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Garcês Soares S, Frazão T, Tuna C, Montes M, Rocha A, Rodrigues Santos L, Carrola P, Carvalho S, Pinho I, Nogueira L, Marques-Cruz M, Presa J. Disorder of Glucose Metabolism and Therapy: Implications on the Natural History of Advanced Chronic Liver Disease. GE - PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024:1-9. [DOI: 10.1159/000541211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Introduction: Hepatogenous diabetes (HD) is a disorder of glucose metabolism (DGM) that develops as a complication of advanced chronic liver disease (ACLD) with an estimated prevalence of 20–70%. It appears to be associated with a larger number of decompensations, but its impact on the natural history of the disease is unclear. The treatment of DGM is hampered by the fact that some therapeutic agents are associated with a risk of complications in ACLD. The aim of this work was to study DGM in a population of patients with ACLD: prevalence, liver disease decompensation episodes, mortality analysis and study of the impact of antidiabetic therapies in patients with ACLD who developed DGM. Materials and Methods: A cohort of consecutive patients with ACLD without previous DGM, who attended a Hepatology clinic in the period of January to June 2015 was selected. Follow-up was carried out for 5 years. Data on age, gender, date of diagnosis and etiology of ACLD, Child-Pugh and MELD-Na classifications at enrollment, development of DGM, and antidiabetic therapy were collected. Logistic regression models for hospitalizations due to decompensated ACLD, ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), hepatocellular carcinoma (HCC), portal vein thrombosis (PVT), infectious complications, acute-on-chronic liver failure (ACLF), and death were built. A survival analysis for patients with and without DGM was also performed. Treatment effectiveness for patients with DGM was assessed. Results: Initially, 221 patients were included, 154 (69.7%) of whom developed DGM after the diagnosis of ACLD. DGM patients presented a significantly higher number of hospitalizations. Odds ratio (OR) for death was not significantly related with DGM. At 5 years of follow-up, 68.9% of patients with DGM were alive, against 81.8% without DGM (p = 0.087). From the 154 patients who were diagnosed with DGM, 42.9% were not receiving pharmacological treatment for DGM. Treated patients were prescribed with either biguanides (34.8%), a SGLT2 inhibitor (8.6%), or insulin (7.7%). Only 1 patient was treated with a GLP-1 analogue. A tendency of OR favoring treatment was observed for biguanides and SGLT2 inhibitors in all outcomes except ascites. In the univariable analysis, the use of biguanides was associated with lower risk of death (OR: 0.84 [95% CI: 0.73–0.96]) and HE (OR: 0.85 [95% CI: 0.73–0.98]). Conclusion: DGM occurs with high prevalence in patients with ACLD and it seems to be related to more hospitalizations, which highlights the importance of its early identification and appropriate therapeutic approach. In the absence of contraindications, biguanides should be considered for treatment of patients with ACLD and DGM as they appear to be associated with a tendency to better outcomes and may present some advantage in terms of survival.
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Maji T, Mahto M, Kumar S, Anand U, Priyadarshi RN, Arya R, Kumar R. Hepatogenous Diabetes as Compared to Type-2 Diabetes Mellitus and Non-diabetes in Patients With Liver Cirrhosis: Magnitude, Characteristics, and Implications. J Clin Exp Hepatol 2024; 14:101411. [PMID: 38699514 PMCID: PMC11061214 DOI: 10.1016/j.jceh.2024.101411] [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] [Received: 12/28/2023] [Accepted: 04/07/2024] [Indexed: 05/05/2024] Open
Abstract
AIM Hepatogenous diabetes (HD) is frequently underestimated among cirrhosis patients. The current study assessed the magnitude, clinical characteristics, and implications of HD in cirrhosis patients as compared to the patients with type-2 diabetes mellitus (T2DM) and non-diabetes (ND) cirrhosis. METHODS In a prospective observational study, 338 consecutive eligible cirrhosis patients were screened for diabetes mellitus. A 2-hour oral glucose tolerance test (OGTT) was used to detect HD. The clinical characteristics, complications, and outcomes were ascertained and compared amongst HD, T2DM, and ND patients. RESULTS In the final study cohort of 316 patients, the proportion of HD, T2DM, and ND was 22.5% (n = 71), 26.3% (n = 83), and 51.3% (n = 162), respectively. HD was the predominant form of diabetes (68.9%) in Child-Pugh class-C cirrhosis. The majority (73%) of HD patients had abnormal OGTT without fasting hyperglycaemia. A lower cut-off of 98.5 mg/dl for fasting blood glucose had a modest sensitivity (72%) and specificity (75%) for predicting HD. In comparison to T2DM patients, HD patients were younger, leaner, and had more advanced cirrhosis. In comparison to ND patients, HD patients were leaner but had higher glycemic indices, serum cholesterol, and arterial ammonia levels. During a median follow-up period of 12 (03-21) months, the frequency of hepatic encephalopathy and variceal haemorrhage were higher in HD and T2DM patients compared to that in the ND group. CONCLUSIONS HD is prevalent in about one fifth of cirrhosis patients. It differs from T2DM and ND in a number of ways, and has association with complications of cirrhosis.
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Affiliation(s)
- Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Mala Mahto
- Department of Biochemistry, All India Institute of Medical Sciences, Patna, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Rahul Arya
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
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Swaroop S, Vaishnav M, Arora U, Biswas S, Aggarwal A, Sarkar S, Khanna P, Elhence A, Kumar R, Goel A, Shalimar. Etiological Spectrum of Cirrhosis in India: A Systematic Review and Meta-analysis. J Clin Exp Hepatol 2024; 14:101291. [PMID: 38544766 PMCID: PMC10964076 DOI: 10.1016/j.jceh.2023.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/01/2023] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Cirrhosis is a significant cause of morbidity and mortality globally and in India. This systematic review and meta-analysis aimed to ascertain the etiological spectrum and changing trends of cirrhosis in India. METHODS We searched electronic databases, including Pubmed/Medline, Scopus, and Embase. We included original studies that reported the etiology of cirrhosis in the Indian population. RESULTS We included 158 studies (adults: 147, children: 11). The overall pooled estimate of alcohol as a cause of cirrhosis in adults was 43.2% (95% confidence interval (CI) 39.8-46.6%; I2 = 97.8%), followed by nonalcoholic fatty liver disease (NAFLD)/cryptogenic in 14.4%, 95% CI (11.7-17.3%; I2 = 98.4%), hepatitis B virus (HBV) in 11.5%, 95% CI (9.8-13.3%; I2 = 96.6%), and hepatitis C virus (HCV) in 6.2%, 95% CI (4.8-7.8%; I2 = 97.2%) of the included patients. The most common cause of cirrhosis in all zones was alcohol-related. Comparison of etiologies over time revealed a reduction in the viral hepatitis-related and an increase in the proportion of alcohol-related and NAFLD/cryptogenic-related cirrhosis. The overall pooled estimates of various etiologies in children were: HBV in 10.7%, 95% CI (4.6-18.7%; I2 = 91.0%), NAFLD/Cryptogenic in 22.3%, 95% CI (9.0-39.2%; I2 = 96.7%), and HCV in 2.0%, 95% CI (0.0-8.5%; I2 = 94.6%). CONCLUSIONS Alcohol is the most common etiology of cirrhosis in adults in India. The proportions of alcohol and NAFLD-related cirrhosis are increasing, and those of viral hepatitis-related cirrhosis are reducing. The results of our meta-analysis will help formulate health policies and the allocation of resources.
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Affiliation(s)
- Shekhar Swaroop
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Umang Arora
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Arnav Aggarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Soumya Sarkar
- Department of Anaesthesia, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Puneet Khanna
- Department of Anaesthesia, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Anshuman Elhence
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Amit Goel
- Department of Hepatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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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: 1] [Impact Index Per Article: 0.3] [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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Gundling F. Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2022; 15:42-52. [DOI: 10.1007/s41969-022-00158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 01/04/2025]
Abstract
Zusammenfassung
Hintergrund
Patienten mit Leberzirrhose entwickeln häufig Störungen des Glukosemetabolismus wie Glukoseintoleranz oder einen hepatogenen Diabetes, welche neben der hepatozellulären Funktionseinschränkung durch die ausgeprägte Insulinresistenz als Folge der chronischen Lebererkrankung verursacht sind.
Diskussion
Empfehlungen mit Leitliniencharakter zur Diagnostik und Therapie des hepatogenen Diabetes fehlen bislang. Im Hinblick auf basistherapeutische Maßnahmen sollte eine ausreichende Deckung des Energie- und Proteinstoffwechsels gewährleistet sein, da ein Großteil der Zirrhosepatienten mangelernährt ist. Bei der medikamentösen Behandlung des hepatogenen Diabetes muss auf die erhöhte Hypoglykämiegefährdung geachtet werden. Aufgrund der Nebenwirkungen sind Biguanide sowie PPAR-gamma-Liganden bei Leberzirrhose kontraindiziert. Geeignete orale Antidiabetika sind insbesondere Sulfonylharnstoffanaloga und kurz wirksame Sulfonylharnstoffe. Wenn eine suffiziente Diabeteseinstellung mit oralen Antidiabetika nicht gelingt, sollte eine prandiale Insulintherapie mit Insulinen von kurzer Wirkdauer oder kurz wirksamen Insulinanaloga eingesetzt werden.
Schlussfolgerung
Die Optimierung einer diabetischen Stoffwechsellage hat neben der Vermeidung typischer diabetischer Spätkomplikationen eine wichtige Bedeutung für die Vermeidung und Reduzierung von Zirrhose-assoziierten Komplikationen wie z. B. gastrointestinalen Blutungsereignissen, hepatischer Enzephalopathie oder dem Auftreten eines hepatozellulären Karzinoms.
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García-Compeán D, Orsi E, Kumar R, Gundling F, Nishida T, Villarreal-Pérez JZ, Del Cueto-Aguilera ÁN, González-González JA, Pugliese G. Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives. World J Gastroenterol 2022; 28:775-793. [PMID: 35317103 PMCID: PMC8900578 DOI: 10.3748/wjg.v28.i8.775] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/19/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, Fdn IRCCS Ca Granda, Endocrine Unit, Padigl Granelli, Milan 20121, Italy
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Felix Gundling
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Diabetics, Metabolism and Infectious Diseases, Sozialstiftung Bamberg, Bamberg 96049, Germany
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka 560-8565, Japan
| | | | - Ángel N Del Cueto-Aguilera
- Department of Gastroenterology and Internal Medicine, Faculty of Medicine, University Hospital, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. José E González and Medical School, Monterrey 64460, Nuevo León, Mexico
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, La Sapienza University, Roma 00161, Italy
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