At what range of serum glucose does it start to spill into our urine?
What is the cellular mechanism of insulin?
Insulin stimulates the synthesis of glucose transporters which gets incorporated into cell membranes.
Insulin also activates these receptors once they are part of the cell membrane, encouraging glucose entrance into the cell for metabolic processing.
In the absence of insulin but high extracellular glucose, what happens to intracellular glucose levels?
Remains at ZERO.
Our brain cells can run on fatty acid metabolism. T/F?
False. They run on glucose only.
What metabolism-related byproduct increases in patients with DM due to their inefficient metabolism of glucose for energy?
What does this result in and how should we treat it?
Free fatty acid metabolism increases due to insufficient glucose metabolism.
This results in free fatty metabolic byproduct of aceto-acetic acid, causing metablic acidosis.
We can treat this by giving insulin, which will drive glucose into cells and decrease fatty acid metabolism (thereby improving their metabolic acidotic state).
What are the four types of DM?
Type I - Absolute insulin deficiency (juvenile onset)
Type II - Adult onset secondary to relative deficiency or desensitization
Type III - Genetic defect resulting in DM
Type IV - Gestational DM
What is Type I DM predominantly a cause of?
Destruction of pancreatic beta islet cells due to auto-immune response or immune response to a virus.
Possible genetic component.
What is Type II DM caused by?
Burning out of pancreatic islet cells in later adult life.
Can also be caused by desensitization of insulin receptors.
Compare the onset of Type I and Type II DM.
Type I - acute and short onset due to an event that usually occurs at a juvenile age.
Type II - chronic and developed over time due to environmental habits. Usually occurs in adults.
How can Type II DM patients become Type I DM patients?
If they completely burn out their pancreatic islet cells and can no longer produce any insulin at all.
What is Type IV DM (gestational) due to?
Often due to hormonal imbalances (progesterone) during pregnancy.
__% of women that experience gestational DM go on to become type II Diabetics later on in life.
30; the other 70% normalize after pregnancy is over and never develop diabetes.
What is 80% of DM etiology characterized by? 10%? The other 5 and 5%?
80%: Obese, mild, maturity-onset
10%: Non-obese, stable, adult-onset
5%: Brittle, adult-onset
5%: Juvenile onset
A small percentage of gestational diabetics require insulin. They take insulin for what ultimate purpose? (Why do they need to control their glucose?)
Control of maternal physiology and fetal development.
What kind of immune cells primarily mediate auto-immune destruction of pancreatic islet cells?
B-cells (humoral mediated immune response)
What is the upper-limit threshold glucose level for a normal adult?
Beyond this, a fasting level indicates DM.
What is the best way to gauge a patient’s baseline glucose level?
Check their serum glucose when they are in a fasting state.
If they have just eaten, they will have a higher than usual glucose level that may not be indicative of their normal serum glucose.
What is considered a pre-diabetic state physiologically?
Islet cells have been stressed to the point of maximum insulin production and glucose levels are rising slowly as time goes on. However, islet cells have not been irreversibly damaged.
Insulin is also becoming less effective due to derangements in insulin receptor activity.
Glucose levels remain relatively steady compared to the diabetic stage.
A good percentage of DM II patients are diagnosed after their glucose levels have been out of control for a while and has caused end-organ damage already. Why?
Slow progression of DM II = symptoms are not as noticeable or easily ignored.
Describe the progression of Type 2 Diabetes by placing these factors in order:
Increased beta cell production of insulin.
Impaired glucose tolerance
Beta cell exhaustion.
Inadequate insulin for degree of insulin resistance
Development of Type 2 DM
- Predisposing factors (obesity, sedentary lifestyle, age, etc..)
- Insulin resistance.
- Impaired glucose tolerance.
- Increased beta-cell production of insulin.
- Beta cell exhaustion.
- Inadequate insulin for the degree of insulin resistance
- Development of Type II DM.
Certain pre-disposing factors make an individual more likely to develop DM II due to burnout of beta islet cells. What are they?
Chronic presence of gall stones
What tests do we adminster to diagnose DM? What are they specific threshold values?
Fasting blood glucose leveles ( >126 mg/dL )
Glucose tolerance test ( > 200 mg/dL)
Note: Glucose tolerance test is often used to test for gestational diabetes. Patient is given a glucose formulation and tested for serum glucose after 6 hours. Their blood serum of glucose should not exceed 200 mg/dL.
Above a serum glucose of _____, glucose leaks into the urine and has a diuretic effect, dehydrating the patient significantly. (give a range)
Certain signs of diabetes are experienced by Type I DM patients due to its acute onset.
What are they and why do they occur?
Frequent urination (glucose > 200 mg/dL becomes a osmotic diuresis)
Dehydration (secondary to osmotic diuresis)
Blurred vision (glucose can spill into the vitrious humor of the eye effecting the way wavelenghts of light travel through the eyeball)
Fruity smelling breath (due to fatty acid metabolism and breakdown of ketone bodies)
Note: these symptoms are also seen in DMI pts undergoing DKA.
What are the 3 acutely life threatening complications of diabetes that we encounter?
- DIabetic ketoacidosis (DKA)
- Hyperosmolar, non-ketotic coma (HNKC)
What subtype of diabetic pts can experience DKA?
What are the symptoms of DKA directly due to?
Lack of glucose delivery to neural cells.
This is secondary to a complete lack of insulin (serum glucose gets really high while intracellular glucose remains near zero).
What are some symptoms of DKA? Which ones can be seen in the early stages of DKA?
Anion-gap metabolic acidosis*
Mental status changes
*Early symptoms of DKA
Acidosis occurs in DKA for by three mechanisms. What are they?
- Accimulation of keton bodies from fatty acid breakdown, releasing aceto-acetic acid.
- Dehydration concentreates acidic ions in serum.
- Tissue hypoperfusion due to intense vasoconstriction causes lactic acidosis.
In DKA, intense extracellular acidosis can eventually lead to intracellular acidosis as _______ exits down the cells charge gradient and gets excreted through the urine.
_____ gets transported into the cell in exchange.
How should we treat DKA?
Fluid hydration (help with perfusion and decrease lactic acidosis)
Replace potassium (slow replacement; necessary due to profound hypokalemia from renal wasting)
Treat hyperglycemia (give insulin and D5W/glucose; give glucose to provide cells with additional fuel source since they are starving)
Correct acidosis if necessary (usually corrected by insulin; may decrease the efficacy of our drugs)
What is HNKC and how does it occur? Who does it occur in? Describe its pathological development.
Hyperosmolar non-ketotic coma.
It occurs mostly in DMII patients due to profound hyperglycemia. DMII pts develop this because even a touch of insulin will prevent ketone-based acidosis (although low levels will not keep glucose levels from rising precipitously).
Usually HNKC develops slowly over time and occurs in DMII pts that are sick and/or not watching their glucose levels.
What happens to the patient’s blood in HNKC?
It becomes hyperosmolar (around 320-340 mOsm). For reference, normal blood osmolality is 290 mOsm.
What are symptoms of HNKC?
Lactic acidosis from tissue hypoperfusion
Renal failure due to hypoperfusion
Comatose state at late stages primarily due to dehydration
How should we treat HNKC?
Use IV fluids to restore perfusion and correct dehydration.
Give insulin to decrease blood glucose.
If you are administering insulin, how often should you check his/her glucose level?
Every 20-30 minutes
Why might you want a diabetic patient to take his/her insulin on the morning of surgery despite the risk of hypoglycemia due to their NPO status?
Surgical stress will cause hyperglycemia so it can act prophylactically.
Usually, this practice is fine, but monitor glucose levels if symptoms of hypoglycemia are seen.
What are signs of hypoglycemia?
Diaphoresis (profuse sweating)
What does the hemoglobin A1C (HgbA1C) lab value test for?
It allows us to assess how tightly controlled a patient’s glucose levels are over the period of 24 hours.
Elevated levels of HgbA1C indicate uncontrolled glucose levels.
HgbA1C is a varient of Hgb that becomes glycosylated. The more of it that exists, the more glucose has been in the blood.
What are normal HgbA1C values? High/diabetic?
Normal = 5 to 6
High/diabetic = ~10
Patients with diabetes are at high risk for CAD. What other factors are also considered high risk for CAD?
High cholesterol (hyperlipidemia)
Higher systolic pressure
The vast majoriy of kidney patients have these two conditions:
Functional changes in nephrons occur almost immediately with the onset of DM. T/F?
What physiological changes occur almost immediately at the onset of diabetes?
Functional changes in the kidneys
Rising blood pressures
Microalbuminuria (excretion of albumin into the urine)
When does your kidneys begin to experience structural changes after the onset of diabetes?
2-5 years after the onset of diabetes
Describe the progression of renal function in DMII. (microalbuminuria, proteinuria, creatinine, ESRD)
Microalbuminuria occurs almost immediately at onset and is due to the breakdown of glomerular membrane (most likely initially due to high glucose excretion).
Proteinuria develops from this ~10 years after onset of DM due to even more extensive renal tissue breakdown (larger proteins are now being wasted)
Elevations in serum creatinine levels precede ESRD.
ESRD takes 15-20 years to develop in a normal DM II pt without any co-morbidities.
Most DMII patients die from _______ before they develop ESRD.
How does diabetes effect a patient’s bones?
As proteins become glycosylated, patients develop arithritic-type issues with their joints, especially at their neck (atlanto-occipital joint)
This means that patients with DM may be less flexible at the C-spine and may be more difficult intubations.
Diabetic patients are prone to infections of the distal limbs. Why?
They are prone to infections due to peripheral neuropathy.
Peripheral neuropathy occurs due to glycosylation of cells and hypoperfusion which damages nerves.
This, in turn, results in injuries that go unnoticed and ulcers that don’t heal well. Both –> increased incident of bad infections
What is the effect of autonomic neuropathy on a diabetic patient’s ability to autoregulate?
What is a commonly seen symptom of autonomic neuropathy in the awake patient?
The diabetic patient’s response to physiologic swings may be slow and less predictable/wider.
Commonly seen symptom of this: orthostatic HoTN.
As the diabetic patient ages, he/she develops a more/less sympathetic baseline and increased/decreased sensitivity to vagolytics. (Choose.)
Note: This results in increased resting HR and desensitization to sympathomimetics.
We’ve talked about blurred vision as a response to vitruous humour accumulation of glucose. What is another potential reason why diabetics can develop blurred vision?
Atrophy of ocular blood vessels due to hypoperfusion
What are some physiologic symptoms that autonomic neuropathy can cause?
Lack of heart rate variability
Decreased response to vagolytics
Neurogenic bladder (lack of bladder control)
How should glucose levels if managed in the intra-operative setting?
Keep glucose levels tightly regulated.
Try to keep levels < 150 mg/dL.
Increased levels of glucose can lead to these things (there’s a lot of answers here but there are 4 of them presented at the end of the lecture that has to do with our anesthetic management)
Impaired wound healing
Hyperosmolality (pee a lot)
Decreased catecholamines in system
Note: impaired wound healing and infections may cause even higher glucose levels due to physiologic stress