Urine glucose testing for diabetes control

Question

A publication in the NCBI bookshelf called Type 2 diabetes: Measuring sugar levels in blood and urine yourself (IQWiG, 2010) it states that

Having sugar in your urine is usually a sign of very high blood sugar levels. The extra sugar in the bloodstream is usually only removed via the kidneys at blood sugar concentrations of 10 mmol/L (180 mg/dL) and above. In order to measure the amount of sugar in your urine, you need a urine test strip and a container for collecting urine.
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To find out what the results mean, the colors on the test strip are compared with the color chart on the package. If the colors on the test strip don’t change, you don’t have sugar in your urine. The more the color changes, the more sugar there is in the urine, and therefore in the blood.

In the answer from @Jan to the question Why does kidney disease result in some things being filtered out but not others? it is pointed out that

healthy kidneys do not excrete glucose or proteins in significant amounts.

and mentions glycosuria which is a rare condition in which the kidneys release glucose into the urine

Renal glycosuria can cause urine glucose levels to be high even if blood glucose levels are normal (Stang & Reed-Guy, 2018).

Seeing as the book on the NCBI bookshelf is talking about urine glucose levels related to type 2 diabetes, (and also talks of type 1 diabetes testing using urine), is urine testing that reliable for checking for high blood glucose levels or the possibility of diabetes in a patient when glucose is generally only released when there is kidney disease?

References

IQWiG. (2010). Type 2 diabetes: Measuring sugar levels in blood and urine yourself. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG). Retrieved from NCBI Bookshelf: https://www.ncbi.nlm.nih.gov/books/NBK279508/

Stang, D. & Reed-Guy, L. (2018). Urine Glucose Test. Healthline. Retrieved from: https://www.healthline.com/health/glucose-test-urine

Answer 1

In short, glucose in urine is useful but not completely reliable test for diabetes mellitus, because:

• It is possible to have diabetes mellitus without glucose in the urine.
• Rarely, glucose in urine can be due to conditions other than diabetes mellitus, and some drugs and other substances can make the test false positive or negative.

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Renal threshold for glucose

By definition, you have diabetes mellitus if your fasting blood glucose levels exceed 126 mg/dL or 200 mg/dL after meals or at any random time (Mayo Clinic).

In a person with diabetes and healthy kidneys, glucose appears in the urine when the blood glucose exceeds 180 mg/dL (10 mmol/L), which is known as "normal renal threshold for glucose" (Clinical Methods, 1990):

The plasma glucose concentration above which significant glucosuria occurs is called the renal threshold for glucose. Its value is variable, and deviations occur both above and below the commonly accepted "normal" threshold of 180 mg/dl. In diabetic patients, the value is reported to vary from 54 to 300 mg/dl.

So, it's exceeding the renal threshold for glucose and not kidney disease that results in glucose in the urine.

Note, that if your blood glucose level in the fasting state is between 126-180 mg/dL, you, by definition, have diabetes mellitus, but glucose will not appear in the urine. So, you need to make a urine test 1-2 hours after a meal.

In adults, the most common cause of glucose in urine is diabetes mellitus (GPNotebook), so the urine test for glucose can be used as the first test for diabetes at home or to indirectly check for blood glucose levels by a person with known diabetes. In the hospital, to confirm diabetes, they will usually perform at least two other tests: fasting blood glucose (FBG) and oral glucose tolerance tsts (OGTT) (Mayo Clinic).

Other causes of glycosuria

Other causes of glucose in urine (glycosuria) are rare and most of them are covered by the umbrella term Fanconi syndrome, in which there is a a combination of increased levels of glucose, phosphate, amino acids and bicarbonate in the urine (Merck Manual):

• Genetic causes of Fanconi syndrome are usually discovered in infancy or early childhood and include:

cysinosis, Wilson disease, hereditary fructose intolerance, galactosemia, oculocerebrorenal syndrome (Lowe syndrome), mitochondrial cytopathies and tyrosinemia.

• Acquired causes of Fanconi syndrome may be discovered in childhood or adulthood and include:

...various drugs, including certain cancer chemotherapy drugs (eg, ifosfamide, streptozocin), antiretrovirals (eg, didanosine, cidofovir), and outdated tetracycline. ...renal transplantation...multiple myeloma, amyloidosis, intoxication with heavy metals or other chemicals, or vitamin D deficiency.

False positive and negative results of glucose in urine

(Clinical Methods, 1990):

• False positive results can be caused by: cephalosporins, penicillins, salicylates, levodopa, uric acid.
• False negative results can be caused by: 5-HIAA (a serotonin metabolite), salicylates and levodopa