Glycosuria is when glucose is present in urine, in amounts that can be detected by the usual techniques.

Pathogenesis

Virtually all the glucose that is filtered through the glomeruli is reabsorbed 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 of 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.

The level of blood glucose at which it spills into the urine is called the renal threshold. Under normal circumstances this is around 10 mmol/L. Diastix®, Medi-Test® and Diabur-Test 5000® are plastic strips carrying glucose oxidase and a colour indicator, usually o-toluidine. They are specific and unlikely to give positive results for substances other than glucose. Glucose oxidase strips have superseded older reagents for reducing substances.

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. Glycosuria in pregnancy, however, must not be dismissed, as it may be the first sign of gestational diabetes.

It has been argued that urine glucose dipstick testing has low sensitivity and low negative predictive value for gestational diabetes. Glycosuria not only depends on the blood glucose level, but is also influenced by diastolic blood pressure.¹

Current National Institute for Health and Clinical Excellence (NICE) guidance suggests that screening (via an oral glucose tolerance test (GTT)) should be offered to women with the following risk factors for developing gestational diabetes mellitus (GDM) at booking:²

• BMI ≥30.
• Previous macrosomic baby ≥4.5 kg or above.
• Previous GDM.
• First-degree relative with diabetes.
• Family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern).

GTT should be done at 16-18 weeks if there is a history of previous GDM. For all other risks, testing should be offered between 24-28 weeks of gestation.

Risk factor screening is controversial and some authorities advocate universal screening for all pregnant women.

Fanconi's syndrome

Inadequate proximal renal tubular resorption of glucose occurs in Fanconi's syndrome. There may be a history of growth failure, rickets, polyuria, polydipsia, or dehydration. This may be idiopathic, inherited or acquired.

Other causes

Some secondary causes of renal glycosuria are:

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• Heavy metal poisoning, such as lead, mercury or after use of out-of-date tetracycline.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

Exclusion of these (by appropriate testing) should only be carried out if otherwise clinically indicated.

Benign glycosuria

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

• 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, GTT, insulin levels and HbA1c are all normal.

Misleading results

Testing sticks using glucose oxidase are specific for glucose. 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 an uncommon occurrence.

Diabetes and glycosuria

Screening test

Routine screening for glycosuria, especially for those who may be considered at high risk or who give a history that may be suggestive of diabetes mellitus, is worthwhile.⁵ The test fulfils all the necessary criteria for a screening test, although the false negative rate is 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 GTT is not used routinely.

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

Document references

1. Buhling KJ, Elze L, Henrich W, et al; The usefulness of glycosuria and the influence of maternal blood pressure in screening for gestational diabetes. Eur J Obstet Gynecol Reprod Biol. 2004 Apr 15;113(2):145-8. [abstract]
2. Diabetes in pregnancy, NICE Clinical Guideline (March 2008); Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the postnatal period
3. Bhimma R, Renal Glucosuria, Medscape, Aug 2011
4. Nagel D, Seiler D, Hohenberger EF, et al; Investigations of ascorbic acid interference in urine test strips. Clin Lab. 2006;52(3-4):149-53. [abstract]
5. Murphy TE Jr; The urinalysis--inexpensive and informative. J Insur Med. 2004;36(4):320-6. [abstract]
6. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, World Health Organization/International Diabetes Federation, 2006

Internet and further reading

• Rahman M, Simmons RK, Harding AH, et al; A simple risk score identifies individuals at high risk of developing Type 2 diabetes: a prospective cohort study. Fam Pract. 2008 May 30. [abstract]
• Diabetes UK: Care recommendation - pregnancy and diabetes (updated April 2008)
• Rutten G; Screening for type 2 diabetes--where are we now? Lancet. 2010 Apr 17;375(9723):1324-6. Epub 2010 Mar 29.