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Rigon FA, Ronsoni MF, Hohl A, Vianna AGD, van de Sande-Lee S, Schiavon LDL. Intermittently Scanned Continuous Glucose Monitoring Performance in Patients With Liver Cirrhosis. J Diabetes Sci Technol 2024:19322968241232686. [PMID: 38439562 PMCID: PMC11571376 DOI: 10.1177/19322968241232686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2024]
Abstract
AIM To evaluate the use of intermittently scanned continuous glucose monitoring (isCGM) in patients with liver cirrhosis (LC). METHODS Observational study including 30 outpatients with LC (Child-Pugh B/C): 10 without diabetes (DM) (G1), 10 with newly diagnosed DM by oral glucose tolerance test (G2), and 10 with a previous DM diagnosis (G3). isCGM (FreeStyle Libre Pro) was used for 56 days (four sensors/patient). Blood tests were performed at baseline and after 28 and 56 days. RESULTS No differences were found in the baseline characteristics, except for higher age in G3. There were significant differences between G1, G2 and G3 in glucose management indicator (GMI) (5.28 ± 0.17, 6.03 ± 0.59, 6.86 ± 1.08%, P < .001), HbA1c (4.82 ± 0.39, 5.34 ± 1.26, 6.97 ± 1.47%, P < .001), average glucose (82.79 ± 7.06, 113.39 ± 24.32, 149.14 ± 45.31mg/dL, P < .001), time in range (TIR) (70.89 ± 9.76, 80.2 ± 13.55, 57.96 ± 17.96%, P = .006), and glucose variability (26.1 ± 5.0, 28.21 ± 5.39, 35.31 ± 6.85%, P = .004). There was discordance between GMI and HbA1c when all groups were considered together, with a mean difference of 0.35% (95% SD 0.17, 0.63). In G1, the mean difference was 0.46% (95% SD 0.19, 0.73) and in G2 0.69% (95% SD 0.45, 1.33). GMI and HbA1c were concordant in G3, with a mean difference of -0.10 % (95% SD [-0.59, 0.38]). CONCLUSION Disagreements were found between the GMI and HbA1c levels in patients with LC. isCGM was able to detect abnormalities in glycemic control that would not be detected by monitoring with HbA1c, suggesting that isCGM can be useful in assessing glycemic control in patients with LC.
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Affiliation(s)
- Fernanda Augustini Rigon
- Graduate Program in Medical Sciences, Polydoro Ernani de São Thiago University Hospital, Federal University of Santa Catarina, Florianópolis, Brazil
| | | | - Alexandre Hohl
- Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil
| | - André Gustavo Daher Vianna
- Curitiba Diabetes Center, Department of Endocrine Diseases, Hospital Nossa Senhora das Graças, Curitiba, Brazil
| | - Simone van de Sande-Lee
- Department of Internal Medicine, Federal University of Santa Catarina, Florianópolis, Brazil
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Zhao Y, Li D, Shi H, Liu W, Qiao J, Wang S, Geng Y, Liu R, Han F, Li J, Li W, Wu F. Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians. Front Endocrinol (Lausanne) 2024; 15:1338465. [PMID: 38495785 PMCID: PMC10941029 DOI: 10.3389/fendo.2024.1338465] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024] Open
Abstract
Objective Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups. Methods We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results. Results In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of 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, no causal association was found between T2DM and HCC, viral hepatitis, or HBV. Conclusion Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.
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Affiliation(s)
- Yue Zhao
- Department of Surgery, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Di Li
- Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Hanyu Shi
- Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Wei Liu
- Department of General Surgery, Shandong Corps Hospital of Chinese People’s Armed Police Force, Jinan, China
| | - Jiaojiao Qiao
- Department of Nursing, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Shanfu Wang
- Department of Surgery, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Yiwei Geng
- School of Statistic and Data Science, Jiangxi University of Finance and Economics, Nanchang, Jiangxi, China
| | - Ruiying Liu
- Department of Nursing, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Feng Han
- Department of Surgery, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Jia Li
- Department of Health and Epidemic Prevention, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Wei Li
- Department of General Surgery, The 980Hospital of the Chinese People's Liberation Army (PLA) Joint Logistics Support Force (Primary Bethune International Peace Hospital of Chinese People's Liberation Army (PLA), Shijiazhuang, Hebei, China
| | - Fengyun Wu
- Department of General Surgery, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
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Wang Y, Dan L, Fu T, Sun Y, Chen J, Mao R. Serum 25-hydroxyvitamin D, type 2 diabetes, and liver-related outcomes: Secondary data analysis of a prospective recruited cohort. Hepatol Commun 2023; 7:e0291. [PMID: 37902501 PMCID: PMC10617905 DOI: 10.1097/hc9.0000000000000291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/19/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND The association of vitamin D deficiency, which is prevalent in type 2 diabetes mellitus (T2DM), with liver disease and related mortality has not been quantified. Our study aimed to (1) investigate whether there is a synergistic association of vitamin D deficiency and T2DM with liver-related outcomes and (2) explore whether high 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a lower risk of liver-related outcomes in T2DM. METHOD Leveraging the data from UK Biobank, we conducted 2 studies: study I assessed the joint associations of vitamin D deficiency [25(OH)D <50 nmol/L] and T2DM with liver-related outcomes among 439,276 participants, and study II explored the associations of vitamin D status with liver-related outcomes among 21,519 individuals with T2DM. Baseline T2DM was identified through medication, laboratory test, and electronic health-related records. Serum 25(OH)D was measured by direct competitive chemiluminescent immunoassay. Liver-related outcomes included 6 liver disease end points and mortality by overall liver disease, chronic liver disease, and severe liver disease. RESULTS During an average follow-up duration of 11.6 years, we observed a significant positive additive interaction effect (all synergy index>1.0) of T2DM and vitamin D deficiency on the risk of liver-related outcomes. Compared with participants without either T2DM or vitamin D deficiency, the multivariable-adjusted HRs of overall liver diseases were 1.29 for participants without T2DM but with vitamin D deficiency, 1.73 for participants with T2DM but without vitamin D deficiency, and 2.19 for participants with both T2DM and vitamin D deficiency. In individuals with T2DM, we observed that participants without vitamin D deficiency were inversely associated with incident liver disease and related mortality (multivariable-adjusted HRs 0.41-0.81) when compared with individuals with vitamin D deficiency. CONCLUSIONS There are positive synergistic associations of vitamin D deficiency and T2DM with liver-related outcomes. Inverse associations between serum 25(OH)D concentrations and liver-related outcomes were observed in individuals with T2DM.
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Affiliation(s)
- Yu Wang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lintao Dan
- Center for Global Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Fu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yuhao Sun
- Center for Global Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Jie Chen
- Center for Global Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Chevalier C, Fouqueray P, Bolze S. Imeglimin: A Clinical Pharmacology Review. Clin Pharmacokinet 2023; 62:1393-1411. [PMID: 37713097 DOI: 10.1007/s40262-023-01301-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2023] [Indexed: 09/16/2023]
Abstract
Imeglimin (PXL008, EMD-387008, Twymeeg®) is a first-in-class novel oral hypoglycemic agent, launched in Japan, for the treatment of type 2 diabetes mellitus. Its mechanism of action targets mitochondrial bioenergetics to ameliorate insulin resistance and to enhance β-cell function. This review summarizes the properties underlying the pharmacokinetic profile of imeglimin, a small cationic drug belonging to the tetrahydrotriazine chemical class, with a complex mechanism of absorption involving an active transport through organic cation transporters (OCTs). Imeglimin absorption decreases when dose increases due to the saturation of the active uptake transport. Post absorption, imeglimin is rapidly and primarily distributed to organs and tissues, and has a half-life ranging from 9.03 to 20.2 h. Plasma protein binding of imeglimin is low, which explains the rapid distribution to the organs observed in all species. Imeglimin is excreted unchanged in urine, indicating a low extent of metabolism. Imeglimin is a substrate of multidrug and toxic compound extrusion (MATE) 2-K and a substrate and inhibitor of OCT1, OCT2, and MATE1. Clinical drug-drug interaction studies confirmed the absence of relevant clinical interaction with substrates or inhibitors of these transporters. Overall, the drug-drug interaction potential of imeglimin is low. Its pharmacokinetics profile has also been characterized in special populations, showing no influence of mild and moderate hepatic impairment but an impact of renal function on imeglimin renal clearance. Dosage adjustment is thus required in moderately and severely renally impaired patients. Imeglimin pharmacokinetics was shown to be insensitive to ethnicity and food intake and to have no effect on QTcF interval.
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Chen N, Qiu X, Ruan H, Huang J, Liu S. Effects of late evening snacks on glucose homeostasis in cirrhotic patients: A meta-analysis. Medicine (Baltimore) 2023; 102:e32805. [PMID: 36800603 PMCID: PMC9936037 DOI: 10.1097/md.0000000000032805] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND Insulin resistance and hepatogenic diabetes are common complications in patients with liver cirrhosis. Previous studies have shown that reducing the fasting phase by supplying a late evening snack (LES) is a potential intervention to improve substrate utilization and liver function. However, the underlying mechanisms need to be further elucidated. The purpose of current meta-analysis is to evaluate effects of LES on glucose homeostasis in cirrhotic patients. METHODS Electronic databases including PubMed, Web of Science, and major scientific conference sessions were searched without language restriction and carried out on March 1, 2022 with an additional manual search of bibliographies of relevant articles. A total of 4145 studies were identified, and 10 studies were eligible for the meta-analysis, comprising 631 patients (319 in the LES group and 312 in the non-LES group). Subgroup analyses were performed to investigate the effect of LES on cirrhotic patients with or without diabetes. RESULTS Analysis showed that LES intervention had significant effects in cirrhotic patients for glycemic parameters on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin respective effect sizes of -8.7, -0.86, and -0.76. Subgroup result revealed that the effect of LES on fasting plasma glucose is higher in cirrhotic patients with diabetes group than cirrhotic patients without diabetes group, and long-term LES supplementation (>2 months) was more beneficial to maintain glucose homeostasis in cirrhotic patients than that of short-term supplementation (<2 months). LES also had significant effect on nutritional metabolic parameters like including albumin and non-protein respiratory quotient. CONCLUSION Meta-analysis indicated that LES not only improved malnutrition in cirrhotic patients with or without diabetes but also maintain glucose homeostasis in cirrhotic patients with diabetes. LES is a promising and simple intervention that beneficial to maintain glucose homeostasis in cirrhotic patients.
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Affiliation(s)
- Ni Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Xinze Qiu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Huaqiang Ruan
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Jiean Huang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Shiquan Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
- * Correspondence: Shiquan Liu, Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, 166 Daxuedong Road, Nanning, Guangxi 530007, PR China (e-mail: , )
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Kumar R, García-Compeán D, Maji T. Hepatogenous diabetes: Knowledge, evidence, and skepticism. World J Hepatol 2022; 14:1291-1306. [PMID: 36158904 PMCID: PMC9376767 DOI: 10.4254/wjh.v14.i7.1291] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 04/27/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India.
| | - Diego García-Compeán
- Department of Gastroenterology, University Hospital, Universidad Autónoma de Nuevo León, México, Monterrey 64700, México
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults. Cancers (Basel) 2022; 14:cancers14071709. [PMID: 35406481 PMCID: PMC8997058 DOI: 10.3390/cancers14071709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 01/06/2023] Open
Abstract
Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002−2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58−24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC—liver cirrhosis (HR = 1.29; 95% CI = 0.48−3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49−7.63)—were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.
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Abstract
Background/Objectives Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. Methods A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. Results HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P < 0.001), incidence of large varices (P < 0.001) and variceal bleeding (P < 0.001). A statistically significant association was noted between HD and Hepatocellular carcinoma (HCC) (P < 0.001). Conclusion Patients with cirrhosis had a high prevalence of IGT, IR, and HD. The presence of HD is well associated with the severity of cirrhosis in the form of higher MELD score (>15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.
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Key Words
- 120-min PG, 120 min plasma glucose
- AASLD, American association for the study of liver diseases
- ADA, American diabetic association
- CLD, chronic liver disease
- CTP score, Child-Turcotte-Pugh score
- DM, diabetes mellitus
- FPG, fasting plasma glucose
- HCC, hepatocellular carcinoma
- HD, hepatogenous diabetes
- HOMA-IR, homeostatic model assessment-insulin resistance
- HVPG, hepatic venous pressure gradient
- HbA1c, glycated hemoglobin
- IGF, insulin-like growth factor
- IGT, impaired glucose tolerance
- IR, insulin resistance
- MELD score, model for end-stage liver disease
- OGTT, oral glucose tolerance test
- SPSS, statistical software for social sciences
- T2DM, type 2 diabetes mellitus
- chronic liver disease
- hepatogenous diabetes
- impaired glucose tolerance
- insulin resistance
- variceal bleeding
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Stempak-Droissart T, Rousset-Jablonski C, Spritzer PM, Lalhou N, Larger E, Pichard C, Plessier A, Gompel A. Impact of vascular liver disease on the menstrual cycle and metabolic status in premenopausal women. Clin Res Hepatol Gastroenterol 2022; 46:101756. [PMID: 34303004 DOI: 10.1016/j.clinre.2021.101756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/03/2021] [Accepted: 06/28/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Vascular liver disease (VLD) are rare liver diseases, which affect women at reproductive ages. Main complications are bleeding (portal hypertension, thrombopenia or anticoagulation related) and thromboembolism. Failure of liver function can occur. Thus endocrine abnormalities management and contraception are challenging. PURPOSE to evaluate the impact on the menstrual cycles and related endocrine abnormalities in women with VLD and respective roles of liver function and portal hypertension. STUDY DESIGN This was a single-center observational cohort study. Forty-seven premenopausal women with vascular liver disease were included for endocrine and gynecological assessments. Endocrine evaluation was performed at inclusion. Tolerance of contraception was followed up and assessed at 3 and 12 months. PARTICIPANTS, SETTING, METHODS Forty-seven women (aged 16-50) followed in a Reference Center for Liver Vascular Disease between February 2009 and November 2016 were included and addressed for gynecological and endocrinological management. Twenty-five women had extrahepatic portal vein obstruction, 17 had Budd Chiari Syndrome and five had a porto-sinusoidal vascular disease. We explored gonadotropin at baseline and after GnRH, testosterone, sex hormone binding globulin (SHBG), androstenedione, GH axis and glucose metabolism. All women underwent pelvic ultrasonography. RESULTS Vascular liver disease was associated with abnormal menstrual cycles in 53% of the women and clinical and/or biological hyperandrogenism and/or a polycystic ovary morphology was identified in 38%. Portal hypertension was correlated to higher testosterone levels (P = 0.04), whereas higher elevated levels SHBG in 28%, correlated with liver failure (P = 0.01). Sixteen had glucose intolerance profile or diabetes. IGF-1 levels were highly correlated with hepatic failure. Abnormal uterine bleeding occurred in 21% of women, 87% of which were due to gynecological pathologies revealed by anticoagulant treatment. Progestin contraception was well tolerated and helped to control bleeding. CONCLUSION AND IMPLICATIONS endocrine abnormalities, prior described in association with cirrhosis, are also identified in patients with vascular liver disease, and require specific management. Glucose intolerance profile is frequent, further studies are needed to assess significant consequences on cardio-vascular system.
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Affiliation(s)
- Tatiana Stempak-Droissart
- Université de Paris, Department of Gynecological Endocrinology, Hôpitaux Universitaires Centre, AP-HP, Paris, France; Department of Obstetrics and Gynecology, Groupe hospitalier Sud Ile de France, Centre hospitalier de Melun, Melun, France
| | | | - Poli M Spritzer
- Université de Paris, Department of Gynecological Endocrinology, Hôpitaux Universitaires Centre, AP-HP, Paris, France; Division of Endocrinology, Hospital de Clinicas de Porto Alegre and Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Najiba Lalhou
- Laboratory of Hormonal Biology, Groupe hospitalier Cochin-Port Royal, AP-HP, Paris, France
| | - Etienne Larger
- Université de Paris, Department of Diabetology, Groupe hospitalier Cochin-PorRoyal, AP-HP, Paris, France
| | - Caroline Pichard
- Department of Endocrinology and metabolic diseases, Groupe hospitalier La Pitié-Salpêtrière, APHP, Paris, Fance
| | - Aurélie Plessier
- Beaujon Hospital, AP-HP, DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Inserm U1149, Centre de Recherche sur l'Inflammation (CRI), Paris, Université Paris 7-Denis-Diderot, ERN Rare liver Clichy, France
| | - Anne Gompel
- Université de Paris, Department of Gynecological Endocrinology, Hôpitaux Universitaires Centre, AP-HP, Paris, France.
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Armandi A, Rosso C, Caviglia GP, Bugianesi E. Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease. Metabolites 2021; 11:155. [PMID: 33800465 PMCID: PMC8000048 DOI: 10.3390/metabo11030155] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/01/2021] [Accepted: 03/01/2021] [Indexed: 02/07/2023] Open
Abstract
Insulin resistance (IR) is defined as a lower-than-expected response to insulin action from target tissues, leading to the development of type 2 diabetes through the impairment of both glucose and lipid metabolism. IR is a common condition in subjects with nonalcoholic fatty liver disease (NAFLD) and is considered one of the main factors involved in the pathogenesis of nonalcoholic steatohepatitis (NASH) and in the progression of liver disease. The liver, the adipose tissue and the skeletal muscle are major contributors for the development and worsening of IR. In this review, we discuss the sites and mechanisms of insulin action and the IR-related impairment along the spectrum of NAFLD, from simple steatosis to progressive NASH and cirrhosis.
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Affiliation(s)
| | | | | | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (A.A.); (C.R.); (G.P.C.)
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Nedyalkova M, Madurga S, Ballabio D, Robeva R, Romanova J, Kichev I, Elenkova A, Simeonov V. Diabetes mellitus type 2: Exploratory data analysis based on clinical reading. OPEN CHEM 2020. [DOI: 10.1515/chem-2020-0086] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
AbstractDiabetes mellitus type 2 (DMT2) is a severe and complex health problem. It is the most common type of diabetes. DMT2 is a chronic metabolic disorder that affects the way your body metabolizes sugar. With DMT2, your body either resists the effects of insulin or does not produce sufficient insulin to continue normal glucose levels. DMT2 is a disease that requires a multifactorial approach of controlling that includes lifestyle change and pharmacotherapy. Less than ideal management increases the risk of developing complications and comorbidities such as cardiovascular disease and numerous social and economic penalties. That is why the studies dedicated to the pathophysiological mechanisms and the treatment of DMT2 are extremely numerous and diverse. In this study, exploratory data analysis approaches are applied for the treatment of clinical and anthropometric readings of patients with DMT2. Since multivariate statistics is a well-known method for classification, modeling and interpretation of large collections of data, the major aim of the present study was to reveal latent relations between the objects of the investigation (group of patients and control group) and the variables describing the objects (clinical and anthropometric parameters). In the proposed method by the application of hierarchical cluster analysis and principal component analysis it is possible to identify reduced number of parameters which appear to be the most significant discriminant parameters to distinguish between four patterns of patients with DMT2. However, there is still lack of multivariate statistical studies using DMT2 data sets to assess different aspects of the problem like optimal rapid monitoring of the patients or specific separation of patients into patterns of similarity related to their health status which could be of help in preparation of data bases for DMT2 patients. The outcome from the study could be of custom for the selection of significant tests for rapid monitoring of patients and more detailed approach to the health status of DMT2 patients.
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Affiliation(s)
- Miroslava Nedyalkova
- Department of Inorganic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia “St. Kl. Ohridski”, 1164 Sofia, 1, Ave. J. Bourchier, Bulgaria
| | - Sergio Madurga
- Department of Physical Chemistry and the Research Institute of Theoretical and Computational Chemistry (IQTCUB) of the University of Barcelona (UB), 08028 Barcelona, C/Martí i Franquès, 1, Spain
| | - Davide Ballabio
- Department of Earth and Environmental Sciences, Chemometrics and QSAR Research Group, University of Milano-Bicocca, Piazza della Scienza, 1, 20126 Milano, Italy
| | - Ralitsa Robeva
- Faculty of Medicine, Medical University – Sofia, Department of Endocrinology, 1431 Sofia, USHATE Acad. Iv. Penchev, Bulgaria
| | - Julia Romanova
- Department of Inorganic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia “St. Kl. Ohridski”, 1164 Sofia, 1, Ave. J. Bourchier, Bulgaria
| | - Ilia Kichev
- Department of Inorganic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia “St. Kl. Ohridski”, 1164 Sofia, 1, Ave. J. Bourchier, Bulgaria
| | - Atanaska Elenkova
- Faculty of Medicine, Medical University – Sofia, Department of Endocrinology, 1431 Sofia, USHATE Acad. Iv. Penchev, Bulgaria
| | - Vasil Simeonov
- Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia “St. Kl. Ohridski”, 1164 Sofia, 1, Ave. J. Bourchier, Bulgaria
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12
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Kislal S, Shook LL, Edlow AG. Perinatal exposure to maternal obesity: Lasting cardiometabolic impact on offspring. Prenat Diagn 2020; 40:1109-1125. [PMID: 32643194 DOI: 10.1002/pd.5784] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 06/25/2020] [Accepted: 07/05/2020] [Indexed: 12/11/2022]
Abstract
Evidence from epidemiological, clinical, and animal model studies clearly demonstrates that prenatal and lactational maternal obesity and high-fat diet consumption are associated with cardiometabolic morbidity in offspring. Fetal and offspring sex may be an important effect modifier. Adverse offspring cardiometabolic outcomes observed in the setting of maternal obesity include an increased risk for obesity, features of metabolic syndrome (hypertension, hyperglycemia and insulin resistance, hyperlipidemia, increased adiposity), and non-alcoholic fatty liver disease. This review article synthesizes human and animal data linking maternal obesity and high-fat diet consumption in pregnancy and lactation to adverse cardiometabolic outcomes in offspring. We review key mechanisms underlying skeletal muscle, adipose tissue, pancreatic, liver, and central brain reward programming in obesity-exposed offspring, and how such malprogramming contributes to offspring cardiometabolic morbidity.
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Affiliation(s)
- Sezen Kislal
- Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lydia L Shook
- Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrea G Edlow
- Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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13
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Costa D, Lourenço J, Monteiro AM, Castro B, Oliveira P, Tinoco MC, Fernandes V, Marques O, Gonçalves R, Rolanda C. Clinical Performance of Flash Glucose Monitoring System in Patients with Liver Cirrhosis and Diabetes Mellitus. Sci Rep 2020; 10:7460. [PMID: 32366878 PMCID: PMC7198519 DOI: 10.1038/s41598-020-64141-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 04/06/2020] [Indexed: 12/22/2022] Open
Abstract
Flash glucose monitoring system (FGMS) is an improved subset of continuous glucose monitoring with a recognized effectiveness on glycemic control, though validation in patients with Liver Cirrhosis (LC) is lacking. To evaluate the accuracy of FGMS in patients with Type 2 Diabetes Mellitus (DM) and LC, a prospective, case-control study was performed in 61 ambulatory patients with LC and DM (LC group, n = 31) or DM (Control group, n = 30). During 14 days, patients performed 4 assessments per day of self-monitoring of blood glucose (SMBG, reference value) followed by FGMS scanning. There were 2567 paired SMBG and FGMS values used in the accuracy analysis, with an overall mean absolute relative difference (MARD) of 12.68% in the LC group and 10.55% in the control group (p < 0,001). In patients with LC, the percentage of readings within Consensus Consensus Error Grid analysis Zone A and A + B were 80.36% and 99,26%, respectively. Sensor clinical accuracy was not affected by factors such as body mass index, age, gender, Child-Pugh score or edematoascitic decompensation. This is the first study to approach FGMS clinical accuracy in LC, revealing a potential usability of this system to monitor glycemic control in this population.
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Affiliation(s)
- Dalila Costa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. .,Gastroenterology Department, Braga Hospital, Braga, Portugal.
| | - Joana Lourenço
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
| | | | - Beatriz Castro
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
| | | | | | - Vera Fernandes
- Endocrinology Department, Braga Hospital, Braga, Portugal
| | - Olinda Marques
- Endocrinology Department, Braga Hospital, Braga, Portugal
| | | | - Carla Rolanda
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.,Gastroenterology Department, Braga Hospital, Braga, Portugal
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14
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Papazafiropoulou A, Melidonis A. Antidiabetic agents in patients with hepatic impairment. World J Meta-Anal 2019; 7:380-388. [DOI: 10.13105/wjma.v7.i8.380] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 08/07/2019] [Accepted: 08/20/2019] [Indexed: 02/06/2023] Open
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15
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Zhong Y, Huang W, Du J, Wang Z, He J, Luo L. Improved Tol2-mediated enhancer trap identifies weakly expressed genes during liver and β cell development and regeneration in zebrafish. J Biol Chem 2018; 294:932-940. [PMID: 30504219 DOI: 10.1074/jbc.ra118.005568] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 11/26/2018] [Indexed: 01/13/2023] Open
Abstract
The liver and pancreas are two major digestive organs, and among the different cell types in them, hepatocytes and the insulin-producing β cells have roles in both health and diseases. Accordingly, clinicians and researchers are very interested in the mechanisms underlying the development and regeneration of liver and pancreatic β cells. Gene and enhancer traps such as the Tol2 transposon-based system are useful for identifying genes potentially involved in developmental processes in the zebrafish model. Here, we developed a strategy that combines a Tol2-mediated enhancer trap and the Cre/loxP system by using loxP-flanked reporters driven by β cell- or hepatocyte-specific promoters and the upstream activating sequence (UAS)-driving Cre. Two double-transgenic reporter lines, Tg(ins:loxP-CFPNTR-loxP-DsRed; 10×UAS:Cre, cryaa:Venus) and Tg(fabp10:loxP-CFPNTR-loxP-DsRed; 10×UAS:Cre, cryaa:Venus), were established to label pancreatic β cells and hepatocytes, respectively. These two double-transgenic lines were each crossed with the Tol2-enhancer trap founder lines to screen for and identify genes expressed in the β cell and hepatocytes during development. This trap system coupled with application of nitroreductase (NTR)/metronidazole (Mtz)-mediated cell ablation could identify genes expressed during regeneration. Of note, pilot enhancer traps captured transiently and weakly expressed genes such as rab3da and ensab with higher efficiencies than traditional enhancer trap systems. In conclusion, through permanent genetic labeling by Cre/loxP, this improved Tol2-mediated enhancer trap system provides a promising method to identify transiently or weakly expressed, but potentially important, genes during development and regeneration.
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Affiliation(s)
- Yadong Zhong
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and.,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
| | - Wei Huang
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and.,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
| | - Jiang Du
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and.,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
| | - Zekun Wang
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and.,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
| | - Jianbo He
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and.,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
| | - Lingfei Luo
- From the Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, and .,Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China
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16
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Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients. INFECTION GENETICS AND EVOLUTION 2018; 66:1-8. [PMID: 30172885 DOI: 10.1016/j.meegid.2018.08.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/15/2018] [Accepted: 08/29/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Chronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. PATIENTS & METHODS In this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930- > G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique. RESULTS Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P < 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection. CONCLUSIONS Our results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters.
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17
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Park YS, Moon YJ, Jun IG, Song JG, Hwang GS. Application of the Revised Cardiac Risk Index to the Model for End-Stage Liver Disease Score Improves the Prediction of Cardiac Events in Patients Undergoing Liver Transplantation. Transplant Proc 2018; 50:1108-1113. [PMID: 29731076 DOI: 10.1016/j.transproceed.2018.01.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 01/22/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Although the revised cardiac risk index (RCRI) is a useful tool for estimating the risk of postoperative cardiac events, whether it improves the prediction of cardiac events in patients undergoing liver transplantation (LT) has not been sufficiently demonstrated. METHODS We retrospectively analyzed 1429 patients who underwent LT. Cardiac events were defined as myocardial infarction, death, or combined events within 30 days after surgery. The RCRI was defined as the number of independent predictors including high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin treatment, and creatinine level >2 mg/dL. Multivariate logistic regression analysis was performed to identify factors independently associated with cardiac events. The additive predictability of RCRI for the Model for End-Stage Liver Disease (MELD) score was assessed using receiver operating characteristic curve analysis. RESULTS Forty-four (3.1%) cardiac events occurred within 30 days after surgery. Both the MELD score (adjusted odds ratio [aOR], 1.05; P = .005) and RCRI (aOR, 4.35; P < .001 for RCRI score 2; aOR, 6.27; P = .009 for RCRI score 3 compared with RCRI score 1) independently predicted postoperative 30-day cardiac events. The model with MELD score plus RCRI was significantly more predictive for postoperative 30-day cardiac events than the model with MELD score alone (C-statistics 0.800 vs 0.757; P = .030). CONCLUSIONS For preoperative risk stratification, RCRI showed additive value to MELD score in predicting postoperative 30-day cardiac events after LT.
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Affiliation(s)
- Y-S Park
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Y-J Moon
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - I-G Jun
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - J-G Song
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - G-S Hwang
- Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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18
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Kiss K, Regős E, Rada K, Firneisz G, Baghy K, Kovalszky I. Chronic Hyperglycaemia Induced Alterations of Hepatic Stellate Cells Differ from the Effect of TGFB1, and Point toward Metabolic Stress. Pathol Oncol Res 2018; 26:291-299. [PMID: 30109568 DOI: 10.1007/s12253-018-0458-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 07/19/2018] [Indexed: 12/16/2022]
Abstract
The deleterious effect of hyperglycemia on the biology of the liver is supported by clinical evidence. It can promote the development of fatty liver, liver fibrosis, even liver cancer as complication of diabetes mellitus. As liver fibrosis is the consequence of hepatic stellate cell (HSC) activation, the questions were addressed whether alterations induced by high glucose concentration are directly related to TGFB1 effect, or other mechanisms are activated. In order to obtain information on the response of HSC for high glucose, LX-2 cells (an immortalized human HSC cell lineage) were cultured in 15.3 mM glucose containing medium for 21 days. The effect of glucose was compared to that of TGFB1. Our data revealed that chronic exposure of high glucose concentration initiated profound alteration of LX-2 cells and the effect is different from those observed upon interaction with TGFB1. Whereas TGFB1 induced the production of extracellular matrix proteins, high glucose exposure resulted in decreased MMP2 activity, retardation of type I collagen in the endoplasmic reticulum, with decreased pS6 expression, pointing to development of endoplasmic stress and sequestration of p21CIP1/WAF1 in the cytoplasm which can promote the proliferation of LX2 cells.
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Affiliation(s)
- Katalin Kiss
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary
| | - Eszter Regős
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary
| | - Kristóf Rada
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary
| | - Gábor Firneisz
- 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi utcA 46, Budapest, H-1085, Hungary
- MTA-SE Molecular Medicine Research Group, Semmelweis University, Szentkirályi utca 46. Budapest, H-1085, Hungary
| | - Kornélia Baghy
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary
| | - Ilona Kovalszky
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.
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Haring RC, Jim MA, Erwin D, Kaur J, Henry WAE, Haring ML, Seneca DS. Mortality disparities: A comparison with the Haudenosaunee in New York State. CANCER HEALTH DISPARITIES 2018; 2:10.9777/chd.2018.10009. [PMID: 31777774 PMCID: PMC6880943 DOI: 10.9777/chd.2018.10009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Identifying health status and disparities for Indigenous populations is the first logical step toward better health. We compare the mortality profile of the American Indian and Alaska Native (AI/AN) population with that of non-Hispanic whites in the Haudenosaunee Nations in New York State, the Indian Health Service (IHS) East region (Nashville Area) and the United States. Data from the linkage of IHS registration records with decedents from the National Death Index (1990-2009) were used to identify AI/AN deaths misclassified as non-AI/AN. Analyses were limited to persons of non-Hispanic origin. We analyzed trends for 1990-2009 and compared AI/AN and white persons in the Haudenosaunee Nations in New York State, IHS East region and the United States. All-cause death rates over the past two decades for Haudenosaunee men declined at a greater percentage per year than for AI/AN men in the East region and United States. This decrease was not observed for Haudenosaunee women with all-cause death rates appearing to be stable over the past two decades. Haudenosaunee all-cause death rates were 16% greater than that for whites in the Haudenosaunee Nations. The most prominent disparities between Haudenosaunee and whites are concentrated in the 25-44 year age group (Risk Ratio=1.85). Chronic liver disease, diabetes, unintentional injury, and kidney disease death rates were higher in Haudenosaunee than in whites in the Haudenosaunee Nations. The Haudenosaunee cancer death rate (180.8 per 100,000) was higher than that reported for AI/AN in the East (161.5 per 100,000).Haudenosaunee experienced higher rates for the majority of the leading causes of death than East AI/AN. These results highlight the importance of Haudenosaunee-specific data to target prevention efforts to address health disparities and inequalities in health.
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Affiliation(s)
- Rodney C Haring
- Office of Community Outreach and Engagement, Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Melissa A Jim
- Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Albuquerque, NM
| | - Deborah Erwin
- Office of Community Outreach and Engagement, Department of Cancer Prevention and Control, Roswell Park Comprensive Cancer Center, Buffalo, NY
| | | | - Whitney Ann E Henry
- Office of Community Outreach and Engagement, Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Marissa L Haring
- Student Research Experience Program in Cancer Science, Department of Educational Affairs, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Dean S Seneca
- Partnership Support Unit, Office for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, GA
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Šestan M, Marinović S, Kavazović I, Cekinović Đ, Wueest S, Turk Wensveen T, Brizić I, Jonjić S, Konrad D, Wensveen FM, Polić B. Virus-Induced Interferon-γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity. Immunity 2018; 49:164-177.e6. [PMID: 29958802 DOI: 10.1016/j.immuni.2018.05.005] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 04/09/2018] [Accepted: 05/17/2018] [Indexed: 01/02/2023]
Abstract
Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin resistance (IR) in obesity, but the physiological role of this mechanism is unclear. It is also unknown whether and how viral infection induces loss of glycemic control in subjects at risk for developing diabetes mellitus type 2 (DM2). We have found in mice and humans that viral infection caused short-term systemic IR. Virally-induced interferon-γ (IFN-γ) directly targeted skeletal muscle to downregulate the insulin receptor but did not cause loss of glycemic control because of a compensatory increase of insulin production. Hyperinsulinemia enhanced antiviral immunity through direct stimulation of CD8+ effector T cell function. In pre-diabetic mice with hepatic IR caused by diet-induced obesity, infection resulted in loss of glycemic control. Thus, upon pathogen encounter, the immune system transiently reduces insulin sensitivity of skeletal muscle to induce hyperinsulinemia and promote antiviral immunity, which derails to glucose intolerance in pre-diabetic obese subjects. VIDEO ABSTRACT.
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Affiliation(s)
- Marko Šestan
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sonja Marinović
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Inga Kavazović
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Đurđica Cekinović
- Department of Infectology, Clinical Hospital Center Rijeka, Rijeka, Croatia
| | - Stephan Wueest
- Division of Pediatric Endocrinology and Diabetology and Children's Research Centre, University Children's Hospital, Zurich, Switzerland
| | | | - Ilija Brizić
- Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Stipan Jonjić
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia; Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Daniel Konrad
- Division of Pediatric Endocrinology and Diabetology and Children's Research Centre, University Children's Hospital, Zurich, Switzerland
| | - Felix M Wensveen
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Bojan Polić
- Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
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Subramaniam S, Wong VWS, Tse YK, Yip TCF, Chan HLY, Wong GLH. Impact of diabetes mellitus and hepatitis B virus coinfection on patients with chronic hepatitis C: A territory-wide cohort study. J Gastroenterol Hepatol 2018; 33:934-941. [PMID: 28949045 DOI: 10.1111/jgh.14003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 08/27/2017] [Accepted: 09/18/2017] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIM Studies have demonstrated a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C (CHC). Furthermore, coinfection with hepatitis B virus (HBV) is common because of its endemicity in Asian-Pacific regions. The aim of the present study was to investigate the impact of DM and HBV coinfection on the clinical outcomes in Chinese CHC patients. METHODS A territory-wide cohort study was conducted using the database from Hospital Authority, the sole public medical service provider in Hong Kong. CHC patients were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary outcome was overall mortality. RESULTS A total of 7149 CHC patients were included. Seven hundred twenty-two (10.1%) patients were coinfected with HBV. Their mean age was 56 years; 69.0% were men. The prevalence of DM was similar in mono-infection and coinfection cohorts (22.3% and 21.3%, respectively). Multivariable analysis identified DM as an independent risk factor for death and antiviral treatment for hepatitis C virus (HCV) as an independent protective factor against death. The 5-year survival of CHC patients with mono-infection was better than that of HBV coinfected patients (62.5% vs 57.0%; P = 0.001). The 5-year survival of patients who did or did not receive antiviral treatment for HCV was 94.7% and 55.2%, respectively (P < 0.001). CONCLUSIONS Hepatitis B virus coinfection and DM were independent risk factors for death in Hong Kong CHC patients. Antiviral treatment for HCV but not HBV was a protective factor against death.
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Affiliation(s)
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Terry Cheuk-Fung Yip
- Department of Statistics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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Hsieh PH, Huang JY, Nfor ON, Lung CC, Ho CC, Liaw YP. Association of type 2 diabetes with liver cirrhosis: a nationwide cohort study. Oncotarget 2017; 8:81321-81328. [PMID: 29113391 PMCID: PMC5655286 DOI: 10.18632/oncotarget.18466] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/18/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The link between the subcategories of liver cirrhosis and type 2 diabetes is not well known. We investigated the association of type 2 diabetes mellitus with alcoholic cirrhosis and cirrhosis without alcohol. METHODS This nationwide cohort study used the Taiwan National Health Insurance Research Database. Cirrhotic individuals and their matched controls were identified from 2001-2008. In all, 9 313 cirrhotic patients aged 20 years or older were matched by age, sex, and index date with the non-cirrhotic individuals (n = 37 252). Cirrhosis was categorized into alcoholic cirrhosis and cirrhosis without alcohol. Type 2 diabetes mellitus was identified from January 2001- December 2011. RESULTS The incidence densities (per 1 000 person-months) of type 2 diabetes were as follows: 1.14 (95% CI: 1.09-1.20) in the non-cirrhotic group, 1.88 (CI 1.76-2.01) in patients with cirrhosis, 1.62 (CI 1.48-1.78) in patients with cirrhosis without alcohol, and 2.92 (CI 2.64-3.23) in patients with alcoholic cirrhosis. The adjusted hazards ratio (aHR) for type 2 diabetes mellitus among cirrhotic individuals was 0.774 (CI: 0.715-0.8934). Alcoholic cirrhotic men had a significantly higher risk of type 2 diabetes (aHR 1.182, CI: 1.046-1.335) compared with non-cirrhotic individuals. Increased risks were seen in men (aHR 1.690; CI: 1.455-1.963) and women (aHR 1.715; CI: 1.113-2.645) with alcoholic cirrhosis compared to those with cirrhosis without alcohol. CONCLUSIONS This study indicates that alcoholic cirrhosis is a significant risk factor for type 2 diabetes mellitus compared with cirrhosis without alcohol.
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Affiliation(s)
- Ping-Hsin Hsieh
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jing-Yang Huang
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Oswald Ndi Nfor
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Chia-Chi Lung
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Chien-Chang Ho
- Department of Physical Education, Fu-Jen Catholic University, New Taipei, Taiwan
| | - Yung-Po Liaw
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
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Gangopadhyay KK, Singh P. Consensus Statement on Dose Modifications of Antidiabetic Agents in Patients with Hepatic Impairment. Indian J Endocrinol Metab 2017; 21:341-354. [PMID: 28459036 PMCID: PMC5367241 DOI: 10.4103/ijem.ijem_512_16] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia. The aim of this consensus group convened during the National Insulin Summit 2015, Puducherry, was to focus on the challenges with glycemic management, with particular emphasis to safety of ADAs across stages of liver dysfunction. Published literature, product labels, and major clinical guidelines were reviewed and summarized. The drug classes included are biguanides (metformin), the second- or third-generation sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and currently available insulins. Consensus recommendations have been drafted for glycemic targets and dose modifications of all ADAs. These can aid clinicians in managing patients with diabetes and liver disease.
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Affiliation(s)
| | - Parminder Singh
- Division of Endocrinology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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De Vincentis A, Pennazza G, Santonico M, Vespasiani-Gentilucci U, Galati G, Gallo P, Zompanti A, Pedone C, Antonelli Incalzi R, Picardi A. Breath-print analysis by e-nose may refine risk stratification for adverse outcomes in cirrhotic patients. Liver Int 2017; 37:242-250. [PMID: 27496750 DOI: 10.1111/liv.13214] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Accepted: 08/02/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The spectrum of volatile organic compounds in the exhaled breath (breath-print, BP) has been shown to characterize patients with cirrhosis and with worse hepatic function. However, the association of different BPs with clinically relevant outcomes has not been described yet. Hence, we aimed to evaluate the association between BPs, mortality and hospitalization in cirrhotic patients and to compare it with that of the "classical" prognostic indices (Child-Pugh Classification [CPC] and MELD). METHODS Eighty-nine cirrhotic patients (M/F 59/30, mean age 64.8 ± 11.3, CPC A/B/C 37/33/19) were recruited and followed up for a median time of 23 months. Clinical and biochemical data were collected. Breath collection and analysis were obtained through Pneumopipe® and BIONOTE e-nose respectively. RESULTS Four different BP clusters (A, B, C, D) were identified. BP clusters A and D were associated with a significantly increased risk of mortality (HR 2.9, 95% confidence intervals [CI] 1.5-5.6) and hospitalization (HR 2.6, 95% CI 1.4-4.6), even in multiple adjusted models including CPC and MELD score (adjusted [a]HR 2.8, 95% CI 1.1-7.0 for mortality and aHR 2.2, 95% CI 1.1-4.2 for hospitalization). CPC C maintained the strongest association with both mortality (aHR 17.6, 95% CI 1.8-174.0) and hospitalization (aHR 12.4, 95% CI 2.0-75.8). CONCLUSIONS This pilot study demonstrates that BP clusters are associated with significant clinical endpoints (mortality and hospitalization) even independently from "classical" prognostic indices. Even though further studies are warranted on this topic, our findings suggest that the e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in cirrhotic patients.
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Affiliation(s)
- Antonio De Vincentis
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Giorgio Pennazza
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | - Marco Santonico
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | | | - Giovanni Galati
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Paolo Gallo
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Alessandro Zompanti
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | - Claudio Pedone
- Chair of Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University, Rome, Italy
| | - Raffaele Antonelli Incalzi
- Chair of Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University, Rome, Italy
- San Raffaele- Cittadella della Carità Foundation, Taranto, Italy
| | - Antonio Picardi
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
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25
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Karnchanasorn R, Ou HY, Lin J, Chuang LM, Chiu KC. Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination. Curr Diab Rep 2016; 16:101. [PMID: 27620495 DOI: 10.1007/s11892-016-0790-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Viral hepatitis has been posited to play a role in the development of type 2 diabetes. Thus, prevention of viral hepatitis through vaccination has the potential to reduce the burden of type 2 diabetes. We have shown that successful hepatitis B vaccination reduces the risk of diabetes by 33 %. Although diabetes can be prevented by behavior modification and pharmaceutical agents, these require significant personal commitment and cost. In contrast, diabetes prevention through hepatitis B vaccination would require little personal commitment and relatively low cost. In this review, we discuss hepatitis viruses A, B, and C and their interaction with diabetes; explore the potential underlying mechanisms and potential for hepatitis vaccination to reduce diabetes; and estimate the medical expense savings that would result from such an intervention. Given the projected increase of diabetes prevalence in the developing regions, where hepatitis B is endemic, exploration of such an intervention is very timely.
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Affiliation(s)
- Rudruidee Karnchanasorn
- Division of Endocrinology, Metabolism and Genetics, Department of Internal Medicine, University of Kansas Medical Center, Kansas, KS, USA
| | - Horng-Yih Ou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan
| | - James Lin
- Department of Gastroenterology, City of Hope National Medical Center, Duarte, CA, USA
| | - Lee-Ming Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, 91010-3000, USA.
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
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Elkrief L, Rautou PE, Sarin S, Valla D, Paradis V, Moreau R. Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int 2016; 36:936-48. [PMID: 26972930 DOI: 10.1111/liv.13115] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Accepted: 03/07/2016] [Indexed: 12/12/2022]
Abstract
Disorders of glucose metabolism, namely glucose intolerance and diabetes, are frequent in patients with chronic liver diseases. In patients with cirrhosis, diabetes can be either a classical type 2 diabetes mellitus or the so-called hepatogenous diabetes, i.e. a consequence of liver insufficiency and portal hypertension. This review article provides an overview of the possible pathophysiological mechanisms explaining diabetes in patients with cirrhosis. Cirrhosis is associated with portosystemic shunts as well as reduced hepatic mass, which can both impair insulin clearance by the liver, contributing to peripheral insulin resistance through insulin receptors down-regulation. Moreover, cirrhosis is associated with increased levels of advanced-glycation-end products and hypoxia-inducible-factors, which may play a role in the development of diabetes. This review also focuses on the clinical implications of diabetes in patients with cirrhosis. First, diabetes is an independent factor for poor prognosis in patients with cirrhosis. Specifically, diabetes is associated with the occurrence of major complications of cirrhosis, including ascites and renal dysfunction, hepatic encephalopathy and bacterial infections. Diabetes is also associated with an increased risk of hepatocellular carcinoma in patients with chronic liver diseases. Last, the management of patients with concurrent diabetes and liver disease is also addressed. Recent findings suggest a beneficial impact of metformin in patients with chronic liver diseases. Insulin is often required in patients with advanced cirrhosis. However, the favourable impact of controlling diabetes in patients with cirrhosis has not been demonstrated yet.
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Affiliation(s)
- Laure Elkrief
- Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève, Genève, Suisse
| | - Pierre-Emmanuel Rautou
- DHU UNITY, Service d'Hépatologie, Hôpital Beaujon, APHP, Clichy, France.,Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.,Inserm U970, Paris Research Cardiovascular Center, Paris, France
| | - Shiv Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Dominique Valla
- DHU UNITY, Service d'Hépatologie, Hôpital Beaujon, APHP, Clichy, France.,Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.,Inserm U1149, Centre de Recherche sur l'Inflammation CRI, Clichy, France
| | - Valérie Paradis
- Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.,Inserm U1149, Centre de Recherche sur l'Inflammation CRI, Clichy, France.,DHU UNITY, Pathology Department, Hôpital Beaujon, APHP, Clichy, France
| | - Richard Moreau
- DHU UNITY, Service d'Hépatologie, Hôpital Beaujon, APHP, Clichy, France.,Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.,Inserm U1149, Centre de Recherche sur l'Inflammation CRI, Clichy, France
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27
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Otete HE, Orton E, Fleming KM, West J. Alcohol-attributable healthcare attendances up to 10 years prior to diagnosis of alcoholic cirrhosis: a population based case-control study. Liver Int 2016; 36:538-46. [PMID: 26560966 DOI: 10.1111/liv.13002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 10/26/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Cirrhosis because of alcohol could be avoided if drinking behaviour could be altered earlier in the disease course. Our aim was to quantify the burden of morbidities in patients prior to alcoholic cirrhosis diagnosis, as this may inform the earlier identification of people at high risk for targeted interventions. METHODS We carried out a case-control study using 2479 incident cases of alcoholic cirrhosis and 24 790 controls identified from 357 primary and secondary care centres in England. We assessed the prevalence of morbidities that are partly attributable to alcohol (namely malignant neoplasms, diabetes, epilepsy, injuries, cardiovascular and digestive diseases) prior to alcoholic cirrhosis diagnosis. We compared prevalence in cases to the control population and used logistic regression to derive odds ratios (95% CI). RESULTS Fifty-eight per cent of cases compared to 29% of controls had had at least one alcohol-attributable condition before cirrhosis diagnosis. The most frequent conditions (proportion in cases vs. controls) were intentional injuries (35.9% vs. 11.9%) and cardiovascular diseases (23.2% vs. 15.6%), followed by diabetes (12.8% vs. 5.3%), digestive diseases (6.1% vs. 1.2%) and epilepsy (5.0% vs. 1.1%). The strongest association with alcoholic cirrhosis was found for digestive diseases [OR 5.4 (4.4-6.7)], epilepsy [OR: 4.4 (3.5-5.5)] and injuries [OR: 4.0 (3.7-4.4)] particularly among those aged 18-44 years. CONCLUSION These data highlight the high burden of other alcohol-attributable conditions in patients prior to alcoholic cirrhosis diagnosis. Reviewing those consistently presenting with any of these conditions more closely could help practitioners reduce/avoid the long-term consequences of development of alcoholic liver disease.
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Affiliation(s)
- Harmony E Otete
- Division of Epidemiology and Public health, School of Medicine, Nottingham, UK.,UK Centre for Tobacco and Alcohol Studies (UKCTAS), University of Nottingham, Nottingham, UK
| | - Elizabeth Orton
- Division of Primary Care, School of Medicine, University of Nottingham, Nottingham, UK
| | - Kate M Fleming
- Division of Epidemiology and Public health, School of Medicine, Nottingham, UK.,UK Centre for Tobacco and Alcohol Studies (UKCTAS), University of Nottingham, Nottingham, UK
| | - Joe West
- Division of Epidemiology and Public health, School of Medicine, Nottingham, UK
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Calzadilla-Bertot L, Vilar-Gomez E, Torres-Gonzalez A, Socias-Lopez M, Diago M, Adams LA, Romero-Gomez M. Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis. Dig Liver Dis 2016; 48:283-90. [PMID: 26797261 DOI: 10.1016/j.dld.2015.12.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/30/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Glucose metabolism abnormalities frequently coexist with liver cirrhosis; however, the impact of these on liver-related outcomes has not been fully investigated. AIMS We examined the influence of glucose abnormalities on overall mortality and liver-related complications in cirrhotic patients. METHODS A prospective cohort of 250 subjects with compensated hepatitis C virus-related cirrhosis and without known diabetes underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks. RESULTS At baseline, 67 (27%) had type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (sHR: 2.2, 95% CI: 1.04-4.6, P=0.04) and hepatic decompensation events (sHR: 1.9, 95% CI: 1.05-3.3, P=0.03) were significantly higher in diabetic patients. Subjects with a HOMA-IR >5 showed higher rates of mortality (sHR: 2.2, 95% CI: 1.03-4.8, P=0.04). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (sHR: 1.7, 95% CI: 1.04-2.9, P=0.03). Overall, 2h-plasma glucose was the most robust predictor of overall mortality (sHR: 2.5, 95% CI: 1.03-6, P=0.04) and decompensation (sHR: 2.7, 95% CI: 1.4-5.5, P<0.01). CONCLUSIONS In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival and increased risk of hepatic decompensation.
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Affiliation(s)
| | - Eduardo Vilar-Gomez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba; Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain.
| | - Ana Torres-Gonzalez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Maray Socias-Lopez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Moises Diago
- Liver Unit, Department of Gastroenterology, Valencia University General Hospital, Valencia, Spain
| | - Leon A Adams
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain
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Zhang J, Shen Y, Cai H, Liu YM, Qin G. Hepatitis B virus infection status and risk of type 2 diabetes mellitus: A meta-analysis. Hepatol Res 2015; 45:1100-9. [PMID: 25601609 DOI: 10.1111/hepr.12481] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 12/22/2014] [Accepted: 01/05/2015] [Indexed: 02/08/2023]
Abstract
AIM Whether hepatitis B virus (HBV) infection increases the risk of type 2 diabetes mellitus (T2DM) is controversial. We carried out a meta-analysis to evaluate the association between HBV infection status and the risk of T2DM. METHODS The PubMed, Embase and Ovid databases were searched for relevant studies on an association between HBV infection and the risk of diabetes. Methodological quality was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale. A fix- or random-effects model was used to summarize odd ratios (OR) and 95% confidence intervals (CI). RESULTS We included seven cohort studies, four case-control and four cross-sectional studies, involving 118 530 participants. The prevalence of T2DM differs by HBV infection status. Pooled estimators indicated a nearly twofold excess T2DM risk with hepatitis B cirrhosis (HBC) status. The summary OR of the risk of T2DM for HBC patients was 1.99 (95% CI, 1.08-3.65) when compared with the non-HBV individuals, and 1.74 (95% CI, 1.43-2.13) when compared with non-cirrhotic chronic hepatitis B (NC-CHB) patients. In contrast, no significant correlation was found between asymptomatic HBV carriers or NC-CHB patients and the incidence of diabetes, compared with non-HBV controls. CONCLUSION Our findings suggest that while HBV itself may not be pro-diabetic, the HBV-derived cirrhosis is an independent risk factor for T2DM.
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Affiliation(s)
- Jian Zhang
- Department of Epidemiology and Medical Statistics
| | - Yi Shen
- Department of Epidemiology and Medical Statistics
| | - Hui Cai
- Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, USA
| | - Yan-Mei Liu
- Department of Epidemiology and Medical Statistics
| | - Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, China
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Huang J, Ou HY, Lin J, Karnchanasorn R, Feng W, Samoa R, Chuang LM, Chiu KC. The Impact of Hepatitis B Vaccination Status on the Risk of Diabetes, Implicating Diabetes Risk Reduction by Successful Vaccination. PLoS One 2015; 10:e0139730. [PMID: 26509504 PMCID: PMC4624985 DOI: 10.1371/journal.pone.0139730] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 09/15/2015] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The liver plays a key role in fuel metabolism. It is well established that liver disease is associated with an increased risk for diabetes mellitus. Hepatitis C virus infection has been known to increase the risk of diabetes. However, much less is known about the role of hepatitis B virus (HBV) infection in diabetes. We examined the association of diabetes based on the vaccination status for HBV. METHODS In this cross-sectional study, we included adult subjects (≥20 y/o) with HBV serology available from the National Health and Nutrition Examination Survey 2005-2010. Diabetes was defined as established diabetes or fasting plasma glucose concentration ≥7.0 mmol/L, 2-hour plasma glucose concentration ≥11.1 mmol/L, or HbA1c ≥ 47.5 mmol/mol (6.5%). Vaccination was based on the reported history and immunization was determined by HBV serology. The odds ratio (OR) with 95% confidence intervals (95% CI) were calculated with consideration of the following covariates: age, gender, BMI, ethnic/racial group, current smoker, current alcohol consumption, family history of diabetes, poverty index, and education. RESULTS This study included 15,316 subjects. Among them, 2,320 subjects was immunized based the HBV serology. Among 4,063 subjects who received HBV vaccination, successful vaccination was only noted in 39% of subjects. The HBV vaccination was not associated with diabetes (OR: 1.08, 95%CI: 0.96-1.23). Serology evidence of HBV immunization was associated with a reduced OR of diabetes (0.75, 95%CI: 0.62-0.90). Successful HBV vaccination was also associated with a reduced OR of diabetes (0.67, 95%CI: 0.52-0.84). CONCLUSIONS Although our study shows the association of HBV vaccination with the reduced odds of diabetes by 33%, a prospective study is warranted to confirm and examine the impact of HBV vaccination in prevention of diabetes.
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Affiliation(s)
- Jean Huang
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California, United States of America; Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, California, United States of America
| | - Horng-Yih Ou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan
| | - James Lin
- Department of Gastroenterology, City of Hope National Medical Center, Duarte, California, United States of America
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Wei Feng
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California, United States of America; Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, California, United States of America
| | - Raynald Samoa
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California, United States of America; Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, California, United States of America
| | - Lee-Ming Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan
| | - Ken C. Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California, United States of America; Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, California, United States of America
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Cai C, Zeng J, Wu H, Shi R, Wei M, Gao Y, Ma W. Association between hepatitis B virus infection and diabetes mellitus: A meta-analysis. Exp Ther Med 2015; 10:693-698. [PMID: 26622377 DOI: 10.3892/etm.2015.2537] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 04/23/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection has been shown by certain studies to be associated with diabetes mellitus (DM); however, the results of these studies were controversial. For that reason, a meta-analysis of the literature was performed in order to determine the association between HBV infection and the prevalence of DM more accurately. The PubMed, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases, as well as the Chinese Science and Technology Journal Database, were searched for literature published until June 2014. The reference lists of all relevant articles were also searched. The summary odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were calculated based on a random-effects model. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were conducted based on study type and region for the purpose of assessing the factors that could potentially affect the outcome. A total of 15 eligible studies (in 14 articles) were selected for the meta-analysis, involving 12,974,690 HBV-infected patients and 231,776,232 controls. The OR for the prevalence of DM was 1.33 (95% CI, 1.09-1.62; P=0.005) between the patients with HBV infection and the controls. The subgroup analysis based on study type revealed a significantly higher prevalence of DM in the HBV-infected group than that in the control group in both case-control (OR, 1.89; 95% CI, 1.08-3.30; P=0.025) and cross-sectional (OR, 1.41; 95% CI, 1.04-1.90; P=0.027) studies. The subgroup analysis based on region revealed a significantly higher prevalence of DM in the HBV-infected group than in the control group in the Asia-Pacific region (OR, 1.67; 95% CI, 1.08-2.58; P=0.022). Compared with uninfected patients, the pooled results suggest that HBV-infected patients have a higher risk of developing DM; however, given the fact that this is a meta-analysis of observational studies, further randomized controlled trials are required in order to reach a more accurate conclusion.
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Affiliation(s)
- Cuixia Cai
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Jun Zeng
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Huihui Wu
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Rong Shi
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Min Wei
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Yuan Gao
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Wenli Ma
- Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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Scheen AJ. Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus. Clin Pharmacokinet 2015; 53:773-85. [PMID: 25091053 DOI: 10.1007/s40262-014-0157-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients.
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Affiliation(s)
- André J Scheen
- Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, University of Liège, Liège, Belgium,
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Shen Y, Zhang J, Cai H, Shao JG, Zhang YY, Liu YM, Qin G, Qin Y. Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls. BMC Gastroenterol 2015; 15:32. [PMID: 25887997 PMCID: PMC4387579 DOI: 10.1186/s12876-015-0263-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 03/04/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. METHODS A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. RESULTS In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. CONCLUSIONS Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China. .,Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Jian Zhang
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Hui Cai
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Jian-Guo Shao
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - You-Yi Zhang
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Yan-Mei Liu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Yan Qin
- Department of Internal Medicine, Singapore General Hospital, Singapore, 169608, Singapore.
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Setiawan VW, Wilkens LR, Lu SC, Hernandez BY, Le Marchand L, Henderson BE. Association of coffee intake with reduced incidence of liver cancer and death from chronic liver disease in the US multiethnic cohort. Gastroenterology 2015; 148:118-25; quiz e15. [PMID: 25305507 PMCID: PMC4274222 DOI: 10.1053/j.gastro.2014.10.005] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 10/02/2014] [Accepted: 10/03/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC) and chronic liver disease (CLD), but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee intake with HCC and CLD in 162,022 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the US Multiethnic Cohort (MEC). METHODS We collected data from the MEC, a population-based prospective cohort study of >215,000 men and women from Hawaii and California, assembled in 1993-1996. Participants reported coffee consumption and other dietary and lifestyle factors when they joined the study. During an 18-year follow-up period, there were 451 incident cases of HCC and 654 deaths from CLD. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression, adjusting for known HCC risk factors. RESULTS High levels of coffee consumption were associated with reduced risk of incident HCC and CLD mortality (Ptrend ≤ .0002). Compared with non-coffee drinkers, those who drank 2-3 cups per day had a 38% reduction in risk for HCC (RR = 0.62; 95% CI: 0.46-0.84); those who drank ≥4 cups per day had a 41% reduction in HCC risk (RR = 0.59; 95% CI: 0.35-0.99). Compared with non-coffee drinkers, participants who consumed 2-3 cups coffee per day had a 46% reduction in risk of death from CLD (RR = 0.54; 95% CI: 0.42-0.69) and those who drank ≥4 cups per day had a 71% reduction (RR = 0.29; 95% CI: 0.17-0.50). The inverse associations were similar regardless of the participants' ethnicity, sex, body mass index, smoking status, alcohol intake, or diabetes status. CONCLUSIONS Increased coffee consumption reduces the risk of HCC and CLD in multiethnic US populations.
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Affiliation(s)
- Veronica Wendy Setiawan
- Department of Preventive Medicine, Keck School of Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
| | - Lynne R Wilkens
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Shelly C Lu
- Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Brenda Y Hernandez
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Loïc Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Brian E Henderson
- Department of Preventive Medicine, Keck School of Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
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The senescent hepatocyte gene signature in chronic liver disease. Exp Gerontol 2014; 60:37-45. [DOI: 10.1016/j.exger.2014.09.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 09/10/2014] [Accepted: 09/16/2014] [Indexed: 12/25/2022]
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Carter SA, Kitching AR, Johnstone LM. Four pediatric patients with autosomal recessive polycystic kidney disease developed new-onset diabetes after renal transplantation. Pediatr Transplant 2014; 18:698-705. [PMID: 25118046 DOI: 10.1111/petr.12332] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/02/2014] [Indexed: 12/11/2022]
Abstract
NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less prevalent in pediatric renal transplant recipients; however, some risk factors for its development in young patients have been defined. We report four pediatric renal transplant recipients with ARPKD who developed NODAT. We review the current pediatric NODAT literature and hypothesize that ARPKD may be an additional risk factor for NODAT.
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Affiliation(s)
- S A Carter
- Department of Nephrology, Monash Children's Hospital, Monash Health, Melbourne, Victoria, Australia
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Wang SP, Wu YP, Lin XJ. Clinical characteristics, prognosis and nursing intervention in hepatogenic diabetes and type 2 diabetes mellitus. Shijie Huaren Xiaohua Zazhi 2014; 22:3722-3726. [DOI: 10.11569/wcjd.v22.i24.3722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the clinical characteristics, prognosis and nursing intervention between patients with hepatogenic diabetes (HD) and those with type 2 diabetes (T2DM).
METHODS: Sixty patients with hyperglycaemia were divided into two groups: an HD group (n = 30) and a T2DM group (n = 30). Oral glucose tolerance test (OGTT) and glucose-stimulated insulin release test were performed in all patients. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbAlc) were determined. All patients were given medical management, hypoglycemic therapy and comprehensive nursing intervention. BSL were compared between before and after nursing intervention.
RESULTS: FBG and HbAlc in the HD group were significantly lower than those in the T2DM group (7.8 mmol/L ± 2.4 mmol/L vs 9.6 mmol/L ± 3.2 mmol/L, 0.065 ± 0.017 vs 0.083 ± 0.027, t = 1.017, 0.976; P = 0.002, 0.004). BSL in the HD group at different time points (0, 30, 60, 120, 180 min) were all significantly lower than those in the T2DM group (P < 0.05). Insulin and peptide C levels in the HD group at different time points (0, 30, 60, 120, 180 min) were all significantly higher than those in the T2DM group (P < 0.05). All patients were given medical management, hypoglycemic therapy and comprehensive nursing intervention. BSL in both the HD group and T2DM group were significantly lower after intervention than before intervention (t = 2. 076, 1.872, 2.301, 1.874; P = 0.003, 0.004, 0.002, 0.004).
CONCLUSION: Hyperinsulinemia is more obvious and BSL is controlled better in HD patients. Comprehensive nursing intervention is conducive to controlling BSL in both HD and T2DM patients.
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Ahn JM, Paik YH, Kim SH, Lee JH, Cho JY, Sohn W, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. Relationship of liver stiffness and controlled attenuation parameter measured by transient elastography with diabetes mellitus in patients with chronic liver disease. J Korean Med Sci 2014; 29:1113-9. [PMID: 25120322 PMCID: PMC4129204 DOI: 10.3346/jkms.2014.29.8.1113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 05/07/2014] [Indexed: 12/17/2022] Open
Abstract
High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
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Affiliation(s)
- Jem Ma Ahn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - So Hyun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Hee Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ju Yeon Cho
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Sohn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Chul Yoo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Yang CH, Chiu YC, Chen CH, Chen CH, Tsai MC, Chuah SK, Lee CH, Hu TH, Hung CH. Diabetes mellitus is associated with gastroesophageal variceal bleeding in cirrhotic patients. Kaohsiung J Med Sci 2014; 30:515-20. [PMID: 25438683 DOI: 10.1016/j.kjms.2014.06.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/04/2014] [Accepted: 04/29/2014] [Indexed: 12/21/2022] Open
Abstract
Diabetes mellitus (DM) has been reported to increase the risk of complications of liver cirrhosis of any etiology and subsequent survival. However, the impact of DM on the development of gastroesophageal variceal bleeding (GEVB) remains unclear. We aimed to elucidate whether DM is an independent risk factor for GEVB among cirrhotic patients. A total of 146 consecutive patients with liver cirrhosis (Child-Pugh Class A, n = 75; Class B, n = 40; and Class C, n = 31) were prospectively enrolled. Data on clinical and biochemical characteristics and history of ascites, GEVB, hepatic encephalopathy, and spontaneous bacterial peritonitis were retrospectively reviewed. Of these 146 patients, 37 (25%) had DM. Patients with DM had significantly higher ratio of Child-Pugh Class B/C (p = 0.043), renal insufficiency (p = 0.002), and history of GEVB (p = 0.006) compared with non-DM patients. GEVB was associated with Child-Pugh Class B/C (p = 0.001), ascites (p = 0.002), hepatic encephalopathy (p = 0.023), and low platelet counts (p < 0.001). Based on stepwise multiple logistic regression analysis, Child-Pugh class B/C [odds ratio (OR) = 4.90, p = 0.003] and DM (OR = 2.99, p = 0.022) were identified as independent predictors of GEVB. In the subgroup analysis, DM significantly correlated with GEVB in patients with Child-Pugh Class A (p = 0.042), but not in patients with Child-Pugh Class B/C (p = 0.128). DM is independently associated with GEVB in cirrhotic patients, especially in those with Child-Pugh Class A.
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Affiliation(s)
- Chun-Hsun Yang
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Yi-Chun Chiu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chih-Hung Chen
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chih-Hsiung Lee
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
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García-Compeán D, Jáquez-Quintana JO, Lavalle-González FJ, González-González JA, Maldonado-Garza HJ, Villarreal-Pérez JZ. Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study. Ann Hepatol 2014; 13:403-410. [PMID: 24927611 DOI: 10.1016/s1665-2681(19)30847-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIMS To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM). MATERIAL AND METHODS We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF- α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-β1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests. RESULTS Significantly higher sTNF-R1 and lower TGF-β1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found. CONCLUSIONS IGT and DM were associated with abnormalities of sTNF-R1 and TGF-β1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - Joel O Jáquez-Quintana
- Gastroenterology Service Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - Fernando J Lavalle-González
- Endocrinology Service, Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - Héctor J Maldonado-Garza
- Gastroenterology Service Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - Jesús Z Villarreal-Pérez
- Endocrinology Service, Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
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Scheen AJ. Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease. Expert Opin Drug Metab Toxicol 2014; 10:839-57. [PMID: 24669954 DOI: 10.1517/17425255.2014.902444] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). AREAS COVERED An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. EXPERT OPINION Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and α-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin.
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Affiliation(s)
- André J Scheen
- University of Liège, CHU Sart Tilman (B35), Center for Interdisciplinary Research on Medicines (CIRM), Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine , B-4000 Liege 1 , Belgium +32 4 3667238 ; +32 4 3667068 ;
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Vespasiani-Gentilucci U, Gallo P, Vincentis AD, Galati G, Picardi A. Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis. World J Gastroenterol 2014; 20:2825-2838. [PMID: 24659875 PMCID: PMC3961987 DOI: 10.3748/wjg.v20.i11.2825] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/25/2013] [Accepted: 01/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a "viral" steatosis which is frequently superimposed to a "metabolic" one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.
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A meta-analysis of the association between gestational diabetes mellitus and chronic hepatitis B infection during pregnancy. BMC Res Notes 2014; 7:139. [PMID: 24618120 PMCID: PMC4007522 DOI: 10.1186/1756-0500-7-139] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 03/04/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) infection during pregnancy is associated with insulin resistance. A meta-analytic technique was used to quantify the evidence of an association between CHB infection and the risk of gestational diabetes (GDM) among pregnant women. METHODS We searched PubMed for studies up to September 5th 2013. Additional studies were obtained from other sources. We selected studies using a cohort-study design and reported a quantitative association between CHB infection during pregnancy and risk of GDM. A total of 280 articles were identified, of which fourteen publications involving 439,514 subjects met the inclusion criteria. A sequential algorithm was used to reduce between-study heterogeneity, and further meta-analysis was conducted using a random-effects model. RESULTS Ten out of the fourteen studies were highly homogeneous, indicating an association of 1.11 [the adjusted odds ratio, 95% confidence interval 0.96-1.28] between CHB infection during pregnancy and the risk of developing GDM. The heterogeneity of the additional four studies may be due to selection bias or possible aetiological differences for special subsets of pregnant women. CONCLUSIONS These results indicate that CHB infection during pregnancy is not associated with an increased risk of developing GDM among pregnant women except those from Iran.
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Lacerda DDS, Santos CF, Oliveira AS, Zimmermann R, Schneider R, Agostini F, Dani C, Funchal C, Gomez R. Antioxidant and hepatoprotective effects of an organic grapevine leaf (Vitis labrusca L.) extract in diabetic rats. RSC Adv 2014. [DOI: 10.1039/c4ra08396b] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Changes on metabolic, biochemical and oxidative parameters in the livers of diabetic rats after chronic administration of an aqueous extract of organic grapevine leaves.
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Affiliation(s)
- Denise dos Santos Lacerda
- Programa de Pós-Graduação em Ciência Biológicas: Fisiologia
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Porto Alegre, Brasil
| | - Carolina Ferreira Santos
- Departamento de Farmacologia – Instituto de Ciências Básicas da Saúde
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Porto Alegre, Brasil
| | | | | | - Ricardo Schneider
- Departamento de Farmacologia – Instituto de Ciências Básicas da Saúde
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Porto Alegre, Brasil
| | | | - Caroline Dani
- Centro Universitário Metodista do IPA
- Porto Alegre, Brasil
- Universidade de Caxias do Sul, UCS
- Caxias do Sul, Brasil
| | | | - Rosane Gomez
- Programa de Pós-Graduação em Ciência Biológicas: Fisiologia
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Porto Alegre, Brasil
- Departamento de Farmacologia – Instituto de Ciências Básicas da Saúde
- Universidade Federal do Rio Grande do Sul (UFRGS)
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Miller BS, Duffy MM, Addo OY, Sarafoglou K. rhIGF-1 Therapy for Growth Failure and IGF-1 Deficiency in Congenital Disorder of Glycosylation Ia (PMM2 Deficiency). J Investig Med High Impact Case Rep 2013; 1:2324709613503316. [PMID: 26425584 PMCID: PMC4586814 DOI: 10.1177/2324709613503316] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background. Congenital disorders of glycosylation (CDG) are a group of rare disorders in which glycosylation required for proper protein-protein interactions and protein stability is disrupted, manifesting clinically with multiple system involvement and growth failure. The insulin-like growth factor (IGF) system plays an important role in childhood growth and has been shown to be dysfunctional with low IGF-1 levels in children with CDG type Ia (PMM2 deficiency). Case report. A 3-year-old Caucasian male with failure to thrive was diagnosed with PMM2-CDG at 5 months of age. Initially, his length and weight were less than −2 standard deviation score, IGF-1 <25 ng/mL (normal 55-327 ng/mL), IGFBP-3 1.0 µg/mL (normal 0.7-3.6 ng/mL), and acid-labile subunit 1.3 mg/L (normal 0.7-7.9 mg/L). Despite aggressive feeding, he continued to show poor linear growth and weight gain. At 17 months, he underwent an IGF-1 generation test with growth hormone (0.1 mg/kg/d) for 7 days; baseline IGF-1of 27 ng/mL (normal 55-327 ng/mL) stimulated to only 33 ng/mL. Recombinant human IGF-1 (rhIGF-1) therapy (up to 130 µg/kg/dose twice daily) was initiated at 21 months of age resulting in an excellent linear growth response with height increasing from −2.73 to −1.39 standard deviation score over 22 months. IGF-1 and IGFBP-3 levels also increased. Conclusion. This is the first case report of rhIGF-1 therapy in a patient with PMM2-CDG. The child had an excellent linear growth response. These results provide additional in vivo evidence for IGF dysfunction in PMM2-CDG and suggest that rhIGF-1 may be a novel treatment for growth failure in PMM2-CDG.
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Affiliation(s)
- Bradley S Miller
- University of Minnesota Amplatz Children's Hospital, Minneapolis, MN, USA
| | - Meghann M Duffy
- University of Minnesota Amplatz Children's Hospital, Minneapolis, MN, USA
| | - O Yaw Addo
- University of Minnesota Amplatz Children's Hospital, Minneapolis, MN, USA
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García-Compeán D, Jáquez-Quintana JO, González-González JA, Lavalle-González FJ, Villarreal-Pérez JZ, Maldonado-Garza HJ. [Diabetes in liver cirrhosis]. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:473-482. [PMID: 23628170 DOI: 10.1016/j.gastrohep.2013.01.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Accepted: 01/31/2013] [Indexed: 02/07/2023]
Abstract
The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.
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Affiliation(s)
- Diego García-Compeán
- Servicio de Gastroenterología y Departamento de Medicina Interna, Hospital Universitario Dr. José E. González, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, México.
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47
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Lai GY, Weinstein SJ, Albanes D, Taylor PR, McGlynn KA, Virtamo J, Sinha R, Freedman ND. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers. Br J Cancer 2013; 109:1344-51. [PMID: 23880821 PMCID: PMC3778279 DOI: 10.1038/bjc.2013.405] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Revised: 06/24/2013] [Accepted: 06/26/2013] [Indexed: 12/11/2022] Open
Abstract
Background: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. Methods: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27 037 Finnish male smokers, aged 50–69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Results: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73–0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48–0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. Conclusion: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.
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Affiliation(s)
- G Y Lai
- Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, 9609 Medical Center Drive, Room 2W136 MSC 9712, Bethesda, MD 20892, USA.
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48
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Saleh O, Baiomy AA, El-desouky A, Zaghloul H, El-Arman M, Dahab GM, Abdel-Rahman MS. Hepatitis C virus genotype distribution in Egyptian diabetic patients: a preliminary study. Arab J Gastroenterol 2013; 14:14-19. [PMID: 23622804 DOI: 10.1016/j.ajg.2013.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2011] [Revised: 09/04/2012] [Accepted: 12/29/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND STUDY AIMS There is controversy regarding whether a specific hepatitis C virus (HCV) genotype is associated with diabetes mellitus. This study aimed to investigate HCV genotype distribution in diabetics and its relation to some clinical and laboratory variables in HCV-positive diabetic versus non-diabetic Egyptians in East Delta. PATIENTS AND METHODS The study included 100 HCV-positive patients of which 66 were diabetic in addition to 35 healthy adults as a control group. Clinical assessment, laboratory measurements of plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α) and liver functions (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)) as well as HCV genotype determination were done, and AST/platelet ratio index (APRI) and Homoeostasis Model of Assessment-Insulin Resistance (HOMA-IR) were calculated. RESULTS The main results were the presence of HCV genotype 3, in 31.8% of the diabetic group and in 26.5% of the non-diabetic group, while the remainder of cases had genotype 4, the predominant genotype in Egypt. This is the first report of the presence of HCV genotype 3 in about 30% of an Egyptian cohort. However, there was no significant difference in genotype distribution between both groups. Further, there were significantly higher values of HOMA-IR, insulin and C-peptide in HCV-positive groups in comparison to the control group, while TNF-α was significantly higher in the HCV-positive diabetic group. However, there were no significant differences between both genotypes regarding these parameters. CONCLUSION Although this study reveals for the first time the presence of HCV genotype 3 in a significant percentage of a group of Egyptian patients, where the majority were diabetic, the association between diabetes and certain HCV genotypes could not be confirmed on the basis of our findings. Hence, taking into consideration the impact of such a finding on the treatment decisions of those patients, further studies are warranted to explore these findings to a greater extent.
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Affiliation(s)
- Omayma Saleh
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura City, Egypt.
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Du Y, Heidemann C, Gößwald A, Schmich P, Scheidt-Nave C. Prevalence and comorbidity of diabetes mellitus among non-institutionalized older adults in Germany - results of the national telephone health interview survey 'German Health Update (GEDA)' 2009. BMC Public Health 2013; 13:166. [PMID: 23433228 PMCID: PMC3599814 DOI: 10.1186/1471-2458-13-166] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Accepted: 02/08/2013] [Indexed: 12/30/2022] Open
Abstract
Background Despite the major public health impact of diabetes, recent population-based data regarding its prevalence and comorbidity are sparse. Methods The prevalence and comorbidity of diabetes mellitus were analyzed in a nationally representative sample (N = 9133) of the non-institutionalized German adult population aged 50 years and older. Information on physician-diagnosed diabetes and 20 other chronic health conditions was collected as part of the national telephone health interview survey ‘German Health Update (GEDA)’ 2009. Overall, 51.2% of contacted persons participated. Among persons with diabetes, diabetes severity was defined according to the type and number of diabetes-concordant conditions: no diabetes-concordant condition (grade 1); hypertension and/or hyperlipidemia only (grade 2); one comorbidity likely to represent diabetes-related micro- or macrovascular end-organ damage (grade 3); several such comorbidities (grade 4). Determinants of diabetes severity were analyzed by multivariable ordinal regression. Results The 12-month prevalence of diabetes was 13.6% with no significant difference between men and women. Persons with diabetes had a significantly higher prevalence and average number of diabetes-concordant as well as diabetes-discordant comorbidities than persons without diabetes. Among persons with diabetes, 10.2%, 46.8%, 35.6% and 7.4% were classified as having severity grade 1–4, respectively. Determinants of diabetes severity included age (cumulative odds ratio 1.05, 95% confidence interval 1.03-1.07, per year) and number of discordant comorbidities (1.40, 1.25-1.55). With respect to specific discordant comorbidities, diabetes severity was correlated to depression (2.15, 1.29-3.56), respiratory disease (2.75, 1.72-4.41), musculoskeletal disease (1.53, 1.06-2.21), and severe hearing impairment (3.00, 1.21-7.41). Conclusions Diabetes is highly prevalent in the non-institutionalized German adult population 50 years and older. Diabetes comorbidities including diabetes-concordant and diabetes-discordant conditions need to be considered in epidemiological studies, in order to monitor disease burden and quality of diabetes care. Definitional standards of diabetes severity need to be refined and consented.
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Affiliation(s)
- Yong Du
- Department of Epidemiology and Health Monitoring, Division of Non-Communicable Disease Epidemiology, Robert Koch Institute, General-Pape-Str. 62-66, D-12101, Berlin, Germany
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Greig F, Rapaport R, Klein G, Akler G, Annunziato R, Miloh T, Arnon R, Florman S, Kerkar N. Characteristics of diabetes after pediatric liver transplant. Pediatr Transplant 2013; 17:27-33. [PMID: 22905982 DOI: 10.1111/j.1399-3046.2012.01779.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Studies of DALT in pediatric recipients describe incidence and risk factors, but diagnostic criteria varied. This study reports characteristics and course of pediatric DALT by established diabetes criteria. Retrospective chart review of pediatric LT recipients evaluated for hyperglycemia (1/1/1997-12/30/2009) and matched, non-diabetic controls. DALT: random blood glucose >11.1 mm, ≥ 2 times, with insulin treatment. DALT diagnosed in 8.0% (24/300) included 7/24 (29.2%) with severe hyperglycemia (>27.7 mm), ketoacidosis in 2/24 (8.3%). At diagnosis, age was ≥ 11 yr old in 22/24 (91.7%); body mass was lean (BMIz -0.2 ± 1.5). Mean blood glucose was 24.6 mm with negative diabetes autoantibodies (19/19) and elevated C-peptide (2.3 nm). DALT onset median 5.0 months included 29.1% >12 months. Insulin duration median 4.6 months included 41.7% >6 months. DALT resolved in 83.3% over 4.9 (0.9-9.1) yr. DALT differed from controls by increased preceding rejections, prednisolone dose, tacrolimus level, and triple immunosuppression (all p < 0.01). In conclusion, pediatric DALT occurred in non-obese adolescents with insulin resistance, distinct from diabetes types 1 or 2. DALT was associated with preceding rejection and increased immunosuppression. Blood glucose monitoring, especially during increased immunosuppression following LT, could allow early diagnosis and reduce morbidity.
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Affiliation(s)
- Fenella Greig
- Division of Pediatric Endocrinology and Diabetes, Mount Sinai Medical Center, New York, NY 10029, USA
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