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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.
I am active in HealthTap, which provides free medical guidance from your cell phone. There is also a fee site at www.afraidtoask.com.
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I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
pathology.org -- my cyberfriends, great for current news and browsing for the general public
EnjoyPath -- a great resource for everyone, from beginning medical students to pathologists with years of experience
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
still handling dozens of requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.
During the eighteen years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at William Carey
for making it still possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
LEARNING OBJECTIVES
Tell how and when to order a "glucose" on a patient. Give the normal range, and compare "blood"
and "plasma" glucose. Tell how the glucose level changes in a tube of blood as it stands.
Give the NDGG criteria for the diagnosis of diabetes mellitus in the nonpregnant adult. Recognize
causes of secondary glucose intolerance.
Distinguish fasting and postprandial hypoglycemia, and cite causes of each. Be well-informed when
talking with patients and friends about "hypoglycemia", and distinguish true hypoglycemia from
epinephrine-related symptoms.
Explain how to use a blood test to distinguish insulinoma from surreptitious injection of insulin
("factitious hypoglycemia").
Tell what information is provided by the glycosylated hemoglobin assay.
Briefly describe:
dumping syndrome
hemoglobin A1c
glucose tolerance tests
gray top tube
renal glycosuria
Whipple's triad
KCUMB Students
Public Database of Human Cancers -- World Health Organization
Stanford Surgical Pathology Criteria -- probably the best resource for the practicing surgical pathologist in an increasingly difficult specialty
Medscape Pathology -- mostly clinical medicine, the best "daily news" of the medical world
Pathology Resident Wiki
Human Pathlogy -- growing resource
Surgical Pathology Atlas -- lots of photos
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Pathopic -- Swiss site; great resource for the truly hard-core
Alabama's Interactive Pathology Lab
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
Karolinska Institutet -- pathology links
Johns Hopkins CPC's
Oklahoma Teaching Cases
Indiana U. Teaching Cases
SUNY Histopathology
West Virginia Case of the Month
Society for ultrastructural pathology -- electron microscope cases
PathologyPics -- where pathologists share favorite images. Thanks!
WebPath:
Internet Pathology
Laboratory -- great siteEd Lulo's Pathology Gallery
Also:
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Medmark Pathology -- massive listing of pathology sites
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
"Big Robbins" -- Endocrine
Lectures follow Textbook
INTRODUCTION
Blood glucose (* dextrose) is one of the most useful and most commonly ordered lab tests. There is a nice review in Ann. Int. Med. 110: 125, 1989.
Most often, it is performed as part of a profile that also includes sodium, potassium, chloride, total carbon dioxide content (i.e., approximately the bicarbonate content), urea nitrogen, and usually creatinine.
Glucose may also be included on the "big" profile that is run on weekday mornings.
In any case, you can always get a stat glucose.
Glucose is most often measured in venous serum.
Normal range for a fasting adult is around 70-105 mg/dL.
Whole blood glucose is around 5-10% lower than serum glucose.
This is because glucose passes freely in and out of the red blood cells, which have a lower content of water than plasma does (why?).
Capillary blood (as from a finger-stick, essentially arterial blood) usually has around 5 mg/dL more glucose than venous blood.
After carbohydrate loading (as during a glucose tolerance test), this difference may increase to 20-70 mg/dL because of increased glucose utilization by peripheral tissues.
Indications for blood glucose testing are frequently encountered. You need this test for:
*Think of diabetes whenever you see an older patient with myocardial infarction, angina, stroke, cataracts, glaucoma, peripheral neuropathy, obesity, proteinuria,foot ulcers, infections, "nervousness", etc., etc.
*There is also some current interest in hyperglycemic response as a prognostic indicator in myocardial infarction, etc.: Q.J. Med. 71: 461, 1989
Future neurologists: Hyperglycemia is coming to be recognized as an important cause of seizures (Epilepsia 32: 315, 1991; Neurology 39: 394, 1989).
"Insulin shock", etc., is a very important cause of convulsions, coma, brain damage (* mechanisms: Stroke 17: 699, 1986), and death. Hypoglycemia can also simulate a stroke, even producing hemiplegia (Ann.Neurol. 18: 510, 1985; Stroke 18: 944, 1987;Practitioner 232: 298, 1988). When you first encounter a patient with coma, draw blood for a glucose level before you administer intravenous glucose.
Remember that neonatal hypoglycemia is common and devastating (Clin. Perinatol. 13: 351, 1986; Arch. Dis. Child. 63: 1386, 1988), and * hyperglycemia is coming to be recognized as a major hazard in very small preemies (J. Ped. 109: 905, 1986).
Consider testing for hypoglycemia in patients who seem to be suffering from anxiety neurosis (especially if there is sweating, trembling, weakness, changes in consciousness), and in obesity. Remember that normal glucose in these patients is the usual finding in the popular "hypoglycemia syndrome", and that these people's sufferings are real. See below.
* METHODOLOGY
Because you will be ordering blood glucose levels so often, you may want to know how they are determined.
The Folin-Wu technique used whole blood. The protein was removed using tungstic acid. Cupric ions were added, which were reduced to cuprous ions by dissolved glucose. The cuprous ions gave a deep blue color with phosphomolybdic acid.
Of course, the test really measured everything that reduced cupric ions. This included glutathione, uric acid, creatinine, ascorbic acid, and other sugars.
All these substances were called "saccharoids".
The Somogyi-Nelson technique was an improvement that used barium hydroxide and zinc sulfate to precipitate the proteins. This combination also removed most of the non-sugar "saccharoids", though ascorbic acid and some uric acid remained. Cuprous ions were generated as in the Folin-Wu technique, and were visualized with arsenomolybdic acid.
Both Folin-Wu and Somogyi-Nelson are now obsolete.
The use of neocuprione to visualize cuprous ions was an improvement, used on many automated chemical profilers.
Ferricyanide techniques were based on the ability of glucose to reduce this yellow complex to colorless ferrocyanide in hot alkaline solution. Again, analytical specificity was a problem.
Ortho-toluidine procedures are still sometimes used. The chemical reacts with aldoses (glucose, galactose, mannose, also with ascorbic acid) to produce a green color at low pH.
A big problem is that the acid destroys the tubing on the machines.
Glucose oxidase techniques are the most popular today. The enzyme generates hydrogen peroxide as it oxidizes glucose. An indicator system visualizes hydrogen peroxide.
The technique is essentially free from interference by other compounds. * An "enzyme electrode" that could be implanted in the body: Anal. Chem. 57: 2351, 1985.
Hexokinase is a reference standard and is sometimes used for routine tests as well. The enzyme converts glucose to glucose-6-phosphatase, which is then measured by its ability to reduce NADP in the presence of added G6PD.
*Future lab scientists: Rarely, hyperviscosity produces a falsely low glucose measurement by certain methodologies; Clin. Chem. 32: 1239, 1986, from U. Mo. Columbia.)
Nowadays, portable hand-held analyzers (Accu-Check II, Glucoscan, others) are popular with diabetics and their physicians. The new ones (for example, "One Touch II") are nearly idiot-proof (J. Fam. Pract. 37: 153, 1993).
*Accu-Check II out-performs Glucoscan: Am. J. Clin. Path. 95: 247, 1991. The Glucoscan does rather poorly on a test in the baby nursery: Clin. Ped. 28: 412, 1989.
*More on instrumentation, for pathologists: Arch. Path. Lab. Med. 117: 711, 1993 (HemoCue B-Glucose, YSI 2300 Sta Glucose, Cobas MIRA, others). Be sure you quality-control both units and operators frequently (Am. J. Med. 93: 419, 1992; Arch. Path. Lab. Med. 113: 1370, 1989; if you do, you can trust your results to about 3-5% unless they're very far from normal-range: J. Clin. Path. 45: 77, 1992).
*Sooner or later, especially with the emphasis on tight control of diabetics to avoid long-term complications, the chronic intravascular blood glucose sensor will become a familiar piece of apparatus as part of the automatic pancreas. For now, read Diabetes 39: 1519, 1990.
INTERPRETATION
Blood glucose levels will decrease at a rate of about 7-10 mg/dL per hour at room temperature unless the red cells are removed or their enzyme systems inhibited.
Fluoride ion is commonly used for this purpose ("gray top tubes" contain oxalate and fluoride).
Leukocytes utilize glucose even more rapidly than red blood cells, and standard tubes do not contain enough fluoride to effectively prevent loss of glucose in many cases of chronic granulocytic leukemia or even polycythemia vera (Arch. Int. Med. 142: 2199, 1982; JAMA 249: 774, 1983). Trypanosomes do the same thing: Lancet 337: 1030, 1991.
Hyperglycemia, whether fasting or after a carbohydrate load (see below), indicates one of the following causes:
Extremely high glucose levels, especially over 1 gm/dL, suggest hyperosmolar nonketotic diabetic coma.
Note that, especially in renal failure, extremely high levels of glucose may not produce a diuresis and thus may not represent an acute emergency. This has only recently become clear. See Arch. Int. Med. 150: 1982, 1990.
cancer of the pancreas, acute or chronic pancreatitis, cystic fibrosis (some cases), hemochromatosis
Cushingism
catecholamine excess (exercise, strong emotions, pheochromocytoma), thyrotoxicosis
glucagonoma, somatostatinoma (Q. J. Med. 68: 559, 1988), acromegaly
pregnancy ("gestational diabetes", see Ob. Gyn. 66: 181, 1985), oral contraceptive use
*thiazide diuretic use (predisposed individuals, see Am. J. Med. 76: 802, 1984), diazoxide administration
*thiamine deficiency (Wernicke-Korsakoff's, etc.)
some cases of chronic hepatic and/or renal disease
genetic syndromes, insulin receptor autoantibodies
"old age" (??)
just plain stress (heart attack, pneumonia, stroke; see Stroke 22: 692, 1991). White-jacket hyperglycemia is real, even when you control for poor home-monitoring technique: Br. Med. J. 305: 1194, 1992. Caveat: "Stress" hyperglycemia in a child is less physiologic and often heralds type I diabetes (J. Ped. 117: 75, 1990).
(Rapid passage of glucose into the jejunum and bloodstream results in a high blood glucose; this in turn causes a large insulin response with a subsequent drop in glucose to abnormally low levels. See below.)
Worth mentioning: High blood glucose by itself makes cerebral infarcts worse and larger. Exactly why remains a mystery. See Neurology 41: 899, 1991; Stroke 19: 608, 1988.
If the blood glucose exceeds the "renal threshold" (i.e., the ability of the kidney to reabsorb all the glucose from the glomerular filtrate), glycosuria results.
Typically, a normal person's renal threshold is around 180 mg/dL, and so most normal people never have glucose in the urine.
*The renal threshold tends to be lower in pregnancy (around 140 mg/dL), and higher in old age and especially in longstanding diabetes (as high as 250 mg/dL).
Some otherwise healthy people have renal glycosuria because of a low renal threshold.
*These differences between people probably cause much more confusion clinically than do the analytical problems with the current urine test strips (i.e., false negatives due to ascorbic acid or ketoacidosis).
Fasting hypoglycemia ("fasting" begins ten hours after eating) generally indicates disease, particularly if serum glucose falls below 50 mg/dL. Workup: NEJM 326: 1020, 1992. Consider:
"Whipple's triad", the classic standard for these patients, is worth remembering: (1) CNS symptoms attributable to glucose deprivation; (2) measured low serum glucose; (3) relief of symptoms by glucose administration.
Adults suspecting of having fasting hypoglycemia are often admitted to the hospital and given only water for 72 hours, or until they become symptomatic and a blood glucose determination shows a low value. (Be careful doing this....)
*A reasonable, cheaper alternative is the old intravenous tolbutamide tolerance test, which is enjoying a resurgence of interest now that it is reasonably well standardized: Mayo Clin. Proc. 64: 1481, 1989.
Postprandial hypoglycemia occurs 1-5 hours after eating. Criteria vary, and investigating suspected cases is not so like to turn up"organic disease". Causes include:
This entity received tremendous attention in the lay press in the late 1970's, and has been blamed for most individual and social problems. (* See, for example, Acta Psych. Scand. 69: 445, 1984; criminologists see J. Am. Diet. Assoc. 85: 361, 1985; Arch. Gen. Psych. 46: 600, 1989 -- I blame stress hormones for the higher violent recidivism among those with lower glucose nadirs; lawyers read "Hypoglycemia and criminal responsibility" in Diabet. Med. 3: 470, 1986. You remember how the San Francisco "Twinkie" murderer escaped justice to the dismay of the same conservatives and liberals who had....)
When certain people are under stress, they tend to get shaky and sickish a few hours after a big meal. These people will self-diagnose hypoglycemia, but only about 25% (if that) have low blood glucose during "attacks".
The real problem with these people seems to be an unusually epinephrine response at the glucose nadir. Epinephrine, not "low glucose", makes them feel "nervous" and "shaky". See JAMA 251: 612, 1984.
Conversely, real hypoglycemia in the absence of high epinephrine is generally unnoticed by patients, especially diabetics (Lancet 2: 966, 1987).
Don't confuse these episodes with "panic attacks"(Am. J. Psych. 143: 654, 1986; Psychosomatics 27:833, 1986).
Until recently, these patients were given five-hour glucose tolerance tests. This is probably worthless (South. Med. J. 79: 285, 1986; NEJM 321: 1421, 1989; the latter considered true post-prandial hypoglycemia to be very rare).
By the way, it is now clear that many people have very low blood glucose levels postprandially without any subjective symptoms. Conversely, if you give home glucose monitors to patients suffering from "hypoglycemic symptoms relieved by eating" (and assume they know how to use them), over years you'll find glucose levels simply aren't lower during "symptoms" (Br. Med. J. 300: 16, 1990).
Appropriate management of these patients is still under discussion.
*Feel free to recommend high-protein, low-carbohydrate, low-caffeine, low-alcohol diets that popular articles recommend for patients self-diagnosing "hypoglycemia", as this does make most of them feel better.
*A "holistic medicine" type cites the hypoglycemia controversies in order to discredit the "illusion" that distinct diseases exist: Soc. Sci. Med. 22: 599, 1986. A rowdy pathologist replies: Soc. Sci. Med. 22: 599, 1986.
*For the evils of refined sugar in producing blood glucose aberrations, see South. Med. J. 75: 1072, 1982 (evil), Diabetes Care 4: 509, 1981 (not so evil), NEJM 309: 1, 1983 and JAMA 251: 2829, 1984 (glycemic response to various carbohydrates does not support the conventional wisdom that "simple sugars" are absorbed faster).
So what level of hypoglycemia "produces symptoms"? It varies widely from person to person.
For non-diabetics, the average is around 53 mg/dL; for poorly-controlled diabetics, the average is around 78 mg/dL (!; NEJM 318: 1487, 1988). There is tremendous variability in both groups.
Caveat: In kids, even mild chronic hypoglycemia impairs thinking: J. Ped. 117: 32, 1990.
Some diabetics have no symptoms at all even at very low glucose levels, and these people may have underlying catecholamine unresponsiveness (J. Clin. End. Metab. 66: 273, 1988) and/or autonomic neuropathy (Br. Med. J. 301: 783, 1990).
All about hypoglycemia: Hosp. Pract. 21: 187, Sept. 1986; Hosp. Pract. 22: 45, Nov. 30, 1987; Mayo Clin. Proc. 60: 844, 1985; Emerg. Med. Clin. N.A. 7: 837, 1989. Future forensic pathologists read Am. J. Forensic Path. 9: 122, 1988.
GLUCOSE TOLERANCE TESTS
Until recently, the glucose tolerance test was the fashionable way to make the diagnosis of diabetes mellitus, especially type II.
All versions of the glucose tolerance test are essentially stimulation tests for insulin.
With normal ability to produce insulin, and normal sensitivity to insulin, the body handles a glucose test normally.
The standard oral glucose tolerance test requires the patient to drink a solution containing 75 gm (or 1.75 gm/kg) of glucose (yuck!) after an overnight fast.
The patient should be in his or her usual state of health, and should have consumed 300 gm of carbohydrate daily on each of the previous three days (that's a lot for some people).
Serum glucose levels are measured at 30, 60, 90, and 120 minutes.
Normally, the serum glucose does not rise above around 150 mg/dL, and is back to normal (or a little below) by 120 minutes.
*Measuring insulin levels concurrently is no longer widely practiced.
If you can get a urine specimen when you draw each sample (good luck), you may be able to learn something about the patient's renal threshold for glucose.
Some endocrinologists now recommend a modified GTT for all pregnant women at 24-28 weeks (Mayo Clin. Proc. 63: 263, 1988; reliability Ob. Gyn. 82: 515, 1993; opposition Am. J. ObGyn. 169: 257, 1993 -- $10,000 worth of lab tests beyond a simple fasting blood sugar resulted in no measurable human benefit.)
Intravenous glucose tolerance tests measure the body's ability to clear an intravenous bolus of glucose.
Serum glucose levels should return to normal by 90-120 minutes. Failure to do so suggests diabetes mellitus.
This test is of course unaffected by altered GI function. ("Dumping syndrome" and malabsorption can produce an abnormal oral glucose tolerance test.)
Glucose tolerance tests are not usually necessary to make the diagnosis of diabetes mellitus.
The NDGG criteria, based on epidemiologic studies, allow the diagnosis of diabetes mellitus (with its prognostic implications) to be made in nonpregnant adults in their usual state of health when any of the following criteria are present (Diabetes 28: 1039, 1979):
*Exactly what's the best way to screen for diabetes when you're doing patient care, and when you're doing epidemiology, is an interesting study. The best I've seen in Arch. Int. Med. 153: 2133, 1993. Diabetes was diagnosed if glucose was >200 mg/dL 2 hours after a standard glucose load. A HgbA1 level of >7.5% picks up 78% of these, a HgbA1c level of >6.3% picks up 80%, and a fasting blood glucose level of >123 mg/dL picks up 88%. Even a dipstick for glycosuria will pick up 64%.
*The WHO criteria are a bit different: Diabetes 38: 1630, 1989.
Please do not schedule glucose tolerance tests for patients while they are being treated for acute myocardial infarction or pneumococcal pneumonia....
Future criteria for the diagnosis of diabetes will take advantage of such long-term indicators of glucose control as glycosylated hemoglobin (see Br. Med. J. 308: 323, 1994 suggests 7.8% means diabetes).
* INSULIN TOLERANCE TEST
This test measures the patient's ability to respond to a standard dose of insulin with a drop in blood glucose.
The patient is prepared as for an oral glucose tolerance test. While fasting, the patient is given insulin 0.1 U/kg as a bolus.
Blood glucose should decrease to about 50% of the fasting level by 30 minutes, and return to normal by 90-120 minutes.
An inadequate response indicates insulin-resistance (Cushingism, obesity, type II diabetes mellitus, anti-insulin antibodies, etc.)
A blunted response is also seen in around half of patients with "familial pure depression" and "bipolar depression" between episodes, and this has been recommended as a procedure to distinguish these entities from other types of depression (Arch. Gen. Psych. 40: 167, 1983).
Conversely, an exaggerated drop in blood glucose identifies a "brittle" patient at great risk for severe hypoglycemia (NEJM 308: 485, 1983). Again, be careful....
GLYCOSYLATED HEMOGLOBIN ("glycosylated", "glycated")
In the past decade, measurements of glycosylated hemoglobin("GHb") has come into widespread use as a measure of long-term diabetic control, its principal indication.
On long-term exposure to glucose, the free amino groups of proteins are slowly and nonenzymatically glycosylated.
*First, unstable aldimines form. Some of these become stable ketoamines.
"Hemoglobin A1" is any hemoglobin A molecule with a single glucose molecule attached in this way. Most often, the glucose is attached to the valine at the N-terminal end of the beta chain. The aldimine form is called pre-Hgb A1c, the ketoamine is Hgb A1c.
While pre-Hgb A1c is labile and reflects blood glucose levels over the previous few hours, Hgb A1c lasts as long as the red blood cell and reflects blood glucose over the previous several weeks.
In normal people and in well-controlled diabetics, Hgb A1c makes up about 3-6% of total hemoglobin.
In poorly-controlled diabetics, Hgb A1c may exceed 20% of total hemoglobin. (Today's techniques remove pre-Hgb A1c, which may make up several additional %).
False increases in measured Hgb A1c may be due to Hgb F or H; false decreases may be due to Hgb S, E, or E. Levels are also lowered by shortened red cell survival time.
*For reviews of the clinical usefulness of this assay, see Acta Med. Scand. S-671: 47, 1983; NEJM 341: 1984; NEJM 310:384, 1984. Serum fructosamine lets you know about diabetic control over the previous few hours.
* Glycosylated serum proteins may be measured in various ways ("fructosamine", etc.; see Arch. Dis. Child. 61: 113, 1986), and might eventually be a useful procedure for monitoring blood glucose control over shorter time intervals. We are already using fructosamine as a monitor for week-by-week control.
C-PEPTIDE
This "connecting peptide" fragment of proinsulin is secreted by the beta cell in equimolar amounts with insulin, and is a good measure of true beta cell activity. (It is cleared only one fifth as rapidly as insulin.)
C-peptide levels in serum will be increased in insulin resistance, insulinoma, tolbutamide (etc.) abuse, and renal failure.
C-peptide levels in serum will be decreased in factitious hypoglycemia produced by surreptitious injection of insulin (Hosp. Pract. 20: 26, March 1985; Hosp. Pract. 22: 123, Aug.1987). Injectable insulin contains no C-peptide.
*C-peptide levels can also be used to estimate endogenous insulin production, especially when anti-insulin antibodies make the usual radioimmunoassay for insulin inaccurate.
*Because C-peptide is excreted in the urine, it may also be measured there, as when serum levels are low.
*For more on C-peptide, see Acta Med. Scand. S-671: 53, 1983.
SELF-MONITORING OF BLOOD GLUCOSE
As we've mentioned, a variety of products to enable diabetics to determine their own blood glucose levels are available. Chemical reagent strips, with or without reflectance meters, are most popular.
These have made a major impact on the day-to-day self-care of diabetics during the last few years, and have made better control much easier.
In addition to the above, check with us for current references and product evaluations.
BIBLIOGRAPHY / FURTHER READING
I urge anyone interested in learning more about blood glucose testing to consult these standard textbooks.
In my notes, the most helpful current journal references are embedded in the text. Students using these during lecture strongly prefer this. And because the site is constantly being updated, numbered endnotes would be unmanageable. What's available online, and for whom, is always changing. Most public libraries will be happy to help you get an article that you need. Good luck on your own searches, and again, if there is any way in which I can help you, please contact me at scalpel_blade@yahoo.com. No texting or chat messages, please. Ordinary e-mails are welcome. Health and friendship!
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