What are the causes of glucosuria?

From the Guidelines

Glucosuria is most commonly caused by diabetes mellitus, where insulin deficiency or resistance leads to elevated blood glucose levels, and can also be caused by other factors such as pregnancy, certain medications, stress-induced hyperglycemia, and rare genetic disorders like Fanconi syndrome or renal glucosuria, as noted in the most recent study 1. The causes of glucosuria can be broadly categorized into several key areas, including:

• Diabetes mellitus, which is the most common cause and results from insulin deficiency or resistance leading to elevated blood glucose levels 1
• Pregnancy, specifically gestational diabetes, which can lead to glucosuria due to insulin resistance and increased blood glucose levels
• Certain medications, such as SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, and canagliflozin), which intentionally cause glucosuria to lower blood glucose levels
• Stress-induced hyperglycemia during severe illness, which can lead to temporary glucosuria
• Rare genetic disorders like Fanconi syndrome or renal glucosuria, where the kidneys' ability to reabsorb glucose is impaired despite normal blood glucose levels due to mutations in the SGLT2 transporter genes
• Certain hormonal conditions like Cushing's syndrome, acromegaly, and hyperthyroidism, which can cause glucosuria by inducing insulin resistance
• Temporary glucosuria may occur during stress, severe infections, or after consuming large amounts of carbohydrates, as noted in 1 and 1. If glucosuria is detected, further testing including fasting blood glucose and HbA1c is recommended to determine the underlying cause, as persistent glucosuria often indicates diabetes requiring appropriate management 1.

From the Research

Causes of Glucosuria

The causes of glucosuria can be attributed to several factors, including:

• Exceeding the threshold for glucose reabsorption by the proximal renal tubule 2, 3
• Impairment of glucose reabsorption in the proximal renal tubule 2, 3
• Familial renal glycosuria, a rare tubulopathy linked to a defect in the sodium-glucose co-transporter 2, encoded by the SLC5A2 gene 2, 3
• Generalized proximal tubular dysfunction 3
• Reduced activity of tubular glucose reabsorption 4
• Genetic mutations affecting the synthesis of the glucose carrier 4
• Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, which can increase urinary glucose and lead to prolonged glucosuria 5
• Impairment of renal tubular function in diabetic patients, leading to glucosuria and potentially albuminuria 6

Types of Glucosuria

There are different types of glucosuria, including:

• Benign familial renal glucosuria, characterized by persistent glucosuria despite normal blood glucose levels 3, 4
• Renal glucosuria, which can occur due to various factors, including genetic mutations and impaired renal function 3, 4
• Euglycemic diabetic ketoacidosis with prolonged glucosuria, associated with the use of SGLT2 inhibitors 5

Mechanisms of Glucosuria

The mechanisms of glucosuria involve:

• The inhibition of sodium-glucose cotransporters in the renal proximal tubules, leading to increased urinary glucose 5
• The impairment of glucose reabsorption in the proximal renal tubule, resulting in glucosuria 2, 3
• The reduction of the glucose threshold and maximal tubular glucose reabsorption in familial renal glycosuria 4