Hepatogenic diabetes

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Overview

  • Diabetes mellitus secondary to cirrhosis of the liver due to causes other than non-alcoholic fatty liver disease.
  • Combination of cirrhosis and diabetes mellitus, including fatigue, loss of appetite, abdominal distension, abdominal pain, nausea and vomiting.
  • Chronic liver diseases other than non-alcoholic fatty liver disease, such as chronic viral hepatitis, etc.
  • Need to take care of both liver damage and diabetes mellitus, with liver protection and glucose reduction as the mainstay of treatment

    • Definition

  • Hepatogenic diabetes mellitus is defined as diabetes mellitus that occurs secondary to cirrhosis of the liver caused by etiologies other than non-alcoholic fatty liver disease (NAFLD), such as hepatitis B virus or hepatitis C virus infection, alcoholic liver disease, autoimmune hepatitis, etc. [1].
  • However, there is no consensus among scholars as to whether diabetes mellitus associated with liver disease is considered a type of diabetes mellitus.
  • This article focuses on the occurrence of diabetes mellitus after cirrhosis (except cirrhosis due to NAFLD).

    • Onset of diabetes mellitus

  • The prevalence of diabetes mellitus in patients with cirrhosis reported in the literature varies widely, ranging from 14% to 71%, due to differences in the etiology of cirrhosis, severity of liver disease, and methods of diagnosing diabetes mellitus [1].
  • The prevalence of diabetes mellitus in combination with cirrhosis is two to four times higher than in normal subjects.

    • Etiology

    Causes

  • The causative agents are various chronic liver diseases that can lead to cirrhosis, such as viral hepatitis, chronic alcoholic liver disease, autoimmune hepatitis, and so on, except for NAFLD.
  • Cirrhosis can lead to hyperinsulinemia, insulin resistance, and abnormal secretion of pancreatic β-cells, which can lead to the development of diabetes mellitus.

    • Symptoms

    Main Symptoms

    Liver disease symptoms

  • Most of the symptoms include weakness, loss of appetite, anorexia, abdominal distension, abdominal pain, nausea and vomiting, and itchy skin.
  • Physical examination reveals yellowing of the skin, liver palms, spider nevus, etc.
    • 肝掌：手掌下部的大鱼际、小鱼际皮肤发红，按压后褪色的现象。
    蜘蛛痣：常见于面部、颈部及胸部，也可见于手、肩及其他部位。外观呈红色针尖样，并有迂曲血管呈放射状向四周延伸，类似蜘蛛；按压中央的小动脉，可褪色。

    Symptoms of diabetes mellitus

    Most patients lack the characteristic manifestations of diabetes mellitus, and only some patients may show typical polydipsia, polyphagia, polyuria, and mild manifestations.

    Other symptoms

    Some patients may be accompanied by bleeding gums, nose bleeding, skin ecchymosis, emaciation, double lower limb edema, etc. Severe patients may have gibberish and coma.

    Consultation

    Department of Medicine

    Endocrinology

    When fasting blood glucose ≥6.1mmol/L and 2-hour postprandial blood glucose ≥7.8mmol/L are found, timely consultation is recommended.

    Gastroenterology

    When there are symptoms such as fatigue, loss of appetite, anorexia, abdominal pain, nausea and vomiting, yellowing of skin and conjunctiva, etc., timely consultation is recommended.

    Emergency Medicine

    When there are emergencies such as babbling, coma, blood in the stool, vomiting blood, etc., it is recommended to consult a doctor immediately.

    Preparation for medical treatment

    Preparation for medical treatment: registration, preparation of documents, and common problems.

    Tips for medical consultation

  • It is recommended to record the time of blood glucose measurement and blood glucose value for the doctor’s reference.
  • In case of vomiting, vomiting blood, blood in stool, etc., you can use your cell phone to take photos of the vomit and stool for the doctor’s reference.

    • Preparation Checklist for Doctor’s Visit

    Symptom list

    Pay particular attention to the time of onset of symptoms, special manifestations, etc.

  • When was the abnormal blood glucose detected? What is the blood glucose level?
  • Is there any loss of appetite, abdominal pain, nausea, vomiting, itchy skin, and how long has it lasted?
  • Is there excessive drinking, eating or urinating?
  • Has there been any change in weight in the last six months?
    • Medical History Checklist
  • Does any blood relative have a history of hepatitis, cirrhosis, or diabetes?
  • Are there any allergies to drugs, food or other substances?
  • Is there a history of heavy alcohol consumption?
  • Are there any diseases such as diabetes, hepatitis, cirrhosis, hypertension, etc.?
    • Checklist

    Test results of the last six months, which can be brought to the doctor’s office

  • Laboratory tests: blood glucose, glycosylated hemoglobin, blood biochemistry, etc.
  • Imaging tests: abdominal ultrasound, abdominal CT, etc.
    • Medication list

    Medication used in the last 3 months, if available, bring along the box or package for medical consultation

  • Glucose-lowering drugs: metformin, acarbose, insulin, etc.
  • Hepatoprotective medications: bicyclol, silymarins, etc.

    • Diagnosis

    Diagnosis is based on

    Medical history

  • History of cirrhosis due to causes other than NAFLD, e.g., hepatitis B virus or hepatitis C virus infection, alcoholic liver disease, autoimmune hepatitis.
  • No previous history of diabetes mellitus.

    • Clinical manifestations

    Symptoms
  • Mostly symptoms of liver disease such as fatigue, loss of appetite, abdominal distension, abdominal pain, nausea and vomiting, itching of the skin.
  • Diabetes mellitus symptoms such as polydipsia, polyphagia and polyuria are mild.
  • Severe patients may have babbling and coma.
    • Physical signs

    Physical examination reveals yellowish coloration of the skin, liver palms, spider nevus, large or shrunken liver, splenomegaly, and positive mobile turbidities.

    Laboratory Tests

    Blood test　

    Combined with hypersplenism, white blood cell count and platelet count are reduced, and red blood cell count may also be reduced.

    Urinalysis　
  • Positive urine bilirubin and increased urinary bilinogen may be seen.
  • Urine sugar may be positive.
    • Stool routine　

    Fecal occult blood test may be positive in combination with gastrointestinal bleeding.

    Liver function

    Decreased albumin, increased serum bilirubin, aminotransferase, alkaline phosphatase, and prolonged prothrombin time may be seen.

    Viral hepatitis marker assay　

    Measurement of hepatitis B, C, and D viruses is performed to clarify the etiology of the disease.

    Measurement of blood glucose and glycosylated hemoglobin
  • Fasting blood glucose is mildly increased or normal, postprandial blood glucose >11.1mmol/L; glycated hemoglobin measurement can reflect the blood glucose situation in the last 2~3 months.
  • Hepatic impairment and anemia can affect the sensitivity of fasting blood glucose and glycosylated hemoglobin in the diagnosis of diabetes mellitus, so it is not recommended to use them alone for the diagnosis of diabetes mellitus in patients with liver cirrhosis.
    • Oral glucose tolerance test

    To understand blood glucose, insulin and C-peptide levels to assist in the diagnosis and treatment of diabetes mellitus.

    Others

    Such as blood ammonia measurement, electrolyte measurement, serum immunology test, serum copper blue protein and other tests to clarify the presence of hepatic encephalopathy, whether there is immune liver disease, hepatomegaly and hepatomegaly.

    Imaging examination

  • Liver ultrasound, liver CT, liver nuclear magnetism, to clarify the morphology and size of the liver, the presence of liver occupancy, etc.
  • Fundus photography, to clarify the fundus of the eye with or without corneal pigment ring.

    • Other examinations

    Gastroscopy for diagnosis and treatment of upper gastrointestinal bleeding.

    Differential Diagnosis

    Cirrhosis combined with type 2 diabetes mellitus (T2DM)

    Cirrhosis combined with T2DM is the presence of T2DM first, followed by cirrhosis, and the main points of differentiation between the two are shown below [1].

    Characteristics Cirrhosis combined with type 2 diabetes mellitus Hepatogenic diabetes mellitusDiabetes onset time before diagnosis of cirrhosis after diagnosis of cirrhosisOnset time of diabetes mellitusBefore diagnosis of cirrhosisAfter diagnosis of cirrhosisBody mass index often increases normal or decreasesBody mass indexOften increasedNormal or decreased

    Nutritional status may be overweight or obese often malnourished

  • Nutritional status
  • May be overweight or obese

    • Often malnourished

  • Fasting blood glucose is often elevated and usually normal
  • Fasting blood glucose

    • Often elevated

    Usually normal

    Microangiopathy often present usually absent

    Microangiopathy

    Frequent

    Usually absent

    Macrovascular lesions often present usually absent

  • Macrovascular lesions
  • Frequent
  • Usually absent

    • Low high risk of hypoglycemia

  • Low risk of hypoglycemia
  • Low
  • High

    • Good liver function or impairment Most impairment

  • Liver function
  • Good or Impaired

    • Mostly impaired

    Treatment

  • Treatment of hepatogenic diabetes mellitus is aimed at improving and protecting liver function, lowering hyperglycemia, and relieving symptoms. Delay disease progression and complications.
  • In patients with hepatogenic diabetes mellitus, glycemic control goals need to be established according to liver function classification and age, and medication and treatment need to be standardized under the guidance of a physician.
  • General Treatment

    • Hepatogenic diabetes mellitus is a chronic disease that requires long-term treatment, and patients should actively cooperate with the treatment.

  • Patients with severe disease need bed rest, while patients with mild disease need to pay attention to the combination of work and rest, as over-exertion can worsen the existing liver disease.
  • Medication

    • Antiviral drugs

    Patients with viral hepatitis, such as chronic hepatitis B or C, need to consider antiviral treatment, such as entecavir, if indicated.

    Hepatoprotective drugs

  • Depending on the condition of the patient, the doctor may use one or two liver-protecting drugs, such as bisabolol, compound glycyrrhizin tablets, etc. They should not be abused.
  • Hypoglycemic drugs
  • Doctors need to choose appropriate hypoglycemic drugs according to the grading of the patient’s liver function, the degree of liver damage, age, tolerance, etc., and should not use the drugs on their own.

    • For patients with cirrhosis, the ideal oral hypoglycemic drugs should have the advantages of less hepatic metabolism, low plasma protein binding rate, not cleared from the liver, short half-life and no risk of hypoglycemia or hepatotoxicity, such as metformin and acarbose.

  • Insulin can be used in cirrhotic patients with any degree of hepatic impairment, but regular monitoring of blood glucose concentrations is required.
  • The application of hypoglycemic drugs needs to follow dose individualization, and the doctor will make adjustments to the dosage of hypoglycemic drugs based on the results of blood glucose monitoring.
  • Others

    • Avoid the use of high-dose diuretics when combined with ascites.

  • When using propranolol to reduce portal pressure in patients with portal hypertension, pay attention to hypoglycemia.
  • Strictly control the use of glucocorticoids.
  • Other treatments
  • Liver transplantation is mainly applicable to patients with intermediate and advanced liver failure due to various causes, which has been poorly treated by aggressive medical therapy; and patients with various types of end-stage cirrhosis.

    • For those who have pancreatic β-cell failure before liver transplantation, combined liver and pancreatic islet transplantation is preferred.

    Prognosis

    Cure

  • In most patients with hepatogenic diabetes mellitus, blood glucose can return to normal with the improvement of liver disease after treatment.
  • Hepatogenic diabetes mellitus is mostly mild, acute and chronic complications of diabetes mellitus are rare, and the prognosis is relatively good.
  • Some Japanese scholars reported that the 5-year survival rate of patients with cirrhosis and diabetes mellitus is 30%, while that of patients without diabetes mellitus is 63%. Therefore, we should actively control and manage the primary liver disease and monitor the changes of blood glucose in the course of diagnosis and treatment.
  • Hazards

    • Hepatogenic diabetes mellitus can cause blood in the stool, vomiting blood, shock, coma, etc., which can be life-threatening.

  • Hepatogenic diabetes mellitus can further aggravate the disorder of hepatic glucose metabolism, and high blood glucose affects the repair of liver cells and aggravates liver disease, resulting in a vicious circle.
  • Daily
  • Daily Management

    • Dietary management

  • Hepatogenic diabetes mellitus patients should eat high protein (mainly high quality protein such as milk, eggs, etc.), high vitamin, low fat, easy to digest food, and control the intake of carbohydrates.
  • Patients with ascites or edema should control sodium intake.
  • Patients with combined hepatic encephalopathy should limit protein intake, which can be gradually increased after the condition improves.
  • Exercise management