What is glycosuria

Glycosuria also called glucosuria, is the presence of glucose in the urine. Glycosuria usually occurs because of either an elevated plasma glucose (high blood glucose), an impaired renal glucose absorptive capacity (impaired kidney function) or both ¹. Glycosuria occurs in all normal individuals in amounts up to 25 mg/dL ². Abnormal (pathologic) glycosuria is defined as urine glucose of more than 25 mg/dL in random fresh urine ³.

The renal tubule will reabsorb almost all the glucose present in the normal glomerular filtrate. Glycosuria occurs when that balance is lost: when the amount of glucose in the glomerular filtrate exceeds the capacity of the renal tubule to reabsorb it. The balance can be lost either when the plasma glucose is elevated (e.g., in diabetes mellitus) or when the absorptive capacity of the tubule is impaired (e.g., in Fanconi syndrome, pregnancy, hereditary renal glucosuria, and acute tubular injury).

The plasma glucose concentration above which significant glycosuria 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 ⁴. Although glycosuria greater than 25 mg/dl is considered abnormal, many commercial semiquantitative urine tests for glycosuria that are available to patients fail to detect glycosuria until it reaches a level of 50–250 mg/dl ³.

The association between blood and urine glucose was first observed in the eighteenth century by Matthew Dobson, an English physician. For many years urine glucose testing was the major method used to monitor glycemic control in diabetes mellitus. Early methods of urine glucose detection included evaporation of urine to reveal sugar crystals and urine sugar fermentation by yeast. Methods based on copper reduction were developed by von Fehling in the nineteenth century and by Benedict at the turn of the twentieth century. In 1941, the Ames Company marketed Clinitest, a copper reduction method, and followed it with Clinistix, a glucose oxidase-based determination. Since then, several companies have marketed glucose oxidase-based tests.

Measurement of glycosuria is an indirect index of the blood glucose concentration, however, and tests for urine glucose must be interpreted with caution. Technical issues such as test sensitivity and variability of renal glucose threshold must be taken into account. Furthermore, the social stigma sometimes associated with handling a body waste product can be a consideration in terms of patient acceptance of the monitoring technique.

These limitations, together with the development of home blood glucose monitoring, have led to a decline in the use of urine glucose for monitoring in diabetes mellitus. Self-monitoring of capillary blood glucose is now the preferred method ¹. Nevertheless, assessment of glycosuria in selected patients continue to find urine glucose testing convenient, noninvasive, inexpensive, and useful ⁵.

Renal threshold for glucose

There is a negative correlation between the renal glucose threshold and the creatinine clearance in Type I diabetics ⁶. Age, heart failure, renal disease (e.g., diabetic glomerulosclerosis), and chronic hyperglycemia are known to raise the renal threshold for glucose. Pregnancy, hyperthyroidism, fever, and exercise decrease it ⁷. In renal disease such as diabetic glomerulosclerosis, a reduced glomerular filtration rate decreases delivery of glucose to the tubule for a given plasma glucose level ⁸. As a consequence, normal tubular reabsorption of filtered glucose allows the plasma glucose value to rise markedly above the usual threshold before glycosuria occurs ³. Thus, as with age in normal individuals, glomerulosclerosis in long-standing diabetes is associated with a raised renal threshold for glucose, and the presence or amount of glucose in the urine becomes of lesser monitoring value.

Renal thresholds in individual patients may ⁹ or may not change ⁴ in the short term, but patients with proteinuria have consistently lower renal thresholds (mean 67 mg/dl) ⁴, and deteriorating renal function in normal individuals tends to result in an increased threshold for glucose ⁸.

Tubular Reabsorption of Glucose

If the renal tubule capacity for glucose reabsorption is impaired for constitutional or acquired reasons, glycosuria can occur with normal plasma glucose concentrations ³. The Fanconi syndrome, pregnancy, and acute tubular necrosis are examples of this phenomenon. Normally, as the level of plasma glucose and the filtered load rises, renal tubular reabsorption of glucose rises linearly until a maximum tubular resorptive capacity is reached ⁶. This maximal tubular reabsorptive capacity ranges from 0.9 to 2.0 mmol/min and is constant for each individual ⁶. The same is true in diabetes. Patients with recent onset of Type I diabetes exhibited a 20% increase in both glomerular filtration rate and maximal tubular reabsorptive capacity ¹⁰. In addition, a reduced glomerular filtration rate in long-term diabetes was accompanied by a lower maximal tubular reabsorptive rate ¹⁰. Glomerulo-tubular balance for glucose was maintained in both situations ¹⁰.

The proximal convoluted renal tubule reabsorbs most of the filtered glucose load both normally and during hyperglycemia. The intermediate segment, between the late proximal and distal tubule, also can reabsorb glucose ¹¹. It acts as a buffer to aid the response to an increased glucose load; overt glycosuria does not occur until its resorptive capacity is exceeded.

Finally, it has not been possible to demonstrate a correlation between urine flow, maximal tubular reabsorptive capacity, and renal threshold for glucose ⁶. In addition, the temporal lag between a significant rise in plasma glucose and increased glycosuria varies between 20 and 120 min ⁷. These points deserve special attention when attempting to infer plasma glucose values from results of testing for glycosuria in unstable patients.

Renal glycosuria

Renal glycosuria also known as renal glucosuria, is a rare condition in which glucose is excreted in the urine despite normal or low blood glucose levels ¹². With normal kidney function, glucose is excreted in the urine only when there are abnormally elevated levels of glucose in the blood. However, in people with renal glycosuria, glucose is abnormally eliminated in the urine due to improper functioning of the renal tubules, which are the primary components of the filtering units of the kidneys ¹³. The revised criteria for diagnosis of renal glycosuria includes: a normal oral glucose tolerance test (OGTT) in regard to plasma glucose concentration, normal plasma levels of insulin, free fatty acids, glycosylated hemoglobin (HbA1c), and relatively stable urinary glucose levels (10 to 100 g/day; except during pregnancy, when it may increase) with glucose present in all urine samples ¹⁴. The urine should contain glucose as the only source of carbohydrate, and individuals should have normal carbohydrate storage and use.

In most people with renal glycosuria, there are no apparent symptoms or serious effects. Rare cases of polyuria (increased urine output), enuresis (involuntary urination), and mild growth and pubertal maturational delay have been reported.

Depending on the screening criteria used, the incidence of renal glycosuria in the general population was approximately 0.29% ¹⁵.

The inherited form of renal glycosuria is called familial renal glycosuria ¹⁴. Familial renal glycosuria is a rare disorder due mainly to mutations in the sodium-glucose cotransporter 2 gene (SGLT2) that are responsible for the majority of cases ¹⁶.

To date over seventy mutations have been identified including missense mutations, nonsense mutations, small deletions and splicing mutations. Most however are missense mutations. It is usually inherited in a co-dominant fashion with incomplete penetrance. Although the pattern of inheritance that best fits familial renal glycosuria is one of co-dominance, increased glucose excretion was not observed in all individuals with similar or identical mutations. Heterozygosity for mutations suggest a role of nongenetic factors or other genes involved in renal glucose transport ¹⁷.

The SGLT2 gene is localized to p11.2 on chromosome 16. It consists of 14 separate exons spanning approximately 7.7kb of genomic DNA, and encodes the 672 amino acid protein SGLT2. Glycosuria in these patients can range from less than 1 to >150g/1.73m² per day (normal value: range 0.03 to 0.3g/day).

In general, renal glycosuria is a benign condition and does not require any specific therapy ¹⁴. Glycosuria may also be associated with tubular disorders such as Fanconi-de Toni-Debre syndrome, cystinosis, Wilson disease, hereditary tyrosinemia, or oculocerebrorenal osteodystrophy (Lowe syndrome) ¹⁴. Renal glycosuria has also been reported in patients with acute pyelonephritis in the presence of a normal blood glucose level. Glucose loss in the urine may vary from a few grams to more than 100g (556 mmol) per day ¹⁴.

The kidneys play an important role in glucose homeostasis. It helps to maintain glucose homeostasis by at least two mechanisms ¹⁸.

• Under normal circumstances, the kidney filters and reabsorbs 100% of glucose, approximately 180 g (1 mole) of glucose, each day. The glucose transporters expressed in the renal proximal tubule ensure that less than 0.5 g/day (range 0.03-0.3 g/d) is excreted in the urine of healthy adults. More water than glucose is reabsorbed resulting in an increase in the glucose concentration in the urine along the tubule. Consequently the affinity of the transporters for glucose along the tubule increases to allow for complete reabsorption of glucose from the urine.
• The kidney produces glucose by gluconeogenesis. The key enzymes of gluconeogenesis are phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These are expressed in the renal proximal tubule only and not the renal medulla. The kidneys produce between 2.0-2.5umol of glucose/kg/min thereby contributing about 20-25% of circulating glucose ¹⁹.

Gluconeogenesis in the kidneys exceeds renal glucose consumption. It is important in the prevention of hypoglycemia, and its inappropriate increase in diabetic patients contributes to the development of hyperglycemia.

As plasma glucose concentration increases, there is concordant increase in the filtered load of glucose. As the rate of glucose entering the nephron rises above 260-350mg/1.73m²/min (14.5-19.5mmol/1.73m2/min), the excess glucose exceeds the reabsorptive capacity of proximal tubule and is excreted in the urine (i.e. glycosuria). In health individuals this equates to a blood glucose concentration of approximately 200mg/dL (11mmol/L), which is believed to be threshold for the appearance of glycosuria ²⁰.

Renal glucosuria is a benign condition, affected individuals do not have any complaints, and only very rarely a propensity to hypovolemia and hypoglycemia has been described. However, morbidity is significant in Fanconi syndrome, Lowe syndrome, and cystinosis. In most affected individuals, no treatment is required. However, some individuals with renal glycosuria may develop diabetes mellitus. Therefore, appropriate testing should be conducted to rule out diabetes and to regularly monitor those with confirmed renal glycosuria ¹³.

The prognosis is excellent with no recorded mortality and the only morbidity being polyuria and enuresis and later a mild growth and pubertal maturation delay observed during a follow-up period of 30 years ²¹.

Renal glycosuria causes

Renal glycosuria is considered an inherited defect of membrane transport (i.e., an abnormal renal transport syndrome). Membrane transport disorders are characterized by abnormalities in the movement (i.e., transport) of one or more compounds across cell membranes. They are thought to result from genetic changes (mutations) causing alterations in specific membrane proteins ¹³.

As noted above, due to impaired renal tubular functioning, renal glycosuria is characterized by a reduction in the blood glucose concentration at which glucose begins to be excreted in urine (reduced renal threshold for glucose) and, in some instances, a reduction in the maximum rate at which glucose may be reabsorbed into the bloodstream (reduced transport maximum [tubular maximum for glucose or mg/min/1.73 m² or “Tm glucose”]).

Researchers have classified renal glycosuria into two major subtypes based upon the presence of such defects:

• type A (low threshold, reduced tubular maximum for glucose) and
• type B (low threshold, normal tubular maximum for glucose).

In addition, investigators have described a form of renal glycosuria termed type 0, in which there is complete absence of renal tubular glucose reabsorption.

Tubular maximum for glucose (Tm glucose, mg/min/1.73 m²) corrected for the glomerular filtration rate (GFR) varies as a function of age. Tm glucose/GFR (mg/mL) presents as follows:

• Infants – 0.9-2.94 mg/mL
• Children – 1.82-2.94 mg/mL
• Adults – 2.31-2.70 mg/mL

The Tm glucose (tubular maximum for glucose) for children expressed in mg/min/1.73 m² is as follows:

• Premature infants – 25-190 mg/min/1.73 m²
• Term infants – 36-288 mg/min/1.73 m²
• Children – 254-401 mg/min/1.73 m²

To date, only loss of function mutations have been identified in renal glucose transporters. Patients with familial renal glycosuria can be characterized according to the amount of glucose excreted in a 24-h urine collection, normalized for body surface: mild renal glycosuria for < 10 g/1.73 m² per day and severe renal glycosuria for ≥10 g/1.73 m² per day ¹⁵.

Familial renal glycosuria is an entity considered to be a benign condition, more a phenotype than a disease. Some of the following have been reported with this condition:

• Polyuria and enuresis and later a mild growth and pubertal maturation
• Episodic dehydration and ketosis during pregnancy and starvation ²²
• Presence of several autoantibodies without clinical evidence of autoimmune disease ²³
• An increased incidence of urinary tract infections ²⁴
• Activation of the renin-angiotensin-aldosterone system, secondary to natriuresis and possible extracellular volume depletion
• Hypercalciuria ²⁵
• Selective aminoaciduria ²⁶

Isolated renal glycosuria with otherwise normal kidney function is thought to be transmitted as an “incompletely” recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.

In autosomal recessive disorders, the condition may not appear unless a person inherits a defective (mutated) gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Early studies suggested that renal glycosuria was transmitted as an autosomal dominant trait, meaning that inheriting just one copy of the disease gene from either the mother or father could result in full expression of the condition. However, more recent research suggests that the trait is incompletely recessive. In other words, individuals who inherit one mutated copy of a gene for renal glycosuria (heterozygous carriers) may have modest glycosuria due to mild reductions in the renal threshold for glucose or the maximum rate at which glucose is reabsorbed. Yet heavy, consistent renal glycosuria is associated with inheritance of two copies of the same gene mutation (homozygosity) for the condition; in addition, it is possible that individuals with renal glycosuria may inherit one copy of two different gene mutations (compound heterozygotes). Investigators have observed that renal glycosuria types A and B have occurred in members of the same family. In such cases, both parents may be normal or may have abnormal renal tubular transport of glucose. Based on such evidence, experts suggest that several different gene mutations affecting one or more renal glucose transport systems may be involved in causing renal glycosuria.

In some affected families (kindreds), renal glycosuria appears to result from mutations of a gene (currently designated “GLYS1”) that has been mapped to the short arm (p) of chromosome 6 (6p21.3). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. Therefore, 6p21.3 refers to band 21.3 on the short arm of chromosome 6.

According to researchers, in such families, the gene for renal glycosuria appears to be closely linked with another, previously identified gene (known as the “HLA” gene) located at this chromosomal region.

Some investigators have also suggested that renal glycosuria may be caused by changes in a gene known as “SLC5A2” (also called the renal sodium-glucose cotransporter gene). However, this gene has been mapped to chromosome 16 (16p11.2).

Further research is needed to learn more about the underlying genetic mechanisms responsible for the transmission and expression of this condition.

Renal glycosuria signs and symptoms

In individuals with renal glycosuria, glucose is excreted in the urine in the presence of normal or low concentrations of blood glucose. With normal renal function, as blood flows through the kidneys, glucose and other substances are filtered from the fluid portion of the blood. The filtrate of the blood then moves through a network of canals known as renal tubules, where most of the filtered substances, including glucose, sodium, and water, are reabsorbed and returned to the bloodstream, while certain unwanted substances are eliminated in the urine. In those with proper renal functioning, glucose is excreted into the urine only when there are abnormally elevated levels of the sugar in the blood. However, in individuals with renal glycosuria, there is a lowered renal threshold to glucose and, in some cases, a reduction in the rate at which the renal tubules are able to reabsorb glucose.

In most affected individuals, renal glycosuria is a benign condition, resulting in no apparent symptoms (asymptomatic). However, in some cases, glycosuria may be pronounced enough to result in excessive urination (polyuria), excessive thirst (polydipsia), and other associated symptoms. Less commonly, under certain conditions, such as pregnancy or starvation, renal glycosuria may be associated with excessively low levels of bodily fluids (dehydration) or a condition in which there is an abnormal accumulation of certain chemical substances (ketone bodies) in bodily tissues and fluids due to excessive breakdown of fats (ketosis).

Laboratory Studies

Consultation with a kidney specialist (nephrologist) may be appropriate to exclude other forms of proximal tubulopathy.

The following studies are indicated in renal glycosuria:

• Urinalysis with microscopic analysis
• Fasting blood glucose concentration
• Serum electrolyte, bicarbonate, phosphorus, and uric acid levels
• Glycosylated hemoglobin levels
• A 24-hour urine collection for amino acids when other tubular abnormalities are present
• Fractional excretion of phosphorus (< 15%), uric acid (< 15%, or uric acid per dL glomerular filtration rate [GFR] < 0.55), sodium (normal limit [NL] approximately 1-3%), potassium (< 25%), bicarbonate (NL < 15%)

Renal glycosuria treatment

Benign renal glycosuria is a self-limiting condition and requires no special medical care. If other associated findings suggest tubular disorders, then appropriate interventions are required. Selective inhibitors of SGLT2 such as dapagliflozin and canagliflozin are a new family of antidiabetic agents recently approved for lowering of blood sugar levels in patients with type 2 diabetes mellitus ²⁷. Dapagliflozin which is 1200-fold more selective for SGLT2 than SGLT1, either as monotherapy or in combination with other antidiabetic agents. SGLT2 inhibitors reduce blood glucose levels in patients with type 2 diabetes mellitus by inhibiting the glucose reabsorption pathway which results in glycosuria. Studies have also shown that SGLT2 inhibitors reduce body weight and systolic blood pressure, mainly due to its diuretic effect i.e. osmotic diuresis following loss of glucose but also mild urinary sodium loss ²⁷.

Glycosuria in pregnancy

Selective screening using glycosuria and random blood glucose is unnecessary in pregnant women and it is ineffective due to its low sensitivity ²⁸. False-positive tests outnumber true positives 11:1. A 50-g oral glucose challenge is a better test. Tests for glycosuria after this blood test are not useful.

More than 22 million prenatal visits occur in the US each year ²⁹. Each pregnant woman averages 7 visits. Most include urine testing for glucose and protein to screen for gestational diabetes and preeclampsia.

Glycosuria is found at some point in about 50% of pregnant women; it is believed to be due to an increased glomerular filtration rate ³⁰. The renal threshold for glucose is highly variable and may lead to a positive test result for glycosuria despite normal blood sugar. High intake of ascorbic acid or high urinary ketone levels may result in false-positive results. Four published studies assessed the value of glycosuria as a screen for gestational diabetes ³¹, ³², ³³, ³⁴ All used urine dipsticks. Three of the 4 most likely overestimate the sensitivity of glycosuria for predicting gestational diabetes.

Routine dipstick screening for protein and glucose at each prenatal visit should be abandoned ²⁸. Women who are known or perceived to be at high risk for gestational diabetes or preeclampsia should continue to be monitored closely at the discretion of their clinician.

The American Diabetes Association recommends blood glucose testing as soon as possible in high-risk women and routinely at 24 to 28 weeks gestation in those at lower risk ³⁵. The American College of Obstetricians and Gynecologists (ACOG) does not address urine testing for glucose ³⁶. The Institute for Clinical Systems Improvement considers urine dipsticks for glycosuria unreliable ³⁷.

Abandoning all but the initial urinalysis may miss a few women with true but unrecognized diabetes mellitus. None of the studies presented above address this problem although screening for diabetes mellitus using urine test strips is not an ideal screening test, identifying only between 30% and 59% of a predominately  middle-aged nonpregnant group ³⁸.

There is no evidence that testing for gestational diabetes before 28 weeks, as might be prompted by urine testing, changes pregnancy outcome. Screening for gestational diabetes by glycosuria is not effective with low sensitivities and low positive predictive values. False-positive tests outnumber true positives 11:1,  leading to unnecessary further testing. Based on the information available, it appears safe to abandon routine urine testing for glucose at every prenatal visit. This recommendation stands regardless of the debate over the value of screening for gestational diabetes by 50-g glucose challenge followed by an oral glucose tolerance test (OGTT) if  indicated ³⁹.

Fasting blood glucose ≥5.1 mmol/L could be applicable for screening at the population level. Where 2-hour oral glucose tolerance test (OGTT) is not available, fasting blood glucose ≥5.6 mmol/L, complemented by the presence of risk factors, could be useful in making therapeutic decision ⁴⁰.

Fasting blood glucose threshold ≥5.1 mmol/L had the highest clinically relevant sensitivity (68%) and specificity (81%), but fasting blood glucose threshold ≥5.6 mmol/L had higher positive predictive value ⁴⁰.

These findings reaffirm the rising prevalence of gestational diabetes mellitus and highlight the need to integrate fasting blood glucose monitoring into all gestational diabetes mellitus screening/diagnostic procedures.

In line with evidence from the hyperglycemia and adverse pregnancy outcome study ⁴¹, and the recommendations from the International Association of Diabetes and Pregnancy Study Group ⁴², the World Health Organization (WHO) updated its clinical guidelines for detecting hyperglycemia in pregnancy in 2013 ⁴³. Similarly, the American Diabetes Association (ADA) updated its guidelines in 2015 in accordance with the recommendations of the International Association of Diabetes and Pregnancy Study Group ⁴⁴. The WHO recommends one-step diagnosing of gestational diabetes mellitus using fasting plasma glucose ≥5.1 mmol/L or 75 g oral glucose intake, followed by 1-hour postprandial glucose ≥10.0 mmol/L. However, 2-hour oral glucose tolerance test (OGTT) ≥8.5 mmol/L performed at any time during pregnancy but preferably between 24 and 28 weeks is highly recommended.

On the other hand, the National Institute for Health and Care Excellence (NICE) considers 2-hour 75 g oral glucose tolerance test (OGTT) performed between 24 and 28 weeks as the ‘gold standard’. Compared with the current WHO/IADPSG/ADA guidelines, NICE’s diagnostic threshold for 2-hour OGTT is 0.7 mmol/L lower (≥7.8 mmol/L), whereas the fasting plasma glucose threshold is 0.5 mmol/L higher (≥5.6 mmol/L) ⁴⁵. Meanwhile, the 1999 WHO diagnostic criteria for FPG was ≥7.0 mmol/L, whereas the 2-hour OGTT was ≥7.8 mmol/L, same as the current NICE guideline. Even though this paper focuses on gestational diabetes mellitus, it is worth noting that the WHO/International Association of Diabetes and Pregnancy Study Group recommend random plasma glucose or 2-hour OGTT ≥11.1 mmol/L at any time during pregnancy as suggestive of clinical (pre-existing) diabetes ⁴³.

1. Cowart SL, Stachura ME. Glucosuria. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 139. Available from: https://www.ncbi.nlm.nih.gov/books/NBK245[↩][↩]
2. Gupta RC, Goyal A, Ghosh R, Punjabi M, Singh PP. Normal range for glucose in urine: age-related changes. Clin Chem. 1982;28:2335.[↩]
3. Davidson JK, Delcher HK, Hall WD 1978 Glucosuria and ketonuria, pp 1035–1039 in Clinical Methods, 2nd Edition, Hurst JW, ed.[↩][↩][↩][↩]
4. Walford S, Page MMcB, Allison SP. The influence of renal threshold on the interpretation of urine tests for glucose in diabetic patients. Diabetes Care. 1980;3:672–674.[↩][↩][↩]
5. Alberti KGMM, Worth R, Home PI 1982 Home blood glucose monitoring: Does it improve diabetic control per se? In Peterson CM, ed., Diabetes Management in the 80’s, New York, Praeger Publishers.[↩]
6. Johansen K, Svendsen PA, Lorup B. Variations in renal threshold for glucose in type I (insulin-dependent) diabetes mellitus. Diabetologia. 1984;26:180–182.[↩][↩][↩][↩]
7. Valenta CL 1983 Urine testing and home blood-glucose monitoring, pp 645–659 in Nurs Clin North Am Vol 18.[↩][↩]
8. Feingold KF. The danger of a changing renal threshold for glucose. Diabetes Care. 1980;3:570–571.[↩][↩]
9. Ohlsen P, Danowski TS, Rosenblum DH, Mreiden T, Fisher ER, Sunder JH. Discrepancies between glycosuria and home estimates of blood glucose in insulin-treated diabetes mellitus. Diabetes Care. 1980;3:178–84.[↩]
10. Mogensen CE. Maximum tubular reabsorption capacity for glucose and renal hemodynamics during rapid hypertonic glucose infusion in normal and diabetic subjects. Scand J Clin Lab Invest. 1971;28:101–109[↩][↩][↩]
11. Wen S-F, Boynar JW Jr, Stoll RW. Mechanism of glycosuria during volume expansion superimposed on subthreshold glucose loading. J Lab Clin Med. 1983;101:708–716.[↩]
12. Renal glycosuria. https://rarediseases.info.nih.gov/diseases/7548/renal-glycosuria[↩]
13. Renal Glycosuria. https://rarediseases.org/rare-diseases/renal-glycosuria/[↩][↩][↩]
14. Renal Glucosuria. https://emedicine.medscape.com/article/983678-overview[↩][↩][↩][↩][↩]
15. Santer R, Calado J. Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin J Am Soc Nephrol. 2010 Jan. 5 (1):133-41.[↩][↩]
16. Calado J, Sznajer Y, Metzger D, Rita A, Hogan MC, Kattamis A, et al. Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion. Nephrol Dial Transplant. 2008 Dec. 23(12):3874-9.[↩]
17. De Marchi S, Cecchin E, Basile A, Proto G, Donadon W, Jengo A, et al. Close genetic linkage between HLA and renal glycosuria. Am J Nephrol. 1984. 4 (5):280-6.[↩]
18. Prié D. Familial renal glycosuria and modifications of glucose renal excretion. Diabetes Metab. 2014 Dec. 40(6 Suppl 1):S12-6.[↩]
19. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010 Feb. 27(2):136-42.[↩]
20. Avner E, Harmon W, Niaudet P. Pediatric nephrology, 5th edn. 5th Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.[↩]
21. Bingham C, Ellard S, Nicholls AJ, Pennock CA, Allen J, James AJ. The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Diabetes. 2001 Sep. 50(9):2047-52.[↩]
22. Scholl-Bürgi S, Santer R, Ehrich JH. Long-term outcome of renal glucosuria type 0: the original patient and his natural history. Nephrol Dial Transplant. 2004 Sep. 19 (9):2394-6.[↩]
23. De Paoli P, Battistin S, Jus A, Reitano M, Villalta D, De Marchi S, et al. Immunological characterization of renal glycosuria patients. Clin Exp Immunol. 1984 May. 56 (2):289-94.[↩]
24. De Marchi S, Cecchin E, Basile A, Proto G, Donadon W, Schinella D, et al. Is renal glycosuria a benign condition?. Proc Eur Dial Transplant Assoc. 1983. 20:681-5.[↩]
25. Schneider D, Gauthier B, Trachtman H. Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. J Pediatr. 1992 Nov. 121 (5 Pt 1):715-9.[↩]
26. Gotzsche O. Renal glucosuria and aminoaciduria. Acta Med Scand. 1977. 202 (1-2):65-7.[↩]
27. Angelopoulos TP, Doupis J. Sodium-Glucose linked transporter 2 (SGLT2) inhibitors–fighting diabetes from a new perspective. Adv Ther. 2014 Jun. 31(6):579-91.[↩][↩]
28. No need for routine glycosuria/proteinuria screen in pregnant women. J Fam Pract. 2005 November;54(11):978-983. https://www.mdedge.com/sites/default/files/Document/September-2017/5411JFP_OriginalResearch.pdf[↩][↩]
29. Graham Center One-Pager. Family physicians’ declining contribution to prenatal care in the United States. NAMCS data. Am Fam Physician 2002; 66:2192. Available at www.aafp.org/afp/20021215/graham.html[↩]
30. Lind T, Hytten FE. The excretion of glucose during normal pregnancy. J Ob Gyn Brit Commonwealth 1972; 79:961–965.[↩]
31. Watson WJ. Screening for glycosuria during pregnancy. Southern Med J 1990; 83:156–158.[↩]
32. Gribble RK, Meier PR, Berg, RL. The value of urine screening for glucose at each prenatal visit. Obstet Gyn 1995; 85:405–410.[↩]
33. Hooper DE. Detecting GD and preeclampsia. J Repro Med 1996; 41:885–888.[↩]
34. Buhling KJ, Elze L, Henrich W, et al. The usefulness of glycosuria and the influence of maternal blood pressure in screening for diabetes. Eur J Obstet Gynecol Reprod Biol 2004; 113:145–148.[↩]
35. American Diabetes Association. Gestational diabetes mellitus: position statement. Diabetes Care 2004; 27:S88–S90.[↩]
36. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Gestational diabetes. Washington, DC: ACOG; 2001: 30:360–372.[↩]
37. Institute for Clinical Systems Improvement. Health Care Guidelines: Routine prenatal care. August 2002:14[↩]
38. Bitzen P-O, Bengt S. Assessment of laboratory methods for detection of unsuspected diabetes in primary health care. Scand J Prim Health Care 1986; 4:85–95.[↩]
39. Helton MR, Arndt J, Kebede M, King M. Do low-risk prenatal patients really need a screening glucose challenge test? J Fam Pract 1997; 44:556–561.[↩]
40. Agbozo F, Abubakari A, Narh C, Jahn A. Accuracy of glycosuria, random blood glucose and risk factors as selective screening tools for gestational diabetes mellitus in comparison with universal diagnosing. BMJ Open Diabetes Research & Care. 2018;6(1):e000493. doi:10.1136/bmjdrc-2017-000493. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014183/[↩][↩]
41. Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002. doi:10.1056/NEJMoa0707943[↩]
42. Metzger BE, Gabbe SG, Persson B, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy: response to weinert. Diabetes Care 2010;33:e98–82. doi:10.2337/dc10-0719[↩]
43. WHO. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. Geneva, Switzerland: World Health Organization, 2013.[↩][↩]
44. American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care 2015;38(Suppl 1):S8–S16. doi:10.2337/dc15-S005[↩]
45. NICE. Diabetes in pregnancy. Management of diabetes and its complications from preconception to the postnatal period. NICE guideline 3 Methods, evidence and recommendations. London, UK: National Institute for Health and Care Excellence and National Collaborating Centre for Women’s and Children’s Health, 2015.[↩]