When should urine be checked for ketones, protein, and glucose in patients with suspected uncontrolled Diabetes Mellitus (DM)?

When to Check Urine for Uncontrolled Diabetes Mellitus

Urine glucose testing is not recommended for routine diabetes care, but urine or blood ketone testing should be performed in ketosis-prone individuals (type 1 diabetes, history of DKA, or those on SGLT2 inhibitors) when they have unexplained hyperglycemia or symptoms of ketosis such as abdominal pain or nausea. 1

Urine Glucose Testing

• Urine glucose testing should NOT be routinely used for diabetes management. 1
• Self-monitoring of blood glucose (SMBG) has supplanted urine glucose testing for most patients due to well-described limitations of urine testing. 1
• Urine glucose testing may only be considered in resource-limited settings where blood glucose monitoring is unavailable, but this is not the standard of care. 1

Urine Ketone Testing: When to Check

High-Risk Populations Requiring Ketone Monitoring

Check urine or blood ketones in the following ketosis-prone individuals: 1

• Patients with type 1 diabetes
• Patients with a history of diabetic ketoacidosis (DKA)
• Patients treated with SGLT2 inhibitors

Specific Clinical Scenarios Requiring Ketone Testing

Test for ketones when any of the following occur: 1

• Unexplained hyperglycemia (blood glucose persistently elevated despite usual treatment)
• Symptoms of ketosis or DKA:
  • Abdominal pain
  • Nausea or vomiting
  • Acute illness or infection
  • Symptoms of metabolic decompensation

Diagnostic Utility

• Urine ketones have 99% sensitivity for detecting DKA with a high negative predictive value (100%), making them excellent for ruling out DKA in hyperglycemic patients. 2
• The presence of urine ketones is highly sensitive for DKA or significant ketosis, with utility in ruling out DKA when negative. 1
• However, blood ketone testing (β-hydroxybutyrate) is preferred over urine testing for diagnosis and monitoring of DKA, as it measures the predominant ketone body directly. 1, 3

Important Limitations and Caveats

Urine Ketone Testing Limitations

• Urine ketone tests only detect acetoacetate and acetone, NOT β-hydroxybutyrate, which is the predominant ketone body in DKA. 1, 3, 4
• This can lead to underestimation of total ketone body concentration and misleading clinical information. 1
• False-positive results can occur with highly colored urine or sulfhydryl drugs (e.g., captopril). 3
• False-negative results can occur with expired test strips or highly acidic urine specimens. 3
• Urine ketone tests are not reliable for monitoring treatment of ketoacidosis because as DKA resolves, β-hydroxybutyrate is oxidized to acetoacetate, causing urine ketones to increase even as the condition improves. 3, 4

Normal Physiologic Ketonuria

• Positive ketone readings can be found in up to 30% of first morning urine specimens in normal individuals during fasting and in pregnant women. 3, 5
• This represents normal physiologic ketosis and should not be confused with pathologic ketosis in diabetes. 3, 5

Preferred Testing Strategy

Blood β-hydroxybutyrate measurement is superior to urine ketone testing for both diagnosis and monitoring of DKA and should be used when available. 1, 3, 6, 4 Specific measurement of β-hydroxybutyrate in blood should be used for diagnosis of DKA and may be used for monitoring during treatment. 1

Action When Ketones Are Detected

When urine or blood ketones are increased, patients should implement sick-day rules and/or seek medical advice immediately. 1 This includes increasing oral fluid intake, monitoring blood glucose and ketone levels every 3-4 hours, and considering additional rapid-acting insulin. 3