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The liver performs many vital functions, including processing, storing, and releasing of sugar in the body:

• All carbohydrates you eat or drink break down into glucose (sugar) in the digestive process, and pass through the liver before being transported to innumerable cells in the body for use as energy.
• More than 50 percent of the sugar absorbed from your meals is taken up by the liver. The liver stores this sugar as sugar reserve mainly in the form of glycogen for use as energy in the future.
• The liver converts glycogen back into sugar, and releases it into the blood when you are not eating and sugar is not entering your system such as:
  • During the night when you are sleeping
  • Between meals
  • For extra energy such as when you exercise
• After 12 to 24 hours of fasting, when your body has not been getting food for energy and the glycogen reserves have also been used, the liver produces sugar from non carbohydrate sources such as from the breakdown of protein and fat in the body. This process, called gluconeogenesis, supplies sugar to the brain because the brain must get sugar for energy.
• Insulin secreted by the pancreas first passes through the liver before it works in the body.

DIABETES AND LIVER DISEASES

Diabetes can be a cause and consequence of a liver disease. Diabetes tends to damage the liver, causing liver dysfunction. A liver disorder, on the other hand, is linked to impairing the blood sugar- related functions of the liver, thereby leading to diabetes.

Diabetes as a Cause of Liver Diseases

Over time, raised blood sugar levels may contribute to various liver complications:

• Diabetes tends to accelerate the process of hardening of the arteries throughout the body, deforming blood vessels and decreasing the blood supply to the organs these vessels serve. The process of hardening of the arteries can also occur in the hepatic artery, which is an important source of blood supply to the liver. When due to accumulation of fatty substances, the hepatic artery becomes hard and narrow, blood flow to the liver is reduced. Insufficient blood flow to the liver deprives the liver of proper nourishment, makes it weak, and exposes it to various types of infection. All these conditions heighten the risk for various liver diseases such as liver dysfunction, and liver failure.
• Raised insulin levels, a typical condition of insulin resistance in type 2 diabetes, promote excess storage of sugar in the liver (glycogen). Too much sugar in the liver is often associated with elevated liver enzymes, abdominal pain, nausea, and vomiting.
• When the blood sugar mechanism goes wrong in diabetes, the liver tends to release excess sugar in the blood, even in fasting.
• Exposure to injection needles in insulin therapy increases the risk for blood contamination and resulting infections such as hepatitis B and C.
• Diabetes, for some unknown reason, has been shown to increase the risk for liver cancer. In the largest study of its kind, researchers from the Department of Veteran Affairs have recently found that diabetes (mainly type 2) doubles the risk of chronic liver diseases and liver cancer. What is ironic is that many times liver diseases show no symptoms and go unnoticed until a severe condition such as liver cancer has occurred.
• Treatment of diabetes and related disorders may cause damage to the liver. Diabetes pills such as chlorpropamide (Diabinese), tolbutamide (Orinase), and troglitazone (Rezulin) can cause serious liver injury. (Rezulin was withdrawn from the market due to the reports that it caused several deaths due to liver failure.) Also, cholesterol lowering drugs of the Statin family, commonly used in people with diabetes, can cause liver injury.

DIAGNOSING LIVER DISEASES

Liver diseases can be detected by any or a combination of several methods:

Observing Common Symptoms

Depending on the severity of a liver disease or disorder, the generalized symptoms may include: yellow discoloration of the skin, nausea, vomiting, fatigue, fever, itching, red boils on the skin, abdominal pain, dark urine, pale stools, fluid retention in the abdomen, breathing problems when you are lying down, and high blood pressure.

Liver problems, when mild, go unnoticed for a long time because the liver is able to overwork despite an ailment. Sometimes a liver problem is detected during routine tests for some other medical condition such as diabetes.

Physical Examination

On physical examination of a patient, the liver may feel larger and harder than normal, which is a sign of liver disease. To confirm the diagnosis, the doctor may order liver function tests and other related tests.

Liver Function Tests (LFTs)

Liver function tests are blood tests that measure liver enzymes circulating in the blood. These tests are usually the first step for diagnosing liver disease. Liver enzymes under normal conditions are contained inside the liver cells. Aliver disease, however, damages these cells and the enzymes start leaking out of the liver cell membranes and spill over into the bloodstream. Raised blood levels of these enzymes generally indicate a problem with liver function. (Sometimes, raised liver enzymes may not be associated with any liver disorder and they may simply be a side effect of some drug.) Reference ranges of these tests vary with laboratories; check with your laboratory to find out what ranges it has adopted. Important liver function tests include:

Albumin
Albumin is a protein made by the liver. In chronic liver diseases such as cirrhosis of the liver, albumin levels become low.

ALT/AST Tests
Alanine Transaminase (ALT) and Aspartate Transaminase (AST) are the two main liver enzymes that are tested. ALT is an enzyme mainly found in liver cells, and its elevation in the blood strongly indicates a liver injury or a liver disease.

AST (previously called SGOT) is an enzyme concentrated not only in the liver, but also found in other parts of the body such as the heart, kidneys, brain, and muscles. This is the reason that apart from being an indicator of liver damage, raised AST levels in the blood may also indicate a heart attack, brain injury, kidney damage, or wasting of muscles. In evaluating a liver disorder, the doctor correlates the AST results with other investigations such as the physical examination, X-rays, and ultrasound scans.

Bilirubin
This is the waste product produced from the breakdown of hemoglobin in your body and is the bile pigment that gives yellow color to your skin. Under normal conditions, the liver processes bilirubin, clears it out of the blood, and sends it into the gallbladder. Only a small amount of these pigments is left in the blood. When liver function becomes defective, the processing of bilirubin is also affected and its levels rise in the blood.

Bilirubin is of two types: direct (conjugated) and indirect (unconjugated). Direct bilirubin becomes high in the blood when bile processed by the liver is not normally flowing into the gallbladder, probably because of a blockage in the gallbladder. On the other hand, the blood level of indirect bilirubin rises from some disorder of red blood cells.

Total bilirubin includes both forms: direct and indirect, and can be measured collectively. A higher than normal level of bilirubin in the blood can be an indicator of a liver disease.

GGT (Gamma-glutamyl Transpeptidase)
GGT is found in the liver, kidneys, spleen, pancreas, heart, and brain. This enzyme becomes abnormally high in the blood in such conditions as inflammation of the liver, excessive use of alcohol, and growth of tumors in the liver. Although not a specific test for liver function, the GGT test helps diagnose a liver disorder.

ALP (Alkaline Phosphatase)
ALP is an enzyme found in the liver, intestines, bones, and white blood cells. In a liver disorder, ALP levels become high in the blood.

Interpreting Liver Function Test

Elevation of liver enzymes in the blood is not by itself a conclusive proof of actual liver disease. The raised levels simply indicate a liver problem, which may be due to a liver disease or some other reason. Sometimes, as noted before, liver enzymes in the blood may increase from the use of certain medicines. These include cholesterol- lowering drugs of the Statin family (Lipitor, Mevacor, Zocor, and others); pain-relieving medications such as aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin), diclofenac (Voltaren);and antibiotics. Liver enzymes raised as a result of medications usually normalize within several weeks after discontinuing the use of the offending drugs. Likewise, GGT enzymes raised from the use of alcohol also normalize after consumption of alcohol is discontinued.

Liver function tests are only one of the several tools used to assess the condition of the liver. When your liver function tests show an abnormality in the liver enzymes, the doctor may order other tests, as well, including an ultrasound scan, MRI, CT scan, and a liver biopsy to confirm the diagnosis of a liver disease.

Doppler Ultrasound

In a Doppler ultrasound, sound waves are used to generate images that can scan blood flow in the blood vessels. A Doppler ultrasound of the liver can detect whether there are blockages in the blood vessels of the liver, interfering with its blood supply.

CT Scan

What an ordinary x-ray cannot see in the liver and other organs, a CT scan can see. When used to scan the liver, the CT scan produces images of the liver that help detect various abnormalities such as a fatty liver and liver enlargement.

Magnetic Resonance Imaging (MRI)

MRI uses radio waves and a strong magnetic field to provide clear and detailed pictures of the organs, including the liver. MRI can detect any abnormality present in the structure of the liver.

Nuclear Imaging

A tiny amount of radioactive substance (isotope) is injected in a vein, which then circulates throughout the body. When this substance reaches the liver, a special camera records the distribution of the radioactive material and puts this information into a computer. Abnormal distribution of the radioactive substance in the liver indicates a problem area.

Liver Biopsy

After administering a local anesthetic, a specimen of the liver tissue is drawn by inserting a needle through the skin. The liver specimen is microscopically examined for determining the extent of inflammation and scarring of the liver.

LIVER DISEASES

As noted before, a two-way relation exists between diabetes and liver diseases. Liver diseases are many, but the following are directly or indirectly related to diabetes:

Fatty Liver

One of the functions of the liver is to process fat and dissolve it in the blood. When this function goes wrong, the unprocessed fat starts accumulating in the liver, leading to its inflammation and fatness. This condition is medically called steatohepatitis and is popularly known as fatty liver.

Usually, obesity and excessive use of alcohol tend to pile up fat in the liver. Sometimes, however, even people who do not drink alcohol can develop this disease for no known reason; a condition known as nonalcoholic steatohepatitis (NASH). Inflammation causes the liver to become enlarged and raises liver enzymes in the blood. Fatty liver is a well recognized condition associated with diabetes. Collecting of fat in the liver, by itself, is not a disease because it causes no damage to the liver.

Diagnosis Fatty liver can be diagnosed through:

• Physical examination
• Liver function tests
• X-ray
• Ultrasound
• CT scan
• Liver biopsy

Prevention and Treatment

To prevent your liver from becoming fatty:

• Lose weight gradually if you carry excess weight.
• Stop drinking alcohol if you drink.
• Achieve good control of blood sugar.
• Bring down blood triglyceride levels if they are high.

Hepatitis B

Hepatitis means inflammation of the liver. Hepatitis B is liver inflammation caused by the hepatitis B virus (HBV). Prolonged infection with hepatitis B heightens the risk for destruction of liver cells (cirrhosis) and liver cancer.

Hepatitis B is a highly infectious disease. It can be transmitted through blood contact of a person infected with hepatitis B, sex with an infected person, sharing personal items such as a toothbrush, towel, or razor having infected blood, or getting a tattoo or body piercing if the tools have someone else’s blood on them.

Diagnosis

A blood test is the only way of detecting the hepatitis B virus. Many times, people infected with hepatitis B present no symptoms and continue to be carriers of the virus.

Prevention

The best defense against hepatitis B is to be vaccinated against it. If you have hepatitis B, all people who live with you should get hepatitis B vaccine.

Treatment

Several drugs are available for treating hepatitis B virus infection. These drugs include Adefovir dipivoxil, lamivudine, entecavir, and telbivudine, to be taken by mouth; and interferon alfa-2b, and pegylated interferon alfa-2a, in injection forms. However, when, over time, the liver stops working from the damage caused by hepatitis B, a new liver may become necessary through liver transplantation.

Hepatitis C

Hepatitis C is the most common form of hepatitis, occurring in about 75 to 85 percent of viral hepatitis cases. Hepatitis C virus (HBV) is mainly transmitted through blood contact of a hepatitis C patient. Some common sources of getting hepatitis infection include sharing syringe needles, getting hemodialysis for a kidney disease (see chapter 3), or having sex with an infected partner. In about 15 percent of the people infected with hepatitis C, the virus is overcome by the body’s immune system itself. But, most people infected with the hepatitis C virus never recover completely and carry the virus throughout their lives. This disease can be mild or severe: when the infection is mild, the infected people carry it throughout their lives without being affected very much. However, people with the severe form of hepatitis C develop liver damage, destruction of liver cells, and may end up with liver failure.

Diagnosis

Most people, infected with the hepatitis C virus, present no symptoms in the early stages of the disease. A blood test is the only way to check for the virus and diagnose hepatitis C.

Prevention

There is no vaccine to prevent hepatitis C. Take preventive measures: be careful in handling blood and blood products; do not share syringe needles; use latex condoms while having sex with multiple partners or an infected partner; and do not donate blood if you have hepatitis C, because giving your blood may infect others.

Treatment

Two drugs — Interferon and ribavarin—have been approved by the Food and Drug Administration (FDA) for treatment of hepatitis C. Interferon is given through injection and aims to strengthen your body’s immune system to fight against the virus. Ribavirin, on the other hand, is taken by mouth and aims to prevent the virus from multiplying itself in the body. Acombination therapy with interferon and ribavarin has been found to be more effective than either of these drugs used alone in the treatment of hepatitis C. The combination therapy, which at present is the treatment of choice, clears the virus in more than 50 percent of patients. In most people, when treatment is discontinued, the virus reoccurs and the treatment has to be repeated. Side effects of interferon include feverishness, extreme fatigue, nausea, loss of appetite, thyroid problems, high blood sugar, hair loss, and skin rash. The side effects of ribavarin, on the other hand, include weakness and paleness, cough, extreme tiredness, irritability, nasal congestion, and skin rash. For most people, the side effects are bearable, but nearly 10 percent of the patients find the side effects unbearable.

A long-acting variety of interferon called Pegulated Interferon has been approved by the FDA. The long-acting interferon allows the patient to receive the injection once-a-week instead of three times weekly under regular interferon therapy.

Cirrhosis of the Liver

Healthy liver cells are damaged and replaced by scars and fibrous tissues in this disease. This damage blocks normal blood and bile flow through the liver. As a result, liver functions, including the vital function of blood purification and removal of toxins, go wrong. When the blood is not purified, all vital organs of the body, including the heart, kidneys, and brain, are served with toxic and poisonous blood that may lead to disastrous infections throughout the body. Extensive damage to the liver leads to liver failure in which the liver is disabled and cannot perform its functions. Such a situation may make liver transplantation necessary. The factors that contribute to cirrhosis of the liver include excessive consumption of alcohol, hepatitis B and C, diabetes, accumulation of excess iron in the liver, and long-standing exposure to toxic substances such as aerosol cleaners, paint, and insect sprays.

Diagnosis

Most people present no symptoms in the early stages of liver cirrhosis. In the early stages of this disease, liver damage is not yet extensive, and even liver function tests are sometimes normal. As the disease progresses, various symptoms begin to appear (noted before). Imaging techniques such as ultrasound, CT scan, MRI, and nuclear imaging can be used to assess the liver’s condition. Nuclear imaging, for example, can show which area of the liver is normal and which area is scarred with cirrhosis. To make a precise diagnosis, a sample of the liver tissue is obtained through a biopsy for microscopic examination.

Prevention

To help prevent cirrhosis of the liver:

• Get immediate treatment if you have hepatitis B or C.
• Control your blood sugar.
• Avoid drinking alcohol.
• Avoid contact with other people’s blood because it might be infected.
• Make sure to wear protective covering while using chemicals such as aerosol cleaners and paint sprays. (Many chemicals, when inhaled, may harm the liver.)

Treatment

The liver damage caused by cirrhosis of the liver is not curable. The goal of treatment is to stop or slow down the progression of the disease. Treatment depends on the cause that contributed to the development of liver damage. If alcohol abuse has been the cause, stop drinking alcohol. If viral hepatitis such as hepatitis B or C has been the cause, get it treated. And if you have diabetes, keep your blood sugar under control.

Hemochromatosis

A hereditary disorder in which your body organs, including the liver, absorb and store too much iron is called hemochromatosis. Bronze discoloration of the skin is often a sign of iron overload in the body. Too much concentration of iron in the liver may cause various diseases, including diabetes, cirrhosis of the liver, and cancer.

Diagnosis

Most people present no symptoms even when iron stores in the liver are quite high. Blood tests are available that measure the amount of iron present in the blood. Liver biopsy (noted before) may be performed to make a precise diagnosis.

Treatment

Drawing the blood is the standard treatment in which 1 to 2 pints of blood are removed each week until iron stores become normal. This treatment may continue for several months or years. Once the iron stores become normal, blood is drawn once every 2 to 6 months throughout the life of the affected person to prevent the rise of iron in the body.

Liver Cancer

People with liver diseases such as chronic hepatitis B and C, iron overload in the liver, and cirrhosis are at increased risk of developing liver cancer.

Diagnosis

Liver cancer can be diagnosed through:

• Abdominal ultrasound, CT scan, and liver biopsy
• Blood tumor test (alpha-fetoprotein), which can make early detection of liver cancer

Treatment

Treatment options include:

• Surgery that removes the cancerous tumor of the liver.
• Liver transplantation. If the cancer is widespread in the liver, the diseased liver may be removed and a healthy liver obtained from a cadaver donor (dead body) may be transplanted. About 80 to 90 percent of all cases of liver transplants are successful. The data of the Organ Procurement and Transplantation Network shows that 84,896 people received liver transplantation in the United States during the period January 1, 1988 to June 30, 2007.

LIVER DISEASES CAN CAUSE DIABETES

Liver diseases damage liver functions, including the function of storage and release of sugar in the blood:

• Excess accumulation of glycogen (sugar reserve) in the liver has been shown to be associated with diabetes.
• NASH, the chronic liver disease noted before, has been found to be associated with insulin resistance and diabetes.
• The liver, when diseased, may fail to release sugar from its stored reserve (glycogen). The body, in such a condition, may not self-correct falling blood sugar, and blood sugar may become too low.
• Excessive absorption of iron (hemochromatosis) in the liver tends to promote glucose intolerance and diabetes.
• Hepatitis C is often associated with diabetes.
• Interferon-alpha therapy for chronic hepatitis C has been shown to increase the risk for type 2 diabetes.
• Cirrhosis promotes insulin resistance in the body and is linked to raised blood sugar levels.
• Liver cancer has been shown to be closely associated with low blood sugar disorder.

Liver disorders and diseases often grow without symptoms in their early stages, and when the symptoms appear, the liver may already have sustained some damage. Liver function in people with diabetes should be monitored through periodic liver function tests. People with diabetes, having raised levels of liver enzymes in a liver function test, should be tested for hepatitis C, the infection to which these people are at increased risk.