What are the causes of glucosuria?

Causes of Glucosuria

Glucosuria occurs primarily due to hyperglycemia in diabetes mellitus, but can also result from renal tubular dysfunction, certain medications, pregnancy, and rare genetic disorders.

Diabetes Mellitus

Diabetes is the most common cause of glucosuria, occurring when blood glucose levels exceed the renal threshold for glucose reabsorption:

• Type 1 Diabetes: Results from absolute insulin deficiency due to autoimmune destruction of pancreatic β-cells 1
• Type 2 Diabetes: Results from insulin resistance and relative insulin deficiency 1
• Gestational Diabetes: Glucose intolerance with onset during pregnancy 1
• Other specific types: MODY, diseases of the exocrine pancreas, endocrinopathies 1

In diabetes, hyperglycemia leads to glucose filtration exceeding the renal tubular capacity for reabsorption (typically around 180 mg/dL), resulting in glucose spillage into urine 1. Classic symptoms include:

• Polyuria
• Polydipsia
• Weight loss
• Blurred vision 1

Renal Causes

Glucosuria can occur with normal blood glucose levels due to renal tubular dysfunction:

1. Primary Renal Glucosuria (Familial Renal Glucosuria):

   • Genetic disorder with defects in the sodium-glucose cotransporter 2 (SGLT2) in proximal tubules 2
   • Normal blood glucose and oral glucose tolerance test
   • Benign condition but can be mistakenly diagnosed as diabetes 3
   • May be classified as types A, B, or O based on transport defect characteristics 2

2. Fanconi Syndrome:

   • Generalized proximal tubular dysfunction
   • Associated with glucosuria, phosphaturia, aminoaciduria, and bicarbonaturia 2

3. Pregnancy-induced glucosuria:

   • Due to increased glomerular filtration rate and decreased tubular reabsorption

4. Chronic Kidney Disease:

   • Advanced CKD can alter glucose metabolism and insulin clearance 1
   • Impaired kidney gluconeogenesis contributes to dysregulation 1

Medication-Induced Causes

1. SGLT-2 Inhibitors:

   • Therapeutic class that intentionally induces glucosuria by blocking glucose reabsorption in proximal tubules 4
   • Used for glycemic control in diabetes

2. Other medications:

   • Corticosteroids
   • Certain antibiotics (e.g., aminoglycosides)
   • Diuretics (high-dose)

Other Causes

1. Stress-induced hyperglycemia:

   • Severe illness, trauma, surgery
   • Due to increased counterregulatory hormones

2. Rare genetic disorders:

   • Novel forms of renal glucosuria with selective amino acid excretion patterns 2

3. Endocrinopathies:

   • Cushing's syndrome
   • Acromegaly
   • Pheochromocytoma
   • Glucagonoma 1

Clinical Significance

• Persistent glucosuria requires evaluation to distinguish between hyperglycemia and renal causes
• In diabetes, glucosuria correlates with risk of diabetic kidney disease 5
• In renal glucosuria, the condition is typically benign but can be mistakenly treated as diabetes, putting patients at risk for hypoglycemia 3

Diagnostic Approach

When glucosuria is detected:

1. Measure blood glucose (fasting and/or random)
2. If blood glucose is normal, perform oral glucose tolerance test
3. Evaluate for other markers of tubular dysfunction (amino acids, phosphate, bicarbonate)
4. Consider medication review and family history

Remember that glucosuria alone is not diagnostic of diabetes and requires correlation with blood glucose levels and other clinical parameters.