Introduction: Diabetes and liver disease are common chronic diseases in China, with overlapping mechanisms, clinical manifestations, and therapeutic targets, making them interrelated risk factors. Co-managing these conditions can help reduce the disease burden. To support the development of diabetes and liver disease co-management in China, our publication, in collaboration with the China Diabetes and Liver Disease Co-management Action Plan (CDL), introduces the CDL Monthly Literature Review column. Each month, we will share research on the mechanisms, diagnosis, and treatment progress related to diabetes with liver disease, and invite experts from related fields in China to provide commentary. We aim to offer valuable insights and assistance to specialists, researchers, and frontline healthcare workers in conducting scientific research and clinical practice.This issue of the CDL Monthly Literature Review will feature six clinical research papers on diabetes and fatty liver disease, liver function abnormalities, and liver-related adverse events. The invited commentary experts for this issue are: Professor Ling Li from Mengchao Hepatobiliary Hospital of Fujian Medical University, Professor Wei Yue from The First Hospital of Lanzhou University, Professor Wanyu Li from The First Hospital of Jilin University, and Professor Ying Li from Tianjin Third Central Hospital.
Commentary Experts
Professor Ling Li
Mengchao Hepatobiliary Hospital, Fujian Medical University Department of Interventional Radiology, Deputy Director, Associate Chief Physician, Ph.D.
Professor Ling Li holds several esteemed positions: a member of the Youth Committee of the 8th Hepatology Branch of the Chinese Medical Association, Executive Member of the Youth Committee of the Interventional Medicine Professional Committee of the China Research Hospital Association, Member of the Hepatobiliary and Pancreatic Interventional Group of the Interventional Medicine Professional Committee of the China Research Hospital Association, and a founding member of the Minimally Invasive Interventional Professional Committee of the Chinese Division of the International Hepatobiliary and Pancreatic Association. Additionally, he is an Executive Member of the 1st Committee of the Interventional Medicine Branch of the Fujian Society of Integrative Medicine. Professor Li has been engaged in clinical and research work on liver diseases, particularly liver tumors and portal hypertension, for 15 years. He specializes in the interventional treatment of liver tumors and portal hypertension. He has undertaken or participated in several national and provincial research projects and has published more than 10 SCI papers.
01: Metabolic Syndrome Traits Increase the Risk of Major Adverse Liver Outcomes in Type 2 Diabetes
Authors: Shang Y, Grip ET, Modica A, et al.
Journal: Diabetes Care, 2024. doi: 10.2337/dc23-1937
Study Overview: Type 2 diabetes (T2DM) is associated with an increased risk of major adverse liver outcomes (MALOs), including cirrhosis and its complications. T2DM patients often exhibit other characteristics of metabolic syndrome (MetS). However, it remains unclear whether the accumulation of MetS traits has a synergistic effect on the risk of developing MALOs. This study included T2DM patients from the Swedish National Registry without a history of liver disease from 1998 to 2021. Besides T2DM, MetS traits included hypertension, low HDL levels, hypertriglyceridemia, obesity, and proteinuria. MALOs events were identified using administrative codes from the national registry as of October 31, 2022, and data were analyzed using Cox regression models. The results showed that having or acquiring additional MetS traits accelerated the progression to MALOs in T2DM patients.
Study Details: The study included 230,992 patients with a median age of 64 years (58% male), among whom 3,215 (1.39%) developed MALOs during a median follow-up of 9.9 years. Compared to patients with one MetS trait (T2DM only) at baseline, those with more than one MetS trait had a higher incidence of MALOs (adjusted hazard ratio [aHR]: 2.33, 95% confidence interval [CI]: 1.53–3.54). The incidence of MALOs increased with the number of MetS traits at baseline (aHR per additional trait: 1.28, 95% CI: 1.23–1.33). During follow-up, the incidence of MALOs increased with the acquisition of additional MetS traits. The MetS trait most associated with MALOs was hypertension (aHR: 2.06, 95% CI: 1.57–2.71).
Commentary: Metabolic syndrome (MetS) comprises a cluster of metabolic abnormalities that can affect the liver. Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered the hepatic manifestation of MetS. In this study, MALOs were defined as ICD-10 diagnoses of cirrhosis, decompensated cirrhosis, and related complications such as esophageal varices, portal hypertension, hepatorenal syndrome, ascites, hepatocellular carcinoma (HCC), or death and liver transplantation due to these reasons. Previous studies have shown that T2DM patients have a higher incidence of MALOs, but the impact of baseline or newly acquired MetS traits on the incidence or progression of MALOs was unclear.
This cohort study utilized the Swedish National Diabetes Registry, which is a high-quality registry with an unprecedentedly large sample size, high coverage, and low loss to follow-up. The results indicated that the incidence of MALOs increased with the number of MetS traits at baseline and with the acquisition of new MetS traits, likely due to MASLD. Compared to previous studies, this study’s population was expanded from MASLD patients to T2DM patients, making the findings more broadly applicable and aligning with guidelines recommending routine MASLD screening for T2DM patients. The study also identified hypertension and chronic kidney disease (CKD) as the parameters most strongly associated with an increased incidence of MALOs, while hyperlipidemia showed no positive correlation. Screening for these parameters can help improve the efficiency of MASLD screening in T2DM patients.
Commentary Experts
Professor Wei Yue
The First Hospital of Lanzhou University Associate Professor, Associate Chief Physician
Professor Wei Yue is an associate professor and associate chief physician at The First Hospital of Lanzhou University. He serves as a national youth committee member of the 7th and 8th Committees of the Hepatology Branch of the Chinese Medical Association, a member of the Hepatology Professional Committee of the Chinese Medical Education Association, a member of the Science Popularization Branch of the Gansu Medical Association, Deputy Chairman of the Hepatobiliary Disease Professional Committee of the Gansu Provincial Association of Chinese Medicine, and a member of the Expert Group of the Gansu Provincial Infectious Disease Medical Quality Control Center.
02: Effects of Empagliflozin on Liver Fat in Metabolic-Dysfunction Associated Steatotic Liver Disease Patients Without Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Cheung KS, Ng HY, Hui RWH, et al.
Journal: Hepatology, 2024. doi: 10.1097/HEP.0000000000000855
Study Overview: The effects of empagliflozin on liver fat in metabolic-dysfunction associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM) are unclear. This investigator-initiated, double-blind, randomized, placebo-controlled trial recruited adult participants from the community. The results indicated that a 52-week treatment with empagliflozin reduced liver fat content in non-diabetic MASLD participants.
Eligible participants were non-diabetic (fasting blood glucose <7 mmol/L and glycated hemoglobin <6.5%) with a magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥5%. They were randomly assigned to the empagliflozin (10 mg/day) or placebo group (1:1 ratio) and treated for 52 weeks. MRI-PDFF was assessed at baseline and the end of treatment (EOT). The primary outcome was the change in MRI-PDFF between the two groups at EOT. Secondary outcomes included the resolution of hepatic steatosis (MRI-PDFF <5%), ALT reduction ≥17 U/L, MRI-PDFF reduction ≥30%, and changes in anthropometric and laboratory parameters at EOT, all analyzed on an intention-to-treat basis. Among the 98 participants recruited (54 males, 55.1%), the median age was 55.7 years (IQR: 49.5–63.4), and 97 patients (49 in the empagliflozin group and 48 in the placebo group; median MRI-PDFF: 9.7% vs. 9.0%) completed the EOT MRI-PDFF assessment. Compared to the placebo group, the empagliflozin group showed a greater median reduction in MRI-PDFF (-2.49% vs. -1.43%, P=0.025), although the resolution of hepatic steatosis was not statistically significant (44.9% vs. 28.6%, P=0.094). There were no significant differences between the two groups in ALT reduction ≥17 U/L (16.3% vs. 12.2%, P=0.564), MRI-PDFF reduction ≥30% (49.0% vs. 40.8%, P=0.417), or composite outcomes (8.2% vs. 8.2%, P=1.000). The empagliflozin group showed greater reductions in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting blood glucose (-0.3 vs. 0 mmol/L), and ferritin levels (-126 vs. -22 pmol/L) (all P<0.05).
Commentary: Currently, there is no recognized treatment for MASLD, which is experiencing a significant increase in incidence. Several studies have shown that empagliflozin can effectively reduce liver fat content in both T2DM and non-T2DM patients, with this reduction closely linked to weight loss and improved insulin sensitivity.
This study employed a randomized, double-blind, placebo-controlled trial design, focusing on non-diabetic MASLD patients. Empagliflozin and placebo treatments were administered, and liver fat content (MRI-PDFF), body weight, BMI, fasting blood glucose, and ferritin levels were assessed after 52 weeks. The results indicated that empagliflozin significantly reduced liver fat content compared to placebo. Subgroup analysis showed that regardless of treatment type, participants who lost weight had a reduction in liver fat content, suggesting that weight loss itself can reduce liver fat. Notably, empagliflozin still reduced liver fat content in participants who did not lose weight, possibly due to reductions in systemic and histological inflammation and oxidative stress. Serum ferritin, an independent predictor of histological severity of hepatic steatosis and advanced liver fibrosis, was significantly reduced by empagliflozin. The conclusion is that a 52-week treatment with empagliflozin can reduce liver fat content in non-diabetic MASLD patients, correlated with reductions in serum ferritin, fasting blood glucose, and BMI, with good safety. The rigorousness and applicability of this randomized, double-blind, placebo-controlled trial lend credibility to these findings.
The innovation of this study lies in its 52-week treatment period, longer than other randomized controlled studies. The study focused on non-diabetic MASLD patients, providing a theoretical basis for the therapeutic effects of empagliflozin in non-diabetic patients. However, limitations include a small sample size, the absence of liver biopsy for fat content assessment, and the fact that participants were all of Chinese ethnicity. Therefore, the findings need further validation through large-scale, multi-center randomized controlled studies in diverse populations.
Commentary Experts
Professor Wanyu Li
The First Hospital of Jilin University Associate Professor, Master’s Supervisor
Professor Wanyu Li is an associate professor and master’s supervisor at The First Hospital of Jilin University. She serves as a youth committee member of the Hepatology Branch of the Chinese Medical Association, a youth committee member of the Genetics Branch of the Chinese Medical Association, and a youth committee member of the Infectious Diseases Branch of the Jilin Provincial Medical Association. Her main research focus is on liver immunology, and she has published multiple SCI articles as the first author and has led several research projects. She has also studied as a visiting scholar at the University of Washington in the United States for one year. She specializes in the diagnosis and treatment of hepatobiliary system diseases.
03: Inhibition of Sodium-Glucose Cotransporter-2 and Liver-Related Complications in Individuals with Diabetes: A Mendelian Randomization and Population-Based Cohort Study
Authors: Chung SW, Moon H-S, Shin H, et al.
Journal: Hepatology, 2024. doi: 10.1097/HEP.0000000000000837
Study Overview: Currently, no drugs have been found to reduce liver-related events. To evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on liver outcomes, Korean scientists conducted a Mendelian randomization study involving two European cohorts and a nationwide Korean population-based cohort. The results indicated that SGLT2 inhibition was associated with a lower incidence of liver-related risk events.
The study identified single nucleotide polymorphisms (SNPs) associated with SGLT2 inhibition and calculated genetic risk scores (GRS) using UK Biobank (UKB) data (n=337,138). A two-sample Mendelian randomization (MR) study was conducted using data from the FinnGen database (n=218,792) and UKB. Simultaneously, a nationwide population-based study was conducted using the Korean National Health Insurance Service (NHIS) database. The study compared liver-related complications (i.e., hepatic decompensation, hepatocellular carcinoma, liver transplantation, and death) between T2DM and fatty liver disease patients treated with SGLT2i (n=13,208) and those treated with DPP4i (n=70,342), matched by propensity score. After calculating GRS with 6 SNPs (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), the GRS-based MR showed that SGLT2 inhibition (1 SD increase in GRS, HbA1c reduction of 0.1%) was negatively correlated with the development of cirrhosis (aOR 0.83, 95%CI: 0.70–0.98, P=0.03), consistent with findings in the two-sample MR (OR 0.73; 95%CI: 0.60–0.90, P=0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group compared to the DPP4i group (aHR 0.88; 95%CI: 0.79–0.97, P=0.01), and this difference remained significant in various sensitivity analyses (aHR=0.72–0.89, P<0.05).
Commentary: This Mendelian randomization study conducted by Korean scientists involved two European cohorts and a nationwide Korean population-based cohort, focusing on the effects of the novel drug SGLT2i on liver outcomes and SNPs associated with SGLT2 inhibition. SGLT2i is recommended by guidelines worldwide for its ability to protect the heart and kidneys through multiple mechanisms and achieve comprehensive management of glucose, heart, and kidney health. By inhibiting SGLT2 in the renal proximal tubule, SGLT2i reduces glucose reabsorption, lowers the renal glucose threshold, and promotes glucose excretion in the urine, thereby achieving glycemic control. However, whether it can reduce liver-related events requires further exploration.
On one hand, this study’s Mendelian randomization based on genetic risk scores showed a negative correlation between SGLT2 inhibition and cirrhosis development, consistent with findings in the two-sample MR. On the other hand, compared to DPP4i, the study found that SGLT2i treatment significantly reduced the risk of liver-related complications, including hepatic decompensation, hepatocellular carcinoma, liver transplantation, and death, in T2DM and fatty liver disease patients. The significant difference in various sensitivity analyses further strengthens the study’s credibility. However, the diagnosis of cirrhosis and other liver-related complications in this study was not based on liver biopsy or liver elasticity imaging, and the mechanisms underlying the hepatoprotective effects of SGLT2i remain unclear and require further investigation.
04: The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes
Authors: Younossi ZM, Golabi P, Price JK, et al.
Journal: Clin Gastroenterol Hepatol, 2024. doi: 10.1016/j.cgh.2024.03.006
Study Overview: Nonalcoholic fatty liver disease (NAFLD), now referred to as metabolic-dysfunction associated steatotic liver disease (MASLD), is closely associated with T2DM. To evaluate the latest global prevalence of NAFLD/MASLD, nonalcoholic steatohepatitis (NASH), now called metabolic-dysfunction associated steatohepatitis (MASH), advanced fibrosis, and mortality in T2DM patients, this study systematically searched PubMed and Ovid MEDLINE for terms related to NAFLD, NASH, and T2DM published from 1990 to 2023. A meta-analysis was conducted using a random-effects model, and risk of bias was assessed using the Joanna Briggs Institute tool. The results indicated a high and rising prevalence of NAFLD/MASLD in T2DM patients, with most NAFLD/MASLD patients having NASH/MASH and a considerable proportion having advanced fibrosis.
Out of 3,134 initially included studies, 123 studies (n=2,224,144 T2DM patients) met the inclusion criteria. An additional 12 studies (n=2,733 liver biopsy-assessed T2DM patients) met the histological assessment criteria. The global prevalence of NAFLD/MASLD in T2DM patients was 65.33% (95%CI: 62.35%–68.18%), rising from 55.86% (42.38%–68.53%) in 1990–2004 to 68.81% (63.41%–73.74%) in 2016–2021 (P=0.073). The highest prevalence of NAFLD/MASLD was in Eastern Europe (80.62%, 75.72%–84.73%), followed by the Middle East (71.24%, 62.22%–78.84%), with Africa having the lowest prevalence (53.10%, 26.05%–78.44%). Among liver biopsy-assessed patients, the global prevalence of NASH/MASH, significant fibrosis, and advanced fibrosis was 66.44% (56.61%–75.02%), 40.78% (24.24%–59.70%), and 15.49% (6.99%–30.99%), respectively. The overall all-cause mortality rate was 16.79/1000 person-years (10.64–26.40), cardiovascular-specific mortality rate was 4.19/1000 person-years (1.34–7.05), non-hepatic cancer-specific mortality rate was 6.10/1000 person-years (0.78–4.88), and liver-specific mortality rate was 2.15/1000 person-years (0.00–2.21).
Commentary: This meta-analysis focuses on the prevalence of NAFLD and NASH in T2DM patients. The relationship between DM and NAFLD is bidirectional and complex, mutually promoting disease progression. DM increases the risk of advanced liver disease in NAFLD, and NAFLD increases the risk of DM complications. However, global epidemiological data on NAFLD and NASH in T2DM patients need further refinement and updating.
This study ultimately included 123 eligible studies involving 2,224,144 T2DM patients, with 12 studies meeting histological assessment criteria. The global prevalence of NAFLD/MASLD in T2DM patients exceeded half, at 65.33%. The prevalence increased over time, reaching 68.81% in 2016–2021, with regional differences. Among patients with liver biopsy data, the global prevalence of NASH/MASH, significant fibrosis, and advanced fibrosis was 66.44%, 40.78%, and 15.49%, respectively. This study also provided all-cause mortality, cardiovascular-specific mortality, non-hepatic cancer-specific mortality, and liver-specific mortality rates.
The study indicates a high prevalence of NAFLD/MASLD in T2DM patients, which has risen significantly in recent years and varies by region. DM increases the risk of advanced liver disease in NAFLD, and the associated mortality rates are high. Limitations of this study include the potential limited representativeness of data from developing countries and the fact that NASH/MASH prevalence is derived only from liver biopsy patients, which may not represent the general T2DM population with NASH.
Commentary Experts
Professor Ying Li
Tianjin Third Central Hospital Associate Chief Physician, Department of Gastroenterology and Hepatology
Professor Ying Li is an associate chief physician at the Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital. She was a visiting scholar at the Mayo Clinic in the USA and is a Ph.D. candidate. She holds several positions, including member and secretary of the Severe Liver Disease and Artificial Liver Group of the Hepatology Branch of the Chinese Medical Association, member of the Hepatology Society of the Tianjin Medical Association, youth committee member of the Integrative Hepatology Society of Tianjin, youth committee member of the Hepatology Professional Committee of the China Research Hospital Association, and expert in the National Hepatobiliary Disease Consultation Team of the Healthy China-Hepatobiliary Prevention and Treatment Action. She has participated in multiple national and provincial research projects, including major national scientific and technological projects of the 11th, 12th, and 13th Five-Year Plans and the 973 Program sub-projects. She has published over 10 SCI and core journal articles and has contributed to two monographs.
05: Impacts of Glucagon-Like Peptide-1 Receptor Agonists on the Risk of Adverse Liver Outcomes in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease Cirrhosis and Type 2 Diabetes
Authors: Elsaid MI, Li N, Firkins SA, et al.
Journal: Aliment Pharmacol Ther, 2024, 59(9): 1096-1110. doi: 10.1111/apt.17925
Study Overview: A retrospective cohort study using real-world data from the MarketScan database from 2012 to 2020 investigated the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on long-term adverse liver outcomes (ALO) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and type 2 diabetes mellitus (T2DM). The results indicated that GLP-1RAs usage was significantly associated with a reduced risk of liver decompensation, portal hypertension, hepatocellular carcinoma (HCC), and liver transplantation (LT) in these patients.
The study included 459 GLP-1RAs patients and 4837 non-GLP-1RAs patients. A Cox proportional hazards model was used to examine the relationship between GLP-1RAs initiation (modeled as a time-dependent variable) and ALO risk, defined as a composite endpoint of the first occurrence of liver decompensation, portal hypertension, HCC, or LT. Overlap propensity score weighting (OPSW) was used to adjust for confounding. Non-GLP-1RAs patients experienced 1411 ALOs (29%) over 7431.7 person-years, while GLP-1RAs patients experienced 32 ALOs (7%) over 586.6 person-years, with a risk rate difference of 13.5/100 person-years (95% CI: 11.4–15.7). Adjusted for OPSW, the ALO risk was reduced by 36% in the GLP-1RAs group (HR: 0.64; 95% CI: 0.54–0.76). GLP-1RAs initiation was significantly associated with reduced risks of liver decompensation (HR: 0.74; 95% CI: 0.61–0.88), portal hypertension (HR: 0.73; 95% CI: 0.60–0.88), HCC (HR: 0.37; 95% CI: 0.20–0.63), and LT (HR: 0.24; 95% CI: 0.12–0.43).
Commentary: GLP-1 receptor agonists are a class of drugs for T2DM treatment, also approved by the FDA for long-term weight management in obese or overweight adults due to their excellent weight loss effects. GLP-1 receptor agonists have been extensively studied in the field of non-alcoholic liver disease, suggesting that they can improve liver fat content and inflammation in non-alcoholic fatty liver disease (NAFLD) patients. Many prospective, randomized, controlled, multicenter clinical studies have focused on the effects of these drugs on liver fat content and fibrosis in NAFLD patients, but the relevant data results are not yet fully published. Further research is needed on the long-term adverse liver outcomes such as liver decompensation, portal hypertension, HCC, and LT.
This study, using real-world data from the MarketScan database from 2012 to 2020, included 459 GLP-1RAs patients and 4837 non-GLP-1RAs patients. A Cox proportional hazards model was used to examine the relationship between GLP-1RAs and ALO risk, with OPSW applied to adjust for confounding. Adjusted for OPSW, the ALO risk was reduced by 36% in the GLP-1RAs group. The reliability and persuasiveness of the results are enhanced by the real-world data and statistical adjustments for confounding. However, the study’s limitations include its retrospective nature, the single-country population, and the lack of detailed racial group stratification. The average follow-up time was 16.5 months, but longer follow-up is needed to assess long-term liver outcomes such as liver decompensation, malignant liver tumors, and liver transplantation. Large-scale, prospective, randomized, controlled, multicenter, long-term studies are needed to validate these findings.
06: Associations between Type 2 Diabetes Mellitus and Chronic Liver Diseases: Evidence from a Mendelian Randomization Study in Europeans and East Asians
Authors: Zhao Y, Li D, Shi H, et al.
Journal: Front Endocrinol (Lausanne), 2024, 15: 1338465. doi: 10.3389/fendo.2024.1338465
Study Overview: Multiple observational studies have suggested a link between T2DM and chronic liver diseases (CLDs). However, the causal relationship between T2DM and CLDs in different ethnic groups remains unclear. Chinese scientists conducted a two-sample Mendelian randomization (MR) study to examine the causal relationships between T2DM and the risks of NAFLD, HCC, viral hepatitis, HBV infection, and HCV infection in European and East Asian populations.
The study initially utilized inverse variance weighting (IVW) to assess the causal relationships between T2DM and CLDs, with a series of rigorous analyses conducted to strengthen the reliability of the MR results. This MR analysis revealed different causal relationships between T2DM and CLDs in East Asian and European populations, suggesting the need for further research to investigate the underlying mechanisms in different ethnic groups. This could provide new insights into early screening and prevention strategies for CLDs in T2DM patients.
In the European population, genetic susceptibility to T2DM increased the risk of NAFLD (IVW: OR=1.3654, 95% CI: 1.2250–1.5219, P=1.85e-8) and viral hepatitis (IVW: OR=1.1173, 95% CI: 1.0271–1.2154, P=0.0098), indicating a positive correlation between T2DM and HCC (IVW: OR=1.2671, 95% CI: 1.0471–1.5333, P=0.0150) and HBV (IVW: OR=1.1908, 95% CI: 1.0368–1.3677, P=0.0134). No causal relationship was found between T2DM and HCV. However, in the East Asian population, T2DM was significantly negatively correlated with NAFLD (ALT: IVW OR=0.9752, 95% CI: 0.9597–0.9909, P=0.0021; AST: IVW OR=0.9673, 95% CI: 0.9528–0.9821, P=1.67e-5) and HCV (IVW: OR=0.9289, 95% CI: 0.8852–0.9747, P=0.0027). Notably, there was no causal relationship between T2DM and HCC, viral hepatitis, or HBV in the East Asian population.
Commentary: There is a complex bidirectional relationship between diabetes and chronic liver diseases (CLDs). T2DM and NAFLD mutually promote each other’s occurrence, with T2DM being a significant predictor of NAFLD progression to NASH and NASH-related cirrhosis. The correlation between HBV infection and diabetes remains controversial, with some studies reporting a fourfold higher incidence of T2DM in CHB patients compared to the general population. HCV infection is a significant risk factor for diabetes, with HCV core protein directly inhibiting insulin signaling, leading to insulin resistance. Chronic HCV and HBV infection increase the likelihood of diabetes once cirrhosis develops. Additionally, diabetes is a major independent risk factor for HCC. The association and mechanisms between diabetes and chronic liver diseases remain a focal point of extensive research.
This study further analyzed the association between diabetes and chronic liver diseases from a genetic perspective in different ethnic groups. The research data came from the DIAMANTE consortium’s diabetes meta-analysis, including 898,130 European and 433,540 East Asian individuals, using inverse variance weighting to assess the causal relationship between T2DM and CLDs. It revealed different causal relationships between T2DM and CLDs in East Asians and Europeans. In Europeans, genetic susceptibility to T2DM increased the risk of NAFLD and viral hepatitis, with a positive correlation between T2DM and HCC and HBV. In East Asians, T2DM was significantly negatively correlated with NAFLD and HCV. The large data volume ensures the reliability of the results.
However, different lifestyles, dietary structures, and habits in different ethnic groups can act as confounding factors affecting the results. The detailed stratification of different ethnic data, such as age, gender, BMI, and liver disease status, may affect the final analysis results. This study focuses on the characteristics of the association between diabetes and chronic liver diseases in different ethnic groups, but it only includes European and East Asian populations. Adding more ethnic data could further enrich the study results. The study also hopes that further research can reveal the mechanisms of the association between diabetes and chronic liver diseases, leading to early screening and prevention. Based on large-scale genetic data, the study suggests that related loci found in genetic analyses could be used as early screening indicators, further deepening the study’s findings.
Editors-in-Chief: Jie Li, Xiaolong Qi
Executive Editors: Nan Geng, Fajun Rui, Liyun Fu
