Module 1 - Diabetes Mellitus Flashcards
Incidence
rate of new cases
on the rise
conveys risk of contracting disease
Prevalence
proportion of actual cases
conveys how widespread disease is
Diabetes Insipidus versus Mellitus
Insipid is a disorder of ADH
Mellitus is a disorder of blood glucose regulation
Exocrine
releases through a duct
Endocrine
Secretion right into the blood stream
Is the pancrease endo or exocrine
Both
Pancreas
Large diffuse abdominal organ functioning as both an endocrine and exocrine gland
made up of acini and islets of langerhans (the two major tissue types)
Acini
Exocrine tissue of the pancreas that secretes into ducts
Releases digestive enzymes like amylase, protease, and lipase as well as sodium bicarbonate
Islets of Langerhans
Endocrine tissue of the pancreas that secretes right into blood - key role in blood glucose levels
takes up 1-2% volume of the pancreas
Has alpha delta and beta cells releasing hormones that regulate glucose levels
Exocrine Pancreatic Function
Acini release digestive enzymes and sodium bicarbonate
Contents are released into the pancreatic duct
Exocrine function here plays an essential role in digestion and absorption of food in the smal;l intestine
Endocrine Pancreatic Function
Involves synthesis and release of hormones produced by specialized cells in the Islets of Langerhans
Key role in blood glucose levels
Different Cells in the Islets of Langerhans
Alpha
Beta
Delta
What do Beta cells and Amylin release?
Insulin
What do alpha cells release
glucagon
What do delta cells release
Somatostatin
Diabetes is not strictly involved with …
Insulin
Other hormones that keep glucose levels high
Catecholamines (EP qand NEP)
Growth Hormones
Glucocorticoids (Cortisol
Insulin, Glucagon, and Somatostatin are what to one another? What do they work to do?
They are counter regulatory hormones and work to keep glucose levels lower/regulate glucose
What counteracts glucagon?
Insulin
Where are the Islets of Langerhans located?
Around the blood vessels surrounding the pancreas
The only hormone known to lower blood glucose ?
Insulin
What cell releases Insulin and what is Insulins action
Beta
Decrease blood glucose by allowing it to enter cells (changes cell membrane makeup to allow cell opening for glucose thus lowering blood glc levels)
What cell releases Glucagon and what is Glucagons action?
Alpha
Increased release of glucose from the liver into the blood to increase blood glc levels. Causes the release of stored glycogen specifically to turn into glucose for use
What cell releases Somatostatin and what is Somatostatins action?
Delta
Extends the use of absorbed nutrients for tissues by blocking increases in glc levels after we eat to allow a slower rise and better control over the glucose levels
Decreases GI activity after ingestion –> extends time over which food is absorbed –> inhibits insulin and glucagon –> extends use of absorbed nutrients by tissues
How much of ingested glucose is used for metabolism?
1/3
How much glucose undergoes Glycogenesis after eating?
2/3
What happens to blood glucose after a meal?
Glucose levels rise –> insulin secreted in response from beta cells
2/3 of glucose stored as glycogen in the liver (Glycogenesis) while 1/3 is used for metabolism
Saturation of tissues with glycogen –> glucose converted to fatty acids –> stored as triglycerides in gat (Lipogenesis)
What happens to blood glucose between meals?
Liver releases glucose to maintain blood glucose within normal limits via Glycogenolysis and potentially gluconeogenesis
Glycogenesis
Glucose converted to glycogen and stored in the liver
Lipogenesis
Excess glycogen in the tissues leads to glucose being converted to 3 fatty acids and adipose cells and then being stored as triglyceride in fat cells
Glycogenolysis
glycogen is broken down to release glucose into the blood
Gluconeogenesis
synthesis of glucose from amino acids, glycerol, and lactic acid
What can be used interchangeably with glucose for energy everywhere but cardiac and skeletal muscles, kidneys, brain, and the liver?
Fatty Acids
Fatty acids cannot normally be used for energy in the brain as it requires steady glucose amount, the only exception is ..
During starvation situations ketone bodies can be used
What occurs if blood sugar is low?
glucagon released by pancreas –> glycogen breakdown is promoted to glucose in the blood
What occurs when blood sugar is high?
- Insulin is released by the pancreas to promote glycogen synthesis in the liver
- stimulates glucose uptake in tissue cells
- Over Saturation with glycogen leads to storage as triglycerides in fat cells
What is the action of Insulin on Glucose
Increase glucose transport into skeletal and adipose tissue
Increase glycogen synthesis
Decrease gluconeogenesis
What is the action of Insulin on Fats
Increase glucose transport into fat cells
Increase Fatty acid transport into adipose cells
Increase triglyceride synthesis within fat cells
Inhibit adipose cell lipase (breaking down triglycerides)
Activates lipoprotein lipase in capillary walls
What is the action of Insulin on Proteins
Increase active transport of amino acids into cells
Increases protein synthesis (anabolism) by increasing transcription mRNA and accelerating protein synthesis by rRNA
Decreases protein breakdown by enhancing use of glucose and fatty acids as fuel (prevents muscle wasting - catabolic)
Normal insulin release only occurs in normal conditions when..
Blood glucose levels are high
Atheroscleorosis
Body fats deposited on lining of blood vessels
HDL
High Density Lipoproteins
The good cholesterol
takes fats on blood cells back to the liver for use
Insulin has a beneficial effect on this process
Want levels greater than 45 and 55 in women and men respectively
LDL
Low density lipoproteins
Lousy bad cholesterol
Levels between 60-80
smaller than HDL so we want more HDL and less LDL as HDL is more effective at moving fats away and preventing atherosclerosis buildup
How does Diabetes mellitus impact cholesterol?
It increases cholesterol levels while increasing LDL and greatly decreasing HDL leading to increased triglycerides and fat/plaque buildup
DM –> Not enough insulin –> no activation –> atherosclerotic buildup as a result –> risk for stroke, heart attack, etc –> elevated LDL, cholesterol and triglycerides with lower HDL
Anabolic Activity
Promotes synthesis
Catabolic Activity
Promotes break down
Why do children with diabetes often lose weight rapidly despite eating a lot and being hungry?
Not enough insulin means protein begins to catabolize and muscle wasting occurs
Proteins are needed for AA production and use in metabolic function
Major activity of Insulin on tissues?
Decrease blood glucose by allowing it to enter cells
Major action of insulin in regards to anabolic action?
Promote synthesis of proteins, carbs, lipids, nucleic acids in liver, muscle and adipose tissue
major action of insulin on the liver
Stimulates the synthesis of glycogen and increases uptake as well as fatty acid synthesis
Inhibits glycogenolysis, gluconeogenesis, and ketogenesis
major action of insulin on muscle
increase uptake of glucose and amino acids
increase glycogen and protein synthesis
inhibit protein catabolism
Major action of insulin on adipose
increase glucose uptake and fat synthesis (Lipogenesis)
decreased fat breakdown (by inhibiting adipose cell lipase)
Major action of insulin on Potassium (K+)
increase potassium uptake by cells (GIK)
Major action of insulin on lipids
metabolism of plasma lipids and lipoproteins WNL ranges
___% of insulin is used or degraded and why
50% - so insulin is released in phases since its half life is 15 minutes
What follows glucose when insulin allow transport into cells?
K+ (potassium) which makes K levels decrease too in the blood
A cell does not need insulin if…
they have special glucose carriers: the brain cells, RBC, endothelial lining cells, glomerular lining cells
GIK Mechanism
Glucose-Insulin-Potassium Mechanism allowing potassium uptake in cells at the same time as insulin allow glucose in
Why may we give glucose and insulin to someone with lower serum potassium levels?
It can instigate intake of potassium to raise levels
it is not a long term effect but it can save lives
Why are too high or too low K levels bad?
Can cause arrhythmia of the heart
Normal function of insulin
increased uptake of blood glucose into cells
decrease blood glucose levels
Excess insulin leads to …
Hypoglycemia
Deficit Insulin leads to..
Hyperglycemia
What can hypoglycemia cause?
Decreased blood glucose:
hunger tremors sweating weakness malaise irritability mental changes coma --> death
What can hyperglycemia cause?
Increased blood glucose:
Polydipsia Polyphagia Polyuria Dehydration Fatigue Mental Changes coma --> death
What are the 3 P’s of Hyperglycemia that define it?
Polydipsia
Polyphagia
Polyuria
Polydipsia
Intense Thirst (to dilute sugars)
Polyphagia
Intense Hunger
Polyuria
increased urinary output (leads to dehydration)
Why is it better to give insulin rather than more food?
because the cells are starving because lack of insulin means they cannot get the glucose in so they need a way in rather than more glucose
How does a blood sugar of 30 differ from one of 400?
normal range is 60-100
30 can be deadly while 400 is less dangerous and more just uncomfortable
What is more dangerous, hypoglycemia or hyperglycemia?
Hypoglycemia
Always assume what if you do not know blood sugar levels?
Assume they have hypoglycemia since it is more dangerous and BE SAFE AND GIVE SUGAR
Glucagon
Secreted by pancreas alpha cells
action opposite of insulin
diabetics may need a glucagon pen in case of emergency
Insulin acts on all body cells, but glucagon…
primarily acts in the liver
How does glucagon travel?
via portal vein to the liver where it exerts its main effects
Function of Glucagon
Stimulate glycogenolysis and gluconeogenesis
Increase lipolysis and output of ketones by the liver
Enhance uptake of amino acids by the liver (can be used for anabolic process or gluconeogenesis)
*It will help form new glucose when glucose is depleted
What occurs to glucagon when blood glucose is high
secretion is inhibited (when low it increases)
How is glucagon related to diabetic ketoacidosis
Increases lipolysis which makes ketone waste products
Action of Glucagon on Glucose
promotes breakdown of glycogen into glucose phosphate
increases gluconeogenesis
Action of Glucagon on Fats
enhances lipolysis in adipose tissue –> liberates glycerol for use in gluconeogenesis
activates adipose cell lipase
enhances lipolysis in adipose tissue –> liberates fatty acids (so they can be used for energy - ketones produced as a waste product!)
Action of Glucagon on Proteins
increases breakdown of proteins into amino acids for use in gluconeogenesis
New glucose, through the help of glucagon, comes from what
Glucagon action on amino acids, fatty acids, and glycerols together
Catecholamines
produced by adrenal medulla
EP and NEP
an important homeostatic mechanism during periods of hypoglycemia as its purpose is to conserve glucose
Function of Catecholamines
maintain blood glucose levels during stress:
mobilize glycogen stores
decreases movement of glucose into body cells (keeps it high in the blood)
inhibits insulin release from beta cells
mobilizes fatty acids from adipose tissues (prevent storage of glucose and keep levels high)
The main purpose of catecholamines is to..
conserve glucose!
Main catecholamines
NEP and EP
where are catecholamines produced?
adrenal medulla
How does hypoglycemia relate to catecholamines?
It activates the bodies stress response - leading to autonomic symptoms like palpitations, shakiness, nervousness, sweating, pallor, irritability, etc
The catecholamines then allow glucose levels to be conserved and maintain glucose levels/raise them
Why is it hard to potentially manage diabetes during a hypoglycemic attack
Symptoms of neuroglycopenia can lead to hypoglycemia of the brain impairing ability to think making it hard to manage (alongside other symptoms like weakness and lethargy)
Growth Hormone’s Function relating to glucose levels
increase protein synthesis in ALL cells of the body (anabolic)
mobilize fatty acids from adipose tissue (to use for fuel)
antagonize the effects of insulin
decrease cellular uptake and use of glucose –> increase blood glucose by 50-100% –> stimulate further insulin secretion
Normally it helps with growth but has an antagonistic effect on insulin
How do the GH levels compare between adults and children
They are the same levels!
What inhibits GH
Insulin and increased levels of blood glucose (so there is not a prolonged effect of elevated GH)
When do GH levels increase
When fasting (and hypoglycemia)
Exercise: running, cycling, etc
Stress: anesthesia, fever, trauma
What does prolonged GH excess cause?
increased glc levels despite increased insulin release –> leads to insulin resistance in peripheral tissue –> this inhibits glc uptake by muscle and adipose tissue and contributes to diabetes
Acromegaly
chronic hypersecretion of GH in adulthood
causes symptoms of glucose intolerance, insulin resistance, and diabetes
Gigantism
GH hypersecretion / excess in childhood
What releases GH
anterior pituitary
Pathway for increased GH?
Hypothalamus –> GHRH –> Anterior Pituitary –> Increased GH
Pathway for decreased GH?
Hypothalamus –> Somatostatin –> Anterior Pituitary –> Decreased GH
Somatostatin is released by …
many places like the hypothalamus, pancreas, and GI tract
it is counterregulatory to GH
Glucocorticoid Hormones
Main: Cortisol (Hydrocortisone)
Synthesized in Adrenal Cortex
Regulates metabolism of glucose
95% of glucocorticoid activity comes from …
cortisol
Functions of Glucocorticoids in relation to diabetes/blood glucose
Regulate metabolism of glucose (critical to survival during periods of fasting and starvation)
Stimulate gluconeogenesis by the liver (increased production (6-10x)
When do glucocorticoid levels increase
During stress: infection, pain, trauma, surgery, prolonged strenuous exercise, acute anxiety
During hypoglycemia: a potent stimulus for secretion of glucocorticoids
Why does chronic stress relate to diabetes
lots of cortisol is released which increases and conserves glucose levels
stress in the hospital can lead to a need for insulin
Ghrelin
Made by GI cells / in the stomach
helps control hunger (no release = no feelings of hunger)
Gastrin
made by stomach/GI cells
important to acid secretion and satiation
Cholecystokinin
released by duodenum
gall bladder contraction
GI motility
pancreatic exocrine secretion functions
Secretin
released by duodenum
related to pancreatic exocrine secretion
GIP
released by duodenum
related to Incretin activity
Motilin
released by duodenum
related to GI motility
Pancreatic Polypeptide
released by pancreas
related to gastric motility and satiation
Oxyntomodulin
released by large intestine
relates to satiation and acid secretion
PYY 3-36
released by large intestine
relates to satiation
GLP-1
glucagon like peptide 1
released in the distal small bowel
works with GIP
incretin hormone released from your gut that signals beta cells to increase insulin secretion and decrease the alpha cells release of glucagon
this one also slows down the rate at which food empties from the stomach and acts on the brain to increase satiety (and suppress glucagon)
GIP
Glucose dependent insulinotropic polypeptide
released in jejunum
incretin hormone released from the gut that signals beta cells to increase insulin secretion and decrease the alpha cells release of glucagon
GLP-1 and GIP mimic the action of ____-
somatostatin
increase the amount of insulin made and act as messengers between the digestive tract and the pancreas
Amylin
similar to somatostatin
released along with insulin from beta cells
has a similar effect as GLP-1 (decrease glucagon levels to decrease liver glucose production; slow rate at which food empties from the stomach; increase satiety by acting on the brain)
Pramlintide
medication that encourages amylin release
Diabetes
disorder of carb, protein, and fat metabolism
mult. etiologic factors
involves absolute or relative insulin insufficiency and/or insulin resistance
glucose cannot be carried into fat and muscle cells –> cell starvation –> fat and protein breakdown
Examples of Etiologic Reasons for Diabetes
genetics
viruses
cancer
obesity
sometimes it cannot be ID’ed
Why is Diabetes referred to as the “Running through of sugar”?
Because the amount of glucose overwhelms the glomerulus and spills into the urine
Absolute Insulin Deficiency
Type 1 Diabetes
Cannot make any endogenous insulin with your beta cells
You end up needing exogenous insulin
Relative Insulin deficiency
not making enough insulin
it is either destroyed early, broken, etc
Insulin Resistance
cells do not use insulin correctly and beta cells may need to make more and more until failing
lack of ability to keep up with production can occur with endogenous insulin, but resistance can occur with exogenous OR endogenous
What problems can insulin resistance lead to?
Diabetes
Heart Problems
What are some insulin issue types that can lead to diabetes
Absolute deficiency (type 1)
no insulin being made (type 1)
relative deficiency
impaired release by pancreatic beta cells
inadequate or defective insulin receptors
production of inactive insulin
insulin being destroyed begore it carries out its action
Types of Cells that do not need insulin for glucose to get into them?
Nerve cells
RBCs
Cells lining the glomerulus
endothelial cells
What can the brain use as emergency energy in severe starvation situations
Ketones from fat breakdown
Cause of death rank for Diabetes in the USA`
7th
risk for death is twice of that for non-diabetics of the same age
The leading cause of end stage renal disease (ERSD) in the US is..
Diabetes
Risk for heart disease and stroke is 2-4 times more for ___ than non
Diabetics
Diabetic Comorbidities for children and adolescents with Type 1 DM
Nephropathy
Hypertension
Dyslipidemia
Celiac Disease
Hypothyroidism
Important HP2020 Diabetes Take aways
Prevalence has increased in the last decade but leveled off
targets have been met
2/3 of diabetics are diagnosed
A1C greater than 9% in 20% of adults
half of diabetic objectives seen little or no change in the last decade
Type 1 Diabetes
Absolute insulin deficiency (cannot make insulin)
Etiology: autoimmune or idiopathic - but strongly autoimmune since attacks on beta cells and langerhans islets occur (occurs in children often)
Treatment: Insulin (only treatment)
Type 1.5 Diabetes
Latent autoimmune disease occurring in adults
Treatment: Oral medicines at first but will need insulin within 5 years
Type 2 Diabetes
Due to: Insulin insensitivity, insulin secreting deficiency, inappropriate gluconeogenesis (either insulin is formed wrong, receptors do not work, or glucose cannot be made right)
Etiology: obesity or genetics
Treatment: Diet, exercise, hypoglycemics, transporter stimulators (first two especially for pre diabetics)
In what form of diabetes is genetics more important?
Type 2
What maybe the etiology and treatment for other specific types of diabetes
Etiology: Malnutrition, Corticosteroid use, secondary to pancreatic cancer, pancreatitis, steroid use, etc
Treatment is based on case
GDM
Gestational Diabetes
etiology: increased metabolic demands of the fetus
Treatment: Diet, metformin, insulin; usually resolves post delivery
If GDM occurs in 2-3 pregnancies in a row what is likely to happen?
It may convert to type 2 diabetes (or potentially type 1)
If someone is diabetic then gets pregnant…
it is NOT GDM, its either 1 or 2
Former names for Type 1 Diabetes
Juvenile Onset (adults could get it, its just less common)
Insulin Dependent (not good name since type II could use insulin too)
IDDM
Type I (people dont know roman numerals)
Former names for type 1.5 Diabetes
Latent Autoimmune Diabetes in Adults (LADA) - Still used
Former names for type II Diabetes
Adult onset (obese children can have occur)
Non insulin dependent (NIDDM) (not good since it could require insulin dependence as well)
Type II (no roman numerals)
Age of onset for Type 1 DM
any age less than 30 usually
Age of onset for type 1.5 DM
ages after 30
Age of onset for type 2 DM
usually after age 40 with 8/10 diagnosed being obese
BUT, as time goes on more and more younger people get this too
Pathophysiology of Type 1 DM
NO insulin production
Pathophysiology of Type 1.5 DM
Damage to beta cells
genetic factors
possible insulin resistance
Pathophysiology of Type 2 DM
produce insulin, BUT not enough or tissues are resistant
Major Complications of Type 1 and 1.5 DM
DKA (Diabetic Ketoacidosis) (Cell Starvation)
Ketones end up being produced from fat breakdown
Major Complications of Type 2 DM
HHNK - Hyperosmolar Hyperglycemic Non Ketotic Syndrome (Less ketosis)
How is HHNK and DKA different
HHNK occurs in type 2 as compared to DKA in 1 and 1.5
In HHNK some insulin is made (just not enough) so there is some glucose getting in leading to no FA breakdown, thus no Ketosis occurs
So HHNK has and increase in blood glc like DKA, but no production of Ketones
But, HHNK is NOT less deadly than DKA
Manifestations of Type 1 Diabetes
Hyperglycemia and Glucosuria
Symptoms in type 1 develop more acutely
3 P’s - Polyuria, Polydipsia, Polyphagia
Weight loss despite normal or increased appetite
(long term) Other: Blurred vision (recurrent), fatigue, paresthesia, recurrent skin infections
Why does Polyuria occur in Type 1 Diabetes?
excessive urination d/t osmotic diuresis when reabsorption capacity of renal tubules exceeded
Why does polydipsia occur in Type 1 Diabetes?
excessive thirst d/t intracellular dehydration including cells of the thirst center and mouth
Why does polyphagia occur in Type 1 Diabetes?
excessive hunger d/t cellular starvation and depletion of cellular stores of CHOs, fats, and proteins
Why does weight loss occur despite normal or increased appetite in type 1 diabetes?
osmotic diuresis; vomiting d/t ketoacidosis occurs
cells end up= using stored CHOs, fats, and proteins for energy since insulin isnt there to move glc into the cells
How does DM interact with the nephron
Glucose is a small molecule that usually gets through the glomerulus and then is brought back through reabsorption in the proximal tubule
However, high glc levels means it cannot be filtered and reabsorbed - ability exceeded - so glc stays in the urine (abnormal)
High osmotic pressure occurs which leads to the kidneys pulling fluid into the filtrate to dilute the high glc levels until its in the collecting duct (where it then is urine) –> this leads to very dilute urine from high tonicity but this relates back to cellular dehydration, polyuria, and polydipsia
Pathogenesis of type 2 Diabetes
Genetic Predisposition and/or Central Obesity
–> FFAs (free fatty acids) (increase initially and decrease later)
–> Increased hepatic glucose output (high glc levels since uptake cannot occur), decreased insulin secretion, decreased glucose uptake
–> TYPE 2 DM
What is instrumental in Type 2 DM and Heart Disease
Central Obesity (Visceral Fat)
It creates free fatty acids since this is active fat
it burns out the beta cells causing Type 2 Diabetes
Manifestations of Type 2 Diabetes
Hyperglycemia and Glucosuria
Only 2 P’s - Polyuria, Polydipsia
Other - Long term:
Recurrent blurred vision from exposure of lens and retina to hyperosmolarity
weakness and fatigue from lowered plasma volume
paresthesia d/t dysfunction of peripheral sensory nerves
Chronic skin infections d/t hyperglycemia and glucosuria favor growth of yeast –> pruritis and vulvovaginitis
often THESE are the symptoms that prompt individuals to seek Tx
What is the difference in manifestation development between Type 1 and Type 2 diabetes?
Type 1 is more acute and quick
Type 2 usually develops more insidiously
Why is there only 2 P’s in type 2 diabetes?
Polyuria occurs in the same mechanism as type 1
Polydipsia may become overlooked, but does occur, since glucose increase is more gradual with no ketoacidosis
there is NO POLYPHAGIA - there is still some insulin bringing some glc in - not starving so they do not have the type 1 intense hunger
Examples of other types/causes of Diabetes
Genetic Defects of Beta Cell Function
Genetic defects in insulin action
diseases of the exocrine pancreas
Endocrinopathies
Drug or chemical induced diabetes
infections
Casual or Random Plasma Glucose (PG)
Diagnostic
Done ANY time of day without regard to time since last meal
Not very useful, especially for treatment
Does not tell much and diagnoses are not based on this
It only tells something if levels are extreme
Fasting Plasma Glucose (FPG) / 2 Hour PG
8 to 12 hours fast for FPG / 2 hour for PG
once preferred d/t ease of administration, convenience, acceptability to patients, and lower cost
Fasting is defined as…
no caloric intake for at least 8 hours
What type of diagnostic diagnoses more people with DM than FPG or HgA1C
2 Hour Plasma Glucose (2 Hour PG)
FPG <126 mg per dL is
Normal (she said in lecture under 100 was normal and 100-126 is pre diabetic)
Oral Glucose Tolerance Test (OGTT)
Used to check for gestational diabetes: done at 24-28 weeks gestation and then 6-12 weeks postpartum if positive
75 g glucose (sugar load) is given after fasting and the blood glucose is checked before, after 1 hour, and after 2 hours
NOT recommended for routine clinical use
How should the blood glucose levels change in OGTT diagnostics?
During fasting it should be low (greater than or equal to 92)
1 hour should raise to above or equal to 180
after 2 hours it should lower some to greater than or equal to 153
What are some diagnostic criteria for diabetes?
A1C greater than or equal to 6.5%
FPG greater than or equal to 126 mg/dL with no caloric intake for at least 8 hours before
2 hour PG greater than or equal to 200 mg/dL during an OGTT
Random plasma glucose great than or equal to 200 mg/dL in a person with classic symptoms of hyperglycemia (3 P’s) ( if there is no hyperglycemia, 1-3 should be checked with repeated testing)
*all should be repeated mult times
Glycated or Glycosylated hemoglobin (HgA1c)
RBC does not need insulin so glucose combines with Hgb but it never unbinds until cell death - so this leads to less oxygen carrying capability
If over saturated, less and less oxygen can be carried
High levels of glycosylation indicate diabetes due to oversaturation of glucose in the blood
HgA1c reflects what?
average blood glucose levels for the last 2-3 months prior to this test
Glycosylation of blood with glucose is…
irreversible until RBC breakdown
Amount of glucose bound to RBC is directly proportional to what?
the amount of glucose exposure over the 120 day lifespan of the RBC
Glycohemoglobin
blood glucose bound to hemoglobin
Normal A1c is? Poor/Diabetic A1c?
< 5.7 (about 5% glycosylation in a normal person) but it is greater than or equal to 6.5 %
Poor is between those two values
How often should A1c be checked?
every 3 months to determine if medicine is working
if there is good control then they may be able to go longer without testing
What may give abnormal A1c results?
diseases effecting Hgb like Anemia
supplements and high cholesterol levels
liver or kidney issues
Goals of Blood Glucose Monitoring
Hgb A1c maintained at 7% or less; AACE/ACE criteria is at <6.5% though
Majority of preprandial blood glucose levels 80-120 mg/dL
Bedtime blood glucose levels between 100 and 140 mg/dL
What does a 275 mg/dL mean plasma glucose correlate to for A1c? What is normal A1c and Mean Plasma Glucose?
275 –> 10% A1c
Normal: 5%; 60-100 mg/dL
If we have the mean plasma glucose we can find ___ and vice versa with a chart
A1C
How did diabetics used to get diagnosed?
They tasted urine for sweetness
Urine glucose is almost obsolete because of blood glucose monitoring but it can be used still
Urine Tests only reflect what
URINE GLUCOSE LEVELS
What influences urine glucose levels
renal threshold for glucose
fluid intake and urine concentraiton
urine testing methods
drugs
ADA recommends testing what in regard to glucose levels?
Blood glucose not urine glucose levels (the influencers can give false/skewed results)
What is still highly important regarding urine tests, especially for type 1 diabetics?
Urine Ketones - these remain important for monitoring diabetic control especially in type 1 who are more prone to DKA
Why are Urine Ketones so important?
Ketones in the urine is an early sign of diabetic ketoacidosis and can be used for diabetics with high blood sugar to detect imminent danger
DKA can occur quickly so we want to screen for complications by finding ketones early
C Peptide Assay
Test for diabetes
C peptide is a connecting peptide for proinsulin (inactive) before becoming insulin (active)
C peptide then stays in the blood and we can measure the amount to measure insulin production
How does Proinsulin (inactive) turn into Insulin (active)_
A and B chains are connected by two sulfide bonds and a C peptide between them - this is the proinsulin
Breaking off the C insulin converts it to active insulin
C Peptide Assays are a reliable indicator for..
pancreatic beta cell function
There is a strong correlation between C peptide levels and …
insulin
C peptide measurements before and after glucagon stimulation may be valuable for assessing what
diabetic insulin therapy
What test delineates type 1 from type 2 diabetes?
glucagon stimulated c peptide tests
C peptide assays can check for diabetes and beta cell function, but also can monitor for …
recovery after incision of insulinoma –> rising c peptide levels suggest recurrence or metastasis
Insulinoma
pancreas tumor that overproduces insulin
3 categories/measurements of increased risk for diabetes?
- Impaired Fasting Glucose (IFG) (From an FPG 100-125 mg/dL)
- Impaired Glucose tolerance (IGT) (2 hour PG in OGTT - 140-199 mg/dL)
- A1C 5.7 to 6.4%
* risk extends below the lower limit of the range and is disproportionately greater at the higher ends of the ranges
* these can also increase risk for cardiovascular disease
The three categories/measurements for increased risk of diabetes should be done for …
any asymptomatic diabetics or any adult overweight or has one or more risk for diabetes
When should the 3 categories of increased risk for diabetes be checked?
begin at 45 and be done in 3 year intervals if normal
also in children and adolescents if they have a risk factor or are obese
What people are at increased risk for diabetes
individuals with higher than normal blood glc levels, but not high enough to be classified as diabetes
Approx 5% of people with prediabetes will progress to diabetes each year
People with weight and lifestyle issues
people with prediabetes have an increased risk for developing type 2 diabetes, heart disease, and stroke
Prediabetic A1C range
5.7 to 6.5
Normal, Pre Diabetic, and Diabetic A1C Levels
Normal is below 5.7%
Pre Diabetes is 5.7-6.4
Diabetes is greater than or equal to 6.5%
Normal, Pre Diabetic, and Diabetic Fasting BG
Normal is <126 mg/dL
Pre Diabetic 100-125 mg/dL
Diabetic is greater than or equal to 126 mg/dL
Normal, Pre Diabetic, and Diabetic Oral GTT
normal is <92 mg.dL fasting
pre diabetic is 140-199 mg/dL
diabetic is greater than or equal to 200 mg/dL at 2 hours
What is diabetic for a random PG/BG
greater than or equal to 200 mg/dL with classic symptoms of hyperglycemia
What are some testing criteria for diabetes in asymptomatic adults
every 3 years starting at 45 regardless of weight:
overweight/obese adults any age AND 1 or more of the following risk factors start earlier:
physical inactivity
1 degree relative with diabetes
high risk ethnicity like in indians and african americans
women: PCOS, infant birth wt > 9#, or GDM
HTN
Dyslipidemia
Cardiovascular disease
history of prediabetes: A1C greater than or equal to .7%, IGT, or IFG
Insulin resistance: severe obesity, acanthosis nigricans
Testing Criteria for Diabetic Asymptomatic Children
Every 3 years beginning at 10 years or at the onset of puberty - if 2 risk factors are present
Overweight (85th BMI or weight >120% of ideal for height) AND 1 of the following risk factors:
family history of diabetes in 1 degree or 2 degree relative, race/ethnicity, insulin resistance (acanthosis nigricans, HZTN, dyslipidemia, PCOS, SGA, birth weight, maternal hx diabetes or GDM during child’s gestation
Recommendations for Asymptomatic Children
diabetes self management education and support
psychosocial issues
treatment guidelines for type 2 diabetes in youth
Acanthosis Nigricans
Skin condition of dark velvety skin
occurs often with diabetes
Metabolic Syndrome (“Syndrome X”)
Central obesity causes an “apple shape” (waist circumference >102 in men and >88 cm in women)
Fasting serum triglycerides > 150 mg/dL
Low HDL cholesterol (<40 mg.dL in men and <50 in women)
Blood glucose greater than or equal to 130/85
Fasting glucose >110 mg/dL
What do you have increased risk for with Metabolic Syndrome (Syndrome X) ?
increased risk for:
atherosclerosis
stroke
coronary heart disease
early death
Additional Signs and Symptoms associated w/ Diabetes
Elevated uric acid levels
fatty liver (especially in concurrent obesity)
progressing to non-alcoholic fatty liver disease
polycystic ovarian syndrome
hemochromatosis (iron overload)
acanthosis nigricans (a skin condition featuring dark patches)
How many pregnancies get Gestational Diabetes?
7%
50% of Gestational Diabetes occurs when what is present?
history in the family
history of stillbirth/spontaneous abortion
fetal anomalies or LGA baby
obesity
advanced maternal age (>35 years)
greater than 5 pregnancies
Why is management of gestational diabetes critical?
there is increased risk of complications
increased mortality
increased fetal abnormalities including macrosomia
hypoglycemia
polycythemia
hyperbilirubinemia
Treatment of Gestational Diabetes includes what?
Blood glucose monitoring - fasting + postprandial
nutritional guidance –> normoglycemia, proper weight gain, avoid ketosis
Macrosomia
very large baby (may have fatty heart or kidneys which are metabolically active - could cause hypoglycemia)
can occur from untreated gestational diabetes
How does Gestational Diabetes develop?
Develops during pregnancy
Type 1 DM discovered during pregnancy and undiagnosed asymptomatic type 2 DM discovered during pregnancy
does NOT include having DM before pregnancy
Must resolve after pregnancy but there is risk of type 2 diabetes
How do glucose levels change during gestational diabetes?
Normal glucose levels in the first half –> develops relative insulin deficiency during the last half of the pregnancy
Risk Assessment for GDM
risk assessment for GDM should be undertaken at the first prenatal visit
women with clinical characteristics consistent with a high risk for GDM should undergo glucose testing as soon as feasible
If they are found not to have GDM at that initial screening, they should be retested between 24-28 weeks of gestation
Women of average risk should have testing undertaken at 24-28 weeks of gestation
How is a test for GDM done
give sugar load of 75 g glucose after fasting for 8 hours then check before glucose, at one hour, and at two hours
How does plasma glucose change temporally (over time) for a normal person?
Normal levels at night will stay stable and then dips and insulin brings it back to baseline –> you eat and it increases then insulin brings it back down and this occurs for all meals. –> at night it flatlines again
In between meals it lowers back to baseline
How does plasma glucose change temporally (over time) for a diabetic?
Its similar to regular but the baseline is higher and it takes longer to lower the blood glucose levels
after they eat it shoots up significantly more and then does not drop as much as a normal person
so continuous high bumps occur never coming back down to baseline between meals
At night it very slowly lowers again to baseline
Why does alcohol have to dry completely for blood glucose testing?
it can cause a false high
What kind of blood does a glucometer check for?
Capillary blood
venous, capillary, and arterial have different levels so you need the right kind of glucometer for the right area
Treatment for Diabetics focuses greatly on …
diet and nutrition (but we have gotten away from special diets), medication, and exercise
sometimes pancreatic implant
What are the therapeutic goals involving diet treatment for diabetics?
Maintenance of near normal blood glc levels (wanna check glycemic index of food)
achieve optimal lipid levels
adequate calories to attain and maintain reasonable weight
prevention and treatment of chronic complications
improvement of overall health through optimal nutrition
What kind of foods have higher glycemic index and what kinds are lower?
High: Simple Carbs
Low: Fiber, Low Natural Sugar Foods
What are there for diabetics rather than specific diets or ADA diets?
No, there is rather a dietary prescription based on nutrition assessment and treatment goals
give simple recommendations –> Increased compliance (even from family)
self management ESSENTIAL
Help from registered dieticians is important!
How should nutrition therapy be done for Type 1 Diabetics?
Based it on individual’s usual food intake
They should be eating at a consistent time sync’d with the action time of their insulin prep use
Need to monitor blood glucose levels and adjust insulin doses for the amount of food they have eaten
insulin regimens should be integrated with lifestyle and adjusted for deviations from usual eating and exercise habits (need to test for both eating and working out)
What can give Type 1 Diabetics undergo to allow considerable flexibility in when and what the individual can eat?
Intensified insulin therapy, such as multiple daily injections or use of an insulin pump
normal testing occurs 3-6 times a day but an insulin pump gives a basal level every hour for more flexibility
How should nutrition therapy be done for Type 2 Diabetics?
Hypocaloric diets and weight loss
Moderate caloric restriction and nutritionally adequate meal plan
spacing of meals and spreading carbohydrate intake throughout the day
may require addition of oral hypoglycemics (or insulin)
How effective in the long run are hypocaloric diets and weight loss in Type 2 Diabetes treatment?
Usually improve short term glycemic levels and have the potential to improve long term metabolic control
BUT, no one proven strategy or method that can be uniformly recommended
What things are reduced in moderate caloric restrictions and nutritionally adequate meal plans for Diabetes Type 2?
Reduction of total fat, especially saturated fat
decrease as little as 250-300 calories a day
losing 5-7% of weight helps blood sugar level control
Why is alcohol moderated in diabetic nutrition?
less than 2 drinks a day because it raises blood sugar
What nutritional recommendation is lower for people with nephropathy?
protein to 10% rather than 10-20%
Benefits of using Exercise for Treatment in Diabetes
improved glc tolerance
weight loss or maintenance of a desirable body weight
improved cardiovascular risk factors
improved response to pharmacologic therapy
improved energy level, muscular strength, flexibility, quality of life, and sense of well being
What are some precautions and considerations when diabetics start exercising?
They should start at a low level and gradually increase to avoid injury, hypoglycemia, or cardiac problems
they should self monitor their blood glc level both before and after exercising
a form of sugar should be available in case of emergency
What is the best exercise to prescribe for a diabetic?
Aerobic activity at 50-70% of maximum oxygen uptake at least 3-4 times a week, and duration of 30-40 minutes/sessions
What is the best form of exercise for diabetics
aerobic exercises
ex: walking, biking, stationary cycling, lap swimming
What is proof of use of glucose available?
Weakness during exercise/ after exercise
Why is insulin never given orally
Insulin is destroyed in the GI tract so it must be administered by injection
How is insulin categorized
According to onset, peak, duration, and action
4 Types of Insulin
Rapid
Short
Intermediate
Long Acting
What is the only type of insulin that insulin pumps use?
Rapid Acting Insulin
In order to ensure a diabetic understands how to give themselves insulin what must occur?
Injectable protocols need to be taught/return demos
What other kinds of medicines can be used for Diabetics other than insulin?
Oral Agents
Injectable non-insulin medications
Examples of Oral Antidiabetic Agents
(just for Type 2 Diabetics)
Alpha Glucoside Inhibitors
Biguanides
Thiazolidinediones
Biguanides
Sulfonylureas
Meglitinides
Where and what does Alpha Glucoside Inhibitors do?
They act on the gut to block how much glucose is absorbed from food (decreased glucose absorption)
Where and what do Biguanides and Thiazolidinediones do?
Act on liver - decrease hepatic glucose output (prevents glucose from the liver release)
Act on cells to increase peripheral glucose uptake
Where and what do Sulfonylureas and Meglitinides do?
Increase insulin production
act on beta cells of the pancreas (must already have working cells for this to work so it does not work in Type 1, only 2)
Pancreatic Transplant
may be done if beta cells are not working
survival rate is higher for an individual is greater than a graft after 1 and 3 years, but the survival decreases in both over time
Not lifesaving, just increases QOL significantly
What is required forever after a pancreatic transplant?
Anti Rejection meds for life –> immunosuppression will result because of these
Pancreatic transplants are NOT ___ ___, but….
not life saving but do improve QOL significantly because this is more convenient than injectable insulin
What current research is occurring regarding pancreatic transplants?
Transplantation of Islet Cells (Langerhans/Beta Cells) - but for now it does not work well
Acute Complications of Diabetes
DKA
Hyperosmolar Hyperglycemia non-Ketotic Coma/Syndrome (HHNK, HHNC, HHNS) - mostly for type 2
Somogyi Effect
Dawn Phenomenon
Hypoglycemia
Main 3 Signs/Manifestations of Dehydration from Hyperglycemia?
Thirst
Increased heart Rate
Warm, dry skin
How does Hyperglycemia lead to Dehydration?
Increase blood glc –> increased blood osmolarity
increased blood osmolarity –> renal threshold exceeded –> osmotic diuresis –> dehydration
Increases blood osmolatiry –> cellular dehydration (cells shrink) –> dehydration
Dehydration –> thirst, increased HR, warm dry skin
One of the first symptoms of hyperglycemia is …
Thirst
Diabetic Ketoacidosis (DKA)
Acute insulin insufficiency with life threatening and dramatic presentation (acute and life threatening)
most typical in Type 1 Diabetes - often the first evidence of the disease
Onset in 1-24 hours - gets bad fast
Presenting History of DKA
one to several days of polyuria, polydipsia
nausea, vomitting, anorexia, acute abdominal pain
Precipitating Factors for DKA
failure to take insulin
infection or other illness
trauma or physical stress
emotional stress and extreme anxiety
pregnancy
continuous insulin pump failure
Pathophysiology/Progression of DKA
Inadequate insulin hinders glc uptake by fat and muscle cells –> glc accumulates in blood –> liver responds by converting glycogen to glucose and releasing into blood –> further blood glc increase –> renal threshold exceeded –> excess glucose excreted in urine
cell starvation –> rapid metabolism of protein for energy –> loss of intracellular K and phosphorus and excessive liberation of amino acids (catabolic process) –> liver converts amino acids to glucose and urea –> blood glc levels grossly elevated –> increased serum osmolarity and glucosuria –> osmotic diuresis leading to dehydration
Conversion of fats into glycerol and FA for energy
How does the conversion of fat to glycerol and FA for energy greatly influence DKA pathophysiology?
FA end up not being metabolized at the same rate of release so they accumulate in the liver and convert into ketones (ketoacids)
Ketones will accumulate in blood and urine causing acidosis (and build up in liver)
Acidosis leads to more tissue breakdown, more ketosis, more acidosis –> shock, death, coma
What is the deadly cycle of DKA?
massive fluid loss from osmotic diuresis –> fluid and electrolyte imbalances and dehydration –> water loss exceeds glucose and electrolyte loss –> hyperosmolarity –> perpetuates dehydration
DEADLY CYCLE: Decreased glucose excretion –> further increased blood glc levels –> hyperosmolarity and dehydration –> shock, coma, death
Physical Manifestations of DKA
Dehydration: Warm dry skin, dry mucous membranes, acute weight loss, tachycardia, weak thready pulse, hypotension
Ketoacidosis: anorexia, nausea, vomiting, acetone breath, abdominal pain, decreased CNS activity leading to lethargy/fatigue/stupor/coma
Compensation (to acidosis): Tachypnea and Kussmaul Respirations
Lab Manifestations of DKA
serum glucvose 250-600 mg/dL
glucosuria
ketonemia and ketonuria
ABGs: acidosis (pH less than 7.3) and decreased bicarbonate (<15 mEq/L)
Increased BUN d/t dehydration
Potassium levels high, low, or normal depending on degree of dehydration and acidosis, but there is total body depletion of K
What is the pathway of cell starvation leading to manifestations of DKA ?
No glucose for ATP production –> breakdown of fat and protein stores –> liver produces ketones –> ketoacidosis –> fruity breath, coma, kussmaul respirations
Kussmaul respirations
deep irregular breathing with pauses in between
Acetone Breath
sweet fruity breath from the ketones in DKA
Treatment for DKA
Fluid replacement (deficit of 5-8 L –> give 1-2 L of NS over 1-2 hours)
IV Regular insulin (cont drip or bolus)
K+ replacement once UO re-established (since K+ moves intracellularly)
Bicarbonate (if pH <7.2, but give cautiously b/c of CNS acidosis)
5% dextrose added when glucose <250
Why is 5% dextrose given when glucose is <250 in DKA treatment?
To prevent a swing in the opposite direction
sudden change in osmolarity can occur when the blood levels are changed to rapidly
Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNK)
relative insulin insufficiency with 50% mortality
DKA does not develop because there is still insulin available
most typical in Type 2 diabetes - often NOT previously diagnosed
How is HHNK onset different from DKA onset?
HHNK is insidious while DKA is acute and quick
Because of this HHNK is 50% higher in mortality than DKA
Presenting History for HHNK
polyuria several days to weeks prior
Precipitating Factors for HHNK
conditions that stress insulin tolerance like peritoneal dialysis, hemodialysis, tube feedings, and TPN
elderly with renal insufficiency
drugs: steroids, diuretics, Dilantin
infection, CVA
What manifestations of HHNK are unique and distinctly different from DKA?
There are neurologic symptoms and deficits that occur that do not occur with DKA
Because of this, sometimes HHNK is mistaken as a stroke
Physical Manifestations of HHNK Syndrome
Severe dehydration (dry mucous membranes and extreme thirst)
Neurologic Symptoms
What are the neurologic symptoms of HHNK
Depressed sensorium lethargy –> coma
deficits: positive babinski’s (ominous), paresis or paralysis, sensory impairment, hyperthermia, hemianopia
seizures
Is Dehydration worse in HHNK or DKA
HHNK
Laboratory manifestations for HHNK
serum glucose > 600 mg/dL
serum osmolarity > 300 mosm (high)
glucosuria
increased bun from dehydration (hypovolemia and decreased renal perfusion)
sodium and potassium WNL
decreased bicarbonate due to lactic acidosis from hypovolemia
NO KETOSIS!!!!!!!!!!!!!!
Is there ketosis in HHNK
No
this is because there is still some insulin present so there is not fat breakdown
Treatment for HHNK Syndrome
restore intravascular volume with NS
continuous IV insulin
potassium replacement
(RESTORE CIRCULATION VOLUME)
What are some other complications from HHNK Syndrome
Thrombosis (from hyperosmolar blood that is more sticky due to dehydration)
Embolus
Pneumonia
ARDS
Insulin Shock is also known as …
Hypoglycemia
What levels of glucose signify Insulin Shock
<50 mg/dL of glucose in the blood
causes many neurologic issues (ANS response, neuroglycopenia, etc)
What is the ANS response of insulin shock (hypoglycemia)
PNS: hunger, nausea, hypotension, bradycardia
SNS: anxiety, sweating, vasoconstriction, tachycardia
What occurs with the sign/symptom Neuroglycopenia (brain not getting enough glucose) for Insulin Shock
Altered cerebral function d/t brain cell starvation
headache
vagueness
decreased problem solving ability (probably cannot self treat at the moment)
slurred speech
emotional lability
convulsions
coma
People at risk for Insulin Shock (Hypoglycemia)
tight control, pump, or multiple injections
Beta blockers d/t no sympathetic effect
autonomic neuropathy
oral hypoglycemic agents
type 2 with excess insulin secretion
error in insulin dose
increased exercise
not enough food
failure to decrease insulin as infection or other stress resolves
How to treat insulin shock?
immediate ingestion of carbohydrates (CHOs)
glucagon IV, SQ, IM
Glucose levels below 30 can lead to…
coma
Onset of Hypoglycemia v DKA v HHNK
Hypo - Rapid
DKA - Slow
HHNK - Slowest / Insidious
Symptoms of Hypoglycemia v DKA v HHNK
Hypo - weak, anxious confused
DKA - N/Vm 3 P’s, headache, irritable, coma
HHNK - similar to DKA< stupor, focal motor seizure
Skin of Hypoglycemia v DKA v HHNK
Hypo - cold moist and pale
DKA - hot flushed and dry
HHNK - very dry
Mucous (membranes) of Hypoglycemia v DKA v HHNK
hypo - normal
DKA - dry
HHNK - very dry
Respirations of Hypoglycemia v DKA v HHNK
Hypo - normal
DKA - hyperventilation
HHNK - normal
Diabetic types at risk for Hypoglycemia v DKA v HHNK
Hypo - both 1 and 2
DKA - 1
HHNK - 2
Blood glucose levels in Hypoglycemia v DKA v HHNK
Hypo - less than 60
DKA - 300 to 800
HHNK - 600 to 4800
Serum Ketones in Hypoglycemia v DKA v HHNK
Hypo - none
DKA - high
HHNK - moderate to none
Plasma pH in Hypoglycemia v DKA v HHNK
Hypo - normal
DKA - acidic
HHNK - normal
Treatment for Hypoglycemia v DKA v HHNK
Hypo - IV glucose and SQ glucose
DKA - insulin F & E
HHNK - Insulin, crystalloids and colloids
Somogyi Effect
Unrecog hypoglycemia at night (or when fasting) –> increased catecholamines, glucagon, cortisol, and GH –> hyperglycemia in the morning –> we increase their exogenous insulin –> more hypoglycemia occurs at night –> vicious and dangerous cycle that repeats leading to insulin resistance eventually
Somogyi effect often goes together with the …
dawn phenomenon
What should be done to limit unneeded exogenous insulin regarding the somogyi effect?
Take blood sugar in the middle of the night/ at 3 am to note the hypoglycemia
Dawn Phenomenon
naturally occurring hormonal effect between 3 am and 5 am there there is a pre dawn hyperglycemia (increase) without antecedent hypoglycemia
could be due to changes in circadian rhythm
it is the liver giving you an “early morning snack”
GH is a possible factor in this
What type of Diabetic is more likely to experience the Dawn Phenomenon
Type 1 Diabetcs
What is the different when the dawn phenomenon is alone, versus when it combines with the Somogyi effect?
alone –> mild hyperglycemia
in combo –> profound hyperglycemia!
When should we check glucose for the dawn effect?
always check at night like at 3am, BUT check at 7 am whether at home or in the hospital since you were not hyperglycemic during the night, only now
What tissue are MOST affects by elevated blood glucose levels?
body cells NOT dependent on insulin to use glucose –> most affected by chronic elevated blood glc levels
- RBCs (less oxygen carrying capacity)
- Glomerular Cells (kidney damage)
- Central and peripheral Nerve cells (neuro deficits)
- Blood vessel cells (leads to atherosclerosis)
What about diabetes kills diabetics?
Not high blood sugar, but the long term damage, dysfunction, and organ failure associated with it
What areas have the most long term damage from hyperglycemia?
Eye - diabetic retinopathy
Kidney - diabetic nephropathy
Nerves - diabetic neuropathy
Heart and blood vessels - atherosclerosis, hypertension, cardio and cerebrovascular disease
Macrovascular Problems (Chronic Complications) of Diabetes
These are chronic issues leading to less circulation:
CV Disease
Cerebrovascular Disease
Peripheral Vascular Disease (PVD)
Microvascular Problems (Chronic Complications) of Diabetes
Issues for Smaller Vessels and Nerves:
Diabetic Neuropathy
Diabetic Nephropathy
Diabetic Retinopathy
Erectile Dysfunction
Erectile dysfunction often brings undiagnosed diabetics in, but what may this symptom indicate?
May mean the heart is not delivering blood effectively!
What/Where are Macrovascular complications from Hyperglycemia
Hyper –> Heart –> CAD (Coronary syndrome, MI, CHF)
Hyper –> Brain –> Cerebrovascular accidents (TIA, CVA, Cognitive impairment)
Hyper –> Extremities –> Peripheral Vascular Disease (ulceration, gangrene, amputation)
All of these can lead to death and or disability
What/Where are Microvascular complications from Hyperglycemia
Hyper –> Eye –> Retinopathy, Cataract, Glaucoma –> Blindness
Hyper –> Kidney –> Nephropathy (microalbuminuria, Gross albuminuria) –> Kidney Failure
Hyper –> Nerves –> neuropathy (peripheral and autonomic) –> amputation
All of these can lead to death and or disability
What are some Long Term Complications of Diabetes
Cardiovascular (accelerated atherosclerosis - CAD, HTN, CVA, PVD)
Eye - retinopathy, cataracts, glaucoma
Renal - nephropathy and glomerulosclerosis
Nervous - axonal and Schwann cell degeneration; sensory and motor nerve alterations
Bone - charcots changes in joints
Skin and Immune - increased susceptibility to infection and delayed wound healing
What are the 2 classifications of peripheral neuropathies?
Somatic and Autonomic
What are the 2 processes causing Neuropathy in Diabetes?
- Thickening of vessel walls that supply nutrients to nerves leading to less blood flow
- Segmental demyelination affecting schwann cells leading to slower nerve conduction
What are some Somatic Neuropathies
Polyneuropathies - paresthesias, impaired sensation, diminished reflexes
Mononeuropathies - involvement of a mixed nerve trunk –> motor and sensory nerves affected
Amyotrophy –> muscle weakness and wasting
motor usually bilateral and symmetric and usually occurs first
clawing of the foot
hypersensitivity of light is secondary to retinopathy
What are some Autonomic Neuropathies
Impaired vasomotor function - postural hypotension
Impaired GI function - gastric atony, diarrhea (from impaired nutrient absorption) (poor gastric tone) (postprandial and nocturnal)
Impaired GU Function - paralytic bladder, incomplete voiding, impotence, retrograde ejaculation
Cranial nerve involvement - extraocular nerve paralysis, impaired pupillary responses, impaired special senses
What is the major cause of death for diabetics?
Cardiovascular Disease
Manifestations of Cardiovascular Disease in Diabetics
Accelerated Atherogenesis (onset earlier age, progression more rapid, manifestations of this are more severe in diabetes) (CAD Means that less blood gets to the heart)
Hyperlipoproteinemia (HDLs lower in uncontrolled in DM)
Abnormal platelet function (more clots and bleeding)
*Decreased HDL, increased LDL, increased atherosclerosis, increased total cholesterol, increased triglycerides
How to manage Diabetic Cardiovascular Disease
management:
Diet
weight loss
exercise
quitting smoking
controlling HTN
A 40 year old with diabetes that does not smoke, no HTN, and has normal cholesterol has ___risk of CVD
half the risk of CVD
CVD increases __x for diabetics with HTN, ___x with high cholesterol, and ___x for smokers
2x HTN
8x High Cholesterol
11x Smoking
Which type of diabetes has a higher eye disease incidence?
type 1 diabetes (5000 new cases a year)
___ is the leading cause of blindness
retinopathy
Retinopathy is ___ and ___ with duration
Retinopathy is progressive and worsens with duration
2 Types of Retinopathy
Non proliferative “background”
Proliferative “neovascularization”
Non Proliferative “Background” Retinopathy
retinal veins tortuous and dilated
exudates contain lipoproteins
hemorrhages
scarring
retinal detachment
Proliferative “Neovascularization” Retinopathy
traction on vitreous –> detachment
treatment involves laser surgery to destroy new blood vessels and stop hemorrhaging or a Vitrectomy
Glaucoma
capillary neovascularization often refractory to treatment
potential retinopathy in diabetics
cataracts are made of sorbitol which is glucose turning into sugar alcohol. It then accumulates to cause glaucoma
damages optic nerve
Cataracts
retinopathy frequent in diabetics
increased sorbitol (glucose turning into sugar alcohol) in the lenses
cloudy dense lense
treatment involves surgery
Blurred Vision
retinopathy in diabetic due to osmotic changes –> takes 6-8 weeks to resolve
Diabetic eye vascularization …
is much more vascularized than in non diabetics
this is proliferative
Number one risk for cataracts is ___ and vice versa
Galucoma
Glaucoma v Cataract as you see it visually
Cataracts have a milky opacity
Glaucoma is more increased pressure leading to blindness
Nephropathy
kidney issues
What occurs early versus late stage nephropathy in diabetics
Early: Kidney hypertrophies, and GFR increases and albuminuria in new onset type 1 diabetes
Late: Basement membrane changes, proliferation and leakiness
Albumin escapes in the blood and less wound healing occurs and less glomerular filtration rate occurs with potential kidney failure in 5 years
Manifestations of diabetic nephropathy
proteinuria
progressive decrease in GFR
ESRD in 5 years with persistent proteinuria
AVOID contrast studies (IVPs, angiograms)
Treatment for Diabetic Nephropathy
dialysis or kidney transplant
How to prevent Diabetic Nephropathy
ACE inhibitors to protect the kidneys
avoid things hard on the kidneys like contrast studies
*not much can be done genetically, but HTN can be treated
How do ACE inhibitors help prevent Nephropathy?
ACE = angiotensin converting enzyme inhibitors (these block receptors to lower BP and protect the kidneys)
Oncotic Pressure
osmotic pressure resulting from the difference between extracellular fluids like protein contents of plasma and interstitial fluids - pressure exerted by proteins on the walls
The most common disabler for diabetics is ___
neuropathy (lack of sensation)
Death is ____ from neuropathy alone BUT ..
death is uncommon from neuropathy alone but significant morbidity and decreases in QOL occur
The key to stopping neuropathy is ..
Prevention !!!
Inspect for trauma, blisters, callouses
assure shoes are a good fit!
Common issues due to Neuropathy and causes of neuropathies
Gangrene
Underlying Osteomyelitis (Bone Infection)
Vessel ischemia and sorbitol damage to Schwann cells lead to this
Neuropathic ulcers especially on the plantar surface of the foot –> penetrating wounds that a person does not feel occur
Common Neuropathic and Lower Extremity issues in Diabetics
Diabetic Foot Ulcer of the Heel
Gangrenous Toe
Yellow Nails
Corns
Calluses
Acanthosis Nigricans - darkening of skin
Charcot Foot
Infection
Candidiasis
Diabetic Foot Disease
Why does diabetes increase susceptibility for infection?
hypoxia
increased glucose to feed microorganisms
decreased WBC delivery through damaged vessels
decreased WBC function –> abnormal chemotaxis and phagocytosis
How do insulin requirements change with diabetic infections
Insulin requirements increase with infections and decrease with resolution
What are some examples of infections for diabetics?
Carbuncles and Furuncles
Vaginal Candidiasis
Carbuncles and Furuncles
Furuncles are infected hair follicles
Carbuncles are groups of furuncles
Candidiasis
Yeast infection on skin or between digits
common in diabetics
Cellulitis
red, warm, swelling, and enlarging of the infected subcutaneous tissue
can present, for example, as red lines and blotches on the skin
Charcot’s Foot
Common in diabetics (neuropathy)
damage to nerves leads to clawing of toes and less padding on the plantar surface of the foot
Decreased sensation and abnormal bone deposition occurs as well
foot cannot be put down correctly
may not feel a broken bone due to lack of sensation
Diabetic Foot Disease
Issues of the foot due to uncontrolled high blood glucose levels in diabetics
commonly leads to amputation and that may be the only treatment available sometimes
effects are due to neuropathy and vascular disease in the feet
requires a yearly check up for the foot disease
can have gangrene and exposed bone covered with granulation tissue that they do not feel
Diabetic Foot Disease accounts for how many amputations a year?
20,000 amputations a year - primarily of toes, feet, and legs
accounts for 1/2 of all non traumatic amputations
may be the only treatment for diabetic foot disease infection
The most common complication leading to hospitalization for diabetics is …
diabetic foot disease
