Hypoglycemia laboratory findings: Difference between revisions
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==Laboratory Findings== | ==Laboratory Findings== | ||
===Defining Hypoglycemia=== | ===Defining Hypoglycemia=== | ||
Hypoglycemia can't be diagnosed only by measuring blood glucose level because it is misleading maneuver with high false positive results.The measurement should be repeated using a collection tube that contains an inhibitor of [[glycolysis]] and processing should not be delayed. | Hypoglycemia can't be diagnosed only by measuring [[blood glucose]] level because it is misleading maneuver with high false positive results. The measurement should be repeated using a collection tube that contains an inhibitor of [[glycolysis]] and processing should not be delayed. | ||
So, Dependence on three characters to diagnose hypoglycemia is the accepted method. It is called [[Whipple's triad]] which includes: | So, Dependence on three characters to diagnose hypoglycemia is the accepted method. It is called [[Whipple's triad]] which includes: | ||
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* If Whipple's triad is demonstrated, [[sulfonylureas]], [[Meglitinide|meglitinides]], and antibodies to insulin should also be measured. | * If Whipple's triad is demonstrated, [[sulfonylureas]], [[Meglitinide|meglitinides]], and antibodies to insulin should also be measured. | ||
|} | |} | ||
[[24-hour|24-hour fasting]] | |||
* Increased release | === [[24-hour|24-hour fasting]] === | ||
* [[Gluconeogenesis]] is the most important factor of glucose production after a prolonged fast.<ref name="pmid8755648">{{cite journal| author=Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC| title=Contributions of gluconeogenesis to glucose production in the fasted state. | journal=J Clin Invest | year= 1996 | volume= 98 | issue= 2 | pages= 378-85 | pmid=8755648 | doi=10.1172/JCI118803 | pmc=507441 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8755648 }}</ref> | * Increased release of [[glucagon]], [[epinephrine]], and [[cortisol]] is the most important factors that keep [[Blood sugar|blood glucose]] concentrations from falling during fasting. | ||
* [[Gluconeogenesis]] is the most important factor of [[glucose]] production after a prolonged fast.<ref name="pmid8755648">{{cite journal| author=Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC| title=Contributions of gluconeogenesis to glucose production in the fasted state. | journal=J Clin Invest | year= 1996 | volume= 98 | issue= 2 | pages= 378-85 | pmid=8755648 | doi=10.1172/JCI118803 | pmc=507441 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8755648 }}</ref> | |||
* If there is a high level of insulin, [[gluconeogenesis]] will be inhibited causing hypoglycemia during fasting. | * If there is a high level of insulin, [[gluconeogenesis]] will be inhibited causing hypoglycemia during fasting. | ||
The fasting is ended when: <ref name="pmid10500929">{{cite journal| author=Service FJ| title=Diagnostic approach to adults with hypoglycemic disorders. | journal=Endocrinol Metab Clin North Am | year= 1999 | volume= 28 | issue= 3 | pages= 519-32, vi | pmid=10500929 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10500929 }}</ref> | |||
* Seventy-two hours have passed | * The fasting is ended when: <ref name="pmid10500929">{{cite journal| author=Service FJ| title=Diagnostic approach to adults with hypoglycemic disorders. | journal=Endocrinol Metab Clin North Am | year= 1999 | volume= 28 | issue= 3 | pages= 519-32, vi | pmid=10500929 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10500929 }}</ref> | ||
* Plasma glucose concentration is ≤45 mg/dL | **Seventy-two hours have passed | ||
* Patient has symptoms or signs of hypoglycemia | **Plasma glucose concentration is ≤45 mg/dL | ||
The precise level of glucose considered low enough to define hypoglycemia is dependent on:<ref name="Cornblath_1990">{{cite journal |author=Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK |title=Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting |journal=Pediatrics |volume=85 |issue=5 |pages=834-7 |year=1990 |pmid=2330247}}</ref><ref name="Cornblath_2000">{{cite journal |author=Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC |title=Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds |journal=Pediatrics |volume=105 |issue=5 |pages=1141-5 |year=2000 |pmid=10790476}}</ref> | **Patient has symptoms or signs of hypoglycemia | ||
* Measurement method | * The precise level of glucose considered low enough to define hypoglycemia is dependent on:<ref name="Cornblath_1990">{{cite journal |author=Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK |title=Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting |journal=Pediatrics |volume=85 |issue=5 |pages=834-7 |year=1990 |pmid=2330247}}</ref><ref name="Cornblath_2000">{{cite journal |author=Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC |title=Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds |journal=Pediatrics |volume=105 |issue=5 |pages=1141-5 |year=2000 |pmid=10790476}}</ref> | ||
* Age of the person | **Measurement method | ||
* Presence or absence of effects | **Age of the person | ||
* The purpose of the definition | **Presence or absence of effects | ||
**The purpose of the definition | |||
=== Identifying the cause === | === Identifying the cause === | ||
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| - | | - | ||
|- | |- | ||
|Exogenous insulin | |Exogenous [[insulin]] | ||
|high | |high | ||
|low | |low | ||
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=== Neonatal hypoglycemia: === | === Neonatal hypoglycemia: === | ||
Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases: | Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases: | ||
* Hypoglycemia that requires prolonged high rates of [[dextrose]] infusion | * Hypoglycemia that requires prolonged high rates of [[dextrose]] infusion | ||
* [[Persistent hypoglycemia]] | * [[Persistent hypoglycemia]] | ||
* Neurologic symptoms | * Neurologic symptoms | ||
* History or physical findings suggestive of metabolic disease | * History or physical findings suggestive of metabolic disease | ||
'''What to measure?''' | |||
==== '''What to measure?''' ==== | |||
* Measure plasma insulin, plasma [[C-peptide]] and [[beta-hydroxybutyrate]] | * Measure plasma insulin, plasma [[C-peptide]] and [[beta-hydroxybutyrate]] | ||
* [[PH|Blood pH,]] [[bicarbonate]], and [[lactate]] | * [[PH|Blood pH,]] [[bicarbonate]], and [[lactate]] | ||
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Surveys of healthy children and adults show that plasma glucose below 60 mg/dL or above 100 mg/dL are found in less than 5% of samples after an overnight fast.<ref name="Meites">{{cite book |author=Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] |title=Pediatric clinical chemistry: reference (normal) values |publisher=AACC Press |location=Washington, D.C |year=1989 |pages= |isbn=0-915274-47-7 |oclc= |doi=}}</ref> | Surveys of healthy children and adults show that plasma glucose below 60 mg/dL or above 100 mg/dL are found in less than 5% of samples after an overnight fast.<ref name="Meites">{{cite book |author=Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] |title=Pediatric clinical chemistry: reference (normal) values |publisher=AACC Press |location=Washington, D.C |year=1989 |pages= |isbn=0-915274-47-7 |oclc= |doi=}}</ref> | ||
In infants and young children, up to 10% have been found to be below 60 mg/dL after an overnight fast. As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people. In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease. | In infants and young children, up to 10% have been found to be below 60 mg/dL after an overnight fast. As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people. | ||
In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease. | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Revision as of 15:45, 25 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
Laboratory investigations of hypoglycemia depend on many tests: plasma glucose should be <55 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, 24-hour fasting and identifying the cause after that.
Laboratory Findings
Defining Hypoglycemia
Hypoglycemia can't be diagnosed only by measuring blood glucose level because it is misleading maneuver with high false positive results. The measurement should be repeated using a collection tube that contains an inhibitor of glycolysis and processing should not be delayed.
So, Dependence on three characters to diagnose hypoglycemia is the accepted method. It is called Whipple's triad which includes:
- Symptoms of hypoglycemia
- A low plasma glucose concentration correlated with symptoms
- Correction of glucose level relieves symptoms
The strategy is to seek Whipple's triad under conditions in which hypoglycemia would be expected:
- If the symptoms occur in the fasting state, that evaluation should be performed during fasting.
- If there is a compelling history of postprandial symptoms, it is reasonable to seek Whipple's triad with frequent, timed plasma glucose measurements and recording of any symptoms after a mixed meal.
- All of the following should be measured:
- Glucose: plasma glucose should be <55 mg/dL.
- Insulin
- C-peptide
- Proinsulin
- Sulfonylurea and meglitinide screen
- Beta-hydroxybutyrate
| Fasting evaluation[1] | Mixed-meal evaluation[2] |
|---|---|
|
|
24-hour fasting
- Increased release of glucagon, epinephrine, and cortisol is the most important factors that keep blood glucose concentrations from falling during fasting.
- Gluconeogenesis is the most important factor of glucose production after a prolonged fast.[4]
- If there is a high level of insulin, gluconeogenesis will be inhibited causing hypoglycemia during fasting.
- The fasting is ended when: [5]
- Seventy-two hours have passed
- Plasma glucose concentration is ≤45 mg/dL
- Patient has symptoms or signs of hypoglycemia
- The precise level of glucose considered low enough to define hypoglycemia is dependent on:[6][7]
- Measurement method
- Age of the person
- Presence or absence of effects
- The purpose of the definition
Identifying the cause
After confirmation of hypoglycemia. Physicians should have history, signs and laboratory results sufficient to help them to identify the cause of hypoglycemia:
| Plasma insulin | C-peptide | proinsulin | Sulfonylurea in plasma | insulin or insulin receptor antibodies | Postprandial symptoms | Fating symptoms | |
|---|---|---|---|---|---|---|---|
| Insulinoma | high | high | high | - | - | - | + |
| Oral hypoglycemics | high | high | high | + [8] | - | - | - |
| Autoimmune hypoglycemia | high | high | high | - | + [9] | - | - |
| NIPHS* | high | high | high | - | - | + | - |
| Exogenous insulin | high | low | low | - | - | - | - |
| Non-islet cell tumors | low | low | low | - | - | - | - |
*(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome
Neonatal hypoglycemia:
Most of the neonatal hypoglycemias are transient but suspected cases as following should be investigated for metabolic diseases:
- Hypoglycemia that requires prolonged high rates of dextrose infusion
- Persistent hypoglycemia
- Neurologic symptoms
- History or physical findings suggestive of metabolic disease
What to measure?
- Measure plasma insulin, plasma C-peptide and beta-hydroxybutyrate
- Blood pH, bicarbonate, and lactate
- Free fatty acids, acylcarnitine profile, plasma free and total carnitine levels
Surveys of healthy children and adults show that plasma glucose below 60 mg/dL or above 100 mg/dL are found in less than 5% of samples after an overnight fast.[10]
In infants and young children, up to 10% have been found to be below 60 mg/dL after an overnight fast. As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people.
In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease.
References
- ↑ Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER; et al. (2009). "Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 94 (3): 709–28. doi:10.1210/jc.2008-1410. PMID 19088155.
- ↑ Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L; et al. (2013). "Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society". Diabetes Care. 36 (5): 1384–95. doi:10.2337/dc12-2480. PMC 3631867. PMID 23589542.
- ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
- ↑ Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996). "Contributions of gluconeogenesis to glucose production in the fasted state". J Clin Invest. 98 (2): 378–85. doi:10.1172/JCI118803. PMC 507441. PMID 8755648.
- ↑ Service FJ (1999). "Diagnostic approach to adults with hypoglycemic disorders". Endocrinol Metab Clin North Am. 28 (3): 519–32, vi. PMID 10500929.
- ↑ Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK (1990). "Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting". Pediatrics. 85 (5): 834–7. PMID 2330247.
- ↑ Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC (2000). "Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds". Pediatrics. 105 (5): 1141–5. PMID 10790476.
- ↑ Perros P, Henderson AK, Carter DC, Toft AD (1997). "Lesson of the week. Are spontaneous hypoglycaemia, raised plasma insulin and C peptide concentrations, and abnormal pancreatic images enough to diagnose insulinoma?". BMJ. 314 (7079): 496–7. PMC 2125998. PMID 9056803.
- ↑ Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P (2009). "Autoimmune forms of hypoglycemia". Medicine (Baltimore). 88 (3): 141–53. doi:10.1097/MD.0b013e3181a5b42e. PMID 19440117.
- ↑ Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] (1989). Pediatric clinical chemistry: reference (normal) values. Washington, D.C: AACC Press. ISBN 0-915274-47-7.