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Physiology Chpt. 43 Porth : Diabetes Mellitus and the Metabolic Syndrome (T III)

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Describe the flowchart of the Regulation of [blood glucose].
1. Decreased Insulin, Increased Glucagon and Gluconeogenesis >>>

2. Increase Blood Glucose >>> >>>

3. a. Increase insulin released from Beta cells >>>

b. decreases glucagon >>>

4. a. removal of glucose from blood >>>

b. decreased hepatic glucose production >>>

4. decreased blood glucose (which feeds back and starts process all over again)
Diabetes Mellitus Type 1 is caused by a lack of what?
insulin, because you don't produce enough
Diabetes Mellitus Type 1 is associated with a high what?
high [blood glucose], aka hyperglycemia
Diabetes Mellitus Type 1 is associated with the breakdown of what?
Fat and Muscle because there is not enough glucose
Db. Mlts Type 1 accounts for what percentage of DM in U.S.?
10 - 20%
Etiology of DM?
AUTOIMMUNE destruction of pancreatic beta cells, autoantibodies

Sooo basically the beta cells are destroyed and they can't do there job which is to produce insulin
Distinguish between Type 1A and Type 1B DM?
Type 1A = immune mediated, genetic predisposition, HLA markers

Type 1B = idiopathic disease, strong genetic pattern, no autoimmunity present
DM Type 2 is a resistance in the body to what?
Insulin
DM type 2 is associated with what 2 things?
Obesity and Increased Age
Increased age is associated with DM type 2 but what do current trends indicate?
that DM 2 is more associated with fat >>> starting to see it more in younger people because of obesity
DM type 2 is NOT associated with what?
HLA markers of autoantibodies (that's type 1)
DM type 2 indicates what about fatty acids?
a high concentration
The high free fatty acids of DM 2 causes what?
1. increases insulin secretion from pancreas (initially higher and then, later, insulin was low)

2. Hepatic stimulation of glucose production
In DM 2 the initial insulin resistance is overcome by what?
elevated insulin release by pancreas
-later the pancreas reserve grows exhausted and insulin production drops
-this is when they may req. daily insulin
In DM 2 which is more important, visceral fat or subcutaneous fat?
visceral (deep)
Not sure what is the exact cause of DM 2 but what do some studys indicate?
they indicate that fat (adipose) cells may produce protein that inh.s insulin usage
Metabolic syndrome contributes to what disease?
Cardiovascular disease
Metabolic syndrome is similar to DM in what way?
Insulin resistance at cellular level like diabetes
Insulin resistance contributes to what 7 things?
1. High [plasma triglycerides]

2. Low [plasma HDL]

3. HTN

4. Systemic inflammation

5. Abnormal fibrinolysis

6. Abnormal function of vascular endothelium

7. Macrovascular disease
What is detected in systemic inflammation?
C-reactive protein/other mediators detected
Abnormal fibrinolysis is a deficiency in what?
deficiency in the breakdown of clots
Examples of Macrovascular disease?
Coronary artery, cerebrovascular, peripheral artery disease
Metabolic syndrome is aka?
Insulin resistance syndrome
Gestational Diabetes Mellitus is due to an intolerance of what?
Glucose intolerance during pregnancy
6 Risk factors of Gestational Diabetes Mellitus?
1. Family history of DM

2. Still births and spontaneous abortions

3. Previous large or heavy-for-date baby

4. Obesity

5. Increased age

6. More than 5 pregnancies
Tx for Gestational Diabetes Mellitus?
1. Close observation of mother and fetus

2. Nutrition: necessary nutrients resulting in normoglycemia
-typically develop diabetes 4-5 years after pregnancy
7 Signs and Symptoms of DM 1 vs. DM 2?
1. Type 1 is sudden
Type 2 is slow

2. Polyuria: Osmotic diuresis due to glucose (1&2)

3. Polyphagia: Due to cell starvation (1 only)

4. Blurred vision: (hyperosmolar fluids in lens due to increased [glucose] deposits on the lens

5. DM1 : weight loss despite eating (polyphagia)

6. DM2 : obesity to begin with (upper body)

7. Polydipsia: dehydration from diuresis (1&2)
What is normal A1C?
4-6%
4 aspects of DM management?
1. Diet (keep glucose stable)

2. Exercise (esp. type 2)

3. Insulin (esp. type 1, injections)

4. Oral antibiotic agents
What is the normal fasting [glucose]?
<100mg/dL
What is prediabetic fasting [glucose]?
between 100-120
What is the fasting [glucose]for a diabetic?
> 120
Oral hypoglycemic agents for DM have to do one of what 2 things?
needs to either increase the sensitivity to insulin or decrease [glucose] in blood

-oral therapies are for DM 2 only
Alpha-glucosidase inhibitors have what effect on DM 2?
decrease glucose absorption in the gut
Biguanides do what for DM 2?
1. Decrease hepatic glucose output

2. Increases peripheral glucose
Examples of Biguanides?
glucophage, metformin
What do Thiazolideniones do for DM 2?
1. Decrease hepatic glucose output

2. Increase peripheral glucose
Both biguanides and Thiazoideniones decrease hepatic glucose output...which is stronger?
biguanides
Both biguanides and Thiazoideniones increase peripheral glucose...which is stronger?
Thiazolidinediones
Thiazolidinediones are aka?
What do they basically do?
TZDs...basically sensitize the body's cells to insulin
What do the beta-cell stimulators do for DM 2?
increase insulin secretion
Give examples of beta-cell stimulators?
glipizide, glyburide
All oral hypoglycemic agents are used to tx what?
type 2 diabetes
3 acute complications associated with diabetes? State the specific type?
1. Ketoacidosis (Type 1)

2. Hyperosmolar hyperglycemic state (type 2)

3. Hypoglycemia (type 1, sometimes type 2)
FFA aka?
Free fatty acids
DKA aka?
diabetic ketoacidosis
DKA is only associated with what?
Only type 1
-lack insulin, excess glucagon
In DKA there is a lack of insulin that leads to what?
cells breakdown triglycerides to form FFA and glycerol
FFA metabolism during DKA forms what?
ketones
DKA is often precipitated with what?
-often precipitated by infection
-non-use of insulin
-alcohol
What kind of derangements are associated with DKA? Name the 3 types?
metabolic derangements
1. increase [glucose] in blood

2. ketosis

3. metabolic acidosis
Mortality rate of DKA?
< 5%
The onset of DKA is what?
slow, long effect
Hyperglycemia concentrations?
250 - 1000+ mg/dL
Describe some things associated with hyperglycemia?
1. Osmotic diuresis

2. dehydration

3. electrolyte disturbances

4. vomiting

5. hypotension

6. tachycardia

7. hypovolemic shock
Some things associated with ketosis?
1. Fruity breath

2. fatty acid metabolism
Some things associated with metabolic acidosis?
1. Low pH

2. low bicarbonate

3. hyperkalemia

4. Kussmaul breathing
What is Kussmaul breathing?
Associated with the metabolic derangement of metabolic acidosis associated with DKA
-compensation by trying to rid of CO2
Treatment for the metabolic derangements of DKA?
fluid and electrolyte replacement
-insulin tx.s the underlying cause
What is a Hyperosmolar hyperglycemic state? (HHS)
A lost of thirst response. Often associated with type 2 diabetes.
What is a Hyperosmolar hyperglycemic state often precipitated by?
decreased fluid intake. So an increased [glucose]
In a Hyperosmolar hyperglycemic state, what is considered a high plasma osmolarity?
> 310 mOsm/L
In a hyperosmolar hyperglycemic state, what is considered a high blood glucose concentration?
> 600 mg/dL
In diabetes a hyperosmolar hyperglycemic state, what is it usually a result of?
usually it is the result of insulin resistance and increased carbohydrate intake
What does hyperosmolarity do to fluid?
Draws fluid from ICF to ECF
-all tissues lose fluid, including the brain
Two signs and symptoms that develop due to a Hyperosmolar hyperglycemic st.
1. Severe Dehydration

2. Neurologic problems
The severe dehydration associated with a hyperosmolar hyperglycemic state can lead to the formation of what?
Thrombus Formation
, Clotting
Some of the neurologic deficits associated with a hyperosmolar hyperglycemic st. (5)
1. Lethargy
2. decreased mental capacity
3. coma
4. seizures
5. Muscle fasciculations (twitching etc)
2 ways of tx of hyperosmolar hyperglycemic st.
1. Rehydration with caution

2. Replacement potassium
In tx of hyperosmolar hyperglycemic st. why must you rehydrate with caution?
Because there is a threat of cerebral edema, too much fluid in the skull
Hypoglycemia is associated with what type of diabetes?
Type 1 & 2
The onset of hypoglycemia is at what pace? What does it typically result from?
rapid, typically resulting from the therapy and tx usually
Some things that may lead to hypoglycemia? (5)
1. too much insulin (dosing error)

2. low food intake

3. stress

4. exercise

5. alcohol
Two general signs and symptoms of hypoglycemia?
1. Neurological issues

2. Activation of ANS issues
Why do the neurological issues in hypoglycemia occur?
because of decreased glucose
5 things associated with neurological issues during hypoglycemia?
1. headache

2. difficulty problem solving

3. altered behavior

4. slurred speech

5. coma
What does the activation of the ANS during hypoglycemia cause?
1. Hunger (Parasympathetic initially)

2. then anxiety

3. tachycardia

4. sweating

5. constriction of skin vessels (sympathetic)
Counterregulatory hormones do what?
overcompensate for the lack of glucose in diabetes
The somogyi effect could be called what kind of phenomenon?
"a rebound phenomenon"
-involves counterregulatory hormones
The Somogyi effect is a cycle of what?
insulin-induced posthypoglycemic episodes
In the Somogyi effect hypoglycemia begets what?
hyperglycemia
What does the somogyi effect result from?
Results from increased levels of catecholamines, glucagon, cortisol, GH
-all counterregulatory hormones
What is the Dawn effect?
Phenomena involving counterregulatory hormones
-an indiv. has increased levels of fasting glucose or insulin requirements, or both between 5 and 9 am.
It is not clear, but the dawn effect may result from a change in what?
a change in the normal circadian rhythm for glucose tolerance
6 Chronic complications associated with diabetes?
1. Diabetic nephropathy

2. Diabetic retinopathy

3. Diabetic peripheral neuropathies

4. Macrovascular disorders

5. Foot ulcers

6. Infections
What is a nephropathy?
a disease of the kidney
What is retinopathy
retina inflammation
What are some macrovascular disorders?
CHD, Stroke, Peripheral vascular disease
3 ways to prevent the chronic complications associated with diabetes?
1. Tight control of bl. glucose levels

2. Maintenance of normal lipid levels (esp. vascular)

3. Control of hypertension
3 pathophysiologic theories of why people have the chronic complications assoc. with diabetes?
1. Polyol pathway

2. Glycoprotein formation

3. Tissue oxygenation
The theory of the polyol pathway effects diabetes how?
1. Glucose change to sorbitol rapidly, then sorbitol changes to fructose slowly...so you end up with too much sorbitol
2. This sorbitol formation leads to cellular swelling
3. effects the lens of the eye, kidney, blood vessels
How does glycoprotein formation have an effect on the chronic complications of diabetes?
1. glycosylation of proteins from high [glucose]
2. normally form in small bl. vessels (eye, kidney, vasculature)
3. change structure of basement membrane
How does tissue oxygenation possibly contribute to the chronic complications of diabetes?
1. Causes glycosylated hemoglobin

2. glycosylated hemoglobin is much poorer at transporting oxygen

3. this decreases oxygenation with increased blood flow (retina, kidneys, etc)
How would you slow the pathophysiologic theories that cause chronic complications?
Insulin will slow them, need to control lipid and glucose concentrations

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