Glycosuria

Glycosuria is when glucose is present in urine in amounts that can be detected by the usual techniques. Normally, virtually all the glucose that is filtered through the glomeruli is resorbed by the proximal renal tubule and so glycosuria represents an abnormal state. The amount of glucose not reabsorbed by the kidneys is usually less than 0.1%. Adults excrete about 65 mg of glucose per day and standard techniques do not detect this level.

There are two basic causes for glycosuria. One is that the level of blood glucose is so high that the renal tubules are unable to reabsorb all that is presented. The other is a failure of the tubules to reabsorb all glucose at a level where this should be possible. The latter is called renal glycosuria.

False positives occur when a substance other than glucose gives a positive result.

The level of blood glucose at which it spills into the urine is called the renal threshold. Under normal circumstances, this is around 10mmol/L. In the days when Fehling's or Benedict's reagents were used to test for glucose, a false positive could be achieved from other reducing sugars or other reducing substances. Sucrose is not a reducing sugar. Tablets such as Clinitest™ detect reducing substances and have the same problem. Nowadays it is much more usual to use plastic strips carrying glucose oxidase and a colour indicator, usually o-toluidine. Trade names include Diastix™, Medi-test™ and Diabur-test 5000™. Hence they are much more specific and unlikely to give positive results for substances other than glucose. For most practical purposes, glucose oxidase strips have superseded reagents for reducing substances.

There may be problems of glycosuria causing false positive tests for alcohol in urine.¹ This is due to glucose and fungal infection and failure to use adequate preservative for specimens.

Elevated Blood Glucose

• If glycosuria occurs because a normal renal threshold has been exceeded, this is usually indicative of impaired glucose tolerance or frank diabetes.
• It can occur in the non-diabetic if a substantial amount of food high in sugar is consumed and transiently overwhelms the insulin response causing hyperglycaemia.
• Other conditions that may cause hyperglycaemia include:
  • Thyrotoxicosis
  • Acromegaly
  • Cushing's syndrome, including administration of corticosteroid drugs
  • Severe anxiety states.
• Very rapid gastric emptying as in dumping syndrome after surgery for peptic ulcers can raise blood glucose above the threshold.
• Stress hormones elevate blood glucose and in the severely ill patient they may elevate glucose beyond the renal threshold.
• Hyperalimentation may also raise the blood glucose above the renal threshold.

Renal Glycosuria

Pregnancy

Pregnancy is associated with a reduced renal threshold. This results from increased renal blood flow so that the tubules are presented with a greater volume each minute. However, glycosuria in pregnancy must not be dismissed as it may be the first sign of gestational diabetes.

It has been argued that urine glucose dip stick testing has low sensitivity and low negative predictive value for gestational diabetes. Glycosuria is not only dependent on the blood glucose level, but highly influenced by diastolic blood pressure.² It has been argued that routine urine screening for glucose and albumin in pregnant women who are not a high risk should be abandoned³ but readers are advised to await authoritative advice before contemplating such action.

Fanconi Syndrome

Inadequate proximal renal tubular resorption of glucose occurs in the Fanconi syndrome. There may be a history of growth failure, rickets, polyuria, polydipsia, or dehydration. This may be idiopathic, inherited, or acquired.
Some secondary causes of renal glycosuria are:

• Oculocerebrorenal Dystrophy (Lowe syndrome)
• Cystinosis
• Wilson's disease
• Interstitial nephritis
• Hereditary tyrosinaemia
• Heavy metal poisoning such as lead, mercury or with out-of-date tetracycline
• Intestinal glucose-galactose malabsorption where the defective sodium-dependent glucose co-transporter protein is also present in the renal tubules.

Benign Glycosuria

Benign glycosuria occurs without such significant pathology and it is divided into 3 categories:

• Type A is called classical glycosuria, with reduction in both glucose threshold and maximal glucose reabsorption rate.
• In type B there is a reduction in the glucose threshold and a normal rate of reabsorption.
• Type O has failure of glucose reabsorption. Plasma glucose, glucose tolerance test, insulin levels and HbA1_C are all normal.

Misleading Results

As mentioned above, the stick tests using glucose oxidase are specific for glucose and other substances do not cause it to change. The small amounts of glucose normally excreted by the kidneys are usually below the sensitivity range of this test but on occasions may produce a colour between the negative and the lowest positive and may be interpreted by the observer as positive.

Ascorbic acid appears to interfere with glucose oxidase strips and may cause false negatives.⁴ This is probably not of great significance.

The problem lies with other tests for reducing substances. False results can arise from ascorbic acid, nalidixic acid, cephalosporins, aspirin, penicillin, L-Dopa or probenecid in the urine. Glucuronic acid, creatinine, uric acid and formaldehyde may all give positive results. Reducing sugars that will be detected include glucose, lactose, fructose, galactose and pentose but not sucrose.

Diabetes and Glycosuria

Screening Test

Routine screening for glycosuria, especially those who may be considered at high risk or who give a history that may be suggestive of diabetes mellitus is well worthwhile.⁵ The test fulfills all the necessary criteria for a screening test although the false negative rate is rather high. Those who have overt diabetes that is untreated will probably have glycosuria on a routine sample but if the result is negative and there is still reason to suspect the condition, blood tests such as fasting blood glucose should be undertaken.

Heavy glycosuria is unlikely to be a false positive but where glycosuria is discovered, it should be followed by blood tests to confirm the diagnosis. A formal glucose tolerance test is not used routinely. Diagnostic criteria are laid down by the World Health Organisation and accepted by national bodies including Diabetes UK.

• Fasting plasma glucose of ≥7mmol/L. Figures of 6.1 to 6.9mmol/L represent impaired glucose tolerance (IGT).
• In a standard GTT, 2 hours plasma glucose of ≥11.1mmol/L. Between 7.8 and 11.1mmol/L is classified as IGT.
• Fasting plasma glucose will fail to diagnose as many as 30% of people with diabetes and a GTT is needed to distinguish IGT.
• HbA1_C has no place in the diagnosis of diabetes.

There is some pressure to lower the thresholds for diagnosis but in 2006 the WHO decided that was inappropriate.

How to perform a glucose tolerance test is described elsewhere.
Checking for glycosuria is a screening test, not a diagnostic test for diabetes. It fulfills the criteria of:

• Cheap
• Easy to perform
• Acceptable
• Reasonably high sensitivity
• High specificity
• The prognosis of the disease to be sought can be significantly improved by early diagnosis.