OVERVIEW

What is hepatogenous diabetes?

Hepatogenous diabetes, as the name suggests, is a disease caused by liver diseases that lead to elevated blood sugar levels.

The liver is a vital organ for maintaining blood sugar balance. Liver diseases such as cirrhosis, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease can interfere with sugar utilization and metabolism, resulting in elevated blood sugar.

Hepatogenous diabetes is classified as one of the "other types of diabetes."

Unlike type 2 diabetes, some cases of hepatogenous diabetes may stabilize as the liver disease improves, with blood sugar levels decreasing or returning to normal. However, similar to type 2 diabetes, neglecting blood sugar control can still lead to corresponding diabetic complications, such as vascular and neurological disorders, though the risk is significantly lower than in type 2 diabetes.

How common is hepatogenous diabetes?

Hepatogenous diabetes is relatively uncommon, accounting for less than 5% of all diabetes cases.

However, due to the high prevalence of various liver diseases—especially the increasing number of patients with alcoholic fatty liver and obesity-related fatty liver in recent years due to lifestyle changes—the number of hepatogenous diabetes cases has been rising.

Among chronic liver disease patients, about 50%–80% exhibit impaired glucose tolerance (prediabetes), of which 20%–30% eventually develop hepatogenous diabetes.

Is hepatogenous diabetes the same as type 2 diabetes?

Hepatogenous diabetes and type 2 diabetes are not the same disease. The main differences include:

• Hepatogenous diabetes falls under the category of other types of diabetes, with a history of chronic liver disease, and diabetes occurs after or concurrently with liver disease.
• Patients with hepatogenous diabetes typically exhibit liver disease symptoms but rarely show the "three excesses and one deficiency" (polyuria, polydipsia, polyphagia, and weight loss) associated with diabetes.
• Diabetic neuropathy, vascular complications, and ketoacidosis are rare in hepatogenous diabetes patients.

SYMPTOMS

What are the common manifestations of hepatogenous diabetes?

• Manifestations of liver disease: Almost all patients exhibit typical liver disease symptoms to varying degrees, such as abdominal distension, fatigue, and poor appetite.

• Manifestations of diabetes: Patients rarely show the classic "three excesses and one deficiency" symptoms (polydipsia, polyuria, polyphagia, and weight loss). They often present with elevated postprandial blood glucose levels, while fasting blood glucose may remain normal. However, postprandial blood glucose levels are significantly higher than the normal range. Additionally, hepatogenous diabetes is more prone to hypoglycemia. In the early stages, hypoglycemic symptoms such as palpitations, profuse sweating, and hunger may be prominent. At this stage, an oral glucose tolerance test (OGTT) often reveals impaired glucose tolerance.

What diseases can hepatogenous diabetes cause?

Vascular complications and ketoacidosis rarely occur. However, if blood glucose control is neglected, leading to long-term fluctuations and instability, corresponding diabetic complications may still arise, though their incidence is significantly lower than in type 2 diabetes.

CAUSES

What causes hepatogenous diabetes?

Hepatogenous diabetes is secondary to chronic damage of the liver parenchyma, primarily seen in non-alcoholic fatty liver disease, alcoholic cirrhosis, viral hepatitis (especially hepatitis C), and hemochromatosis.

Which population is more prone to hepatogenous diabetes?

Hepatogenous diabetes is common in middle-aged and elderly men, with an increasing prevalence as age advances, likely because chronic liver diseases are more prevalent in this demographic.

Is hepatogenous diabetes contagious?

Hepatogenous diabetes itself is not contagious, but the underlying liver diseases that cause it may be, such as viral hepatitis.

Is hepatogenous diabetes hereditary?

Most cases of hepatogenous diabetes are not hereditary.

However, a few liver diseases that lead to hepatogenous diabetes, such as hereditary hemochromatosis and Wilson's disease, are genetic.

These liver diseases can be passed on to offspring, increasing their risk of liver disorders, but hepatogenous diabetes may not necessarily develop.

DIAGNOSIS

How to Diagnose Hepatogenous Diabetes?

When diagnosing hepatogenous diabetes, doctors primarily refer to the following criteria:

• The internationally recognized diagnostic standards for diabetes proposed by the WHO Expert Committee in 1999: fasting blood glucose ≥ 7.0 mmol/L, or 2-hour postprandial blood glucose ≥ 11.1 mmol/L after a 75g oral glucose tolerance test (OGTT), or random blood glucose ≥ 11.1 mmol/L.

• A clear history of liver disease before or concurrent with the onset of diabetes.

• Evidence of liver dysfunction or impairment through clinical manifestations, laboratory tests, or imaging results.

• No family history of diabetes, mild or absent diabetes symptoms, and no common diabetic complications.

• Insulin release tests show elevated fasting plasma insulin levels, with poor or delayed postprandial insulin response. Serum C-peptide release tests are generally normal or decreased, with a reduced C-peptide-to-insulin ratio.

• Exclusion of type 1 diabetes, type 2 diabetes, and secondary hyperglycemia caused by pituitary, pancreatic, renal, or thyroid diseases, as well as drug-induced hyperglycemia (e.g., diuretics, glucocorticoids, antihypertensives, contraceptives).

What Tests Are Needed for Hepatogenous Diabetes?

The following laboratory tests are generally required:

• Blood glucose tests: Blood tests to confirm diabetes diagnosis, including fasting and postprandial blood glucose measurements. Since hepatogenous diabetes often presents with mild fasting hyperglycemia but significant postprandial hyperglycemia, postprandial glucose testing is particularly important. An oral glucose tolerance test (OGTT) may be performed if necessary: fasting blood glucose is measured, followed by ingestion of 300 mL water containing 75g glucose (prescribed by the hospital), with blood glucose measured again after 2 hours. Avoid strenuous activity, additional food intake, and drink only small amounts of water if thirsty during this period.

• Insulin and C-peptide release tests: Blood tests conducted alongside OGTT to assess insulin and C-peptide secretion, aiding diagnosis.

• Glycated hemoglobin (HbA1c) test: A blood test unaffected by meals. Hepatogenous diabetes patients often have splenomegaly and hypersplenism, leading to increased red blood cell destruction and shortened lifespan, which may result in HbA1c levels being lower than actual blood glucose levels.

• Liver function tests: Fasting blood tests.

• Lipid profile: Fasting blood tests including triglycerides, cholesterol, HDL-C, and LDL-C to help identify the cause of liver disease.

• Hepatitis virus testing: Such as HBV antigen/antibody tests, viral DNA quantification, and HCV testing to determine the etiology of liver disease.

• Liver ultrasound, CT, or MRI: To assess liver conditions, such as the degree of cirrhosis.

Which Diseases Can Hepatogenous Diabetes Be Confused With? How to Differentiate?

Hepatogenous diabetes and diabetic liver disease share features of both liver disease and diabetes, making them easily confused.

Diabetic liver disease is a chronic complication caused by diabetes-induced structural and functional abnormalities in the liver.

In diabetic liver disease, liver dysfunction or hepatomegaly occurs after diabetes onset, excluding viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, parasitic infections, or other liver diseases. Liver function improves and hepatomegaly reduces with better blood glucose control, distinguishing it from hepatogenous diabetes.

Hepatogenous diabetes and type 2 diabetes both present with hyperglycemia, leading to potential confusion.

However, hepatogenous diabetes patients often have pre-existing liver issues before hyperglycemia develops, lack the classic "three polys and one loss" symptoms of type 2 diabetes, and primarily exhibit postprandial hyperglycemia. Chronic complications typical of type 2 diabetes are rare.

With dietary control and liver disease treatment, some patients' diabetes symptoms may resolve, differing from type 2 diabetes.

TREATMENT

Which department should I visit for hepatogenous diabetes?

For hepatogenous diabetes, you should visit the endocrinology department as well as the hepatology or gastroenterology department.

Can hepatogenous diabetes resolve on its own?

Hepatogenous diabetes will not resolve on its own without treatment. Prolonged blood sugar fluctuations and hyperglycemia can gradually worsen the condition and may lead to diabetes-related complications.

How is hepatogenous diabetes treated?

Since hepatogenous diabetes occurs secondary to liver disease, treating the underlying liver condition is crucial and key. Protecting and improving liver function often leads to varying degrees of improvement in diabetes symptoms.

At the same time, blood sugar management should also be addressed through individualized comprehensive treatment, including diet, exercise, glucose-lowering medications, and insulin therapy tailored to the patient's specific condition.

Does hepatogenous diabetes require hospitalization?

Hospitalization is necessary if there are significant short-term changes in the condition, worsening symptoms, or poorly controlled blood sugar fluctuations.

What medications are used to treat hepatogenous diabetes?

Medications for hepatogenous diabetes include oral hypoglycemic agents and insulin or its analogs. Due to impaired liver glucose metabolism and reduced insulin clearance, treatment differs from that of typical type 2 diabetes.

When liver function is severely impaired (e.g., transaminase levels more than 2.5 times the upper limit of normal), oral hypoglycemic drugs may be less effective, and insulin therapy is recommended. Since liver dysfunction also affects insulin metabolism, short-acting or rapid-acting insulin is preferred to avoid accumulation and hypoglycemia.

Depending on the patient's condition, oral hypoglycemic drugs or a combination of oral medications and insulin may be used to control blood sugar.

Additionally, some oral hypoglycemic drugs have potential hepatotoxicity, and pre-existing liver disease may increase the risk of liver damage. Regular liver function monitoring is necessary during treatment.

Below is a brief overview of commonly used hypoglycemic medications:

• Biguanides: The representative drug is metformin, which can be used in hepatogenous diabetes. Metformin primarily improves insulin sensitivity and reduces insulin resistance. Its advantages include reducing the risk of liver cancer and hepatic encephalopathy while improving survival rates. A potential drawback is the rare risk of lactic acidosis. Liver function should be monitored during use.

• Thiazolidinediones: The representative drug is pioglitazone, which can be used in hepatogenous diabetes. Pioglitazone enhances insulin sensitivity and reduces insulin resistance. Benefits include improving fatty liver and reducing hepatitis or liver fibrosis, but it may cause edema. Liver function should be monitored.

• Sulfonylureas: Representative drugs include glibenclamide, glipizide, gliclazide, and glimepiride. These are not recommended for hepatogenous diabetes due to an increased risk of hypoglycemia and potential adverse effects on the liver.

• Meglitinides: Representative drugs include repaglinide and nateglinide. These are also not recommended for hepatogenous diabetes due to similar risks of hypoglycemia and liver-related side effects.

• α-Glucosidase inhibitors: Drugs include acarbose, voglibose, and miglitol, which can be used in hepatogenous diabetes. They slow carbohydrate absorption and reduce postprandial blood sugar. Benefits include reduced ammonia production and lower risk of hepatic encephalopathy, but they may cause temporary transaminase elevation and bloating.

• DPP-4 inhibitors: Drugs include sitagliptin and linagliptin, which can be used in hepatogenous diabetes. They stimulate insulin secretion, suppress glucagon, delay gastric emptying, and reduce appetite. Advantages include low hypoglycemia risk and minimal liver metabolism, but some patients may experience gastrointestinal discomfort.

• SGLT-2 inhibitors: Drugs include dapagliflozin and empagliflozin, which can be used in hepatogenous diabetes. They lower blood sugar by promoting glucose excretion in urine. Benefits include weight loss, blood pressure reduction, and lower uric acid levels, but they may increase the risk of urinary tract infections.

• Insulin: Can be used in hepatogenous diabetes. The type of insulin should be selected based on the patient's needs, with precautions to prevent hypoglycemia. Short-acting or ultra-rapid insulin is preferred for postprandial hyperglycemia, with gradual dose adjustments and frequent blood sugar monitoring. For fasting glucose control with long-acting insulin, nighttime blood sugar (especially between 2:00–3:00 AM) should be closely monitored to avoid severe hypoglycemia. If the daily insulin dose exceeds 200 U, it may indicate insulin resistance, and increasing the dose blindly should be avoided.

Can hepatogenous diabetes be completely cured?

Some cases of hepatogenous diabetes may stabilize as liver disease improves, with blood sugar levels decreasing or even returning to normal, allowing discontinuation of hypoglycemic drugs. Even after full recovery, maintaining a healthy diet and lifestyle is essential.

DIET & LIFESTYLE

What should patients with hepatogenous diabetes pay attention to in their diet?

• In daily life, eat small, frequent meals and avoid foods high in sugar or fat. You can eat more fresh vegetables and moderate amounts of high-quality protein foods such as milk, eggs, fish, shrimp, lean meat, and poultry.

• About 50% of patients with liver cirrhosis suffer from malnutrition. For these patients, ensure adequate daily calorie and protein intake to avoid worsening malnutrition.

• For patients with complications of liver cirrhosis, choose an appropriate diet plan based on their condition.

• For cirrhosis patients with esophageal varices, pay attention to selecting suitable high-fiber foods.

• If hepatic encephalopathy is present, protein intake should be restricted.

• For specific dietary precautions, consult a nutritionist for further advice.

What should patients with hepatogenous diabetes pay attention to in daily life?

Patients with hepatogenous diabetes in stable condition can engage in appropriate physical exercise, focusing on light aerobic activities such as walking, tai chi, or square dancing, for 30–50 minutes per session, 3–5 times a week. However, the duration and intensity of exercise should be determined based on the patient's physical strength, endurance, and liver function.

Patients with active hepatitis should limit physical activity. Those with ascites or edema should avoid moderate to intense physical exertion.

PREVENTION

Can Hepatogenous Diabetes Be Prevented? How to Prevent It?

Hepatogenous diabetes can be prevented.

• For patients with non-alcoholic fatty liver disease, those who are overweight or obese should actively lose weight and cooperate with doctors for lipid-lowering treatment.

• For patients with alcoholic fatty liver disease, the primary measure is to abstain from alcohol.

• Additionally, receiving hepatitis vaccinations as recommended, using standardized blood products, and using condoms during intercourse can help prevent viral hepatitis infections.

How to Prevent Hepatogenous Diabetes from Causing Other Diseases?

Hepatogenous diabetes requires sufficient attention. Early diagnosis is crucial. A balanced diet, appropriate exercise, active treatment of liver diseases, and proper blood sugar control are essential for preventing complications of hepatogenous diabetes.