FINAL: DIABETES

Question 1

Where is insulin produced?

Answer 1

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 **

Question 2

What is DM and what does it affect?

Answer 2

a GROUP of metabolic disorders

• Impaired metabolic functioning affecting fat, carbs, and protein metabolism
• Characterized by HYPERglycemia (in all types)

Question 3

Who is DM more prevalent in?

Answer 3

all age groups but affects more of the minority population and older adults (65+):

1. American Indian/Alaskan Natives
2. Black
3. Hispanic
4. Asian
5. White

** it is the 7th leading COD in the USA **

Question 4

What can DM cause in a patient?

Answer 4

○ 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)

Question 5

What are some historical perspectives of DM?

Answer 5

• 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

Question 6

Which diabetes develops as a child?

Answer 6

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)

Question 7

Describe some elements of type II diabetes:

Answer 7

○ 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 **

Question 8

What are some contributing factors to hyperglycemia?

Answer 8

• 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

Question 9

Describe the effects of the pancreatic hormone insulin:

Answer 9

○ 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.

Question 10

What controls glucose levels?

Answer 10

□ 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

Question 11

What is the pathogenic process of diabetic hormones?

Answer 11

▪ 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

Question 12

What is the effect of glucagon in the body and when is it used?

Answer 12

○ 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

Question 13

What is the effect of amylin in the body and when is it used?

Answer 13

○ 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

Question 14

What is the effect of somatostatin in the body and when is it used?

Answer 14

○ 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.

Question 15

What 4 hormones control the regulation/absorption of glucose, AA, & fatty acids?

Answer 15

• insulin
• glucagon
• amylin
• somatostatin

Question 16

What is incretin (GILA MONSTER) and its effects on the body?

Answer 16

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)

Question 17

What are the two main types of incretins and what are they degraded by?

Answer 17

• GIP
• GLP-1

** GIP and GLP-1 are rapidly degraded by the DPP-4 Enzyme **

Question 18

What is exenatide and when is it used?

Answer 18

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???

Question 19

What are some other specific types of diabetes?

Answer 19

○ 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)

Question 20

How is DM diagnosed?

Answer 20

• 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

Question 21

How is gestational diabetes diagnosed and treated?

Answer 21

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 **

Question 22

What causes islet cell destruction in type 1 DM?

Answer 22

** 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

Question 23

What are the s/sx of type I DM?

Answer 23

○ 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

Question 24

How is Type I DM treated?

Answer 24

through exogenous INSULIN (primary), Medical Nutrition Therapy (MNT), and physical activity

Question 25

When should pts w/type I DM check their insulin?

Answer 25

○ 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

Question 26

What are some r/f for T2DM?

Answer 26

○ 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)

Question 27

How can T2DM be delayed or prevented?

Answer 27

○ 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

Question 28

What causes T2DM?

Answer 28

``` ○ 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) ```

Question 29

What is the patho for T2DM?

Answer 29

○ 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

Question 30

What are the s/sx of T2DM?

Answer 30

○ 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

Question 31

How is T2DM treated?

Answer 31

○ 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

Question 32

Facts about prediabetes:

Answer 32

▪ 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 ***

Question 33

What test monitor/manage T2DM?

Answer 33

- 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)

Question 34

Facts about T2DM in children:

Answer 34

○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

Question 35

What are the effects of catecholamines on BG?

Answer 35

- 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

Question 36

What are the effects of glucocorticoid hormones on BG?

Answer 36

- 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

Question 37

When does DKA occur and what problems result?

Answer 37

○ 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

Question 38

What are some r/f for DKA?

Answer 38

□ 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

Question 39

What are some s/sx of DKA?

Answer 39

▪ 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

Question 40

What is the patho for DKA?

Answer 40

▪ 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

Question 41

What are the expected lab findings of a pt diagnosed with DKA?

Answer 41

▪ 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

Question 42

How is DKA treated?

Answer 42

▪ 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

Question 43

What is hypoglycemia and how is it caused?

Answer 43

- 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 ```

Question 44

What are the s/sx of hypoglycemia?

Answer 44

▪ 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

Question 45

What is the patho for hypoglycemia?

Answer 45

▪ 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.)

Question 46

How is hypoglycemia treated?

Answer 46

``` ▪ 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. ```

Question 47

What is HHS and when does it occur?

Answer 47

Hyperglycemic Hyperosmolar State, occurs when BG >600 and plasma osmolarity is above 320 mOsm/L

Question 48

What can HHS result in?

Answer 48

○ 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

Question 49

The BG level is ______ in hypoglycemia and ______ in DKA

Answer 49

below 53; above 250

Question 50

The normal FBG level is:

Answer 50

< 100

Question 51

Hypoglycemia is usually felt with a glucose level of:

Answer 51

< 50-60

Question 52

A person with hypoglycemia should receive:

Answer 52

glucose IV (rule of 15: give 15g of glucose every 15 minutes, 3x)

Question 53

A person with DKA should receive:

Answer 53

IV insulin and electrolytes

Question 54

What are some chronic complications of DM?

Answer 54

- 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

Question 55

What is the patho of polyol pathway?

Answer 55

▪ 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

Question 56

What is the patho of formation of glycoproteins?

Answer 56

▪ 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

Question 57

What is the patho of tissue oxygenation?

Answer 57

▪ RBC dysfunction that interferes with the release of O2 from the hemoglobin

Question 58

What is the patho of protein kinase C?

Answer 58

▪ 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

Question 59

What is the ADA recommendations for diabetic pts with blindness/retinopathy issues?

Answer 59

▪ Annual dilated pupillary exam

Question 60

What should be assessed when considering neuropathy of diabetic pts?

Answer 60

○ 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

Question 61

How can a pt prevent peripheral neuropathy?

Answer 61

``` ▪ 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 ```

Question 62

What are some DCCT research conclussion?

Answer 62

- 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

Question 63

How can DM be managed in adults?

Answer 63

1. Dietary Management 2. Rx for exercise (150 min/week) 3. Hyperglycemic Control ○ Control through insulin administration or oral agents (except Type I) or both 4. Monitor Blood Glucose levels 5. 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 6. Manage Dyslipidemia ○ LDL's between 70-100 ○ HDL above 50 ○ Triglycerides below 150 - Change their lifestyle! ○ Increase activity, promote weight loss, and smoking cessation