Glycosuria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Glycosuria or glucosuria is an abnormal condition of osmotic diuresis due to excretion of glucose by the kidneys. The most common cause of glycosuria is untreated diabetes mellitus. The condition occurs when plasma glucose levels rise above kidney threshold for glucose reabsorption. At this point, the excess plasma glucose will not be reabsorbed in the proximal tubule and is excreted in the urine. When the excess glucose is excreted in the urine, it makes water enter the urine due to high osmolarity of the urine. This leads to the characteristic symptom of high urine volumes. Glycosuria can be either a physiologic response of the body to elevated blood glucose levels, such as alimentary glycosuria; or it can be a pathologic phenomenon. When glycosuria occurs at normal plasma glucose concentrations due to decreased renal threshold for glucose reabsorption, it is reffered to as renal glycosuria. Glycosuria has been targeted as a therapeutic option for diseases such as diabetes mellitus, as induction of glycosuria leads to better glycemic control and decreases risk of cardiovascular diseases in diabetic patients.

Causes

Conditions

• Diabetes mellitus
• Pregnancy

Drugs Causing Glycosuria

• Chlorpromazine
• Cidofovir
• Hydrochlorothiazide
• Prednisolone
• Streptozocin
• ACE Inhibitors (Captopril, Enalapril)
• SGLT2 Inhibitors

Other chemicals causing glycosuria

• Ethanol
• Arsenic

Historical Perspective

• Glycosuria was first discovered by von Mering and Minkowski in 1889.

Classification

Glycosuria can be classified into the following groups, based on the etiology of glucose excretion in urine:

• Alimentary glycosuria
• Renal Glycosuria
• Diabetic glycosuria
• Iatrogenic glycosuria
• Glycosuria as part of a syndrome or disease (e.g. Fanconi syndrome or Wilson disease)

Pathophysiology

• The pathogenesis of glycosuria is characterized by either increased plasma glucose or decreased proximal tubule threshold for glucose excretion.
• Genetic mutations can contribute to pathogenesis in glycosuria, especially renal glycosuria, these mutations include: SLC5A2 and HNF1A.
• When plasma glucose levels exceed 180 mg/mL, the excess glucose will not be reabsorbed and is excreted in urine. However, proximal tubule threshold for glucose reabsorbtion varies among individuals and in difference stages of one's life span.

Clinical Features

Simultaneous excretion of glucose and water into urine leads to:

• Polyuria
• polydipsia

Differentiating Glycosuria from other Diseases

• When excessive amounts of glucose is found in urine, the following diagnoses should be in mind:

• Diabetes Mellitus
• Renal glycosuria
• Alimentary glycosuria
• Fanconi syndrome (presence of glucose as well as other solutes in urine)
• Wilson disease

Different causes of glycosuria can be differentiated based on:

Disease	History and symptoms					Laboratory findings								Additional findings
	Polyuria	Polydipsia	Polyphagia	Weight loss	Weight gain	Serum glucose	Urinary Glucose	Urine PH	Serum Sodium	Urinary Glucose	24 hrs cortisol level	C-peptide level	Serum glucagon
Type 1 Diabetes mellitus	+	+	+	+	-	↑	↑	Normal	Normal	N/↑	Normal	↓	Normal	Auto antibodies present (Anti GAD-65 and anti insulin anti bodies)
Type 2 Diabetes mellitus	+	+	+	+	-	↑	↑	Normal	Normal	↑	Normal	Normal	↑	Acanthosis nigricans
MODY	+	+	+	-	+	↑	↑	Normal	Normal	↑	Normal	Normal	N	-
Transient hyperglycemia	-	-	-	-	-	↑	↑	Normal	Normal	↑	Normal	Normal	N/↑	In hospitalized patients especially in ICU and CCU
Steroid therapy	+	-	-	-	+	↑	↑	Normal	Normal	↑	↑	N/↑	N/↑	Acanthosis nigricans,
RTA 1	-	-	-	+	-	Normal	Normal	↑	Normal	↑	Normal	Normal	Normal	Hypokalemia, nephrolithiasis
Glucagonoma	-	-	-	-	-	↑	Normal	Normal	Normal	-	Normal	Normal	↑	Necrolytic migratory erythema
Cushing syndrome	-	-	-	-	+	↑	-	Normal	↓	N/↑	↑	Normal	Normal	Moon face, obesity, buffalo hump, easy bruisibility

Epidemiology and Demographics

• The prevalence of glycosuria in general population is approximately 3000-5000 per 100,000 individuals worldwide.
• Prevalence of glycosuria is increasing due to:
  • Increased incidence of DM.
  • Increased use of medications such as SGLT2 inhibitors (in order to decreased blood glucose levels to reach a better glycemic control).

Age

• Patients of all age groups may develop glycosuria.

• As the patients' age increases, glycosuria increases due to decreased kidney threshold for glucose reabsorption.

Gender

• Glycosuria affects both men and women.

• Glycosuria is more common among males.

Race

• The incidence of glycosuria varies among different nationalities, however; there is no propensity to a specific race.

Risk Factors

• SLC5A2 mutation causes familial renal glycosuria
• Diabetes mellitus
• Exposure to medications or chemicals causing glycosuria.

Natural History, Complications and Prognosis

• Early clinical features include polyuria, polydipsia, hypoglycemia and weight loss due to excretion of glucose as a source of energy.
• Common complications of glycosuria include polyuria, polydipsia, and mild growth retardation.
• Glycosuria increases as the patients age due to decreased renal threshold for glucose excretion.
• Prognosis is generally excellent. There are no reports of mortality directly attributed to glycosuria.

Diagnosis

Diagnostic Criteria

Diagnosis of glycosuria depends on the type of glycosuria:

For renal glycosuria:

• Glycosuria in the face of normal blood glucose levels, normal glycosylated hemoglobin and normal free fatty acids
• Glycosuria independent of carbohydrate consumption
• No diabetic symptoms

For Alimentary glycosuria:

• Normal fasting blood sugar
• Normal 2-hours post-prandial blood glucose
• Maximum blood glucose levels exceeding 180 mg/mL

Diabetic glycosuria:

• Glycosuria in the setting of known diabeties mellitus

Symptoms

• Symptoms of glycosuriamay include the following:

• Polyuria
• Polydipsia
• Weight loss

Physical Examination

Patients with glycosuria generally appear normal in physical examination.

In specific conditions, such as pregnancy or starvation, patients may:

• Appear dehydrated
• Have ketosis

Laboratory Findings

• Presence of glucose in urine sample.

• Blood sugar may or may not be elevated epending on the pathophysiology and the cause of glycosuria.
• Beside glucose, other solutes can be found in urine, depending on the pathophysiology and the cause of glycosuria.

Other Diagnostic Studies

• Microscopic urine analysis.
• Urine sample test for presence of glucose using glucose oxidase reagent strips.

Treatment

Medical Therapy

• Tight glycemic control in cases of diabetes mellitus.

Prevention

• There are no primary preventive measures available for glycosuria except for that of glycemic control.

• Diet high in protein can lower the proportion of glucose in diet and reduce glucose excretion in urine.

See also

• Renal glycosuria