Model diagnostics revealed no serious multicollinearity issues (variance inflation factor < 5), and sensitivity analyses using stratified Cox regression for covariates violating proportional hazards assumptions confirmed the robustness of these findings (Supplementary Tables 1 and 2). Kaplan-Meier survival curves indicated that the lean T2DM group had the lowest survival rate, followed by non-lean T2DM, lean non-T2DM, and non-lean non-T2DM (Log-rank P < 0.001, Table 2, Figure 2). Compared to the non-lean non-T2DM group, the lean T2DM group had cumulative mortality increases of 32.7% (95%CI: 22.4%-41.3%) and 46.7% (95%CI: 31.7%-57.0%) at 5 and 10 years, respectively, with corresponding number needed to harm values of 3.1 and 2.1. This extremely low number needed to harm value emphasizes the significant clinical risk of this subgroup for adverse outcomes (Supplementary Table 3).
Figure 2 Kaplan-Meier survival analysis for liver-related mortality according to lean type 2 diabetes mellitus phenotype.
A: Survival comparison among non-lean non-type 2 diabetes mellitus (T2DM), lean non-T2DM, non-lean T2DM, and lean T2DM groups (P < 0.001); B: Kaplan-Meier survival curves for non-lean non-T2DM and lean T2DM phenotype groups after propensity score matching. T2DM: Type 2 diabetes mellitus.
Table 2 Cox regression analysis of lean type 2 diabetes mellitus phenotype as an independent predictor of liver-related mortality in primary biliary cholangitis patients.
Interaction and stratified analysis of lean and T2DM
Multivariable Cox analysis incorporating the interaction term between T2DM and lean status indicated a significant synergistic effect on the risk of mortality in PBC patients (interaction HR = 2.546, 95%CI: 1.342-4.831, P = 0.004). Further stratified analysis revealed that T2DM significantly increased the risk of mortality only in lean patients (HR = 2.33, 95%CI: 1.68-3.24, P < 0.001), while there was no significant effect in non-lean patients (HR = 0.74, 95%CI: 0.41-1.33, P = 0.314). Similarly, lean status only increased the risk of mortality in patients with T2DM (HR = 2.17, 95%CI: 1.23-3.83, P = 0.008), whereas there was no statistical difference in patients without T2DM (HR = 0.82, 95%CI: 0.55-1.22, P = 0.321). High mortality risk was observed only in patients with both T2DM and lean phenotype (Table 3, Figure 3).
Figure 3 Forest plot showing hazard ratios and 95% confidence intervals for the stratified analysis of type 2 diabetes mellitus and lean interaction effects in primary biliary cholangitis patients.
T2DM: Type 2 diabetes mellitus.
Table 3 Cox regression analysis of lean phenotype and type 2 diabetes mellitus status interaction effect in primary biliary cholangitis patients.
To overcome potential selection bias, PSM was employed to conduct a 1:1 nearest neighbor matching analysis between the lean T2DM group (n = 129) and the non-T2DM non-lean group (n = 258). Nine covariates, including age, sex, TBil, alanine aminotransferase, alkaline phosphatase, albumin, platelet count, INR, and anti-mitochondrial antibodies, were included as matching variables. After matching, the standardized mean differences for all baseline characteristics were < 0.1, achieving balance (Table 4, Figures 4 and 5). Cox proportional hazards regression analysis of the matched cohort showed that the risk of liver-related adverse outcomes in the lean diabetes group remained significantly higher than in the control group (HR = 1.63, 95%CI: 1.13-2.34, P = 0.008, Figure 2). Kaplan-Meier survival curves demonstrated a significant separation in survival distributions between the two groups (Log-rank test P = 0.027, Figure 2). Sensitivity analyses with different caliper widths and adjustment methods further confirmed the robustness of these results. Overall, the analysis indicated that lean T2DM status is an independent and robust risk factor for mortality in PBC patients, with its effect not influenced by baseline confounding factors.
Figure 4 Propensity score distributions before and after matching between lean type 2 diabetes mellitus and non-lean non-type 2 diabetes mellitus primary biliary cholangitis patients.
T2DM: Type 2 diabetes mellitus.
Figure 5 Covariate balance before and after propensity score matching between lean type 2 diabetes mellitus and non-lean non-type 2 diabetes mellitus groups.
Alb: Albumin; PLT: Platelet; TBil: Total bilirubin; AMA-M2: Anti-mitochondrial antibody M2; INR: International normalized ratio; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase.
Table 4 Baseline characteristics stratified by type 2 diabetes mellitus-lean and non- type 2 diabetes mellitus non-lean phenotypes before and after propensity score matching in primary biliary cholangitis patients, median (interquartile range)/n (%).
To further validate the robustness of the conclusions, Cox regression analysis was conducted after excluding patients with fatty liver, hypertension, and coronary heart disease. The results confirmed that lean T2DM status (HR = 1.872, 95%CI: 1.243-2.818, P = 0.003) remains an important independent predictor of liver-related adverse outcomes in PBC patients, thereby validating the robustness of our initial findings (Table 5).
Table 5 Sensitivity analysis: Impact of lean type 2 diabetes mellitus phenotype on adverse outcomes in primary biliary cholangitis patients.
This study represents the first systematic evaluation of the association of lean T2DM on the prognosis of patients with PBC. Through a retrospective cohort study involving 877 PBC patients, we discovered that lean T2DM is not only an independent risk factor for mortality but, more importantly, that the coexistence of T2DM and lean phenotype exhibits a significant synergistic effect. PSM and sensitivity analyses further confirmed the statistical robustness of these findings.
PBC patients inherently possess a susceptibility to lipotoxicity, primarily stemming from cholestasis-induced lipid metabolism disorders. Cholestasis directly impairs the liver’s capacity to clear and process lipids and their toxic metabolites[18]. During PBC progression, intrahepatic bile acid accumulation triggers a series of pathological changes: Bile acid profile abnormalities manifest as significant elevation of toxic bile acids (such as taurocholic acid) and reduction of protective secondary bile acids (such as deoxycholic acid); nuclear receptor regulatory disruption, particularly suppression of the farnesoid X receptor signaling pathway[19,20]; impaired fatty acid β-oxidation pathway leads to progressive accumulation of toxic lipids in the liver, forming a “lipotoxic microenvironment”[21]. Simultaneously, cholestasis induces the formation of abnormal lipoprotein X, where this abnormal lipoprotein structure dramatically reduces the clearance efficiency of cholesterol and harmful lipids, further exacerbating the liver’s lipotoxic burden[22].
Based on the high susceptibility to lipotoxicity, the pattern of ectopic fat deposition in lean diabetic patients represents a significant additional factor. Due to limited subcutaneous adipose tissue expansion capacity[23], when dietary intake or endogenous lipid production exceeds the storage capacity of fat tissue, excess lipids tend to deposit ectopically in non-adipose organs such as the liver[24,25]. While this “fat spillover” phenomenon may show minimal association with adverse outcomes in healthy livers, in patients with PBC whose livers are already in a state of high lipotoxicity, the continuous accumulation of ectopic fat is associated with hepatocytes progressively losing their repair and compensatory functions in the context of inflammation, oxidative stress, and nutritional disorders. Our results, which demonstrate significantly elevated levels of TBil and TBAs along with a deterioration in protein synthesis function and immune status in lean T2DM patients with concurrent PBC, directly support this pathological mechanism.
Additionally, the core pathological characteristic of lean T2DM, β-cell functional deficiency[26], not only manifests as continuously declining insulin secretion capacity and secretion pattern imbalance but also impairs hepatic lipid metabolism regulation, promoting ectopic fat deposition and exacerbating intrahepatic lipotoxicity accumulation[27]. Lean type 2 diabetes is associated with sarcopenia, characterized by reduced muscle quality and function, linked to elevated fasting plasma glucose and diabetes[28,29]. This effect synergizes with PBC’s inherent fat-soluble vitamin deficiencies (particularly vitamin D) and protein absorption impairments[14,30], further affecting muscle protein synthesis. As nutritional reserves gradually deplete, patients’ ability to tolerate various stress factors significantly decreases, making them more susceptible to infections, liver function decompensation, and liver failure, ultimately forming a vicious cycle of “cholestasis-metabolic disorder-malnutrition-immune imbalance”. This phenomenon closely corresponds with the “obesity paradox” commonly observed in chronic diseases, where in heart failure, chronic kidney disease, and even chronic liver disease, moderate fat and muscle reserves help buffer energy fluctuations, provide metabolic reserves, and reduce adverse event risks[31]. In contrast, lean diabetic patients with PBC lack sufficient physiological reserves to cope with disease progression and treatment-related stress, thus exhibiting significantly worse prognosis, which further confirms the synergistic effect of diabetes and lean phenotype on liver-related mortality risk.
From a clinical perspective, this study provides a novel predictive tool for assessing liver-related mortality risk in PBC patients. Given the synergistic effect of diabetes and lean body weight phenotype, early intervention is recommended for PBC patients with normal or low body weight. Particularly for patients with concurrent diabetes, implementing individualized and comprehensive management strategies can maximize patient outcomes.
However, the study has certain limitations. As a single-center retrospective cohort study, it may have selection bias, information bias, survival bias, and treatment-indication bias. The external validity of results requires validation through multicenter studies. Meanwhile, the definition of lean diabetes primarily relies on BMI and metabolic syndrome diabetes criteria. This definition cannot comprehensively reflect metabolic heterogeneity, such as body fat distribution, muscle mass, and glycemic changes. This may affect accurate determination of lean diabetes and prognosis. Furthermore, due to limitations in sample size and follow-up time, certain potential confounding factors may not be fully controlled. These aspects require not only larger-scale, longer-term prospective, multi-regional center studies for further clarification, but also more basic research evidence to confirm the relationship between lean diabetes and PBC.
CONCLUSION
In conclusion, this study systematically elucidates the significant adverse impact of lean diabetes on PBC patient prognosis. Incorporating body weight status and glucose metabolism assessment into routine PBC patient management, and implementing precise, comprehensive intervention strategies for lean diabetes patients, may significantly improve long-term outcomes in this high-risk population, providing new perspectives and evidence for individualized precision medicine in PBC.
Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF; PBC Consortia; Canadian PBC Consortium; Chinese PBC Consortium; Italian PBC Study Group; Japan-PBC-GWAS Consortium; US PBC Consortium; UK-PBC Consortium. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.J Hepatol. 2021;75:572-581.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 123][Cited by in RCA: 127][Article Influence: 25.4][Reference Citation Analysis (0)]
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).JAMA. 2001;285:2486-2497.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 20476][Cited by in RCA: 21013][Article Influence: 840.5][Reference Citation Analysis (2)]
Padilla-Martinez F, Szczerbiński Ł, Citko A, Czajkowski M, Konopka P, Paszko A, Wawrusiewicz-Kurylonek N, Górska M, Kretowski A. Testing the Utility of Polygenic Risk Scores for Type 2 Diabetes and Obesity in Predicting Metabolic Changes in a Prediabetic Population: An Observational Study.Int J Mol Sci. 2022;23:16081.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 2][Cited by in RCA: 4][Article Influence: 1.0][Reference Citation Analysis (0)]
Salvatore T, Galiero R, Caturano A, Rinaldi L, Criscuolo L, Di Martino A, Albanese G, Vetrano E, Catalini C, Sardu C, Docimo G, Marfella R, Sasso FC. Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes.Int J Mol Sci. 2022;24:658.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 31][Reference Citation Analysis (0)]
Krishnamoorthy R, Grant A, Sheldon P, Delahooke T. PWE-277 Fracture prevalence and vitamin D status in primary biliary cirrhosis: the Leicestershire experience.Gut. 2012;61:A410-A411.
[PubMed] [DOI] [Full Text]
