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Second, because of the baseline difference between the study and comparison groups, we used propensity score matching before Cox regression. However, the unmatched group is not included in the analysis after the propensity score matching method used.
This reduces the generalizability of the study results and makes the lack of robustness of our final analysis results. In order to confirm the results, we also performed the Cox regression as the main analysis without propensity score matching. The crude HR for day of cirrhotic patients with hypoglycemia before and after propensity score matching method were 6.
After Cox regression analysis, the adjusted HR for day of cirrhotic patients with hypoglycemia before and after propensity score matching method were 5.
The survival of cirrhotic patients with hypoglycemia were affected by many factors, such as underlying diseases, liver reserved, infections, …etc. In fact, we could not analyze all factors by Cox regression method, and these factors may skew the results before and after adjusting for confounders.
However, the hypoglycemia is still an important prognostic factor in the day mortality of cirrhotic patients regardless of the propensity score matching or Cox regression analysis.
Finally, the hypoglycemia was defined by ICD-9 coding number and we could not validate that. This is the limitation of this database we used. However, we excluded the patients with underlying diabetes mellitus.
This may partially decrease the bias of this study. In conclusion, this nationwide population-based study showed that hypoglycemia is a very important prognostic factor in the day mortality of cirrhotic patients, especially in those with underlying HCC.
The data that support the findings of this study are available from National Health Insurance Research Database NHIRD in Taiwan but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
Data are however available from the authors upon reasonable request and with permission of NHIRD in Taiwan. Kumar R. Hepatogenous diabetes: an underestimated problem of liver cirrhosis.
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JPEN J Parenter Enteral Nutr. Furukawa M, Kinoshita K, Yamaguchi J, Hori S, Sakurai A. Sepsis patients with complication of hypoglycemia and hypoalbuminemia are an early and easy identification of high mortality risk.
Intern Emerg Med. Ssekitoleko R, Jacob ST, Banura P, Pinkerton R, Meya DB, Reynolds SJ, Kenya-Mugisha N, Mayanja-Kizza H, Muhindo R, Bhagani S, et al. Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis.
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With special reference to types and localization of HBsAg in the tumor cells. Download references. Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No.
School of Medicine, Tzu Chi University, Hualien, Taiwan. Department of Mathematics, Tamkang University, Tamsui, Taiwan. You can also search for this author in PubMed Google Scholar. T-HH, C-WT and H-FL: study concept and design; acquisition of data; analysis and interpretation of data and drafting of the manuscript; C-CT and T-HH: statistical analysis.
All authors read and approved the final manuscript. Correspondence to Hsing-Feng Lee. The study protocol was carried out in accordance with the Declaration of Helsinki.
Because all of the data from the Taiwan National Health Insurance Research Database NHIRD is de-identified, the Institutional Review Board of the Buddhist Dalin Tzu Chi Hospital IRB B waived the requirement for informed patient consent and the need of informed consent for ethical approval.
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Hung, TH. et al. Prognosis of hypoglycemia episode in cirrhotic patients during hospitalization. BMC Gastroenterol 21 , Download citation. Received : 14 February Accepted : 03 August Published : 09 August Anyone you share the following link with will be able to read this content:.
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Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Studies have shown that hyperglycemia in cirrhotic patients increases mortality. Methods The Taiwan National Health Insurance Database was searched, and cirrhotic patients without baseline diabetes mellitus who presented with hypoglycemia upon hospitalized from to were included in the study.
Results The overall day mortality rate was Conclusions Hypoglycemia is a very important prognostic factor in the day mortality of cirrhotic patients, especially in those with underlying HCC.
Introduction Liver is a metabolic organ that plays an important role in glucose metabolism. Study sample The database was searched for patients discharged between January 1, and December 31, with a primary or secondary diagnosis of cirrhosis ICDCM codes Results The database was searched for patients discharged between January 1, and December 31, with the diagnosis of liver cirrhosis.
Table 1 Demographic characteristics of the hypoglycemia groups Full size table. Table 2 Adjusted hazard ratios of risk factor for day mortality of cirrhotic patients Full size table. Full size image.
Discussion In this present study, we demonstrated that cirrhotic patients who had a hypoglycemic episode during hospital admission had a higher day mortality rate than those without hypoglycemia. Availability of data and materials The data that support the findings of this study are available from National Health Insurance Research Database NHIRD in Taiwan but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
References Kumar R. Article CAS Google Scholar Nouel O, Bernuau J, Rueff B, Benhamou JP. Article CAS Google Scholar Pfortmueller CA, Wiemann C, Funk GC, Leichtle AB, Fiedler GM, Exadaktylos AK, Lindner G.
Article Google Scholar Forner A, Llovet JM, Bruix J. Article Google Scholar Qu Q, Wang S, Chen S, Zhou L, Rui JA. Article Google Scholar Hagel S, Bruns T, Herrmann A, Stallmach A, Schmidt C. Article CAS Google Scholar Nishida T, Tsuji S, Tsujii M, Arimitsu S, Haruna Y, Imano E, Suzuki M, Kanda T, Kawano S, Hiramatsu N, et al.
Article Google Scholar Chen CW, Chen YY, Lu CL, Chen SC, Chen YJ, Lin MS, Chen W. Article Google Scholar Kobayashi K, Cooper GS, Chak A, Sivak MV Jr, Wong RC. Article Google Scholar Vagionas A, Tigas S, Oikonomou P, Pentheroudakis G, Malamou-Mitsi V, Pavlidis N.
Each admission in the database was assigned one principal diagnosis, up to 40 secondary diagnoses, and 25 procedures. These variables are defined via the International Classification of Disease, 10th revision, and Clinical Modification ICDCM codes.
Target population age was 18 years and older. Using ICDCM codes, we identified patients who carried a diagnosis of cirrhosis and hypoglycemia.
The comorbidities included were chronic kidney disease CKD , alcoholism, hepatocellular carcinoma HCC , hypertension HTN , cachexia, hepatorenal syndrome HRS , hepatopulmonary synd-rome HPS , hepatic failure, spontaneous bacterial peritonitis SBP , ascites, varices, smoking and obesity body mass index BMI of more than Diabetic patients were exclu-ded from this study to rule out the probability of iatrogenic hypoglycemia.
Intensive care unit ICU admission was defined as any patient who had cardiac arrest or needed vasopressors or mechanical ventil-ation. Figure 1 demonstrates the study population Figure 1. The statistical analysis was done using STATA software, version The demographic and clinical charact-eristics of patients with cirrhosis and hypoglycemia and those without hypoglycemia were described using descriptive statistics.
In this study, multivariate logistic regression analyses were performed to deter-mine factors associated with in-hospital mortality. Out of 1,, patients carrying the diagnosis of cirrhosis, it was found that 31, patients 1.
The mean age of patients with cirrhosis and concurrent hypoglycemia was nearly the same but slightly less than patients without hypo-glycemia While male gender was more predominant in both groups, percentage of females in the cirrhosis with hypoglycemia group was more pronounced compared to the cirrhosis without hypoglycemia group The white race percentage was nearly identical and the most prevalent in both groups ~ Black race prevalence was higher in hypoglycemia group In terms of hospital characteristics, both groups were more likely to be in a large hospital in the southern region Table 1.
Regarding comor-bidities, the prevalence of CKD, alcoholism, HCC, cachexia, HRS, hepatic failure and SBP were more pronounced in the cirrhosis and hypoglycemia group. HTN, smoking and obesity were more prevalent in the cirrhosis without hypoglycemia group Table 1.
This was also reflected on the multivariate analysis as patients with cirrhosis and hypoglycemia had a higher chance of dying during hospitalization compared to those without hypogl-ycemia after adjusting for other possible confounders OR 6.
Interestingly, patients with HRS had the highest chance for in-hospital mortality, followed by hepatic failure. Cachexia, SBP, varices, ascites, HPS, HCC and CKD were associated with a modest increase in odds of in-hospital mortality.
On the other hand, HTN, obesity and smoking were associated with a statistically significant decrease in odds of in-hospital mortality Table 3. Mortality, vasopressor usage, mechanical ventilation, cardiac arrest and ICU admission were significantly higher in cirrhotic patients with hypoglycemia compared to cirrhotics without hypoglycemia Table 2.
Moreover, patients with cirrhosis and hypoglycemia had a higher chance of having cardiac arrest during hospitalization and to be admitted to the ICU. Tables 4, 5, 6 and 7 summarize these findings.
Figure 2 demonstrates OR plots. Figure 1: Flow chart of the study population after applying inclusion and exclusion criteria. Abbreviations: CKD, chronic kidney disease; HCC, hepatocellular carcinoma; HRS, hepatorenal syndrome; HPS, hepatopulmonary syndrome; SBP, spontaneous bacterial peritonitis.
Table 1: Clinical and demographic characteristics of cirrhotic patients with hypoglycemia vs no hypoglycemia. Table 2: Clinical outcomes in cirrhotic patients with hypoglycemia vs no hypoglycemia. Abbreviations: OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; CKD, chronic kidney disease; HCC, hepatocellular carcinoma; HRS, hepatorenal syndrome; HPS, hepatopulmonary syndrome; SBP, spontaneous bacterial peritonitis.
Table 3: Univariate and multivariate analysis of factors associated with in-hospital mortality in cirrhotic patients with hypoglycemia. Table 4: Univariate and multivariate analysis of factors associated with mechanical ventilation in cirrhotic patients with hypoglycemia. Table 5: Univariate and multivariate analysis of factors associated with vasopressor use in cirrhotic patients with hypoglycemia.
Table 6: Univariate and multivariate analysis of factors associated with cardiac arrest in cirrhotic patients with hypoglycemia. Table 7: Univariate and multivariate analysis of factors associated with ICU admission in cirrhotic patients with hypoglycemia. Figure 2: Odds ratio plots for a: in-hospital mortality, b: mechanical ventilation, c: vasopressor use, d: cardiac arrest and e: ICU admission in patients with liver cirrhosis.
In this retrospective nationwide inpatient population study, we demonstrated that the occurrence of in-hospital hypoglycemia in patients with cirrhosis is associated with increased in-hospital mortality and worse outcomes compared to patients with cirrhosis who do not experience hypoglycemia.
Our study showed higher mortality rates in cirrhotic patients who developed a hypoglycemia episode during hospital-lization compared to patients with normal blood sugar level.
This is consistent with what is described in the current literature [4, ]. Pfortmueller et al. Our study demon-strated a significantly higher chance of in-hospital mortality and ICU admission even after adjusting for decompensating factors such as ascites, HRS, HPS, SBP, hepatic failure, and HCC.
One population-based retrospective study done in Taiwan by Hung et al. This study also showed that the cirrhotic patients with concurrent HCC also had a higher day mortality rate than those without HCC [6].
Compared to Hung et al. study, our study had a larger patient sample. The results of this study are more generalizable, as Hung et al did not comment on race, while the population of our study was multi-racial. The heightened mortality associated with hypoglycemia may be explained by the presence of cirrhosis-related complications and the elevated risk of sepsis.
In this study, patients with hypoglycemia were also more likely to present during the hospital-lization with a complication of cirrhosis, such as HRS, hepatic failure, ascites, and SBP. The presence of these comorbidities typically adds complexity to clinical management and compounds the higher mortality rate of compensated cirrhosis [].
This may reflect that hypoglycemia itself is an indicator of advanced cirrhosis and appears concurrently with its known complications. Furthermore, the occurrence of cirr-hosis-related complications is often related to sepsis.
Patients with cirrhosis are more susceptible to deve-loping bacterial infection and suffer higher mortality from sepsis [1]. Saiman et al. Hypogly-cemia per se is associated with elevated mortality in the setting of sepsis, regardless of cirrhosis also being present [].
Future studies could focus on the utility of adding hypoglycemia to calculations for risk stratification and prognosis including transplant priority in cirrhotic patients. In our study, we found that hypoglycemia was associated with greater severity of illness, including increased risk of ICU admission, shock requiring vasopressors, mechanical ventilation, and cardiac arrests.
However, the reason for such critical illness was not specified, but it is plausible that sepsis could account for the majority of cases. Hypoglycemia may be an important early predictor of inpatient septicemia and in-hospital mortality in patients with cirrhosis, and may portend the development of severe illness with multiorgan failure leading to ICU admission, and subsequently mechanical ventilation, initiation of vasopressor therapy, and ultimately cardiac arrest [5, 8].
Sepsis itself may cause aberrant glucose homeos-tasis due to systemic inflammation and relative adrenal insufficiency, although this may also be related to impaired hepatic glucose metabolism due to liver fibrosis, cirrhosis-related adrenal insufficiency, or malnutrition [3, 6, 12, 15].
Thus, hypoglycemia may be a poor prognostic indicator of either impending acute clinical deterioration or represent a long-term sequela of chronic liver disease. Hypoalbuminemia is also a common finding in cirrhosis and has been linked to higher mortality in septic patients with hypogly-cemia [14].
However, our data did not include diagnoses of hypoalbuminemia in the patient sample. In keeping with the increased likelihood of acute complications related to cirrhosis, hypoglycemia was also associated with a longer length of stay and total hospital charges. This is likely related to the higher incidence of these complications and the additional resources required to manage them.
Incorporating an understanding of prognostication in cirrhosis may be important for future development of healthcare policy and inpatient hospital resource utilization. Hypogly-cemia was more likely to occur in females than males.
Although this remains unclear, this discrepancy could be related to differences in sex-hormone effects on liver physiology [16]. Furthermore, Black race was also associated with greater incidence of hypogly-cemia.
It is possible that genetic, socioeconomic, and other demographic variables contribute to illness complications [17]. This study has several limitations which include the inability to categorize patients based on their MELD score which is used for prognostication and risk of short-term mortality in cirrhosis [18].
Our data may suggest that hypoglycemia tends to occur more frequently in patients with decompensated liver disease. Given that the MELD score correlates with degree of liver dysfunction, it is possible that hypogl-ycemia may correlate similarly [19].
Our study does not account for individuals who had a diagnosis of sepsis, and with the current data we may only hypo-thesize that sepsis could account for a majority of cases with severe illness.
Moreover, due to the nature of the NIS database, our observations reflect admiss-ions and not individual patients. Therefore, the unit of analysis is the admission. Given the inability to account for multiple admissions for a given patient in the NIS, our conclusions may be confounded by the risk of repeat hospitalization.
Thus, our reported rates may be viewed as over-estimates of a per patient admission rate. Mortality rates, however, are unlikely to be affected. Under-or over-coding can lead to mis-classification, although the large number of patients in the database strongly mitigates against substantial misclassification bias.
NIS undergoes data quality assessment annually to ensure the internal validity of the data. In conclusion, hypoglycemia in a nationwide diverse population of hospitalized non-diabetic inpatients with cirrhosis was associated with higher day mortality and rate of critical illness as suggested by an elevated rate of ICU admission, mechanical ventilation, and shock requiring vasopressor medication.
In addition, these patients had a longer length of hospital stay and higher total hospital charges. These outcomes were observed even when controlling for various comor-bidities and complications due to decompensated cirrhosis.
Hypoglycemia in cirrhotic patients may be an important prognostic factor as an early indicator of sepsis and could forebode a prolonged hospital stay due to critical illness, hence such patients should be monitored carefully for signs of worsening clinical status.
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. This retrospective chart review study was done using the NIS deidentified database.
Therefore an IRB approval was not obtained. CiteScore: 2. Acceptance Rate: Time to first decision: Time manuscript received to accepted: 16 weeks. Discover More: Journal Homepage. Stay Home.
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The database was searched for patients discharged between January 1, and December 31, with a primary or secondary diagnosis of cirrhosis ICDCM codes These ICD-9 codes have been used in past studies to identify patients with cirrhosis in Taiwan.
A total ofcirrhotic patients were screened. In clinical practice, an important common cause of hypoglycemia is the overdose of medications related to treat diabetes mellitus. In order to avoid the effect of these medications, patients with underlying diabetes mellitus were excluded from the study.
Hypoglycemia was defined by ICDCM code A total ofcirrhotic patients without baseline diabetes mellitus were included. Of these, patients were enrolled only if they had hypoglycemia noted during the hospital stay.
If a patient had multiple hospitalizations for hypoglycemia during the study period, only the first episode was included in the analysis. Finally, a total of cirrhotic patients with hypoglycemia were enrolled.
We used one-to-four propensity score matching to match a control group non-hypoglycemia group to the study group by age, gender and liver-related complications the presence of either hepatic encephalopathy, variceal bleeding or ascites.
We collected for analysis the confounding factors of age, gender, hepatic encephalopathy ICDCM code We used the presence of albumin supplementation to define the hypoalbuminemia in our study because the serum albumin level could not be identified from the database.
The individuals in this study were classified into three groups: low SES, medium SES, and high SES. The bacterial infections included were bacteremia, cellulitis, pneumonia, biliary tract infection, necrotizing fasciitis, empyema, brain abscess, urinary tract infection, septic arthritis, perianal abscess, liver abscess, bacterial meningitis and spontaneous bacterial peritonitis.
The etiology of liver cirrhosis such as hepatitis B or hepatitis C could not be well obtained from the inpatient dataset we applied because of the coding limitation from this dataset.
This is the reason the hepatitis B or C were not analyzed in this study. Cirrhotic patients often also present with HCC ICDCM code In subgroup analysis, we calculated the hazard ratios HRs of hypoglycemia in the short-term mortality among these patients with concurrent HCC.
Propensity score was performed to match analysis including age, gender and underlying comorbidities to minimize potential confounding effects.
The Cox regression model was used to identify the risk factors associated with mortality. All Data were analyzed by the SPSS statistical package for Windows version The database was searched for patients discharged between January 1, and December 31, with the diagnosis of liver cirrhosis.
After review of the database and application of the inclusion and exclusion criteria, patients with cirrhosis and hypoglycemia were included in the study as the hypoglycemia group.
With propensity score matching, cirrhotic patients without hypoglycemia were included as the non-hypoglycemia group. Of the cirrhotic patients with hypoglycemia, the mean age was Of the cirrhotic patients without hypoglycemia, the mean age was Table 1 shows the demographic characteristics of the two groups.
Because of the propensity score matching, factors such as cancer, alcoholism, renal function impairment, complication conditions, cachexia, SES, CCI, hypoalbuminemia, bacterial infections, the cirrhosis-related complications, gender and age were not significantly different between the two groups.
The overall day mortality was After Cox regression modeling adjusting for age, sex and other comorbid disorders, the HR for day mortality of the hypoglycemia group was 4. Other risk factors for day mortality of cirrhotic patients included one cirrhotic-related complication HR, 2.
Other factors, including male HR, 1. The statistically significant prognostic factors were summarized in Table 2.
The flowchart for this study were shown in Fig. The cumulative survival plots for the patients with and without hypoglycemia were shown in Fig.
The flowchart of this study. HCC hepatocellular carcinoma, RFI renal function impairment, CCI Charlson Comorbidity Index, High SES High socioeconomic status.
To evaluate the role of hypoglycemia in cirrhotic patients with HCC, subgroup analysis were performed. In cirrhotic patients with underlying HCC, the HR for day mortality of those with hypoglycemia was 6.
In cirrhotic patients without underlying HCC, the HR for day mortality for those with hypoglycemia was 4. For confirming the result, we also performed the Cox regression as the main analysis without propensity score matching.
The results were listed as Additional file 1 : Appendix 1. The hypoglycemia is still an important prognostic factor in the day mortality of cirrhotic patients. In this present study, we demonstrated that cirrhotic patients who had a hypoglycemic episode during hospital admission had a higher day mortality rate than those without hypoglycemia.
In addition, the cirrhotic patients with concurrent HCC also had a higher day mortality rate than those without HCC. To our best knowledge, this is the first population-based study to discuss short-tern mortality in cirrhotic patients with a hypoglycemic episode during admission.
Our present findings were similar to those of a previous study. Pfortmueller et al. showed that hypoglycemia is associated with increased mortality in cirrhotic patients with acute decompensation [ 3 ].
However, our study revealed that cirrhotic patients had higher short-term mortality regardless of the decompensated status. In this present study, we also showed that cirrhotic patients with concurrent HCC had a higher mortality rate than those without HCC.
Paraneoplastic syndromes are not uncommon in HCC patients. Several studies have been shown that HCC patients with paraneoplastic syndromes, including hypoglycemia, have poor prognosis [ 51112 ]. Therefore, not surprisingly, in our present study, cirrhotic patients with concurrent HCC had poor prognosis.
Some reasons might explain why cirrhotic patients with a hypoglycemic episode during admission are at higher risk of short-term mortality.
First, hypoglycemia is a sign of malnutrition. Dozens of studies have shown that malnutrition contributes to increased mortality during admission [ 131415 ]. Second, patients with severe infection with sepsis have a poor prognosis when hypoglycemia occurs at admission [ 161718 ].
In one recent publication, Furukawa et al. found higher mortality in septic patients with hypoglycemia and hypoalbuminemia at admission [ 16 ]. Thus, these septic patients are in greater need of immediate intensive treatment during admission.
In other words, according to our current findings, cirrhotic patients who had a hypoglycemic episode during admission were also those who needed intensive care. Third, hypoglycemia may be associated with adrenal insufficiency [ 192021 ].
Liver cirrhosis has been reported as being to some degree an adrenocortical dysfunction [ 192223 ]. Thus, cirrhotic patients with hypoglycemia have an inappropriately low response of the adrenal glands to stimulation and increased mortality.
Lastly, severe liver fibrotic disease is associated with poor glucogensis [ 24 ].
: Hypoglycemia and liver function| The Connection Between Type 2 Diabetes and Liver Disease | We found that the incidence of hypoglycemia in the present study was The specific mechanism of hypoglycemia in patients with acute on chronic liver failure remains unclear. It is speculated that factors such as reduced food intake, compromised liver metabolic capacity, glycogen depletion and gluconeogenesis disorders, and disruption of the inactivation of hypoglycemic hormones 8 , 9 may account for the occurrence of hypoglycemia in patients with severe liver dysfunction. At present, the research on hypoglycemia in patients with liver failure 10 - 12 is mostly limited to animal experiments, primarily discussing the related molecular regulation mechanism, and there is still a lack of research on the clinically significant topic of risk factors and prognosis of hypoglycemia in patients with acute on chronic liver failure. The present study confirmed that hypoglycemia was related to liver cirrhosis, a higher MELD score, and lower FIB. Patients with liver cirrhosis often have portal hypertension, which leads to gastrointestinal congestion and decreased appetite. In addition, patients often need to avoid consuming foods rich in protein to prevent hepatic encephalopathy, resulting in a negative nitrogen balance in energy metabolism. The MELD score has been widely used to evaluate liver function and prognosis. A higher MELD score directly reflects poor liver function, in which the inactivation of insulin is substantially compromised 13 , Honda et al. FIB is one of many coagulation factors synthesized by the liver, and it has been demonstrated to be decreased in acute liver failure In this study, FIB reduction was found to significantly increase the risk of hypoglycemia, which is consistent with previous relevant reports Univariate and multivariate analysis showed that the short-term prognosis of patients with hypoglycemia was significantly worse than that of patients without hypoglycemia. A study of patients with decompensated cirrhosis without diabetes by Hung et al. In contrast, the day mortality of patients without hypoglycemia was only 7. The guidelines of the American Society of Critical Care Medicine also suggested that preventing and improving hypoglycemia in patients with severe liver disease helps to improve patient outcomes In a meta-analysis comprising eight previous clinical trials, Chen et al. Currently, the American Society for Parenteral and Enteral Nutrition 21 and the European Society for Clinical Nutrition and Metabolism 22 recommend that patients with severe liver dysfunction should consume extra night-time meals to improve their nutritional metabolism and prevent the adverse effects of hypoglycemia. This study is the first to systematically investigate the incidence, risk factors, and prognosis of hypoglycemia in patients with acute on chronic liver failure. However, this study also had several limitations, including its retrospective nature, single-center design, and small sample size. Therefore, it is necessary to carry out prospective, multi-center studies with larger sample sizes in the future to validate and generalize the results of this study. In conclusion, this study found that hypoglycemia was common in patients with acute on chronic liver failure, and is related to poor prognosis. Patients with cirrhosis, a higher MELD score, and a significant decrease in FIB were more likely to develop hypoglycemia. Therefore, medical staff should pay attention to blood glucose management and avoid hypoglycemia by enhancing blood glucose monitoring, adjusting diet structure, and adding meals before bed. However, given that this study is a single-center, retrospective analysis, future prospective, multi-center research is needed. Reporting Checklist: The authors have completed the STROBE reporting checklist. The authors have no conflicts of interest to declare. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4. What is known and what is new? What is the implication, and what should change now? Figure 1 Study flow chart. Table 1 Comparison of the general characteristics and laboratory test results between the hypoglycemia and non-hypoglycemia groups. Table 2 Analysis of the risk factors for hypoglycemia in patients with acute on chronic liver failure. Table 3 Univariate analysis results of the risk factors for day mortality in patients with acute on chronic liver failure. Liver-related event-free survival. No significant difference was seen A , B , C. Table 3 shows the multivariate analysis of factors contributing to event-free survival using the Cox proportional hazards model. In univariate analysis, branched-chain amino acids BCAA , Child—Pugh class, HbA1c, and hypoglycemia were identified as factors contributing to event-free survival. Hepatic glycogen storage is decreased in patients with CLD Postprandial glucose uptake from the blood by the liver is delayed, resulting in hyperglycemia. In addition, patients with CLD have a reduced storage capacity for hepatic glycogen, resulting in inadequate glucose release from the liver into the blood during fasting, and impaired gluconeogenesis, leading to hypoglycemia; therefore, the management of diabetes in patients with liver disease can be difficult The metabolic state of patients with CLD after an overnight fast is similar to that observed in healthy individuals after 2—3 days of starvation. For this reason, patients with CLD have large fluctuations in blood glucose levels, and nocturnal hypoglycemia often occurs. In the analysis focusing on glucose fluctuation, there was a weak correlation with DM parameters such as HbA1c and GA, and a strong correlation with MAGE, a classical fluctuation parameter Fig. The SD of mean glucose level as measured by FGM can be considered a surrogate index for MAGE. The CV was also examined as a measure of fluctuation; however, SD had a stronger correlation with MAGE. In our previous study, the SD was In the present study, the SD value of blood glucose was There was no significant relationship between glucose fluctuations and liver-related events. The CGM system has been reported to be useful in detecting hidden abnormalities in blood glucose fluctuations in patients with type 2 DM and CLD Abnormal blood glucose fluctuations have also been reported to be a risk factor for sleep disturbance and decreased quality of life in patients with LC 6. However, glucose fluctuation does not predict liver-related events such as encephalopathy, infection, and liver failure, which are more severe in patients with CLD. Similar results indicating that hypoglycemia is more important than blood glucose fluctuations have been reported, although not in patients with liver disease In this study, hypoglycemia, as determined by the FGM system, was identified as a significant factor closely associated with liver-related events. Hypoglycemia plays an important role in inflammation, thrombotic events, and endothelial dysfunction by inducing oxidative stress Previous reports have shown that hypoglycemia is an important prognostic factor for short-term mortality in patients with cirrhosis In addition, hypoglycemia has been reported to be associated with nutritional deficiencies, infections, and poor glucogenesis 17 , The presence of DM itself is associated with infections, variceal hemorrhage, and encephalopathy 19 , Previous reports have consistently shown that hypoglycemia is an important factor in liver-related events. Therefore, it is reasonable to accept hypoglycemia as a risk factor for liver-related event-free survival in our study. Hypoglycemia measured using the FGM system showed a higher frequency in the total patient population Previous studies of continuous blood glucose measurement using iPro2 have shown that hypoglycemia is infrequent Compared to iPro2, FGM has a long measurement period of up to 14 days, making it easier to detect hypoglycemia. It has been reported that CGM systems using FreeStyle Libre Pro can detect hypoglycemia better than point-of-care capillary glucose testing In addition, glucose measurements using this CGM system have been reported to be slightly lower than blood glucose levels Furthermore, Glycated hemoglobin A1c HbA1c and glycoalbumin are the gold standard indicators of glycemic control in diabetes. However, HbA1c cannot adequately represent the glycemic control status in patients with CLD because of the short lifespan of erythrocytes caused by hypersplenism. Glycoalbumin is affected by impaired albumin metabolism; in patients with CLD, the half-life of serum albumin is prolonged owing to decreased albumin synthesis Therefore, it is difficult to accurately monitor the glycemic control status in patients with CLD. The FGM system has enabled the identification of hypoglycemia in patients with CLD at a high risk of liver-related events. It is an excellent system for detecting latent hypoglycemia during a routine examination in a population with apparently good glycemic control, including in those with low HbA1c and glycoalbumin levels. Late evening snack LES with BCAA supplementation is considered to be effective in improving protein-energy nutrition 23 and avoiding nocturnal hypoglycemia in patients with CLD. In this study, BCAA and LES with BCAA were administered to Since all patients had type 2 DM, the possibility that they avoided calorie intake was considered, and there is a potential opportunity for intervention in the future. A limitation of this study is that it was a single-centre retrospective analysis and there were no treatment interventions based on the FGM system measurements. Whether an intervention for hypoglycemia with FGM leads to a reduction in liver-related events is unknown 24 and is a subject for future research. Another limitation is that the FGM system measurements were performed under health insurance and patients with CLD without therapeutic intervention for DM were not monitored by the FGM system. Despite these limitations, this is the first report to describe the relationship between hypoglycemia identified using the FGM system and liver disease-related events. These results suggest that the FGM system, in addition to measuring glucose levels, is useful for predicting the occurrence of liver-related events. Petrides, A. Glucose metabolism in cirrhosis: A review with some perspectives for the future. Diabetes Metab. Article CAS PubMed Google Scholar. Bianchi, G. et al. Prognostic significance of diabetes in patients with cirrhosis. Hepatology 20 , — CAS PubMed Google Scholar. El-Serag, H. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology , — Article PubMed Google Scholar. Imano, E. Significance of oral glucose tolerance test for the diagnosis of diabetes mellitus in patients with liver cirrhosis. Kishimoto, M. Verification of glycemic profiles using continuous glucose monitoring: Cases with steroid use, liver cirrhosis, enteral nutrition, or late dumping syndrome. Haraguchi, M. Glucose fluctuations reduce quality of sleep and of life in patients with liver cirrhosis. Battelino, T. Continuous glucose monitoring and metrics for clinical trials: An international consensus statement. Lancet Diabetes Endocrinol. Marling, C. Characterizing blood glucose variability using new metrics with continuous glucose monitoring data. Diabetes Sci. Article PubMed PubMed Central Google Scholar. Service, F. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19 , — Owen, O. Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. Article CAS PubMed PubMed Central Google Scholar. Tolman, K. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care 30 , — Zhou, J. Reference values for continuous glucose monitoring in Chinese subjects. Diabetes Care 32 , — Honda, F. Evaluation of glycemic variability in chronic liver disease patients with type 2 diabetes mellitus using continuous glucose monitoring. PLoS ONE 13 , e Kim, Y. Impact of glycemic variability and hypoglycemia on adverse hospital outcomes in non-critically ill patients. Diabetes Res. Papachristoforou, E. Association of glycemic indices hyperglycemia, glucose variability, and hypoglycemia with oxidative stress and diabetic complications. Hung, T. Prognosis of hypoglycemia episode in cirrhotic patients during hospitalization. BMC Gastroenterol. Olson, J. Intensive care of the patient with cirrhosis. Hepatology 54 , — Furukawa, M. Sepsis patients with complication of hypoglycemia and hypoalbuminemia are an early and easy identification of high mortality risk. Coman, L. Association between liver cirrhosis and diabetes mellitus: A review on hepatic outcomes. Rosenblatt, R. Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis. Liver Dis. Galindo, R. Comparison of the freestyle libre pro flash continuous glucose monitoring CGM system and point-of-care capillary glucose testing in hospitalized patients with type 2 diabetes treated with basal-bolus insulin regimen. Diabetes Care 43 , — Koga, M. Clinical impact of glycated albumin as another glycemic control marker. Fukushima, H. Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: Comparison with daytime administration. JPEN J. Park, C. The effectiveness of continuous glucose monitoring in patients with type 2 diabetes: A systematic review of literature and meta-analysis. Diabetes Technol. Download references. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki City, Nagasaki, , Japan. You can also search for this author in PubMed Google Scholar. Conception and design of the study: R. Correspondence to Ryu Sasaki. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Sasaki, R. Hypoglycemia measured by flash glucose monitoring system predicts liver-related events in chronic liver disease patients. Sci Rep 13 , Download citation. Received : 01 March |
| Introduction | The day mortality rate in the hypoglycemia group was markedly higher than that in the non-hypoglycemia group ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBil, total bilirubin; Alb, serum albumin; Scr, serum creatinine; INR, international normalized ratio, WBC, white blood cell count; FIB, fibrinogen; MELD, model for end-stage liver disease. AST, aspartate aminotransferase; TBil, total bilirubin; FIB, fibrinogen; MELD, model for end-stage liver disease; OR, odds ratio; CI, confidence interval. A total of Compared with the patients in the survival group, the deceased group had a significantly higher proportion of patients with liver cirrhosis, hepatic encephalopathy, gastrointestinal bleeding, hepatic ascites, higher MELD scores, and hypoglycemia. Binary logistic regression analysis Table 4 showed that hepatic encephalopathy, cirrhosis, a higher MELD score, and hypoglycemia were associated with an increased risk of day mortality in patients with acute on chronic liver failure. This study examined the incidence, risk factors, and impact of hypoglycemia on the short-term prognosis in patients with acute on chronic liver failure. We found that the incidence of hypoglycemia in the present study was The specific mechanism of hypoglycemia in patients with acute on chronic liver failure remains unclear. It is speculated that factors such as reduced food intake, compromised liver metabolic capacity, glycogen depletion and gluconeogenesis disorders, and disruption of the inactivation of hypoglycemic hormones 8 , 9 may account for the occurrence of hypoglycemia in patients with severe liver dysfunction. At present, the research on hypoglycemia in patients with liver failure 10 - 12 is mostly limited to animal experiments, primarily discussing the related molecular regulation mechanism, and there is still a lack of research on the clinically significant topic of risk factors and prognosis of hypoglycemia in patients with acute on chronic liver failure. The present study confirmed that hypoglycemia was related to liver cirrhosis, a higher MELD score, and lower FIB. Patients with liver cirrhosis often have portal hypertension, which leads to gastrointestinal congestion and decreased appetite. In addition, patients often need to avoid consuming foods rich in protein to prevent hepatic encephalopathy, resulting in a negative nitrogen balance in energy metabolism. The MELD score has been widely used to evaluate liver function and prognosis. A higher MELD score directly reflects poor liver function, in which the inactivation of insulin is substantially compromised 13 , Honda et al. FIB is one of many coagulation factors synthesized by the liver, and it has been demonstrated to be decreased in acute liver failure In this study, FIB reduction was found to significantly increase the risk of hypoglycemia, which is consistent with previous relevant reports Univariate and multivariate analysis showed that the short-term prognosis of patients with hypoglycemia was significantly worse than that of patients without hypoglycemia. A study of patients with decompensated cirrhosis without diabetes by Hung et al. In contrast, the day mortality of patients without hypoglycemia was only 7. The guidelines of the American Society of Critical Care Medicine also suggested that preventing and improving hypoglycemia in patients with severe liver disease helps to improve patient outcomes Portenier, and Anna Mae Diehl. The study received funding from the National Institutes of Health and the Endocrine Fellows Foundation. Skip to main content. Front Page News Releases In The News Organization News Features Social Media Duke Health Blog. Published May 18, Updated May 18, Share Tweet. Research Endocrinology. Previous Duke Health Sends Supplies to India to Assist with Covid Crisis. To supplement the limited sugar supply, the liver makes alternative fuels called ketones from fats. This process is called ketogenesis. The hormone signal for ketogenesis to begin is a low level of insulin. Ketones are burned as fuel by muscle and other body organs. And the sugar is saved for the organs that need it. Take a moment to review the definitions and illustrations above. When you have diabetes, these processes can be thrown off balance, and if you fully understand what is happening, you can take steps to fix the problem. Self assessment quizzes are available for topics covered in this website. To find out how much you have learned about Facts about Diabetes , take our self assessment quiz when you have completed this section. The quiz is multiple choice. Please choose the single best answer to each question. |
| Cirrhosis Hypoglycemia: What You Should Know | This study examined the incidence, risk factors, and impact of hypoglycemia on the short-term prognosis in patients with acute on chronic liver failure. We found that the incidence of hypoglycemia in the present study was The specific mechanism of hypoglycemia in patients with acute on chronic liver failure remains unclear. It is speculated that factors such as reduced food intake, compromised liver metabolic capacity, glycogen depletion and gluconeogenesis disorders, and disruption of the inactivation of hypoglycemic hormones 8 , 9 may account for the occurrence of hypoglycemia in patients with severe liver dysfunction. At present, the research on hypoglycemia in patients with liver failure 10 - 12 is mostly limited to animal experiments, primarily discussing the related molecular regulation mechanism, and there is still a lack of research on the clinically significant topic of risk factors and prognosis of hypoglycemia in patients with acute on chronic liver failure. The present study confirmed that hypoglycemia was related to liver cirrhosis, a higher MELD score, and lower FIB. Patients with liver cirrhosis often have portal hypertension, which leads to gastrointestinal congestion and decreased appetite. In addition, patients often need to avoid consuming foods rich in protein to prevent hepatic encephalopathy, resulting in a negative nitrogen balance in energy metabolism. The MELD score has been widely used to evaluate liver function and prognosis. A higher MELD score directly reflects poor liver function, in which the inactivation of insulin is substantially compromised 13 , Honda et al. FIB is one of many coagulation factors synthesized by the liver, and it has been demonstrated to be decreased in acute liver failure In this study, FIB reduction was found to significantly increase the risk of hypoglycemia, which is consistent with previous relevant reports Univariate and multivariate analysis showed that the short-term prognosis of patients with hypoglycemia was significantly worse than that of patients without hypoglycemia. A study of patients with decompensated cirrhosis without diabetes by Hung et al. In contrast, the day mortality of patients without hypoglycemia was only 7. The guidelines of the American Society of Critical Care Medicine also suggested that preventing and improving hypoglycemia in patients with severe liver disease helps to improve patient outcomes In a meta-analysis comprising eight previous clinical trials, Chen et al. Currently, the American Society for Parenteral and Enteral Nutrition 21 and the European Society for Clinical Nutrition and Metabolism 22 recommend that patients with severe liver dysfunction should consume extra night-time meals to improve their nutritional metabolism and prevent the adverse effects of hypoglycemia. This study is the first to systematically investigate the incidence, risk factors, and prognosis of hypoglycemia in patients with acute on chronic liver failure. However, this study also had several limitations, including its retrospective nature, single-center design, and small sample size. Therefore, it is necessary to carry out prospective, multi-center studies with larger sample sizes in the future to validate and generalize the results of this study. In conclusion, this study found that hypoglycemia was common in patients with acute on chronic liver failure, and is related to poor prognosis. Patients with cirrhosis, a higher MELD score, and a significant decrease in FIB were more likely to develop hypoglycemia. Therefore, medical staff should pay attention to blood glucose management and avoid hypoglycemia by enhancing blood glucose monitoring, adjusting diet structure, and adding meals before bed. However, given that this study is a single-center, retrospective analysis, future prospective, multi-center research is needed. Reporting Checklist: The authors have completed the STROBE reporting checklist. The authors have no conflicts of interest to declare. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4. What is known and what is new? What is the implication, and what should change now? Figure 1 Study flow chart. Table 1 Comparison of the general characteristics and laboratory test results between the hypoglycemia and non-hypoglycemia groups. Table 2 Analysis of the risk factors for hypoglycemia in patients with acute on chronic liver failure. The high levels of insulin and suppressed levels of glucagon during a meal promote the storage of glucose as glycogen. The liver supplies sugar or glucose by turning glycogen into glucose in a process called glycogenolysis. The liver also can manufacture necessary sugar or glucose by harvesting amino acids, waste products and fat byproducts. This process is called gluconeogenesis. These include: the brain, red blood cells and parts of the kidney. To supplement the limited sugar supply, the liver makes alternative fuels called ketones from fats. This process is called ketogenesis. The hormone signal for ketogenesis to begin is a low level of insulin. Ketones are burned as fuel by muscle and other body organs. And the sugar is saved for the organs that need it. Take a moment to review the definitions and illustrations above. When you have diabetes, these processes can be thrown off balance, and if you fully understand what is happening, you can take steps to fix the problem. Self assessment quizzes are available for topics covered in this website. To find out how much you have learned about Facts about Diabetes , take our self assessment quiz when you have completed this section. The quiz is multiple choice. Please choose the single best answer to each question. |
| Study Finds Link Between Blood Sugar and Liver Disease Progression | Duke Health | What is the implication, and an should change Omega- for hair growth Several studies have Mood enhancer music Omega- for hair growth that HCC patients Hypogltcemia paraneoplastic syndromes, including hypoglycemia, have poor prognosis [ 51112 ]. View Large Download. Save Preferences. D Standard deviation of mean glucose did not differ between patients with and without hypoglycemia. |
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