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Diabetic Ketoacidosis (DKA)

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Diabetic ketoacidosis is a life-threatening side effect of diabetes that occurs when the body uses fat as fuel instead of sugar. Infection and missed insulin treatment is often the cause of DKA, but studies also show some SGLT2 inhibitor drugs can cause it.

Diabetic ketoacidosis is a dangerous complication of diabetes. About 14 percent of all diabetic hospital admissions are because of DKA. Diabetic ketoacidosis can cause a diabetic coma and death, and is responsible for 16 percent of all diabetes-related deaths.

Diabetic ketoacidosis is most common among children and adolescents who have Type 1 diabetes, but diabetics of all ages can experience the complication. It is very uncommon for a type 2 diabetic to experience diabetic ketoacidosis, but studies link certain medications called SGLT2 inhibitors to the condition. Some of these drugs include Invokana (canagliflozin), Farxiga (dapagliflozin) and Jardiance (empagliflozin).

DKA occurs when the body begins using fats as fuel rather than glucose, or sugar. In a person with normal insulin levels, insulin aids the body in using sugar as fuel. When the body is deficient in insulin the body cannot use sugar for fuel and it uses fat instead. Breaking down the fats causes the creation of acidic chemicals called ketones, which can build up in the body. Ketones are poisonous in high levels and can cause organs to malfunction.

Studies show infection, missed or irregular insulin treatments and a new diagnosis of diabetes are the cause of diabetic ketoacidosis 40 percent, 25 percent and 15 percent of the time, respectively. The average cost of hospitalization for diabetic ketoacidosis in the U.S. is $13,000 per patient.

Symptoms of Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis can develop relatively quickly — around 24 hours in most cases. Abnormally great thirst (polydipsia) and frequent urination (polyuria) are typically the first symptoms most people notice.

Other common DKA symptoms are:

  • Weakness
  • Decreased alertness
  • Stomach pain
  • Nausea and vomiting
  • Decreased perspiration
  • Fruity-smelling breath
  • Flushed face
  • Dry skin
  • Disorientation and confusion

For patients who know they have Type 1 diabetes, symptoms of DKA may also include rapid weight loss in newly diagnosed patients, and a history of missed insulin injections because of vomiting, failed insulin pump or psychological reasons.

Diabetic ketoacidosis may also be associated with an infection. If this is the case, patients may also notice symptoms like fever, cough, chills, labored breathing and joint pain. A common side effect of DKA is severe dehydration.

Ketosis vs Ketoacidosis

Ketosis and ketoacidosis are often confused. Both relate to ketones, the natural blood acids the body produces when it burns stored fat to make energy. Normally the body uses sugar, or glucose, as fuel. Insulin aids in this process. Some people cannot use sugar for fuel — for example, if someone is on a low-carbohydrate diet or if they are a diabetic with low insulin — so the body uses fat instead. People on a low-carb diet enter dietary or nutritional ketosis. Like DKA, ketosis causes the production of ketones.

Most studies agree that dietary ketosis is not dangerous and people with or without diabetes may eat lower carbohydrate levels safely. However, there have been a few cases of DKA brought on by ketosis. In one case from 2006, a nondiabetic woman consuming less than 20 grams of carbs per day repeatedly experienced ketoacidosis.

When to See a Doctor

Health professionals consider DKA a medical emergency, and it can be a fatal condition. If a person with diabetes experiences any of the symptoms of DKA — most notably vomiting, labored breathing, decreased consciousness or fruity-smelling breath — it’s important they contact their doctor immediately.

Over-the-counter urine ketone testing kits are also available, and may give a clearer picture as to whether the patient is experiencing DKA. If a person with diabetes takes one of these tests and it indicates they have moderate or high urine ketone levels, they should contact their doctor immediately.

DKA can quickly lead to a hyperglycemic coma and possibly death. If a patient’s family doctor is unreachable, they should call 911 or go to the nearest emergency room.

NegativeLess than 0.6 mmol/L*

Urine Ketone Levels
Low to moderate 0.6 – 1.5 mmol/L*
High 1.6 – 3.0 mmol/L*
Very high More than 3.0 mmol/L*

*millimoles per liter

Causes of DKA

Food consumption, insulin therapy and insulin shock can all affect the body’s insulin levels and therefore cause diabetic ketoacidosis.

The body uses glucose to feed muscle and brain function. These cells cannot absorb the glucose, however, without the help of insulin. If a person has low levels of insulin and cannot use glucose for fuel, the body thinks it’s starving and switches to a secondary fueling system that uses fat and protein instead. This produces ketones. Because the person has low insulin, however, the body never stops producing ketones. The buildup of acidic ketones leads to DKA and an imbalanced pH. This causes organs to stop functioning properly, eventually leading to a diabetic coma and death if left untreated.

Because people with Type 1 diabetes have naturally occurring high blood sugar and low insulin levels, DKA is most common in this group. However, people with Type 2 diabetes can experience hypoglycemia — also known as a low blood sugar episode, “insulin reaction” or “insulin shock” that are caused by insulin therapy or diabetic medications — that may also lead to DKA. This condition is very rare.

Diabetic Ketoacidosis and SGLT2 Inhibitors

Although diabetic ketoacidosis can occur naturally in some diabetics, scientists recently discovered certain drugs —called sodium-glucose cotransporter-2 inhibitors, or SGLT2 inhibitors — can also cause the life-threatening condition. Doctors often prescribe SGLT2s to treat Type 2 diabetes in adults. The drugs cause the kidneys to remove sugar in the body through urine, effectively lowering a patient’s blood sugar.

SGLT2 inhibitors include:

  • Canagliflozin (Invokana, Invokamet)
  • Dapagliflozin (Farxiga, Xigduo XR)
  • Empagliflozin (Jardiance, Glyxambi)

On May 15, 2015, the U.S. Food and Drug Administration released a drug safety communication warning doctors and users of the correlation between the drug and the development of DKA. According to the communication, the FDA received reports of 73 cases of DKA between March 2013 and May 2015 in SGLT2 patients. Many of the patients had lower blood glucose levels than typically seen in DKA cases, which caused delayed diagnosis of the complication and delayed treatment. All of the patients went to the hospital or emergency room.

As a result, the FDA has updated the warning labels and prescription recommendations for SGLT2s. Besides DKA, other side effects of the drug include kidney problems, serious urinary tract infections, yeast infections and dehydration.

Diabetic ketoacidosis rarely occurs in type 2 diabetics, but taking a prescription for SGLT2 inhibitors increases the risk of developing the complication. Doctors also sometimes prescribe the drugs to Type 1 diabetics, although the FDA has not approved the drug for use in Type 1 diabetics.

DKA Testing and Diagnosis

The simplest way to diagnose diabetic ketoacidosis is through monitoring urine ketone levels. While doctors can perform urinalysis to examine the levels, diabetics can also self-monitor their ketones at home using over-the-counter urine ketone testing kits. If a person’s ketone level is 1.5 millimoles per liter or higher, the person should contact their doctor or go to the emergency room right away, as they very likely have DKA.

Doctors also regularly use blood tests to diagnose diabetic ketoacidosis. Health care providers also use these tests to examine blood sugar, ketone and blood acidity levels. High levels for any of the three can indicate diabetic ketoacidosis.

In the case of blood sugar, a person’s blood sugar levels will rise if they do not have enough insulin to carry the sugars into cells for fuel. The body will use fat and protein for this process if it cannot use sugar, leading to even more hyperglycemia and high blood sugar levels. As a result of this process, the body produces ketones that enter the bloodstream. Ketones are acidic compounds that can quickly raise a person’s blood acidity and cause organs to malfunction.

Once diagnosed, a doctor may also perform additional tests to determine if something else, like an infection, caused the DKA, and to check if the ketoacidosis has manifested any complications. These tests include urinalysis, chest x-ray, electrocardiogram and blood electrolyte tests.

Treatment for DKA and its Complications

Most emergency rooms can treat people with mild ketoacidosis. Research shows treatment is more successful, however, if it’s administered in an intensive care unit for the first one or two days of hospitalization.

Treatment for DKA mostly consists of insulin therapy, electrolyte replacement and fluid replacement. Insulin therapy will reverse the diabetic ketoacidosis process. The goal of therapy is to get blood sugar levels below 240 mg/dL and to reduce blood acid levels. To avoid experiencing DKA again, patients must follow a normal insulin therapy regimen.

DKA also causes severe dehydration and mineral depletion. During treatment, the patient will receive fluids to help rehydrate the body and dilute high blood sugar levels. The patient will also receive electrolytes to replace depleted stores.

Depending on a patient’s diagnosis, DKA treatment may also involve other layers of treatment, including antibiotics if an infection caused the ketoacidosis or a diabetes treatment plan if the condition was previously undiagnosed.

Early diagnosis and treatment of diabetic ketoacidosis is crucial to a positive prognosis. Although diabetic ketoacidosis has a mortality rate of 0.2 – 2 percent, the complication can be deadly, especially when the patient also experiences a coma, hypothermia or oliguria — a condition where a patient produces too little urine.

Prevention

Diabetic ketoacidosis is completely preventable. The most successful prevention plan is a commitment to the patient’s diabetes treatment plan, which often includes a healthy diet, exercise and diabetes medication or insulin. Missed or altered insulin injections are among the main causes of diabetic ketoacidosis.

Monitoring the patient’s blood sugar level is a key part of successful diabetes treatment and therefore DKA prevention. For some people, this includes speaking with their doctor about adjusting their insulin dosage.

Using over-the-counter urine ketone testing kits to monitor ketone levels is also a good way to keep track of blood acid levels. This alert people to high ketone levels before the condition worsens.

Education is also an important part of prevention. People with diabetes and their parents or loved ones should be familiar with the symptoms of DKA so if they manifest, they can act quickly. Staying fully informed on medications is a part of this.

Lawsuits & Litigation Surrounding Ketoacidosis

Some patients who have suffered from diabetic ketoacidosis have filed lawsuits against Invokana maker Janssen Pharmaceuticals. In one case, a Georgia woman claims her quality of life was diminished by the diabetic ketoacidosis side effect. Her doctor put her on the drug for treatment of Type 2 diabetes in 2013. Two weeks after taking Invokana, Paula Brazil was taken to a local hospital for treatment of nausea and vomiting. Doctors at Hamilton Medical Center diagnosed her with diabetic ketoacidosis. Her attorneys say Brazil will suffer, both physically and emotionally, for the rest of her life.

Other lawsuits make similar claims. A California woman was hospitalized in an intensive-care unit after taking Invokana, a lawsuit alleges. No one told Jennifer Anzo of the potential risks from the drug, her suit says. The Stockton woman used the drug for three months before she was hospitalized and diagnosed with diabetic ketoacidosis.

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