HEPATOGENOUS DIABETES PDF

The prevalence of diabetes mellitus in cirrhotic patients is much higher than that in the general population. Two types of diabetes are usually seen in patients with cirrhosis: type 2 diabetes mellitus and hepatogenous diabetes HD. Increased levels of advanced glycation end products and hypoxia-inducible factors have been implicated in the pathogenesis of HD. Patients with HD typically present with normal fasting glucose, but abnormal response to an oral glucose tolerance test, which is required for the diagnosis.

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The journal's aim is to publish articles focused on basic, clinic care and translational research that seeks to prevent rather than treat the complications of endstage liver disease. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years.

CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.

SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field. Insulin resistance in muscular, hepatic and adipose tissues as well as hyperinsulinemia, seem to be pathophysiologic bases for HD. Diabetes develops when defective oxidative and nonoxidative muscle glucose metabolism develops. HD in early cirrhosis stages may be sub clinical. Only insulin resistance and glucose intolerance may be observed.

As liver disease advances, diabetes becomes clinically manifest, therefore HD may be considered as a marker for liver function deterioration. HD is clinically different from that of type 2 DM since it is less frequently associated with microangiopathy and patients suffer complications of cirrhosis more frequently as well as increased mortality.

Insulin resistance and HD associate to a decrease in the sustained response to antiviral therapy and an increased progression of fibrosis in patients with CHC. Diabetes treatment is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs that are frequently prescribed to these patients. This paper will review current concepts in relation to the pathopysiolo-gy, the impact on the clinical outcome of cirrhosis, and the therapy of HD.

Finally, the role of HD as a risk factor for the occurrence and exacerbation of hepatocel-lular carcinoma HCC will also be reviewed.. The liver has an important role in the metabolism of carbohydrates because it is responsible for balancing blood glucose. Diabetes mellitus DM in patients with compensated liver cirrhosis may be sub clinical. In these cases, an oral glucose tolerance test OGTT may detect glucose intol-erance.

Patients with HD suffer complications of cirrhosis more frequently causing death. The treatment of HD is complex due to the presence of liver damage and the hepatotoxicity of oral hypoglyce-mic drugs frequently prescribed to these patients. There-fore, pharmacological therapy must be closely monitored for the risk of hypoglycemia.

This paper will review the new concepts found in literature regarding: a factors involved in the genesis of HD; b the impact of HD on the clinical outcome of patients with liver disease, and c the treatment of diabetes in cirrhotic patients. Similarly, it will review the role of HD as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma HCC.

NASH associates with visceral obesity, hypertriglyceridemia, and virtually all patients suffer insulin resistance. Obesity by itself is an independent risk factor for severe liver disease. These adipokines impair several metabolic functions in muscle, liver and pancreas leading to insulin resistance, hyperglycemia, and hyperinsulinemia; these abnormalities disrupt metabolism of lipids in the liver.

In a study conducted by The National Health and Nutrition Examination Survey, a risk 3-fold higher for DM and CHC was identified in individuals over 40 years old, compared with those patients with non-C chronic hepatitis. Moreover, the insulin resistance in these patients is an inde-pendent risk factor for steatosis in relation to the severity of fibrosis.

It has been observed that HCV induces insulin resistance regardless of the body mass index and the fibrosis stage. In a study conducted in a transgenic animal model, the HCV core protein was able to induce insulin resistance, steatosis, and DM.

All these disorders —related to intracellular signals of insulin— could block the transactivation of GLUT-4, which might result in the blocking of the glucose uptake at the cellular level.

Notwithstanding, it has been reported that patients with CHC and insulin resistance have a less sustained response to peginterferon plus ribavirin treatment compared with patients without insulin resis-tance 22 , 30 Figure 1. The impact of insulin resistance and HD on the clinical outcome of patients with chronic liver disease.

HD is associated with an increased rate of complications of cirrhosis such as esophageal varicose veins and liver failure as well as increase of mortality. HD is a risk factor for occurrence and complications of hepatocellular carcinoma HCC. In a recent study patients with biopsy-proven CHC and normal fasting glucose 32 In the opposite side, others have suggested that the eradication of HVC did not reduce the risk of DM in patients with CHC and normal fasting blood glucose during a period of 8 years of monitoring after treatment.

Patients with sustained response had a similar incidence of DM compared with those who did not respond to treatment Patients with alcoholic liver disease have a high relative risk of suffering diabetes. Hereditary hemochromatosis is a disease characterized by iron accumulation in several organs — particularly in the liver — because of a disorder of the metabolism of this metal.

This abnormality is produced by a mutation of the HFE gene. In addition, the iron can infiltrate the pancreas and myocardium. In the pancreas, the concentration of iron is predominantly in the acinus of exocrine secretion. The pathophysiology of HD is complex and not precisely known. Insulin resistance in peripheral tissues adipose and muscular tissue plays a central role in the glucose metabolism disturbance. Furthermore, diabetes mellitus develops as the result of progressive impairment in insulin secretion together with the development of hepatic insulin resistance leading to fasting hyperglycemia and a diabetic glucose tolerance profile 37 , 38 Figure 2.

Physiopathology of hepatogenous diabetes. One of the main abnormalities is insulin resistance in muscular cells and the hepatic tissue. Insulin resistance in muscle impairs non-oxidative and oxidative glucose metabolism. The reduction of insulin clearance by the damaged liver and the presence of portosystemic shunts in one hand and the desensitization of the beta cells of the pancreas produced by diverse factors on the other hand may produce hiperinsulinemia.

Discrimination between HD and type 2 DM may be difficult. In a recent study, comparing patients with HD vs.

Therefore, insulin resistance in liver cirrhosis was higher than the type 2 DM, and impairment of hepatic insulin degradation might be an important mechanism of hiperinsulinemia in liver cirrhosis. The effect of HD in the clinical outcome of cirrhosis and HCC has been evaluated in only few studies.

Neither the Child-Pugh nor the Model for End-Stage Liver Disease MELD Scores which are widely used as prognostic instruments of morbidity and mortality in the short and long term in cirrhotic patients includes in their parameters the DM or glucose intolerance. In a retrospective-prospective study 98 with diabetes of eligible patients were followed during 6 years after inclusion into the study: were alive at the end of follow-up.

The larger mortality rate in patients with diabetes was not due to complications of diabetes but to an increased risk of hepatocellular failure. Diabetes was no longer a risk factor as a covariate in a subgroup of patients when varices were added but was again significant when patients who died of gastrointestinal bleeding were excluded. In another original study carried out in patients suffering from cirrhosis and refractory ascites on a waiting list for liver transplantation, the HCC and DM, but not the Child-Pugh score, were independent predictive factors of mortality.

Insulin resistance and diabetes mellitus may affect cognition in patients with hepatitis C cirrhosis. In a study, cirrhotic patients were prospectively evaluated for the presence of hepatic encephalopathy HE according to the West-Haven criteria as well as by means of two psychometric tests and fasting plasma ammonium levels.

Nutritional status, fasting plasma glucose and insulin resistance were also determined. Mul-tivariate analysis showed that the time needed to perform number connection test A was independently correlated to age, the Child-Pugh score, diabetes and malnutrition P 47 Certainly, more studies are needed in order to confirm these interesting findings.

Nishida et al studied a group of 56 patients with cirrhosis and normal fasting blood glucose. By a multiple regression analysis, only serum albumin and DM were independent negative predictive factors of survival.

In a recent case and control study that included patients, the DM prevalence was more frequent in patients with HCC compared with controls Nevertheless, others suggest that DM only in presence of other risk factors may be relevant in the genesis of HCC. In fact, some studies show that in diabetic patients with HCV, liver fibrosis and alcohol heavy consumption, the risk of having HCC increases. In another study involving patients suffering from HCC, those who had DM had 1-year mortality rate higher than those patients without DM.

Additionally they had more extensive disease. The mechanisms by which HD worsens the clinical course of liver cirrhosis have not been clearly established.

Firstly, DM by accelerating liver fibrosis and in-flammation would give raise to severe liver failure. Secondly, DM may increase mortality by increasing the incidence of bacterial infections in the cirrhotic patient. This paradoxal hyperadiponectinemia may be due to a reduced extraction by the liver. Regarding the second mechanism, DM may worsen immunosuppression of cirrhotic patients thus increasing the incidence of severe infections that may have deleterious effect on liver function.

Cirrhotic patients with spontaneous bacterial peritonitis have an in-hospital high mortality rate due to sepsis, liver failure, and hepa-torenal syndrome. In the other hand patients with esoph-ageal variceal bleeding through a mechanism of intestinal translocation, have a high incidence of infections that increase their in-hospital mortality rate. In the future, the precise mechanisms by which DM may worsen liver function must be clarified, since their manipulation may be useful for reduction of complications.

Clinical manifestations of HD in early stages of cirrhosis are virtually absent. Future research should clarify the impact of HD in the natural history of cirrhosis and the benefices of its early diagnosis and treatment for reduction of mortality. The treatment of HD is complex since it has particular characteristics that make it different from type 2 DM: 1 About half of patients have malnutrition; 2 When diag-nosis of HD is performed, most of patients have end-stage liver disease; 3 Most of the oral hypoglycemic drugs are metabolized in the liver; 4 Patients often have episodes of hypoglycemia.

Change of lifestyle. The initial treatment of patients suffering from mild to moderate hyperglycemia and compensated liver disease may be the lifestyle change, since at this stage the insulin resistance is a dominant factor. However, very restrictive diets may aggravate malnutrition of these patients and physical exercise, which improves insulin resistance, may not be advisable for patients with liver inflammation. Patients with HD and advanced stages of liver disease may require the use of oral hypoglycemic drugs.

However, most of these drugs are metabolized in the liver; therefore, the blood glucose levels during treatment should be closely monitored in order to avoid hy-poglycemia.

Metformin is a biguanide that is relatively contraindicated in patients with advanced liver failure and in those who continue to ingest alcohol, due to the risk for lactic acidosis. In comparison to disease controls treated only with lifestyle, all patients treated with metformin had partial biochemical response mean ALT Insulin secretagogues. Alpha-glycosidase inhibitors. These drugs can be useful in patients suffering from liver cirrhosis, since its action mechanism is by reducing the bowel-level carbohydrates absorption, thus reducing the risks for postprandial hyperglycemia.

In a randomized double-blind controlled trial involving patients with compensated liver cirrhosis and insulin-treated DM, the control of postprandial and fasting blood glucose levels improved significantly with the use of acarbose, an alpha-glycosi-dase.

Additionally, the patients had a reduction in plasma ammonia levels and an increase in the frequency of bowel movements.

These drugs may be particularly useful in cirrhotic patients with DM, since they increase the insulin sensitivity. However, troglitazone has been withdrawn from the market because of its potential hepato-toxic effects. Nevertheless, rosiglitazone and pioglita-zone are apparently safer drugs in patients with liver disease. These drugs may normalize amino transaminases, reduce insulin resistance, and improve histological features.

Insulin requirements in the cirrhotic patient with diabetes may vary.

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Hepatogenous Diabetes: An Underestimated Problem of Liver Cirrhosis

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A 1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes. Hepatogenous diabetes : Is it time to separate it from type 2 diabetes?

CONECTOR HARTING PDF

Hepatogenous diabetes: Is it a neglected condition in chronic liver disease?

The journal's aim is to publish articles focused on basic, clinic care and translational research that seeks to prevent rather than treat the complications of endstage liver disease. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact. SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.

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