What is the management approach for a patient with significantly elevated urine glucose, normal hemoglobin A1c (HbA1c), normal urine protein, and negative urine ketones?

Evaluation for Renal Glucosuria

This clinical presentation—markedly elevated urine glucose (>1000 mg/dL) with normal HbA1c, normal urine protein, and negative ketones—is most consistent with renal glucosuria, a benign condition where the renal threshold for glucose reabsorption is abnormally low, and you should confirm this diagnosis with an oral glucose tolerance test while simultaneously measuring timed urine glucose to demonstrate normal blood glucose with persistent glucosuria. 1

Immediate Diagnostic Steps

Confirm Blood Glucose is Normal

• Obtain fasting plasma glucose and repeat HbA1c to verify glycemic control is truly normal 2
• The normal HbA1c effectively rules out diabetes mellitus as the cause of glucosuria 2
• Consider point-of-care glucose testing or self-monitoring blood glucose over several days to capture glucose patterns 2

Perform Oral Glucose Tolerance Test with Timed Urine Collection

• Administer standard 75g oral glucose tolerance test 1
• Collect urine specimens at baseline, 1 hour, and 2 hours post-glucose load 1
• Renal glucosuria is confirmed when blood glucose remains normal (<140 mg/dL at 2 hours) but urine glucose remains persistently elevated 1
• This diagnostic approach using "Marbles' criteria" distinguishes renal glucosuria from diabetes mellitus 1

Rule Out Other Causes

Exclude Fanconi Syndrome

• Measure urine phosphate, uric acid, amino acids, and bicarbonate 1
• Check serum phosphate, uric acid, and bicarbonate levels 1
• Fanconi syndrome presents with generalized proximal tubular dysfunction, not isolated glucosuria 1
• The presence of normal urine protein makes Fanconi syndrome less likely but does not absolutely exclude it 1

Assess Renal Function

• Obtain serum creatinine and calculate eGFR 3
• Chronic kidney disease can affect glucose handling, though typically CKD causes reduced glucosuria due to decreased filtered glucose load 3
• In advanced CKD with severe hyperglycemia, glucose may account for only a small fraction of urinary osmoles due to impaired concentrating ability 4

Verify Medication History

• Confirm the patient is not taking SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin), which intentionally cause glucosuria 2
• SGLT2 inhibitors lower the renal threshold for glucose reabsorption and would produce this exact clinical picture 2

Clinical Significance and Management

Renal Glucosuria is Benign

• If renal glucosuria is confirmed, no treatment is required—this is a benign condition that does not progress to diabetes or cause complications 1
• The critical management issue is avoiding misdiagnosis as diabetes mellitus, which would lead to inappropriate hypoglycemic therapy 1

Critical Pitfall to Avoid

• Never initiate antidiabetic medications based on urine glucose alone when blood glucose and HbA1c are normal 1
• A case report documented a patient with renal glucosuria who developed symptomatic hypoglycemia after being mistakenly treated with oral hypoglycemic agents for presumed diabetes 1
• Urine glucose testing is insensitive and nonspecific for detecting hyperglycemia, with wide variation in blood glucose for any given urine glucose concentration 5

Long-term Follow-up

• Reassess HbA1c annually, as renal glucosuria does not protect against developing diabetes mellitus in the future 2
• No specific monitoring of urine glucose is needed once the diagnosis is established 1
• Counsel the patient that this condition is benign and does not require dietary restrictions or lifestyle modifications beyond standard health maintenance 1