FINAL: DIABETES Flashcards
Where is insulin produced?
in the BETA islet cells of the pancreas:
○ Alpha Islet cells produce glucagon
○ Insulin released form the B cells is not the true form used by the cells
▪ There’s a process of activation
○ The insulin then attaches to many cells
▪ Mainly muscle, fat, and tissue cells
▪ There are certain cells that don’t use
insulin
○ Without insulin attaching to the cell, glucose CANNOT enter the cell
** diabetes is a disease where the body doesn’t produce or use insulin properly **
What is DM and what does it affect?
a GROUP of metabolic disorders
- Impaired metabolic functioning affecting fat, carbs, and protein metabolism
- Characterized by HYPERglycemia (in all types)
Who is DM more prevalent in?
all age groups but affects more of the minority population and older adults (65+):
- American Indian/Alaskan Natives
- Black
- Hispanic
- Asian
- White
** it is the 7th leading COD in the USA **
What can DM cause in a patient?
○ Number 1 cause of blindness
○ Number 1 cause of END-stage Renal Disease (ESRD)
▪ Number 2 = HTN
○ Number 1 cause of lower extremity of amputations
○ Major r/f for MI and CVA
○ Large medical expenses and diminished QOL (1/3 of medicare budget)
What are some historical perspectives of DM?
- Egyptians found urine to be sweet
- Greeks described polydipsia (excess thirst) and polyuria of sweet urine
- Research in the US (1921) Banting & Best discovered the hormone insulin in dogs
Which diabetes develops as a child?
Type I: they MUST inject insulin or they will die
** ABSOLUTE INSULIN DEFICIENCY **
▪ Caused by either:
□ Type 1A- Immune mediated response
(autoimmune destruction of B cells)
□ Type 1B - Idiopathic (unknown etiology)
Describe some elements of type II diabetes:
○ Most common
○ Can be managed w/ diet
○ Others take oral meds that stimulate the pancreas and the insulin process
○ Progressive disease
▪ After about 10 yrs, they are likely to
need to have insulin supplements
▪ Due to exhaustion of cells
○ Combination of decreased insulin production and cellular resistance to insulin
** Unmanaged Type II can lead to Beta cell exhaustion and lack of insulin production and require insulin injections **
What are some contributing factors to hyperglycemia?
- Pancreas:
○ Impaired insulin secretion/production - GI:
○ Absorption of glucose from diet - Liver:
○ Inappropriate glucose production
▪ Breaks down glycogen stores even if
there is BG from GIT absorption - Muscle:
○ Decreased insulin-stimulated glucose
uptake
▪ Glucose sparing for the brain and other
vital organs
Describe the effects of the pancreatic hormone insulin:
○ Secreted by B cells in pancreas
○ Lowers the blood glucose by attaching to cells’ insulin receptors, allowing glucose to enter the cell
▪ If there is excess glucose, it is stored as
glycogen
○ Prevents the breakdown of fat and glycogen stores in the liver and lipid tissues
▪ Works to build fat to reduce the blood
sugar levels
▪ Also inhibits gluconeogenesis
○ Increases protein synthesis, fatty acid transport into ADIPOSE tissues
▪ Increases transport of AA into protein
cells
○ Inhibits the lipase in adipose- preventing breakdown of fats
○ Target Cells:
▪ Some cells don’t require insulin for
glucose uptake (liver, brain, RBC)
▪ All other cells require insulin to uptake
glucose into the cells.
What controls glucose levels?
□ Insulin secretion
□ Uptake of glucose by peripheral tissues
□ Glucose production in the liver
- Can either store glucose as glycogen or
through gluconeogenesis -> breakdown
glycogen stores to increase blood glucose
levels
- Liver can inappropriately increase blood
glucose levels in diabetics
What is the pathogenic process of diabetic hormones?
▪ Autoimmune destruction of B cells (type I)
▪ Insulin resistance (type II)
□ Obesity is a risk factor for type II
▪ Diminished tissue responsiveness to insulin
□ Leads to hyperglycemia, then eventually
overt diabetes
What is the effect of glucagon in the body and when is it used?
○ It increases blood glucose levels
▪ Coverts stored glycogen in liver to
glucose
▪ Released of glucagon stimulated by low
blood sugar levels
○ Used for children with HYPOglycemia to induce the liver to break down glycogen stores to increase blood glucose levels
What is the effect of amylin in the body and when is it used?
○ Islet amyloid polypeptide
○ Co-secreted from the B cells of the pancreas (along with insulin)
○ Released in response to nutritional stimuli
▪ Slows the movement of food through
the stomach to lower the postprandial
blood glucose (2 hours after meals)
□ Blood sugar should be normal at this
time (below 140)
□ Persons with diabetes, manage the
level between 140-180
▪ This is the clinical significance (lowers
postprandial glucose)
○ May cause degeneration of the beta cells and contribute to development of T2DM
What is the effect of somatostatin in the body and when is it used?
○ Released by the Delta pancreatic cells
○ Inhibits the release of insulin & glucagon
○ Decreases GI activity after ingestion of food
▪ Thus increasing the amount of time it
takes for the food to absorbed into the
bloodstream
○ Clinical significance: synthetic forms of hormone not used in diabetes but used in acromegaly and other growth hormone disorders.
What 4 hormones control the regulation/absorption of glucose, AA, & fatty acids?
- insulin
- glucagon
- amylin
- somatostatin
What is incretin (GILA MONSTER) and its effects on the body?
Intestinal hormones in response to ingestion of food
▪ Increases the insulin response to get
glucose in the cells
▪ Responses to incretin in T2DM is
decreased (not as effective)
What are the two main types of incretins and what are they degraded by?
- GIP
- GLP-1
** GIP and GLP-1 are rapidly degraded by the DPP-4 Enzyme **
What is exenatide and when is it used?
a synthetic GLP-1 that is resistant to the DPP-4 enzyme, and thus lasts longer in the bloodstream
□ Since the synthetic GLP-1 is in the
bloodstream longer, it potentiates the
insulin release
▪ Given by injection to potentiate insulin release
▪ A synthetic DPP-4 agent (Januvia) has been developed to decrease hyperglycemia
□ DPP-4 AGENT used to deactivate DPP-4
ENZYME
□ Is that why the DPP-4 agent is used to
decrease hyperglycemia???
What are some other specific types of diabetes?
○ Most of the times these are genetic in nature
○ Endocrine disorders (Cushing’s): Prolonged cortisol release, causes increased/prolonged gluconeogenesis
○ Diseases of the Pancreas (pseudocysts)
○ Gestational DM: develops during pregnancy (may or may not end after pregnancy)
How is DM diagnosed?
- Fasting Blood Glucose (FBG)- (Traditional Method)
○ 126 mg/dl or higher
▪ Diagnostic of DM
▪ Normal = 70-100
○ This is the blood glucose after 8 hrs of
fasting - Hgb A1C
○ 6.5% or higher to Dx
▪ Normal is about 4-6%
▪ Diabetic want to keep it below 7%
○ Shows how long the RBC has been in
circulation and being glycosylated
(coated) with glucose
▪ Hgb is saturated with glucose over
time
▪ If you have high blood glucose levels
for a long time, the A1C level will be
higher
> Like in poorly managed diabetes,
there is circulating glucose in the
blood and it glycosylates the RBC - 2 hours Plasma Glucose
○ 200 mg or higher to Dx
▪ This is postprandial (2 hours after
meals)
○ This test is done by giving an oral dose
of glucose
▪ Oral Glucose Tolerance Test (OGTT) of
75 grams of glucose - With signs of HYPERglycemia, do a random glucose screening
○ Anything over 200 mg = DM
How is gestational diabetes diagnosed and treated?
Dx:
○ FBG = 92+
○ 1 hr = 180 mg/dl or higher
○ 2 hr = 153
Tx:
○ Preferably treated with INSULIN supplements
○ Or can use glyburide or Metformin
** ANY FORM/DEGREE OF HYPERGLYCEMIA is teratogenic and can cause abnormalities **
What causes islet cell destruction in type 1 DM?
** IT IS A MULTIFACTORIAL DISEASE **
○ Genetic predisposition
- Genetics
□ Diabetes can aggregate in families
□ Concordance rate for twins is 50%
□ Exact mode of inheritance is unknown
○ Autoimmunity (The reason someone has Type I DM, the CD4 & CD8 (T-cells) are attacking the pancreas and causing a total inability to produce insulin)
▪ 90% pts have circulating islet cell
antibodies within a year of Dx
▪ Approximately 10% have other
autoimmune disorders include:
□ Grave’s Disease, & Addison’s Disease
○ Environmental insult/effects
▪ Viruses are suspected as initiators the
insult and causes Type I diabetes
▪ There has probably been a long latency
period of the virus in the body with
subsequent beta cell loss
▪ Chemical toxins and ingestion of cows
milk as an infant
What are the s/sx of type I DM?
○ Polydipsia, polyuria, polyphagia, & weight loss
▪ Increase the eating but losing weight
▪ Glucose is a very large molecule
□ As it move through renal tubule, it filters
out as urine and it draws water through
osmosis.
□ Some weight loss is due to the loss of
water weight
> And also due to the glucose being
excreted as urine and not going into the
cells for use/storage
□ GLUCOSE IS AN OSMOTIC DIURETIC
(polyuria)
> Causing the thirst, hunger, and weight
loss
○ Most common in younger population (under 30)
○ Leaving untreated can progress to Diabetic Ketoacidosis (DKA) = coma/death
How is Type I DM treated?
through exogenous INSULIN (primary), Medical Nutrition Therapy (MNT), and physical activity
When should pts w/type I DM check their insulin?
○ Fasting Blood Glucose as needed to monitor Diagnoses
○ Need blood glucose monitors when injecting insulin
▪ Type I check a minimum of 4 times per
day before meals
○ A1C- check this 3-4 times annually for T1 & T2
○ Medicare/Medicaid will cover most of these costs
What are some r/f for T2DM?
○ Need a FHx of Type II in a 1st or 2nd degree relative
○ Minority races/ethnicity
○ Signs of insulin resistance (metabolic syndrome)
▪ HTN, dyslipidemia, PCOS, acanthosis
nigricans (dark streak across the neck)
○ Low birth weight; Maternal Hx of gestational DM during pregnancy
○ Hx of GDM
○ DM related complications:
▪ Neuropathy, nephropathy, retinopathy
(damage to the retina), gastroparesis
(extremely bad diarrhea and damage to GI
nerves)
How can T2DM be delayed or prevented?
○ Target the pt to lose 7% total body wt. loss and increase physical activity to at least 150 min/wk
○ Metformin can be used for prevention of Type II
▪ Used in those with impaired glucose
tolerance, impaired fasting glucose or an
A1C of 5.7 -6.5%
▪ Especially used in those with high BMI,
below the age of 60, and prior to onset of
GDM
○ Individualized MNT (med. Nutritional therapy)
▪ Registered dietician used to change
nutritional behaviors
○ Diabetes Testing for Asymptomatic Adults
▪ If they are asymptomatic, of any age, are
overweight/obese, or who have at least 1
risk factor = get tested annual
▪ If no risk factors = annual testing at 45
▪ Repeat every 3 if first test was normal
What causes T2DM?
○ The presence of insulin resistance
▪ Decreased number of insulin receptors
(associated with obesity)
▪ Person is usually producing insulin but
there is still hyperglycemia
○ Beta Cell Failure in the future
▪ Due to exhaustion
▪ Then they will REQUIRE INSULIN
INJECTIONS
○ Genetics
▪ Concordance rate b/w twins is 90%
▪ No evidence of autoimmunity (like in
Type I)What is the patho for T2DM?
○ Insulin resistance
▪ Insulin resistance is the MAIN etiology
of Type II DM
▪ Impaired attachment of insulin to the
target cell
▪ Results in elevated blood glucose levels
○ Inappropriate liver glucose production (especially at night)
○ Dyslipidemia
▪ LDL’s & triglycerides are high (HDL’s are
low!)
▪ Free floating Fatty Acids and
Triglycerides will accumulate in the liver…
This causes the liver to
be less responsive to insulin and results in
INAPPROPRIATE GLUCOSE PRODUCTION
BY THE LIVER
▪ Dyslipidemia In Type II DM:
> There’s an eventual decrease in insulin
release by the Beta Cells, resulting in
abnormal lipid values
- Increased LDL’s
- Increased Triglycerides
- Decreased HDL’s
- The increased Triglycerides &
decreased HDL’s are indicators of
Metabolic Syndrome
What are the s/sx of T2DM?
○ Hyperglycemia
○ Most common over the age of 40
▪ Between the age of 30-40, is the
grey/unknown zone (Type I most
prevalent in under 30)
○ Acute classical signs like in Type I
○ Usually present with signs of complications-
▪ Vision blurring, fatigue, paresthesias,
skin infxn, foot ulcers, vulvovaginitis (yeast
infxn)
□ Vision Blurring- glucose is chunky
causing vessels in the eye to burst..
- Eye starves with no O2 causing death
and vision blurring/blindness
How is T2DM treated?
○ Dietary management
▪ Individualized diet plan to focus on mild-
moderate weight loss
▪ Limit fat intake to less than 30% calories
from fat
▪ Count your carbs – should be eating the
same number of carbs throughout the day
every day
▪ Maintain normal protein levels
□ Can be contraindicated with those with
kidney disease
○ Exercise
▪ 150 min/wk
▪ Exercise is shown to decrease blood
sugar and also promotes weight loss
○ Oral meds
▪ Lower blood glucose
▪ Usually start with 1 med, and then can
increase number of meds
□ Usually start with Metformin then add
another if needed
▪ Insulin injections may be needed
Facts about prediabetes:
▪ Diabetes = 126+
▪ Prediabetes = 100-125.9
▪ Normal is 70-100
▪ Significance
□ Only applies to Type II DM
□ Diagnostic Criteria:
- Impaired glucose tolerance- post
prandial (140-180)
- Impaired Fasting Blood Glucose = 100-
125
- HbA1C = 5.7-6.4%
** Diabetes Prevention Study- maintaining good glucose control, is heavily significant in preventing serious complications **
What test monitor/manage T2DM?
- Glycosylated (HbA1c)
○ Goals for diabetics = LESS THAN 7%
▪ If there are other medical issues, the
goal is held to below 8%
□ More loose with the guidelines due
to other health issues (normal = 4-6%) - Self-Monitoring of Blood Glucose (finger stick)
Facts about T2DM in children:
○The obesity epidemic in children has caused a rise in Type II in children
○ Risk Factors:
▪ Low levels of exercise (no PE in school)
▪ High fat levels in food in school lunches
▪ Coke/Soda/Vending machines in
schools
○ Metformin is used to treat/prevent
What are the effects of catecholamines on BG?
- Epi, and Norepi raise BG levels during times of stress
○ Released by the Adrenal Gland
○ Usually in trauma situations, post-op,
and other times of severe stress (bodily
stress), they will have hyperglycemia
even though they may NOT have Dx DM - Catecholamines inhibits the release of insulin, and promotes glycogenolysis by converting stored glycogen to glucose
What are the effects of glucocorticoid hormones on BG?
- Raise BG by stimulating the liver to break down glycogen stores
- Can actually cause DM in “borderline” persons
- CORTISOL drugs (prednisone, etc.) can make it difficult to maintain normal BG levels
○ These drugs are typically given to
transplant pts. Which causes them to
become Diabetic
When does DKA occur and what problems result?
○ Occurs when diabetes is out of control (more common in T1DM)
○ 3 major metabolic problems:
▪ Hyperglycemia - Dangerously high
levels of glucose
▪ Ketosis (presence of ketones in the
blood)
▪ Metabolic acidosis (ketones are acid
bodies)
> Body tries to normalize the acidosis
caused by ketones and depletes the
stores of NaCO3
What are some r/f for DKA?
□ Newly diagnosed
□ Not taking sufficient insulin (you will die)
□ Too little exercise, too much food, Stress, infxn
- All of these cause an increase in BG levels
▪ Slow onset over several days…… unlike hypoglycemia
What are some s/sx of DKA?
▪ Classical Signs of DM (3 P’s)
▪ Abdominal pain/tenderness
▪ Fruity Breath (due to ketones in the blood)
▪ Kussmaul’s Respirations
▪ Hypotension/hypovolemic (due to polyuria)
▪ Decreased Level of Consciousness
□ Will progress to coma if no intervention
(INTERVENTION MUST BE INSULIN)
▪ Death can result from metabolic acidosis and hypovolemic shock
What is the patho for DKA?
▪ Body switches from carb metabolism to fat metabolism
▪ Ketones are intermediate products from incomplete metabolism of fat
□ Will be able to measure ketones in the
blood and urine
▪ Ketones are acid bodies, causing acidosis
▪ Kussmaul’s Respirations: Body will try to compensate with increasing respirations (very rapid
deep respirations)
□ Body is trying to blow off CO2, to
balance the acid levels in the body
What are the expected lab findings of a pt diagnosed with DKA?
▪ Hyperglycemia (Blood Glucose above 250 mg/dL)
▪ Low Bicarbonate (less than 15)
▪ Decreased pH/acidic (less than 7.3)
▪ Ketonemia & Ketonuria
□ Ketones are present in the blood and
the urine
▪ Sodium levels are low & Potassium levels are elevated
□ DKA causes hyperosmolality of
extracellular fluid
□ Thus Intracellular Water & K+ shifts to
the extracellular component
□ This causes a “pseudo-hyponatremia”
due to the intracellular-extracellular fluid
shift
- AKA sodium levels are relatively low
How is DKA treated?
▪ GIVE IV INSULIN
▪ Replace low electrolytes and monitor them every hour
▪ Usually admitted to the ICU
▪ Need to identify the underlying cause then treat the cause
What is hypoglycemia and how is it caused?
- When BG is < 53 or 70; its an acute complication of DM and requires fast intervention to prevent coma or death
- Causes include:
▪ Too much insulin or oral agents
(metformin),
▪ Too much exercise
▪ Too little food
What are the s/sx of hypoglycemia?
▪ Confusion, HA, slurred speech, hunger, hypotension, diaphoretic, pale, tachy (in children, physical behavior changes result)
▪ Sweaty, pale, cool, clammy & increased HR due to the stress of the situation
▪ Each personal responds differently
▪ Sometimes, the person can be unable to feel the effects of low BG
□ Called Hypoglycemia Unawareness
□ Very dangerous… will go straight into
coma if unaware of sxs
What is the patho for hypoglycemia?
▪ Low BG means that the cells are starving and unable to conduct proper cell functions (the brain must have glucose)
▪ The sympathetic nervous system is activated (inc. HR, sweating, HA, confusion, etc.)
How is hypoglycemia treated?
▪ Administer 15 g of glucose (15 x 15)
□ Candy, orange juice, etc.
▪ Then follow with complex carb
□ Milk, bread, etc.
▪ If unconscious, give IV 50% glucose
□ Glucagon can be given to Type I pt.What is HHS and when does it occur?
Hyperglycemic Hyperosmolar State, occurs when BG >600 and plasma osmolarity is above 320 mOsm/L
What can HHS result in?
○ Dehydrated due to increased osmolality (review)
○ Depressed sensorium
▪ Limited ability to respond cognitively to
situation
▪ Different from clinical depression
○ Can cause cerebral edema due to hyperosmolality!
▪ Includes severe potassium loss and
severe dehydration
□ Potassium loss results from the diuretic
actions of the hyperosmolar state
○ Main focus is HYDRATION….. Not insulin
○ Seen most frequently in elderly people with Type II due to the insidious onset
○ Complications:
▪ Severe K+ loss
▪ Cerebral edema (and its effects)
▪ Severe Dehydration
The BG level is ______ in hypoglycemia and ______ in DKA
below 53; above 250
The normal FBG level is:
< 100
Hypoglycemia is usually felt with a glucose level of:
< 50-60
A person with hypoglycemia should receive:
glucose IV (rule of 15: give 15g of glucose every 15 minutes, 3x)
A person with DKA should receive:
IV insulin and electrolytes
What are some chronic complications of DM?
- blindness, amputations, renal failure (Need an annual microalbumenuria exam), CAD, MI (most common COD in DM is cardiac complications)
Types of chronic complications:
○ Peripheral Neuropathy (nerve damage…
think of foot ulcers, etc.)
○ Nephropathy
○ Retinopathy
○ Skin lesions & foot ulcers
What is the patho of polyol pathway?
▪ Hydroxyl Groups (OH-) on the glucose are converted to Sorbitol & Fructose
□ Sorbitol causes swelling and clouding in
the lens of the eye (NOT retinopathy)
▪ Polyol Pathway affects the eye lens, kidneys, nerves, & blood vessels
What is the patho of formation of glycoproteins?
▪ Glycoproteins are usually found in the basement membranes of capillaries
▪ Increased levels of blood glucose favors the formation of even more of the Glycoproteins
□ Causes a disruption of capillary
exchange due to narrowing of the vessel
▪ Affects the Eye, Kidney, & Vascular System
What is the patho of tissue oxygenation?
▪ RBC dysfunction that interferes with the release of O2 from the hemoglobin
What is the patho of protein kinase C?
▪ Protein Kinase C is an intracellular signaling molecule
□ Regulates vascular functions:
- Permeability, vasodilation, endothelial
activation, & growth factor signaling
▪ DM causes an increase in Protein Kinase C
□ Activation of PKC in the retina, kidney, &
nerves can cause vascular damage
□ Also causes disorders in mitochondrial
function
What is the ADA recommendations for diabetic pts with blindness/retinopathy issues?
▪ Annual dilated pupillary exam
What should be assessed when considering neuropathy of diabetic pts?
○ Majority of DM population has some form of nerve damage
○ Recommendation is to check their feet without shoes/socks at every provider visit
▪ Looking for hair loss, thickened nails,
check their sensation
○ Foot and Leg:
▪ Thickening of the basement membrane
of the capillaries supplying the nerve (dec.
blood flow could lead to necrosis)
▪ Demyelination occurs causing a slowing
in nerve conduction
▪ Sensory neuropathy = loss of
pain/pressure sensation
▪ Yearly foot care appts w/specialist
How can a pt prevent peripheral neuropathy?
▪ Control blood sugar!!!!!! ▪ Daily inspection of feet ▪ Always wear shoes inside and outside ▪ Don't use heating pads ▪ Break in new shoes gradually ▪ Trim nails carefully
What are some DCCT research conclussion?
- Intensive therapy with insulin-dependent DM, delays the onset and slows the progression of retinopathy
- Intensive therapy reduces the risk of albuminuria (protein in the urine) and thus slows the progression of End Stage Renal Disease (ESRD)
- Intensive Insulin Therapy reduces the risk of long term complications!!!
○ But there is a 3x risk of HYPOGLYCEMIA
How can DM be managed in adults?
- Dietary Management
- Rx for exercise (150 min/week)
- Hyperglycemic Control
○ Control through insulin administration or
oral agents (except Type I) or both - Monitor Blood Glucose levels
- Monitor Blood Pressure
○ Must be lower than 130/80
○ Achieved through ACE Inhibitors or ARB
▪ Usually need to use 2+ agents to keep
BP down - Manage Dyslipidemia
○ LDL’s between 70-100
○ HDL above 50
○ Triglycerides below 150
- Change their lifestyle!
○ Increase activity, promote weight loss,
and smoking cessation
