Urine Ketones - What They Mean and False Positives

Ketones are produced when the body breaks down fat for energy. When the body needs to breakdown fat in this way, then ketones will be detected in blood and urine. This is likely to occur when carbohydrates are either in short supply or cannot be metabolised or made available for metabolism. Blood measurement is more accurate¹ but urine testing is more widely available and more widely used. Blood monitoring is quicker and may ultimately be used more often at home.² Blood monitoring is used in hospital in emergencies.^{3 4} However for selective screening of diabetics urinalysis is still used widely.

Metabolically severe insulin deficiency (relative or absolute) produces hyperglycaemia and ketoacidosis. Insulin lack increases release of fatty acids from adipose stores and reduces the rate of fat synthesis. Lipolysis is further increased by increased catecholamines, cortisol, growth hormone and glucagon. The free fatty acids are transported to the liver for conversion to ketone bodies which serve as fuels for muscle and fat. Excess production of ketone bodies (aceto-acetate and beta-hydroxybutyrate) gives rise to ketoacidosis. Beta-hydroxy butyrate accounts for 75% of ketones.⁵

Urine is tested for ketones as part of monitoring of type 1 diabetes mellitus. This may be important in healthy diabetics under extreme circumstances (for example in sports and when climbing or exercising at altitude) but also in medical circumstances when diabetic control may be difficult.

Monitoring of ketones is important in diabetic patients:

• When the diet is low in carbohydrates, exercise levels are high or a combination of both.
• In pregnancy and in gestational diabetes.
• When blood sugars are high (over 15 mmol/l).⁵
• In diabetic ketoacidosis or with suspected ketoacidosis. Diabetic ketoacidosis should be suspected with:
  • Vomiting
  • Nausea
  • Abdominal pain
• When diabetic patients feel unwell. This is when diabetics are at risk of developing diabetic ketoacidosis.
• All patients using insulin pumps.⁵

Diabetic patients who detect high levels of ketones in their urine should seek medical advice immediately.

The urine test for ketones is performed using test strips available on prescription. Strips dedicated to ketone testing include:

• Ketostix®
• Ketur test®
• Combination strips such as Ketodiastix® are available but not on the NHS.

Testing should be performed according to manufacturers instructions. The sample should be fresh and uncontaminated. The result will usually be expressed as negative or positive (graded 1 to 4).⁶

Normally only small amounts of ketones are excreted daily in the urine (3-15mg). Diabetic patients who detect high levels of ketones should seek immediate medical advice. High or increased values may be found in:

• Poorly controlled diabetes
• Diabetic ketoacidosis
• Starvation:
  • Not eating for prolonged periods (12 to 18 hours)
  • Anorexia nervosa
  • Bulimia nervosa
  • Alcoholism
• Poisoning (for example with isopropanol)
• Ether anaesthesia
• Alkalosis
• Some metabolic disorders

The main purpose of testing is to detect diabetic ketoacidosis. A false positive is regarded as a positive result which is not likely to signal the start of diabetic ketoacidosis or agents which give a positive result in the absence of ketones.Testing may not be helpful and can be misleading if there is a chance of false positives. This may occur in non-diabetic (as well as in diabetic patients):

• Positive test result but 'no' ketones:
  • Some medication:
    • Levodopa for example sinemet
    • Phenazopyrazine
    • Valproic acid
    • Vitamin C
  • Dehydration
• Positive result and ketones present but not relevant to diabetic ketoacidosis:
  • High fat diets (for example the Atkins diet)
  • Some metabolic disorders and inborn errors of metabolism (ketones but low or normal blood glucose)⁷
  • Starvation (as above)
  • Poisoning
  • Ether anaesthesia
  • Alkalosis

Most urine testing kits detect acetoacetate not the predominant ketone beta-hydroxybutyrate. It is possible for the test to be negative with high levels of beta-hydroxybutyrate and then as ketoacidosis improves and ketone levels fall the urine test becomes positive (to acetoacetate).