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Define glycosuria. Classify its causes and describe the methods of detection.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Glycosuria = the presence of detectable glucose in the urine.

  • Normally the urine contains less than 25 mg/dL, which routine tests do not detect

Renal Handling of Glucose

Glucose freely filtered at the glomerulus → Reabsorbed in the proximal convoluted tubule by SGLT-2 (90%) and SGLT-1 (10%) → Transport is saturable → Above the transport maximum (Tm) of about 350 mg/min → Glucose appears in urine

  • Renal threshold = 180 mg/dL — the blood level at which glucose first appears in urine
  • Splay — glycosuria begins a little below the calculated threshold because nephrons differ in their individual capacity

Classification of Causes

TypeBlood glucoseCauses
Hyperglycaemic glycosuriaRaisedDiabetes mellitus; also Cushing, acromegaly, phaeochromocytoma, thyrotoxicosis, severe stress, steroids
Renal glycosuriaNormalLowered renal threshold — familial renal glycosuria (SGLT-2 mutation), pregnancy, Fanconi syndrome, chronic kidney disease
Alimentary (lag storage)Transient peakAfter gastrectomy, in hyperthyroidism — rapid absorption overwhelms the threshold briefly
Drug-inducedNormal or lowSGLT-2 inhibitors — deliberate therapeutic glycosuria

CLINICAL PEARL

Glycosuria is not diabetes. A normal blood glucose with glycosuria means a low renal threshold, most often pregnancy. Conversely, the elderly and those with renal disease may have a raised threshold and show no glycosuria despite marked hyperglycaemia — which is why urine testing is unreliable for diagnosis.

Detection Methods

MethodPrincipleSpecificity
Glucose oxidase stripGlucose oxidase → H2O2 → chromogen with peroxidaseSpecific for glucose
Benedict testReduction of cupric to cuprous oxide in alkaliDetects any reducing sugar — glucose, galactose, fructose, lactose, pentose
Rothera testNitroprussideFor ketones, not sugar
  • A positive Benedict with a negative glucose oxidase strip means a non-glucose reducing sugar — suspect galactosaemia in an infant, or essential fructosuria, or lactosuria in late pregnancy. A classical examination question
  • False negatives on strips — large doses of vitamin C, or old strips
  • False positives on Benedict — ascorbic acid, salicylates, some antibiotics, homogentisic acid

Applied Aspects

  • Urine glucose is no longer used to diagnose or monitor diabetes — blood testing has replaced it entirely, because the renal threshold varies so widely between individuals
  • Glycosuria in pregnancy is common and usually physiological, from increased GFR and reduced tubular reabsorption; it still warrants a glucose tolerance test to exclude gestational diabetes
  • SGLT-2 inhibitors deliberately induce glycosuria of 50–80 g/day, lowering glucose independently of insulin; the cost is an increased risk of genital fungal infection and, rarely, euglycaemic ketoacidosis

All questions in Carbohydrate Metabolism II: Glycogen, HMP & Diabetes

  1. Q1Describe glycogenesis and glycogenolysis with their regulation. Compare liver and muscle glycogen. ★
  2. Q2Describe the HMP shunt with its reactions and significance. Explain the importance of NADPH and add a note on G6PD deficiency. ★
  3. Q3Classify diabetes mellitus. Describe the metabolic changes and the biochemical basis of its complications. ★
  4. Q4Describe the metabolism of fructose and galactose. Discuss the disorders arising from blocks in these pathways. ★
  5. Q5Describe the structure, synthesis, secretion and metabolic actions of insulin. Add a note on insulin resistance. ★
  6. SN1Describe the biochemical basis, precipitating factors and features of G6PD deficiency. ★
  7. SN2Describe the formation, significance and limitations of HbA1c. ★
  8. SN3Define metabolic syndrome. Give its diagnostic criteria and biochemical basis. ★
  9. SN4Define glycosuria. Classify its causes and describe the methods of detection. ★
  10. SN5Write a short note on galactosaemia. ★
  11. SN6Classify glycosaminoglycans with their functions. Add a note on the mucopolysaccharidoses.
  12. SN7Describe the uronic acid pathway and its significance.

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