UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: Disorders of glucose metabolism, such as impaired glucose tolerance (IGT) and diabetes mellitus (DM), frequently occur in cirrhosis. We aimed to evaluate who needs to be undertaken a 75-g oral glucose tolerance test (OGTT) to find underlying subclinical diabetes.
METHODS: This prospective study included 713 patients with either compensated (Child-Turcotte-Pugh [CTP] class A) or decompensated cirrhosis (CTP class B/C) without previous DM history. All patients underwent a 75-g OGTT. The patients were divided into three groups: normal glucose tolerance (NGT), IGT, and newly diagnosed DM (subclinical DM).
RESULTS: Among 713 patients, NGT was diagnosed in 139 (19.5%), IGT in 252 (35.3%), and subclinical DM in 322 (45.2%) patients, respectively. During a median follow-up period of 42.0 months, the cumulative survival rates of patients were as follows: NGT, 75.6%; IGT, 57.6%; and subclinical DM, 54.8%. Overall, IGT (adjusted hazard ratio [aHR], 1.605; 95% confidence interval [CI] = 1.009-2.553; P = 0.046) and subclinical DM (aHR, 1.840; 95% CI = 1.183-2.861; P = 0.001) were identified as independent predictors of mortality. In patients with compensated cirrhosis (n = 415), neither IGT nor subclinical DM conferred a higher mortality risk. However, among patients with decompensated cirrhosis (n = 298), those with IGT (aHR, 2.394; P = 0.015) and subclinical DM (aHR, 2.211; P = 0.022) showed a survival rate worse than those with NGT. In addition, subclinical DM was identified as an independent risk factor for infection (aHR, 2.508; P = 0.007).
CONCLUSIONS: IGT and subclinical diabetes by OGTT are associated with an unfavorable prognosis in cirrhosis, and the effect is pronounced in the decompensated state.
RESULTS: gov, Number NCT04828512 (https://clinicaltrials.gov/ct2/show/NCT04828512).

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.

OBJECTIVE: Associations between the disturbances in glucose homeostasis and prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remain unclear. This study was conducted to investigate the clinical characteristics of disturbances in glucose homeostasis and their associations with 90-day mortality in patients with HBV-related ACLF.
METHODS: Ninety-six patients with HBV-related ACLF without pre-existing diabetes were prospectively included. Glucose abnormalities were diagnosed based on fasting plasma glucose and oral glucose tolerance test results on admission and during follow-up. Homeostasis model assessment was used to establish insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS) and HOMA2-β-cell function (HOMA2-β). Multivariate Cox proportional hazards analysis was used to identify independent risk factors for death within 90 days after admission.
RESULTS: Among 96 patients with ACLF, 51 (53.1%) had diabetes, 29 (30.2%) had impaired glucose tolerance (IGT), and 17 (17.7%) had hypoglycemia. Patients with diabetes had significantly lower levels of HOMA2-β than did patients with normal glucose tolerance. Of 22 patients with diabetes or IGT and without anti-hyperglycemic treatment, 8 (36.4%) exhibited regression of their glucose metabolism disorders after a follow-up of 32.8 ± 28.8 days, and higher platelet levels were associated with regression. Twenty-five patients (25.0%) with ACLF died of liver failure within 90 days. Diabetes [odds ratio (OR) 3.601, 95% confidence interval (CI) 1.342-9.661] and age (OR 1.045, 95% CI 1.010-1.082) were the independent risk factors associated with mortality.
CONCLUSIONS: Impaired pancreatic β-cell function is related to diabetes development, and diabetes is associated with high mortality in patients with chronic HBV-related ACLF.

Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.

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.

A 54-year-old male with liver cirrhosis (Child-Pugh score 5) presented with severe hepatogenous diabetes (HbA1c 12.6%). Contrast-enhanced CT showed a large portosystemic shunt from the inferior mesenteric vein to the left internal iliac vein. Glucose monitoring showed postprandial hyperglycemia and reactive hypoglycemia. After balloon-occluded retrograde transvenous obliteration (BRTO) and partial splenic transarterial embolization, postprandial hyperglycemia was diminished. Seven months later, HbA1c had improved from 12.6% to 6.7%. In this case, postprandial hyperglycemia occurred by direct delivery of glucose into the systemic circulation via the shunt, and fasting hypoglycemia occurred during treatment with oral antidiabetic agents and insufficient gluconeogenesis. BRTO of the portosystemic shunt resulted in improvement in hepatogenous diabetes.

BACKGROUND: Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes.
OBJECTIVE: We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed.
METHODS: Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included.
RESULTS: Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes.
CONCLUSIONS: Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.