The clinically relevant ketoacidoses to be discussed include diabetic ketoacidosis DKA , alcoholic ketoacidosis AKA , and starvation ketoacidosis. DKA is a potentially life-threatening complication of uncontrolled diabetes mellitus if not recognized and treated early.

It typically occurs in the setting of hyperglycemia with relative or absolute insulin deficiency. The paucity of insulin causes unopposed lipolysis and oxidation of free fatty acids, resulting in ketone body production and subsequent increased anion gap metabolic acidosis.

Starvation ketoacidosis occurs after the body is deprived of glucose as the primary source of energy for a prolonged time, and fatty acids replace glucose as the major metabolic fuel.

DKA can occur in patients with diabetes mellitus, most frequently associated with relative insulin deficiency. This may be caused by precipitating physiologic stress or, in some cases, maybe the initial clinical presentation in patients with previously undiagnosed diabetes.

Some of the more common risk factors that can precipitate the development of extreme hyperglycemia and subsequent ketoacidosis are infection, non-adherence to insulin therapy, acute major illnesses like myocardial infarction, sepsis, pancreatitis, stress, trauma, and the use of certain medications, such as glucocorticoids or atypical antipsychotic agents which have the potential to affect carbohydrate metabolism.

AKA occurs in patients with chronic alcohol abuse. Patients can have a long-standing history of alcohol use and may also present following binges. Acetic acid is a product of the metabolism of alcohol and also a substrate for ketogenesis.

The conversion to acetyl CoA and subsequent entry into various pathways or cycles, one of which is the ketogenesis pathway is determined by the availability of insulin in proportion to the counter-regulatory hormones, which are discussed in more detail below. Under normal conditions, cells rely on free blood glucose as the primary energy source, which is regulated with insulin, glucagon, and somatostatin.

As the name implies, starvation ketoacidosis is a bodily response to prolonged fasting hypoglycemia, which decreases insulin secretion, shunting the biochemistry towards lipolysis and the oxidation of the by-product fatty acids to ensure a fuel source for the body. According to the morbidity and mortality review of the CDC, diabetes itself is one of the most common chronic conditions in the world and affects an estimated 30 million people in the United States.

Age-adjusted DKA hospitalization rates were on the downward trend in the s but have steadily been increasing from thereafter till the mids at an average annual rate of 6. For AKA, the prevalence correlates with the incidence of alcohol abuse without racial or gender differences in incidence.

It can occur at any age and mainly in chronic alcoholics but rarely in binge drinkers. For starvation ketosis, mild ketosis generally develops after a to hour fast. It can be seen in cachexia due to underlying malignancy, patients with postoperative or post-radiation dysphagia, and prolonged poor oral intake.

Ketone bodies are fat-derived fuels used by tissues at the time of limited glucose availability. Hepatic generation of ketone bodies is usually stimulated by the combination of low insulin levels and high counter-regulatory hormone levels, including glucagon.

Low insulin levels are seen inherently in as either an absolute or relative deficiency in type I diabetes or a relative deficiency with insulin resistance in type 2 diabetes. In alcoholic or starvation conditions, low insulin levels are secondary to absolute or relative hypoglycemia.

This unfavorable ratio of insulin to glucagon activates hormone-sensitive lipase, which breaks down triglycerides in peripheral fat stores, releasing long-chain fatty acids and glycerol.

The fatty acids undergo beta-oxidation in the hepatic mitochondria and generate acetyl-CoA. With the generation of large quantities of acetyl-CoA in the more severe forms of each of these conditions, the oxidative capacity of the Krebs cycle gets saturated, and there is a spillover entry of acetyl-CoA into the ketogenic pathway and subsequent generation of ketone bodies.

An increased anion gap metabolic acidosis occurs when these ketone bodies are present as they are unmeasured anions. Alcoholic ketoacidosis [5] occurs in patients with chronic alcohol abuse and liver disease and usually develops following abrupt withdrawal of alcohol or an episode of acute intoxication.

It is not uncommon for the ingested ethanol to have already been metabolized, leading to low or normal serum levels when checked. In addition to this, the increased NADH further suppresses gluconeogenesis and reduces free glucose, perpetuating ketogenesis.

This usually happens after 2 or 3 days of fasting. After several days of fasting, protein catabolism starts, and muscles are broken down, releasing amino acids and lactate into the bloodstream, which can be converted into glucose by the liver. This biochemical process is responsible for the wasting and cachexia seen during starvation.

Patients with DKA may have a myriad of symptoms on presentation, usually within several hours of the inciting event. Symptoms of hyperglycemia are common, including polyuria, polydipsia, and sometimes more severe presentations include unintentional weight loss, vomiting, weakness, and mentation changes.

Dehydration and metabolic abnormalities worsen with progressive uncontrolled osmolar stress, which can lead to lethargy, obtundation, and may even cause respiratory failure, coma, and death. Abdominal pain is also a common complaint in DKA. Patients with AKA usually present with abdominal pain and vomiting after abruptly stopping alcohol.

On physical exam, most of the patients with ketoacidoses present with features of hypovolemia from gastrointestinal or renal fluid and electrolyte losses. In severe cases, patients may be hypotensive and in frank shock. They may have a rapid and deep respiratory effort as a compensatory mechanism, known as Kussmaul breathing.

They may have a distinct fruity odor to their breath, mainly because of acetone production. There may be neurological deficits in DKA, but less often in AKA. AKA patients may have signs of withdrawal like hypertension and tachycardia.

There are signs of muscle wasting in patients with starvation ketoacidosis like poor muscle mass, minimal body fat, obvious bony prominences, temporal wasting, tooth decay, sparse, thin, dry hair and low blood pressure, pulse, and temperature.

The initial laboratory evaluation of a patient with suspected DKA includes blood levels of glucose, ketones, blood urea nitrogen, creatinine, electrolytes, calculated anion gap, arterial blood gases, osmolality, complete blood count with differential, blood cultures and urine studies including ketones, urinalysis, urine culture, chest radiograph, and an electrocardiogram.

Hyperglycemia is the typical finding at presentation with DKA, but patients can present with a range of plasma glucose values. Although ketone levels are generally elevated in DKA, a negative measurement initially does not exclude the diagnosis because ketone laboratory measurements often use the nitroprusside reaction, which only estimates acetoacetate and acetone levels that may not be elevated initially as beta-hydroxybutyrate is the major ketone that is elevated.

The anion-gap is elevated, as mentioned above, because ketones are unmeasured anions. Leukocytosis may indicate an infectious pathology as the trigger and cultures are sent from blood, urine, or other samples as clinically indicated.

Serum sodium is usually relatively low because of shifts of solvent water from the intracellular to extracellular spaces because of the osmotic pull of hyperglycemia. Hence, normal or elevated serum sodium is indicative of severe volume depletion.

Serum potassium levels may be elevated due to shifts from the intracellular compartment for exchange with acids in the absence of insulin and normal or low potassium, indicating an overall depleted body store and subsequent need for correction before initiation of insulin therapy.

In AKA, transaminitis, and hyperbilirubinemia due to concurrent alcoholic hepatitis may also be present. The alcohol level itself need not be elevated as the more severe ketoacidosis is seen once the level falls, and the counter-regulatory response begins and shunts the metabolism towards lipolysis.

Hypokalemia and increased anion-gap are usually seen with similar mechanisms to those seen in DKA. Hypomagnesemia and hypophosphatemia are common problems seen in the laboratory evaluation due to decreased dietary intake and increased losses.

As mentioned above, the direct measurement of serum beta-hydroxybutyrate is more sensitive and specific than the measurement of urine ketones.

Starvation ketoacidoses patients may again have multiple electrolyte abnormalities due to chronic malnutrition, along with vitamin deficiencies. The pH may not be as low as in DKA or AKA, and the glucose levels may be relatively normal.

After the initial stabilization of circulation, airway, and breathing as a priority, specific treatment of DKA requires correction of hyperglycemia with intravenous insulin, frequent monitoring, and replacement of electrolytes, mainly potassium, correction of hypovolemia with intravenous fluids, and correction of acidosis.

Given the potential severity and the need for frequent monitoring for intravenous insulin therapy and possible arrhythmias, patients may be admitted to the intensive care unit.

Blood glucose levels and electrolytes should be monitored on an hourly basis during the initial phase of management. Aggressive volume resuscitation with isotonic saline infusion is recommended in the initial management of DKA.

Volume expansion not only corrects the hemodynamic instability but also improves insulin sensitivity and reduces counter-regulatory hormone levels.

After starting with isotonic saline, the subsequent options can be decided on the serum sodium levels that are corrected for the level of hyperglycemia. Normal or high serum sodium levels warrant replacement with hypotonic saline, and low sodium levels warrant continuation of the isotonic saline.

Like mentioned above, potassium levels are usually high because of the transcellular shifts due to the acidosis and the lack of insulin. When the potassium levels are low, this means that the total body potassium is low, and hence, insulin therapy should be postponed till at least the level of serum potassium is greater than 3.

Otherwise, a further drop in levels would put the patient at risk for cardiac arrhythmias. In the 3. The treatment of the acidosis itself is more controversial.

Treatment with sodium bicarbonate therapy is controversial. It has been studied and found to provide no added benefit when the arterial blood pH is greater than 6.

Several studies have found higher potassium requirements in patients receiving bicarbonate. Studies in children have observed a possible association between bicarbonate therapy and cerebral edema. AKA typically responds to treatment with intravenous saline and intravenous glucose, with rapid clearance of the associated ketones due to a reduction in counter-regulatory hormones and the induction of endogenous insulin.

Thiamine replacement is important in alcohol-related presentations, including intoxication, withdrawal, and ketoacidosis, and should be initially done parenterally and after that maintained orally.

Electrolyte replacement is critical. Potassium losses that occur through gastrointestinal GI or renal losses should be monitored and replaced closely as glucose in the replacement fluid induces endogenous insulin, which in turn drives the extracellular potassium inside the cells.

Also of paramount importance is monitoring and replacing the magnesium and phosphate levels, which are usually low in both chronic alcoholism and prolonged dietary deprivation as in starvation.

The treatment of starvation ketoacidosis is similar to AKA. Patients need to be monitored for refeeding syndrome, which is associated with electrolyte abnormalities seen when aggressive feeding is started in an individual starved for a prolonged time. The resultant insulin secreted causes significant transcellular shifts, and hence similar to AKA, monitoring and replacing potassium, phosphate, and magnesium is very important.

Hyperosmolar hyperglycemic state HHS occurs in the setting of insulin resistance and is more typical of type 2 diabetes. There is sufficient insulin in patients with HHS to suppress lipolysis and production of ketone bodies, but inadequate amounts to prevent the hyperglycemia, dehydration, and hyperosmolality, characteristic of HHS.

An illness or event that leads to dehydration will often precipitate the hyperglycemia associated with HHS. The development of HHS is less acute than DKA and may take days to weeks to develop. HHS typically presents with more extreme hyperglycemia and mental status changes compared with DKA.

HHS typically presents with normal or small amounts of urine or serum ketones. Lactic acidosis is an alternative cause of an increased anion gap metabolic acidosis. Lactic acidosis is found with tissue hypoperfusion, hematological malignancies, and various medications.

Rhabdomyolysis is a diagnostic consideration in a patient with a history of alcohol use disorder and an anion gap metabolic acidosis, but this condition is frequently associated with hyperkalemia, hyperphosphatemia, hypocalcemia, and a urinalysis positive for blood with no erythrocytes visible on urine microscopy.

Acute abdominal surgical emergencies, such as acute pancreatitis, should be considered differentials when abdominal pain is the main presentation. The American Association of Clinical Endocrinologists and the American College of Endocrinology have reviewed reported cases of DKA in patients taking SGLT2 inhibitors.

Therefore, rather than relying on the presence of hyperglycemia, close attention to signs and symptoms of DKA is needed. In May , the US Food and Drug Administration FDA issued a warning [B] that treatment with sodium-glucose transporter-2 SGLT2 inhibitors, which include canagliflozin, dapagliflozin, and empagliflozin, may increase the risk of diabetic ketoacidosis DKA in patients with diabetes mellitus.

The FDA Adverse Event Reporting System database identified 20 cases of DKA in patients treated with SGLT2 inhibitors from March to June Diabetes, once diagnosed, is mostly managed with changes in diet, lifestyle, and medication adherence.

The goal is to prevent high glucose levels, which helps prevent diabetic complications. To prevent the complications of diabetes like ketoacidosis, the condition is best managed by an interprofessional team that includes the diabetic nurse educator, dietician, nurse practitioner, pharmacist, primary care provider, and an endocrinologist; all these clinicians should educate the patient on glucose control at every opportunity.

Empowering the patient regarding management is hence of the utmost importance. Diabetes self-management education DSME and diabetes self-management support DSMS are recommended at the time of diagnosis of prediabetes or diabetes and throughout the lifetime of the patient.

DSMS is an individualized plan that provides opportunities for educational and motivational support for diabetes self-management. DSME and DSMS jointly provide an opportunity for collaboration between the patient and health care providers to assess educational needs and abilities, develop personal treatment goals, learn self-management skills, and provide ongoing psychosocial and clinical support.

The diabetic nurse should follow all outpatients to ensure medication compliance, followup with clinicians, and adopting a positive lifestyle. Further, the nurse should teach the patient how to monitor home blood glucose and the importance of careful monitoring of blood sugars during infection, stress, or trauma.

The physical therapist should be involved in educating the patient on exercise and the importance of maintaining healthy body weight. The social worker should be involved to ensure that the patient has the support services and financial assistance to undergo treatment.

The members of the interprofessional team should communicate to ensure that the patient is receiving the optimal standard of care. Improved outcomes and reduced costs have been associated with DSME and DSMS.

Disclosure: Pranita Ghimire declares no relevant financial relationships with ineligible companies. Disclosure: Amit Dhamoon declares no relevant financial relationships with ineligible companies. This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.

You are not required to obtain permission to distribute this article, provided that you credit the author and journal. This is so that they will be able to spot the symptoms of DKA, too.

Here Kate tells us about when her son Llewis became seriously ill with DKA and was diagnosed with type 1 diabetes soon after. Although most common in people with type 1 diabetes, people with type 2 diabetes can sometimes develop DKA. In her video Kate mentions the 4Ts which are the four most common signs of type 1 diabetes.

They are:. The early signs of DKA can often be treated with extra insulin and fluids if it is picked up quickly. These symptoms are sometimes referred to as a 'diabetic attack', but this can also refer to other things, such as hypoglycaemia. You might notice these signs developing over 24 hours but they can come on faster, especially in children or if you use a pump.

If you spot any of these symptoms it is a sign that you need to get some medical help quickly. If your blood sugar is high, check for ketones. You can check your blood or your urine for ketones.

A blood test will show your ketone levels in real time but a urine test will show what they were a few hours ago. If you have type 1 diabetes you should get either a blood ketone monitor or urine testing strips for free from the NHS.

If you have high ketone levels in your blood and suspect DKA, you should get medical help straight away. DKA is serious and must be treated in hospital quickly. Left untreated, it could lead to a life-threatening situation.

You'll also be closely monitored to make sure there are no serious problems with your brain, kidneys or lungs. You'll be able to leave hospital when you're well enough to eat and drink and tests show a safe level of ketones in your body. You can help avoid DKA by monitoring your blood sugar levels regularly and altering your insulin dose in response to your blood sugar levels and what you eat.

Your blood sugar levels could be higher than normal when you are unwell.

If your DKA is a result of an infection or illness, your doctor will treat that as well, usually with antibiotics. At the hospital, your physician will likely give you intravenous IV fluids to help your body rehydrate.

During a DKA event, you usually lose a lot of fluids, which can reduce the amount of blood flowing through your body. Fluid replacement helps restore typical blood flow. It also helps treat dehydration , which can cause even higher blood sugar levels.

Electrolytes are electrically charged minerals that help your body, including the heart and nerves, function properly. Electrolyte replacement is also commonly done through an IV. The emergency care team will also monitor several other blood test results that indicate when insulin therapy is no longer needed.

When your blood sugar and other test readings are within an acceptable range, your doctor will work with you to help you avoid DKA in the future. DKA occurs when insulin levels are low. Our bodies need insulin to use the available glucose in the blood. Turning fat into energy produces ketones.

When too many ketones build up, your blood becomes acidic. This is diabetic ketoacidosis. Although DKA is less common in people who have type 2 diabetes, it does occur. A diagnosis of ketosis-prone diabetes is more likely for:. Testing for ketones is one of the first steps for diagnosing DKA.

If you have type 1 diabetes, you should have a supply of home ketone tests. These test either your urine or your blood for the presence of ketones. According to the American Diabetes Association , you should test for ketones:. Urine test strips change color to signal the presence of ketones in your urine.

The indicator on the strip will change color. Compare the test strip to the results chart. Blood ketone testers are also available. These are usually combination devices that can measure both glucose levels and ketone levels.

The test strip is inserted into a monitor device to test for the presence of ketones in your blood. A doctor will likely do a test to confirm the presence of ketones in your urine. They will usually also test your blood sugar level. Other tests your doctor may order include:. There are many ways to prevent DKA.

You can lower your risk of DKA with proper management of your diabetes:. Call your doctor if you detect moderate or high ketones in a home test. Early detection is essential. DKA is serious, but it can be prevented. Follow your diabetes treatment plan and be proactive about your health.

ask your care team about getting a continuous glucose monitor or flash monitor if you do not already have one. follow the sick day rules you've been given by your care team when you're ill.

Page last reviewed: 08 June Next review due: 08 June Home Health A to Z Back to Health A to Z. Diabetic ketoacidosis. Check if you have diabetic ketoacidosis DKA Symptoms of diabetic ketoacidosis DKA include: feeling thirsty needing to pee more often stomach pain, feeling sick or being sick diarrhoea breathing more deeply than usual breath that smells fruity like pear drop sweets or nail polish remover feeling tired, sleepy or confused blurred vision The symptoms usually develop over 24 hours, but it can be faster.

Checking your blood glucose and ketones If you have diabetes and have any of the symptoms of DKA, check your blood glucose. If you use a meter to test for ketones in your blood: under 0. Important These ketone levels are a guide.

Urgent advice: Call your diabetes care team now or get help from NHS if:. You have diabetes and: your blood glucose is high and your insulin treatment is not working to reduce it, even if your ketones are normal your ketones are slightly high 0. Do follow the treatment plan agreed with your diabetes care team, including adjusting your insulin dose when you need to check your blood glucose regularly ask your care team about getting a continuous glucose monitor or flash monitor if you do not already have one test for ketones when your blood glucose is high and when you're ill follow the sick day rules you've been given by your care team when you're ill contact your care team if you're not sure what to do.

DKA usually develops slowly. But when vomiting occurs, this life-threatening condition can develop in a few hours. Early symptoms include the following:. DKA is dangerous and serious. You can detect ketones with a simple urine test using a test strip, similar to a blood testing strip.

Ask your health care provider when and how you should test for ketones. When you are ill when you have a cold or the flu, for example , check for ketones every four to six hours.

If your health care provider has not told you what levels of ketones are dangerous, then call when you find moderate amounts after more than one test.

Often, your health care provider can tell you what to do over the phone. Do NOT exercise when your urine tests show ketones and your blood glucose is high. High levels of ketones and high blood glucose levels can mean your diabetes is out of control.

Check with your health care provider about how to handle this situation. Diabetes Complications. Know the warning signs of DKA and check urine for ketones, especially when you're sick. What are the warning signs of DKA?