Diabetes II Flashcards
3 main effects of chronic hyperglycemia
- Glycation of proteins
- Accumulation of sorbital inc ells
- Increased/inappropriate activation of protein kinase C
Glycation of proteins due to hyperglycemia results in
Glucose binds to protein chain and can cause slow, permanent cross linking that leads to pathology.
Abnormal cross linking.
It affects hemoglobin and collagen in vessel walls.
Causes microvascular dysfunction.
Accumulation of sorbital in cells causes
Cellular edema. May cause cataracts and nerve dysfunction due to swelling.
Increased/inappropriate activation of protein kinase C causes
Vasoconstriction of smooth muscle
Vascular permeability–> leaky vessels
Basement membrane thickening
Abnormal angiogenesis
how can glycation of proteins lead to AGEs (advanced glycation end products)
If glucose binds to protein, it can cause an enzyme activity change and increase oxidative stress/inflammatory reactions in days- weeks. (early glycation products)
In months- years, they can transition to advances glycation end products that are permanent. The proteins cross link and lead to pathology.
Another name for glycation process
Maillard reaction
What occurs during early glycation products
Occurs in days-weeks from glucose binding to protein in days to weeks. Causes oxidative and inflammatory reactions.
How does sorbitol cause edema
Once sorbitol is produced inside a cell, it cannot get out. It attracts water that remains in the cell. This causes edema and injury.
What increases sorbitol levels in cells?
If glucose levels are elevated, they will diffuse more readily into cells. Cells only use 3% for energy. The remaining extra glucose is converted to sorbitol. Sorbitol cannot travel outside the cell- trapped. Water loves sorbital, so water enters the cell and causes edema.
Hyperglycemia causes an increase in ___, which causes an increase in PKC
DAG diacylglycerol
Increase in PKC results in what?
Blood flow abnormailities Angiogenesis Capillary occlusion Vascular occlusion ^^ all affect eyes
Also:
pro-inflam gene expression
Oxidative stress
How does diabetes mellitus affect macrovascular
Coronary artery disease- CAD, MI, CHF
Peripheral artery disease- amputations
Cerebrovascular disease- Transient ischemic attacks, stroke
Other- Immunosuppression and hearing loss due to neuropathy
2 most common causes of death in people with Type II DM
Coronary artery disease, cerebrovascular disease (stroke)
Peripheral artery disease (ex of macrovascular complication)
Atherosclerosis in major arteries of legs– causes downstream problems in lower legs/feet. May cause ulcerations and gangrene infections. Need amputations.
Prevalence of cerebrovascular disease with DM increases with
Duration of disease
Insulin resistance –> hyperglycemia –> ____ –> Accelerated atherosclerosis –> Vascular damage
Endothelial dysfunction due to blood vessel problem
Microvascular chronic complications of DM
Retinopathy
Neuropathy
Nephropathy
Root cause of microvascular complications
Endothelial glycation damages endothelium. Results in a thickening of the basement membrane, which decreases oxygen transmission.
Loss of pericytes causes a small out pouching of blood vessel- micro aneurysm that will leak blood.
Glycated platelets and RBC will stick to damage endothelium and can form thrombosis that may obstruct blood vessels and cause ischemia or rupture and cause exudate/blood leakage.
Prevalence of diabetic retinopathy
28-33%
Diabetic Nephropathy
Leading cause of renal failure due to glomerulosclerosis (scarring of glomerulus)
Most common cause of death in type 1 diabetics
Increases albumin in urine
Sclerosis vs stenosis
Sclerosis= scarring Stenosis= narrowing
Diabetes is the number 1 cause of
End stage renal disease- will qualify pt for medicare
Most common cause of death in type 1 diabetic
Diabetic nephropathy
Leading cause of renal failure
Diabetic nephropathy by gomerulosclerosis- scarring.
Diabetic nephropathy risk factors
*Hyperglycemia
*Hypertension
genetic predisposition
Hypercholesterolemia
Smoking
How to tx nephropathy
Control underlying disorder- diabetes/HTN
Hemodialysis- filter out bad products that kidney can’t get rid of on it’s own. Ex: Albumin.
How does chronic hyperglycemia cause kidney probs
Increased renal blood flow (hyper fusion) results in increased glomerular pressure and protein glycation that causes glomerular damage. Eventually decreases the efficiency of the kidney and causes renal failure.
Diabetic Neuropathy
- What is it?
- How many diabetics does it affect?
- What causes it?
Demyelination of nerves throughout the body
60-70% of diabetics
Caused by hyperglycemia, lack of insulin, ischemia, duration and control of diabetes
Peripheral neuropathy
Most common diabetic neuropathy. Affects peripheral nerves in toes/feet/legs/hands/arms.
Sensory before motor
Causes impaired sensation- numb, tingles, weakness. Muscle wasting
Damaged blood vessels = affects myelin= demyelination= affects integrity
Most common diabetic neuropathy
Peripheral neuropathy
Peripheral neuropathy affects _ before _
Sensory before motor
Causes impaired sensation- numb, tingles, weakness. Muscle wasting
4 types of neuropathy
Autonomic
Proximal
Peripheral
Focal
Autonomic neuropathy results in
Bladder incontinence
Impotence
Diarrhea
Perspiration
Proximal neuropathy
Pain in thighs, hips, leg weakness
Focal neuropathy
Important for us. Affects any nerve in the body. Ex: cranial nerve palsy.
Pericytes
Supportive cell around vessels that regulate capillary blood flow in the CNS and retina. Once pericytes are damaged/destroyed, the capillaries become leaky or occluded and can cause micro aneurysms.
Glycated RBC/platelets stick to the damaged endothelium and lead to endothelial breakdown and thrombosis. Causes hemorrhages or ischemia.
Why should you always ask patients when they were diagnosed with diabetes?
Incidence of retinopathy increases with duration of DM.
Diabetes dx 10 yrs ago? __% incidence of retinopathy
What about diagnoses 15 years ago?
10 years- greater than 50%
15 years- 90%
1 cause of blindness in working population
DM
Diabetic retinopathy risk factors
Smoking, HTN, pregnancy
What directly correlates to diabetic retinopathy
Length of time you have had diabetes
A1C percentage
Magic A1C that will greatly reduce chances of pt developing diabetic ret
7%
Diabetes increases risk of developing cataracts by ___%
40%
How does diabetes cause cataracts
Excess glucose is converted to sorbitol and lens fibers swell- causes apoptosis and ROS
myopic shift
Due to lens swelling. Decreased amp and early onset presbyopia.
Diabetic pts are __x glaucoma risk
2x
How can diabetes affect the cornea
Decreased sensitivity bc neuropathy
Why are optometrists such big players in tx/management of diabetes?
Increased A1c results in the highest risk of developing retinopathy out of all other microvascular complications. optometrist most likely to dx
Diabetic Ketoacidosis
- What causes it?
- What type of diabetes usually associated
- What level of glucose in blood
- Caused by absence of insulin
- Type I more common
- Hyperglycemia levels over 200mg/dl causes this
Lack of glucose causes cells to burn ___
Fat
Insulin being absent leads to keto acidosis how?
INsulin absent? Glucagon is unable to be suppressed, telling liver to release glucose into blood from glycogen stores. Excess glucose in the blood isn’t used and is converted to ketones by fatty acid metabolism. Ketones are acidic, which causes the blood to become acidic.
Hyperglycemia + hyper ketosis + acidosis = DKA
Classic Triad in DKA
Hyperglycemia greater than 200 mg/dl
hyperketosis- ketones present in blood/urine
acidosis- pH less than 7.3 or bicarb less than 15mmol/L
Signs/symptoms of DKA
Altered mental status due to lack of glucose
Fruity breath due to acetone (biproduct from ketone breakdown)
Hyperventilation in attempt to get rid of Co2 and raise pH to a more basic level
Kussmaul breathing
Hyperventilation in attempt to stabilize pH of blood by releasing CO2. Goal is to make blood pH more basic
Complications if DKA continues
Cerebral edema
Coma
Death
How to Tx DKA
Blood glucose normalization with insulin
Hypoglycemia emergency
- Most commonly caused by what
- Most common in Type I or II?
- Blood glucose levels
Most commonly caused by insulin overdose in type I diabetes- on bigger doses of insulin.
Hypoglycemia: less than 70 mg/dl
Severe hypoglycemia: 50-55mg/dl Emergent!
Signs/symptoms of hypoglycemia
Nervous Sweating Tremor Muscle weakness HA Confusion Loss of consciousness w decreased respiration Coma
How to tx hypoglycemia
Treat with rapid glucose infusion, glucagon injection and close monitoring.
Blood sugar crashing- need glass of OH or emergency glucose tablets
