1
Q
Gestational Diabetes (4)
A
- Any degree of glucose intolerance in which the first onset is recognized during pregnancy, there is a challenge with glucose homeostasis.
- Women with gestational diabetes have impaired ability to elevate plasma insulin
* Their pancreas can’t produce high enough insulin levels in order to overcome the normal insulin resistance that is occuring during late pregnancy - This is thought to be correlated with an underlying pancreatic impairment
- She will most likely develop T2DM later
2
Q
Early Phase of Glucose/Insulin Levels in Pregnancy
A
- Mom is increasing her fat stores
* Priority of mom’s body during this time is to increase fat stores - This is achieved by increasing tissue sensitivity to insulin which allows for greater glucose uptake (so increased insulin = decreased gluocse levels)
* Mom’s BS is going to baby to fuel baby’s growth, it is going to fuel mom’s tissues, and is being used to increase fat store in mom
3
Q
Late Phase of Glucose/Insulin Levels in Pregnancy (3)
A
Insulin resistance phase (accomplished by hpl), so that there will be more glucose for mom and baby. Simultaneously, mom’s insulin levels increase as a way to try and keep mom normal glycemic
- Mom starts to breakdown fat stores and use them as the primary source of energy
* The priority is to preserve blood glucose for mom and baby’s brain
* This is because there is a larger baby in you that will need more blood glucose - During last few weeks of pregnancy, baby needs to increae glycogen stores in it’s liver and must gain fat because once it is born it must provide its own glucose regulation
- Mom becomes insulin resistant during late phase of pregnancy
* This resistance is a result of human placental lactogen hormone
* Hpl directly antagonizes insulin receptors and causes mom to be insulin resistant
* Simultaneously, mom’s insulin levels go up; this is designed to keep mom normal glycemic
4
Q
Classic Manifestations of DM (4)
A
In order of how they appear…
- Hyperglycemia
- Glucosuria
- Polyuria
- Polydipsia
*Hyperglycemia causes glucosuria –> When BS gets above renal threshold then the person will urinate out some amount of glucose –> The glucose in urine causes osmotic diuresis –> polyuria –> Dehydration from water loss causes polydipsia
5
Q
Hyperglycemic Coma
A
“Hyperosmolar Coma”
If plasma glucose levels get too high to the point where the plasma osmolarity is too high, it can cause disturbed mental function leading to potential coma
6
Q
Signs of Hyperglycemia (3)
A
- blurred vision (hyperosmolar fluid)
- paresthesias- dysfunction of peripheral nerves
- Infections – UTI/Candida
*This is especially true of T2DM
7
Q
Pathophysiology leading to DM Hyperglycemia (3 steps)
A
1st: Eat food and BS increases
2nd: Due to insulin problems, liver can’t access the glucose and then assumes you are in a post-absorptive state
3rd: Liver starts to breakdown glycogen stores and release glucose into the bloodstream
* This is why T2DM medications are aimed at reducing liver’s ability to produce glucose
8
Q
Polyphagia
A
excessive hunger/increased appetite; usually only present in T1DM
9
Q
Early Morning Hyperglycemia: Dawn Phenomenon (4)
A
- Increased levels of glucose between 5am-9am
- Increased levels of insulin requirements
- 2/2 circadian rhythm
- In type I and type II
10
Q
Early Morning Hyperglycemia: Somogyi Effect
A
- “Rebound hyperglycemia;” pattern of undetected hypoglycemia followed by hyperglycemia
- Hypoglycemia incidence leads to increased in-counter regulatory hormones: catechloamines, glucagon, cortisol, GH
11
Q
Hypoglycemia levels (adults and neonates)
A
- For an adult it starts around 60-70mg/dL
2. For neonates it starts around 40mg/dL
12
Q
Hypoglycemia (2)
A
- The most common acute complication of T1DM, but also occurs with T2DM
- Represents a miss-calculation of the timing or dose of the treatment compared to the timing of meals
13
Q
Hypoglycemia: Exercise and sick (2)
A
- When you exercise your skeletal muscle doesn’t need insulin to take up glucose, and you will take up more glucose; so if you exercise, you don’t need as much insulin
- If you are sick or have any stress going on, you need more insulin
* The tighter your glucose regulation = the greater risk you are at being hypoglycemic
14
Q
Autonomic symptoms of Hypoglycemia (6 and reason behind them)
A
First symptoms are autonomic
Adrenergic:
- Tremors/shakiness
- Anxiety
- Palpitations
- Tachycardia
Cholinergic:
- Sweating
- Hunger
- Whenever the SNS turns on, it releases catecholamines, which tends to elevate BS a little
- Also will have release of glucagon which will elevate BS
- Designed to be a bridge between now and when you can get food in you
- These feelings are to make you aware of the fact that you are becoming hypoglycemic and trigger you to eat something
- If you don’t and your BS drops, the manifestations will be neurologic
15
Q
Neurologic symptoms of hypoglycemia (7)
A
- Weak/fatigued/drowsy
- headache
- behavior change
- confusion
- diplopia,
- difficulty speaking,
- seizures, coma
*person can seem drunk and acting inappropriately
16
Q
Repeated episodes of hypoglycemia
A
- Unawareness with repeated episodes
* If you get exposed to this stimulus continuously, your body will respond less to it - If you are diabetic and have had several episodes of hypoglycemia, it’s very possible that the next time you get hypoglycemic you wont have any autonomic symptoms but immediately experience neurologic symptoms
* Because you’ve had repeated episodes, you no longer have the initial autonomic response
Can be very dangerous !!!
17
Q
Glucose Counter-Regulation
A
- Decreased Insulin Secretions: increased hepatic glucose and decreased glucose used by muscles
- Increased Glucagon Secretions: glyconeogenesis, glyconeolysis
–> Activation of SNS
18
Q
Dibaetic Ketoacidosis (3)
A
Extremely high BS!
- Develops when there is an absolute deficiency of insulin or a increase in a counter-regulatory hormone like catecholamines or glucagon (most commonly T1DM)
- In the absence of insulin there is accelerated fat breakdown, and increased fat metabolism leads to development of keto-acids
- Occurs with increased frequency with infection, trauma, surgery, or myocardial infarction, or increased stress from other sources
19
Q
DKA Characteristics (5)
A
- DKA can begin at 250mg/dL blood glucose or higher
- pH will be 7.3 or lower
- Will have plasma positive for ketones
- May have urine positive for ketones
- People with type II DM don’t really get DKA because there is an adequate level of insulin to maintain fat stores
20
Q
DKA Symptoms (9)
A
- Kussmaul respirations (hyperventilation in an attempt to compensate for acidosis),
- postural dizziness
- CNS depression
- ketonuria
- nausea, vomiting
- polyuria
- dehydration
- stuporous state
- If severe enough, may be hypotensive or have tachycardia, abdominal pain or tenderness
21
Q
Pathophysiology of DKA (5)
A
Absolute insulin deficiency leading to…
- Decreased glucose uptake and accelerated muscle breakdown to free amino acids to feed gluconeogensis to the liver
* The liver is breaking down glycogen stores and pumping out glucose and contributing to the hyperglycemia - Fat stores in the absence of insulin that are breaking down; Accelerated lipolysis, freeing fatty acids that are then metabolized to produce ketones
- Build up of keto-aids causes metabolic acidosis
- If the acidosis progresses and becomes severe, it can cause depression of CNS function and can lead to coma
- The hyperglycemia will cause the osmotic diuresis, glucosuria, etc. (DM symptoms)
* Dehydration can become quite severe
22
Q
Potassium and DKA
A
- With acidosis, potassium shifts out of cells (as H ions move into cells)
* Will expect patient’s K levels to be high (hyperkalemic) - Insulin brings K into cells; so if the person is insulin deficient it will further keep K out of cells
- Patient will appear dehydrated and hyperkalemic
* But they aren’t really hyperkalemic, in fact, they are hypokalemic because K has been pushed out of cells and urinated out
23
Q
DKA Treatment
A
Difficulty with treating DKA is trying to manage the hyperkalemia knowing the patient is vulnerable to being hypokalemic with fluid management
- They can also become hypokalemic if you give insulin to treat the DKA
- Need to watch K levels very carefully because the treatment may cause you to need to give K if levels decrease
24
Q
Hyperosmolar Hyperglycemic Nonketotic Syndrome (HHNK) (3)
A
- Usually seen in T2DM, similar to DKA minus the acidosis
* because HHNK is seen in individuals with enough insulin to maintain fat stores - There is hyperglycemia leading to osmotic diuresis and dehydration
- Accelerated fat breakdown does not occur
25
HHNK Classification (2)
1. Insulin levels are high enough to suppress lipolysis but not high enough to facilitate glucose entry into skeletal muscle and fat tissue.
2. Occurs with glucose levels about 600mg/dL
* Plasma osmolarity will also be high due to the hyperglycemia (will be in range of 310)
26
Clinical Manifestations of HHNK (4)
1. Hyperglycemia
2. Glucosuria
3. Polyuria
4. Polydipsia
27
Chronic Complications of DM: Pathophysiology (3)
1. Chronic complications represent the effects of chronic hyperglycemia on certain cell types of the body
* Generally speaking, vascular tissue and nervous tissue are very vulnerable to damage as a result of chronic hyperglycemia
2. This is because neuronal cells and endothelial cells cannot regulate the amount of glucose that enters their cells
* Because glucose diffuses into these cells
3. Get altered intracellular metabolism
28
Macrovascular Disease Complications (5)
Disease of large blood vessels...
1. Coronary artery disease (atherosclerosis)
2. Cerebrovascular disease (CVD)
3. Peripheral vascular disease (peripheral arteriole disease)
4. Can lead to MI, ischemic heart disease, etc.
5. Plaques usually form in arteries that perfuse the lower limbs; this is why you see DM patients with poor circulation to legs
* Leads to diabetic gangrene of lower legs and also formation of ulcers
29
Microvascular Disease Complication: Renal (3)
1. Endothelial cells in glomerular capillaries are especially vulnerable to hyperglycemic damage
2. Glomerular basement membrane starts to thicken and it eventually progresses to glomerularsclerosis (scaring of glomerular capillaries)
3. This progressive damage starts cascade of compensatory hypertrophy and hyperfiltration of the rest of the nephrons, and these nephrons can’t keep up and you get cascading towards renal insufficiency then failure
30
Phase I Diabetic Retinopathy (3)
Non-proliferative phase
1. Aneurysm, hard exudates, hemorrhage
2. See these areas of damage to the capillaries
3. May see some edema, but vision mainly isn’t impaired (unless the edema occurs at the macula)
31
Phase II Diabetic Retinopathy (4)
Proliferative phase
1. Growth of abnormal blood vessels
2. As capillaries start to die off, retina becomes hypoxic
3. With chronic hypoxia, there is angiogenesis; start to see new capillaries form and when the new capillaries form, they may hemorrhage and bleed
4. If blood gets into vitrius it will impair vision
* Very bad complication of this is that as the blood vessels are forming it can cause detachment of retina → full vision loss
32
Sensory Neuropathy (6)
1. Tends to occur first (before autonomic neuropathy)
2. Will be most noticeable in extremities, especially of lower limbs
3. Usually occurs bilaterally and symmetrically
4. Characterized as a dulled perception of vibration and temperature
5. In some patients it can manifest as being very painful
6. For most patients, it is a dulling of sensation
33
Alidenia
Enhanced sensitivity to light touch, so light touch feels painful
34
Autonomic Neuropathy
1. Tends to occur with longstanding neuropathy/diabetes
2. Autonomic nerves are affected and autonomic reflexes/functions are dulled
3. Can affect GI function, can cause n/v/loss of appetitite
4. Can cause erectile dysfunction
5. Can cause dysfunction of autonomic reflexes of cardiovascular system, especially baroreflex
* Without baroreflex, patients can have extreme orthostatic hypotension (autonomic dysreflexia)
35
Autonomic Dysreflexia
A result of autonomic neuropathy; patients have extreme orthostatic hypotension due to dulled baroreflex sensation
36
Chronic DM: Infections (4)
1. Patients with chronic hyperglycemia are prone to chronic infections
2. Bacteria love glucose, so they will proliferate at a faster rate
3. Patient will also have poor healing
4. Someone can end up losing limbs due to impaired sensation + chronic infection + poor healing + poor circulation
37
How obesity leads to insulin resistance
1st: Hypertrophy of adipocytes; if you force body to store more fat, it will cause cells to hypertrophy
2nd: Reaches a point where it can no longer hypertrophy, and that stimulates production of new fat cells
3rd: Once you produce new fat cells, you can't lose them even if you lose weight
Hypertrophy adipocytes --> injury --> inflammation --> inflammatory cytokines --> macrophages
4th: The macrophages that responded to hypertrophy of adipocytes cause chronic inflammation
5th: Chronic inflammation causes insulin resistance and disruption of insulin signaling pathway in fat, skeletal muscle, and liver cells (especially TNF-alpha)
* Being obese leads to chronic inflammation which results in insulin resistance
38
How free fatty acids lead to insulin resistance
1st: Obesity causes elevated circulating free fatty acids
2nd: FFAs directly contribute to insulin resistance
* Chronic inflammation causes increased lipolysis in adipose tissue which elevates circulating FFAs
