Diabetes

Front 1

Two main problems that go awry with endocrine system

Back 1

1) problem with hormone levels: too much or too little
-i.e. excessive secretion

2) Problem with receptor or receptor organ
-i.e. changes in number of receptors
-hormone doesn't fit, change in receptor shape, abnormal damage

Front 2

What are the main important hormones in blood sugar regulation?

Back 2

Insulin

Glucagon

Front 3

Closer look at insulin's role in blood sugar regulation?

Back 3

-secondary reactions happening
-insulin does not take glucose into cell
-instead, insulin helps the cell be able to receive glucose
-just know you need insulin to have movement of glucose into cell

Front 4

Closer look at glucagon?

Back 4

enzyme that facilitates glycogen into glucose
-this reaction is triggered by low BS in body, when you need extra sugar to meet demands of exercise, helps body get more glucose from storage form (glycogen) to the form cells use (glucose)

Front 5

Balancing act of insulin and glucagon?

Back 5

control of BS a balancing act, insulin reduces BS and glucagon in opposition trying to elevate BS

Front 6

Other hormones involved in BS control?

Back 6

Involved in more peripheral, unique situations

Epinephrine "fight or flight"
-increased glycogenolysis (glycogen polymers to glucose monomers, also happens w/ IV/IM glucagon in DM emergencies)
-decreased insulin release

Growth hormone
-decreased cellular uptake of glucose

Cortisol "stress"
-increased gluconeogenesis: i.e. f/ lipid/fat "neo" = new, noncarb source

Front 7

What is diabetes?

Back 7

A group of metabolic disorders characterized by hyperglycemia secondary to defectsin insulin secretion, insulin action, or both

Front 8

Type I DM characteristics.
-need for insulin?
-types?
-genetic?

Back 8

Exogenous insulin necessary for survival

Types:
Nonimmune-i.e. getting it secondary to another condition like pancreatitis
Immune-more common with Type I

-High familial risk

Front 9

DM Type I Patho
-There is a class of antigens called...
-Describe its role

Back 9

Class of antigens called Histocompatibility Leukocyte Antigen or HLA Class II Alleles

-HLA alleles code for chromosomes, and having certain antigens make you more or less susseptible to DM, all about how body recognizes its own cell as self or non self, if body recognizes it as self immune system doesn't attack, if not it will attack, recognition is screwed up and recognizing it as foreign-autoimmune d/o

Front 10

DM Type I patho
-There also may be a ___ componenet

Back 10

Viral component
-also often a viral component to onset, a virus may trigger general immune response, and immune system attacks itself instead of just virus, or virus may damage beta cells directly on pancreas, also part of it has to do with HLA receptors, if have susceptible receptors and exposed to virus may trigger DM

Front 11

DM Type I Patho:
-but what is the bottom line to the development of DM Type I?

Back 11

HLA sets the platform for susceptibility, then:

environmental-infection, virus, something causing beta cells to be destroyed, also immune response that alters beta cells and the way they look so the immune response triggers

bottom line is destruction of the beta cells leads to not enough insulin

Front 12

DM Type I

3 factors

Describe 1st

Back 12

Genetic Predisposition

-HLA-linked genes and other genetic loci

which along with environmental insults cause another set of issues

Front 13

DM Type I

3 factors

Describe 2nd

Back 13

Environmental Insult

Viral infection
and/or
Damage to Beta cells

which along with genetic predispositions cause another set of issues

Front 14

DM Type I

3 factors

Set of issues caused by previous two factors?

Back 14

Immune response against normal Beta cells

Immune response against altered B cells

Front 15

DM Type I

3 factors

So then what do these issues lead to? 3rd factor..

Back 15

Autoimmune attack
-Beta cell destruction
---->
TYPE 1 DIABETES

Front 16

DM Type 1

What is the Islet of Langerhans?

Back 16

where beta and alpha cells hang out
-becomes noticeably deformed in DM

Front 17

DM Type 2 Characteristics

-need for insulin?
-familial?

Back 17

Usually adult onset
-over 40
-gestational

Exogenous insulin is not always necessary for survival

Familial link

Front 18

DM Type 2 patho

What are the 3 factors?

Back 18

Insulin Resistance

Decreased Insulin

Increaed Glucagon

Front 19

DM Type 2 Patho

Closer look at first factor

Back 19

Insulin Resistance

-insulin is present, but nothing is happening, why? maybe decreased receptors for insulin on cell membrane, or they are there but not properly functioning

-reduced insulin receptors
-dysfunction of receptors

Front 20

DM Type 2 Patho

Closer look at second factor

Back 20

Decreased Insulin

decreased number of beta cells or improper functioning of beta cells

-B cells: decreased number or decreased function (b/c of amyloid deposits at pancreas)
-abnormal insulin molecule
-insulin antagonist

Front 21

DM Type 2 Patho

Closer look at third factor

Back 21

Increased Glucagon

amylin is important-inhibits glucagon from working, inverse relationship, so decrease in amylin leads to increase in glucagon and increase in glucose..so dysfunction in regulation of glucagon and therefore glucose generation

-so increased glucagon causes decrease in amylin
-amylin is released by beta cells with insulin, inhibits glucagon

Front 22

Type 2 DM

Risks

Back 22

obesity, BMI, waist curcumference

Front 23

Type 2 DM

Role of fat tissue and 2 effects

Back 23

fat tissue-does things in body, releases substances that can impact what's going on with beta cells

two main effects:
Adipokines
FFA

Front 24

Type 2 DM

First effect r/t fat tissue

Back 24

Adipokines
-group of proteins secreted f/ adipose tissue
-some promote insulin resistance and some reduce insulin resistance.
Obesity-the promoters are more abundant than the ones that reduce

Front 25

******Type 2 DM

Second effect r/t fat tissue

Back 25

FFA

released, decrease beta cell function
-along with adipokines can cause inflammation: -messengers released in inflammatory process, messengers may antagonize insulin and ability to function on peripheral tissue

Front 26

Type 2 DM

So overall obesity causes..

Back 26

dysfunctions in
adipokines
FFA
inflammation

leading to insulin resistance and changes in beta cells, beta cell failure

Front 27

Type 2 DM

Sum of all contributers

Back 27

excessive lipids
increased glucose production from liver itself
defective insulin secretion from pancreas
..all have a role, not to mention CHO intake

Front 28

Hyperglycemia

What is it?

Back 28

food intake (especially CHO) and/or

increased release of glucagon and too little insulin from beta cells

= hyperglycemia, pushing BS up

Front 29

Hyperglycemia

4 Common Symptoms

Back 29

Polyuria

Polydipsia

Fatigue

Hyperventilation

Front 30

Hyperglycemia

1st common symptom closer look

Back 30

Polyuria

high BS-glucose in blood, so water in cells around blood is gonna wanna go into the blood, what osmotic diuresis is, blood has high BS, high osmolarity, pulls water in, higher blood volume so body tries to urinate it out

Front 31

Hyperglycemia

2nd common symptom closer look

Back 31

Polydipsia

triggers thirst receptors in body, b/c body thinks there's not enough water enough b/c of osmotic diuresis, to reduce osmolarity of blood

Front 32

Hyperglycemia

Closer look at third symptom

Back 32

low glucose into cells, cells don't function as well, also acidosis if occuring can cause changes in consciousness levels, glucose feeds/fuels cells-so cell doesnt have energy to function, glucose in blood but not crossing cell barrier to cell b/c no insulin to facilitate the movement into cell

Front 33

Hyperglycemia

Closer look at fourth common symptom

Back 33

Hyperventilation

f/ metabolic acidosis

Front 34

Measuring Hyperglycemia

-3 tests that measure amounts of BS in blood

Back 34

-random blood sugar
-fasting blood sugar
-oral glucose tolerance test

Front 35

*******Measuring Hyperglycemia

another, different test - what is it?

Back 35

Hemoglobin A1C

glycoselated hemoglobin-hemoglobin that has glucose stuck to it, RBCs are different cuz glucose can enter them w/o insulin, so high BS = elevation of BS inside RBC, so glucose becomes incorporated in hmg and remains there consistently until RBC dies, doesn't change according to insulin, also a time dependent measurement, 3 month prior data

-BS is a snapshot with a camera of that moment, A1C is record of past 3 months

Front 36

Diabetics can have normal ___ but high ___

Back 36

nml fasting BS

high Hmg 1AC

Front 37

DM Complications

Acute: BS too low
-sx
-MOA
-prevention

Back 37

Hypoglycemia

sweaty, dizzy, relieved with eating/drinking sugar

patho-too much insulin, without enough carb to "cover it", contributing factors-running around shopping, activity burned up glucose from breakfast, activity/exercise, also did not eat as much lunch (from case study)

Other sx: palpitations, sympathetic nervous system activity-tremor, sweats, HA, irritability

advice for future-always have snack on hand, take glucometer

Front 38

Complications Diabetes

Acute: involving ketones..
-how do you know?
-MOA
-sx

Back 38

diabetic ketoacidosis

How do you know? ketones in urine are definitive, other sx-weight loss, glucometer not reading it (too high for reading), thirst/soda

What is the mechanism of the complication? BS too high, his body is breaking down fat to get energy b/c the glucose is not entering the cell, even tho glucose is present don't have insulin to move it to cell, so body goes into "starvation mode" - first thing breaks down fat-called ketosis, acids are released


Any other symptoms? polydipsia-BS is so high, osmotic diuresis pulling water in

Front 39

Diabetes Complications

Acute: not involving ketones
-how do you know?
-MOA

Back 39

Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNKS) - pretty rare but it can happen

How do you know? high glucose, no ketones, recent illness, Type 2 (can occur with T1 but more common with T2)

What is the mechanism of the complication? high BS-higher osmolarity of the blood, which means water wants to move into blood that's voided out, but you still have high sugar, so you end up losing volume, blood more osmolar, cycle happens where blood is more concentrated, but the body still produces a little bit of insulin so ketosis is suppressed,
so the big issue in this situation in addition to high BS is dehydration

Front 40

********Complications of DM
Chronic: retionopathy

what is it? & what are the stages?

Back 40

chronic-years of high BS

retionopathy: where you start to have changes in blood flow thru the vessels of the retina, end up having ischemia at the retina, and the retina tries to correct it by growing new blood vessels to bring more oxygen, but new vessels leads to damage to retina, 3 stages refer to vessels

nonproliferative-no new vessels
2 preproliferative-ischemia no new vessels
3 proliferative-new vesels

Front 41

****Chronic Complication of DM

More about retinopathy
-causes _____ loss
-____ _____ is present

Back 41

periocyte loss-periocytes are in endothelium of cells
-they are undifferentiated cells
-periocyte's role is regulating blood flow in capilaries, lose them lose regulation of blood flow

nonenzyomatic glycoselation is present (caused by high BS)
-this is a glucose molecule that attaches to structures like lipids, nucleic acids
-in vessels have endothelium and basement membrane (background)
-nonenzyomatic glyoselation causes thickening of basement membrane (bottom layer of cells in vessel)
-thickening cause reduced nutrient movement across membrane, reduced oxygen and other things

Summary....
-lose periocytes lose autoregulation of vessels
-also due to nonenzomatic glucoselation leads to decreased nutrients which leads to changes in blood vessels and can lead to ischemia
-aneurysms can also cause damage to vessels
-can lazer to reduce growth

Front 42

*******DM Complications

Chronic: retionopathy
How does the body try to compensate? what's the problem with this?

Back 42

-change of flow, blood flow thru vessels, change of oxygen across vessel wall
- leads to ischemia of retina, not enough oxygen to retina
-so retina tries to form new bv/capilaries
-problem is vitrous gel inside of eye, thick, that gel can adhere to new blood vessels and traction can damage retina
-blood vessels can hemorrhage
-retionopathy causes blurred vision

Front 43

DM Complications

Chronic-nephropathy

Back 43

-changes in blood flow
-hyperglycermia causes hyperfusion (increased renal blood flow) through kidney, worsened if you have HTN
-protein glycation is nonenzomatic glucoselation and sticks to proteins causing damage
-leads to damage to glomerulus (end of capilaries that the blood flows through and then you have bowman's capsule start of filtration in kidney)
-straining spaghetti, glomerulus is like strainer so water/electrolytes go thru glomerulus and out, proteins and blood cells stay in normally but not with diabetic nephropathy

Front 44

DM Complications

Nephropathy: What causes protein glycation?

What does protein glycation cause?

Back 44

Increased protein excretion (due to increased RBF f/ hyperglycemia) leads to protein glycation and glomerular damage
-normally protein doesn't go through glomerulus b/c its negatively charged and doesn't fit

Protein Glycation causes:

HTN. &

Glomerular damage
-loss of negative charge
-glomerulosclerosis (scaring of glomerulus)
-thickening of basement membrane
-mesangial expansion (increased space in glomerulus)

leading to...
decreased GFR and renal failure

Front 45

DM Complications

Chronic-Neuropathy

Back 45

Increase in BS causes various changes so you have free radicals (oxygen molecules with an extra electron that binds things and causes them to not work, i.e. neurons)

-Shwan/myelin sheath is action potential in neuron-dysfunction causes loss or change in signaling ability leading to neuropathy

-also polyol pathway-sorbitol causes glucose broken down different pathway which also leads to neuropathy

Changes from the following lead to neuropathy:
-oxidative stress
-glucose breakdown
-change in conduction

Front 46

DM Complications

Chronic-Neuropathy
Types and examples

Back 46

S/Sx: sensory and functioning

Peripheral: numbness and tingling or pain, loss of feeling
-often toes/feet first sx

Autonomic Neuropathy:
-delayed stomach emptying
-frequent diarrhea/constipation
-postural low blood pressure
-sexual dysfunction
-silent heart attack*********
-----no pain sensation in the chest
-----Jin: prone to small vessels with neuropathy; ischemic stroke, not hemorrhagic strok

Front 47

Chronic Complications of Diabetes Mellitus: premature atherosclerosis of diabetes

Macrovascular Disease: what is it and 3 conditions

Back 47

Macrovascular Disease:


-Coronary Artery Disease
-Stroke**********
-Peripheral Artery disease

Front 48

Macrovascular Disease:absence of CAD

Back 48

MI (death of heart muscle as a result of coronary artery occlusion) is a major cause of death in DM
-So is cardiomyopathy (myocardial dysfunction in the absence of CAD)

Front 49

*********Macrovascular Disease:

Stroke

Back 49

-ischemic stroke more common than hemorrhagic stroke
-HTN, hyperglycemia, and dyslipidemia are definitive risk factors

Front 50

Diabetes Complications
Chronic-Infection

Back 50

increased risk of infx due to
1) impaired vision f/ retinal changes and impaired touch by neuropathy may cause skin breakages, once that occurs increased risk for infx d/t hypoxia
2) microvascular and macrovascular complications cause decreased O2 supply to tissue, and increased glycosylated hmg in RBC impedes release of O2 to tissue
3) pathogens multiply rapidly once reach tissue d/t glucose supply
4) decreased blood supply f/ vascular changes decreases WBC to affected area
5) WBC impaired by ischemia and hyperglycemia, chemotaxis and phagocytosis abnml