Year 2 Endocrine Week 1

Front 1

What is the major endocrine organ responsible for glucose homeostasis?

Back 1

Endocrine pancrease = Islet of langerhans

Front 2

What are the two main hormones produced by the pancreas and what action do they serve for glucose homeostasis?

Back 2

Insulin - promotes glucose uptake from the blood into the cell, stored for later.
Glucagon - promotes glucose mobilization/release from tissues thereby increasing blood glucose levels.

Front 3

What is the difference between endocrine and exocrine glands?

Back 3

Exocrine glands secrete their products into ducts/lumens.
Endocrine secretes directly into the blood.

Front 4

What are the 4 types of cells found in endocrine pancreas and what do they produce?

Back 4

1) (A) alpha-cells = glucagon
2) (B) Beta-cells = insulin
3) (D) delta -cells = somatostatin
4) (F) PP cells - pancreatic polypeptide (PP)

Front 5

Where are the various cell types located within the Islet of langerhans?

Back 5

beta-cells (60%) are located in the medulla (core) and all the other cells are located in the periphery (mantle) spread throughout.

Front 6

The pancreas is very vascular - in what direction does blood flow?

Back 6

B-A-D
beta -> alpha-> delta cells

Front 7

What innervates the pancreas? What neurotransmitters are involved?

Back 7

ANS
PNS = vagal (ACh, and VIP)
SNS = celiac ganglia (NE and NPY)
SNS innervates the adrenal gland which releases E which then acts on the pancreas

Front 8

What is proinsulin and what is its form?

Back 8

Proinsulin is a precursor to the mature insulin.
It is comprised of an A and B chains (linked by disulfied bonds) and a C-peptide.

Front 9

How is proinsulin processed to make mature insulin?

Back 9

In the secretory granule where it is stored, proinsulin is cleaved by prohormone convertase PC1/3 and PC2 into insulin and C-peptide in equimolar amounts.

Front 10

In general terms, what regulates insulin secretion?

Back 10

GLUCOSE
There are also neuronal, hormonal and nutrients that can stimulate insulin but they require the presence of glucose (glucose-dependent)

Front 11

What neural agents help regulate insulin secretion and what effect do they have?

Back 11

1) PNS - vagal (ACh) - (+) stimulates
2) SNS (NE/E) - (-) inhibitory

Front 12

What hormones help to regulate insulin secretion?

Back 12

1) Incretins which are released from the GI tract following food absorption
- GIP & glucagon-like peptide 1 (GLP-1 7-36) -(+) stimulatory
- somatostatin (-) inhibitory
2) Islet of langerhands - glucagon

Front 13

If glucagon is counterregulatory to insulin, then why does glucagon stimulate insulin secretion?

Back 13

When glucagon is released in the body it increases the blood glucose levels but to get the glucose into the cells for utilization, you need some insulin around.

Front 14

What nutrients regulate insulin secretion?

Back 14

Glucose - (+) stimulates insulin secretion
Arg, lys (aa) - (+)

Front 15

How does elevated glucose levels stimulate insulin secretion? What is the step-by-step mechanism?

Back 15

Beta-cells are glucose sensors
1) glucose enters the beta cell via GLUT-2 transporter
2) Glucose is phosphorylated to G-6-P by glucokinase in the cell
3) Via glycolysis, G-6-P is made into ATP, increasing the intracellular ATP levels
4) Increased ATP, causes the ATP-sensitive K+ channel to close
5) Beta-cell depolarizes
6) Activates voltage-dependent Ca+2 channel
7) Influx of Ca+2 into the cell increasing the intracellular Ca+2 levels
8) Increased iCa+2 signals release of insulin from storage secretory granules.

Front 16

What is the rate limiting step for glucose stimulated insulin secretion?

Back 16

Glucokinase phosphorylation = glucose sensor of the beta cell.

Front 17

How is glucose-independent secretion of insulin occur?

Back 17

Sulfonylurea receptors (SUR) located near the K+ channels can be activated by sulfonylureas which leads to closure of the K+ channel, depolorization and increased iCa+ levels and insulin secretion.
Also, leucine-independent secretion of insulin can occur.

Front 18

What is the overall action of insulin?

Back 18

Insulin is anabolic therefore promoting energy storage.
Insulin also plays a huge role in growth and development.

Front 19

What are the major tissue targets of insulin (where is glucose stored as glycogen)?

Back 19

Liver
Skeletal muscles
Fat

Front 20

What acute effects does insulin have on carbohydrate metabolism in the muscle, adipocytes and liver?

Back 20

Overall action is increased glucose storage and utilization.
1) Muscle - increased glucose utilization (glycolysis) or storage (glycogen)
2) Adiopocytes - increased storage of glucose as fat by converting glucose to glycerol which is then made into Triglycerides
3) Liver - increased storage (glycogen) and glucose utilization (glycolysis) but it also decreased glycogenolysis and gluconeogensis

Front 21

Define glycogenolysis?

Back 21

Break down of glycogen into glucose (activated by glucagon).

Front 22

Define gluconeogenesis?

Back 22

Formation of glucose from non-carbohydrate carbon susbtrates such as pyruvate.

Front 23

How does insulin increase glucose uptake into the cell (mechanism)?

Back 23

On the target cell (liver, muscle, adipocytes), insulin binds to the receptor on the surface
2) Triggers release of GLUT4 transporter from a intracellular vesicle
3) GLUT 4 is translocated and inserted into the target cell's membrane
4) Glucose is transported into the cell via GLUT4
5) GLUT4 transporter is recycled.

Front 24

What acute metabolic effect does insulin have on fat metabolism?

Back 24

Increases fat storage in adipocyte tissues by increasing FA & TG synthesis.
Makes sure there is storage but no breakdown

Front 25

Specifically, how does insulin increase fatty acid and triglyceride synthesis in the adipocytes?

Back 25

1) Stimulation of lipoprotein lipase - breaks down lipoproteins into FFA so that they can enter the adipocyte.
2) Inhibits lipase thereby decreasing lipolysis (breakdown of TG into FFA)
3) Stimulation of FA synthesis from glucose (whatever glucose that wasn't converted into glycogen in the liver is made into FA)

Front 26

What acute metabolic effect does insulin have a protein metabolism?

Back 26

Overall, insulin increased aa synthesis and inhibits proteinolysis (protein breakdwn).
In the muscle & liver increases protein synthesis.
In the muscle it also increases aa uptake.

Front 27

Overall, what affect does insulin have on acute metabolism?

Back 27

If there is lots of glucose available in the blood this signals insulin secretion which essential increased synthesis, storage and utilization of energy stores and inhibits the breakdown and release of more glucose into the blood.

Front 28

How does insulin effect chronic metabolism?

Back 28

Changes the gene expression of many metabolic enzymes, increasing expression of anabolic enzymes and decreasing expression of catabolic enzymes

Front 29

What effect does insulin have on cell growth?

Back 29

Insulin stimulates cell growth and DNA synthesis.

Front 30

How is glucagon initially synthesize?

Back 30

Glucagon is synthesized as a large (huge) precursor called proglucagon.
Depending on the tissue location, the proglucagon is processed into either glucagon (islet alpha-cells) or glucagon-like peptide (GLP-1/2) in intestinal endocrine cells.

Front 31

In general terms, what regulates glucagon secretion?

Back 31

Just like insulin secretion, glucagon is regulated via neural, hormonal or nutrients with glucose being the most important.

Front 32

What effect does the PNS and SNS have on glucagon secretion (neural)?

Back 32

Both PNS and SNS stimulate glucagon secretion (i.e. stress increases SNS in which you need more glucose in the blood for energy).

Front 33

What hormones stimulate and inhibit glucagon secretion?

Back 33

1) Gastrointestinal hormones
- GIP and CCK (+)
- GLP-1 7-36 and somatostatin
(-)
2) Islet hormones:
- Insulin and somatostatin (-)

Front 34

What nutrients have an effect on glucagon secretion?

Back 34

1)* Glucose* (most NB) - decreased bld glucose (+) for glucagon. Low bld glucose (-) for glucagon secretion
2) Arg and ala stimulate (+) glucagon secretion

Front 35

Besides insulin and glucagon, what are 4 other islet hormones?

Back 35

1) Somatostatin
2) Islet amyloid polypeptide (IAPP)
3) Pancreatic polypeptide (produced by F-cells)
4) Ghrelin

Front 36

Where in the body is somatostatin produced?

Back 36

Found in many tissues in the body including, hypothalamus, gut, stomach and islet

Front 37

What effect does islet somatostatin have on glucagon and insulin secretion?

Back 37

Somatostatin is released in response to glucose and it inhibits for glucagon and insulin.

Front 38

What physiological role does islet amyloid polypeptide (IAPP)?

Back 38

Synthesized in the beta-cells and secreted with insulin.
Inhibits gastric emptying and suppressed appetite.
May play a role in the progession of Type 2 DM by forming amyloid deposits in the islets.

Front 39

What roles does the pancreatic peptide play in the body?

Back 39

Stimulated via the PNS (vagal -ACh)
Causes negative energy balance by suppressing appetite and gastric emptying while increasing E expenditure.

Front 40

What role does ghrelin (islet hormone) have in the body?

Back 40

Stimulates appetite.

Front 41

What type of enzyme is the insulin receptor and what is its components?

Back 41

The insulin receptor found on target cells is a tyrosine kinase.
It has two extracellular alpha-subunits and two transmembrane beta-subunits.
Binding of insulin to the TK receptor activates auto/phosphorylation of tyrosine and serine and causes release of GLUT 4, translocation and uptake of glucose into the cell!

Front 42

What is the major site of action of glucagon?

Back 42

Liver - increases hepatic output of glucose thereby increasing blood glucose

Front 43

How does glucagon increased blood glucose levels through the liver?

Back 43

1) Increases glycogenolysis - glycogen storages in the liver are converted to glucose
2) increases gluconeogenesis - non-CHO carbons are made into glucose.

Front 44

What other endocrine regulators affect carbohydrate metabolism?

Back 44

1) Glucocorticoids (cortisol)
2) Growth hormone
3) ANS (SNS and PNS)

Front 45

What affect does GC (cortisol) have on CHO metabolism?

Back 45

Counterregulatory to insulin therefore it increases blood glucose levels.
Increases hepatic gluconeogenesis and increases hepatic response to glucagon.
Inhibits glucose uptake into muscle and adipose tissue.
Important role in the maintenance of blood glucose levels during fasting.

Front 46

What affect does growth hormone have on CHO metabolism?

Back 46

1) counterregulatory to insulin therefore increases blood glucose levels
2) Inhibits insulin action on other tissues

Front 47

What affect does the ANS have on CHO metabolism?

Back 47

1) SNS (NE/E) - directly stimulates hepatic glucose output
2) PNS (ACh) - stimulate hepatic glucose uptake

Front 48

At what blood glucose levels (mM) do the various hormones involved in CHO metabolism kick in?

Back 48

1) Insulin production decreases at bld glucose levles <4.6
2) Glucagon levels increase at 3.8
3) E levels increase at 3.8
4) GH levels increase 3.7
5) Cortisol levels increase at 3.2
Tightly regulated to prevent hypoglycemia (medical emergency because the brain gets starved of glucose);

Front 49

Define diabetes?

Back 49

Chronic, incurable disease characterized by elevated blood glucose levels (hyperglycemia) due to defective insuling secretion, action or both.

Front 50

What are some symptoms of diabetes?

Back 50

Thirsty
Frequent urination
Hunger
Weight loss (but intaking lots of calories)
"starvation in the midst of plenty"

Front 51

What is the definite diagnosis for diabetes?

Back 51

Elevated blood glucose levels (hyperglycemia)
Post-prandial or fasting blood sugar

Front 52

What are the two most common types of diabetes? What are some other rarer causes?

Back 52

Type 1 & 2 make up 95% of the causes of diabetes.
Others include, virus-induced, drug-induced, pancreatitis, genetic defect in beta cells, endocrinopathies

Front 53

Why do diabetics get elevated ketone bodies and/or ketone acidosis?

Back 53

With dysfunction insulin, the glucose has no way of getting into the cells therefore the brain is deprived of glucose. The only other energy source it can use is ketones therefore when starved of glucose the body will convert fatty acids into ketones which can be used by the brain as energy.

Front 54

What is another name for Type 1 DM and what is the age of onset?

Back 54

AKA insulin-dependent DM (IDDM) and juvenile onset.
Compared to Type 2 it is more a ketosis-prone diabetes (elevated ketones in the blood)

Front 55

What is the cause of Type 1 DM?

Back 55

Autoimmune attack on the beta cells.
Genetic and environmental component

Front 56

Explain the pathogenesis of Type 1 DM?

Back 56

Initially you are born with a genetic predisposition.
Initial insult (i.e. infection) causes the immune system to recognize self as foreign producing autoantibodies against the beta cells (i.e molecular mimicry)
Progressive the immune system attacks and decreases beta cell mass causing pre and then full blown diabetes.

Front 57

What evidence is there to support that Type 1 DM is an autoimmune disease?

Back 57

1) T-cells infiltrate the islet
2) Islet cell antibodies (ICA) (i.e insulin, GAD)
3) Strong genetic association with certain HLA loci
4) Associated with other autoimmune diseases.

Front 58

What evidence is their to support that Type 1 DM has a environmental component to it (besides just genetic)?

Back 58

1) Disease susceptibility is inherited - you inherit the risk, not the disease.
2) Identical twins are only 50% likely to get it if the other one has it.
3) Viruses associated with Type 1
4) Diets associated with type 1(i.e. breast milk vs. cow's milk)

Front 59

What viruses have been shown to be associated with Type 1 DM?

Back 59

Coxsackie virus
Mumps
Rubella

Front 60

What evidence is there to support a genetic component to Type 1 DM?

Back 60

1) Many different loci (17) associated with Type 1
2) Closest association with MHC II --> HLA (i.e. HLA-DR4 increases relative risk 10x)

Front 61

What roles do T-cells play in Type 1 DM?

Back 61

T cells (both CD4+ (helper) and CD8+(cytotoxic)) are responsible for destruction of the beta cells by recognizing beta cell autoantigens (i.e. insulin.
T-cells are the beta cell destroyers.
T-cells can be adoptively transferred

Front 62

What role do B cells play in Type 1 DM?

Back 62

B cells produce the islet cell autoantibodies (ICA) - which can be detected before disease onset.
B cells (and their antibodies) are more a marker of disease rather then the destoryers of beta cells

Front 63

What are some prevention and therapy strategies being used for Type 1 DM?

Back 63

1) Prevention
a) Immunosuppression - CD3 antibodies blocking T cells
b) peptide therapy (insulin-DPT-1)
c) Lifestyle intervention

2) Therapy
a) insulin
b) islet transplant

Front 64

What are some limitations of islet cell transplants?

Back 64

1) Shortage of donors
2) Life long immunosuppression to prevent allograft rejection
3) Most will be back on insulin in 5 years

Front 65

What is another name for Type 2 DM and what is the age of onset?

Back 65

Non-insulin dependent DM (NIDDM)
Adult onset

Front 66

Compared to Type 1, why is Type 2 diabetes considered ketosis-resistant diabetes?

Back 66

In Type 2, insulin is still being produces it is just the action is reduced.
Therefore uptake of glucose in the cell is still occurring, it just isn't keeping up therefore not as much ketones need to be made to compensate.

Front 67

Comparably, what is incidence rate of Type 1 DM? Type 2?

Back 67

Type 1 = 1:400
Type 2 = 1:20

Front 68

What causes hyperglyemia in a Type 2 DM patient?

Back 68

Defects in insulin action (increased insulin resistance) and insulin secretion.

Front 69

What evidence is there to show that Type 2 DM has both a genetic and environmental component?

Back 69

1) Genetic - identical twins 100% likely to get Type 2 if the other twin has it
- Increased prevelance in certain ethnicities

2) Environmental - associated with sedentary lifestyle and high fat diet

Front 70

What is the natural history of Type 2 DM?

Back 70

As we age and become more obese, our body becomes more insulin resistant therefore it takes more insulin to uptake the same amount of glucose.
To compensate, the beta cells have to increase their insulin production until the point where they get burnt out and can not longer produce enough insulin to compensate for the high glucose levels.

Front 71

What is "impaired glucose tolerance " (IGT)?

Back 71

Early progression of Type 2 DM in which bld glucose levels are slightly higher then normal as this is the stage when the beta cells are starting to fail therefore decreased insulin secretion - beginning stages of diabetes onset.

Front 72

What are the 3 stages in the progression Type 2 DM? Relate to blood glucose levels.

Back 72

1) Early Impaired glucose tolerance (IGT)- normal FBS but abnormal oGTT.
2) Overt, mild diabetes - FBS ~7 (on the boarder)
3) Severe diabetes - FBS >9

Front 73

What changes in insulin occur in mild and severe Type 2 DM?

Back 73

Mild = insulin resistance present with insulin secretion present but insufficient
Severe = Insulin secretion greatly impaired or absent

Front 74

How would you treat someone with early IGT? Mild diabetes? Severe DM?

Back 74

1) IGT - diet and exercise
2) Mild = diet and exercise + hyopglycemic agents (sulfonylurea) + insulin-sensitizing agents (metaformin).
3) Severe = insulin

Front 75

What is Type 2 DM strongly associated with - what increases your risks?

Back 75

Strongly associated with obesity, particularly intraabdominal mass.
Close relationship between BMI and insulin resistance

Front 76

What is "Syndrome X"?

Back 76

Name for a common syndrome invovling:
a) Obesity
b) Diabetes
c) Hyperlipidemia
d) Hyperinsulinemia
e) HTN

Front 77

What are 4 characteristic changes that occur in insulin secretion in Type 2 DM?

Back 77

1) Decreased glucose sensing - decreased glucose-induced insulin secretion
2) Decreased proinsulin processing
3) Inability to adapt to increasing insulin resistance
4) Progressive decline in insulin secretion.

Front 78

What are 4 possible causes of Type 2 DM disease progression?

Back 78

1) Glucose and lipotoxicity - high levels of glucose and FFA are toxic to beta cells
2) Beta cell exhaustion - due to increased insulin resistance and hyperglycemia
3) Proinflammatory cytokines - beta cells release cytokines during hyperglycemic stress
4) Islet amyloid deposits - IAPP is secreted with insulin - crystalizes.

Front 79

What is the risk of a person with a first degree family relative of type 2 DM, also getting it?

Back 79

~12% compared to 5% on the general population (background)
Type 2 DM has a much larger genetic component then Type 1 DM.

Front 80

Which one has more a genetic component, Type 1 or Type 2 DM?

Back 80

Type 2, however it still confers risk of disease.
In approx 5% a single gene mutation may be enough to cause disease (rather then the two-hit hypothesis)

Front 81

What is MODY?

Back 81

Maturity Onset diabetes in youth - a single gene mutation causes DM.
Autosomal dominant mutation - beta cell gene defect in th the gene that regulates beta-cell mass/function.

Front 82

What four MODY genes have been identified and responsible for decrease beta cell insulin secretion (defect)?

Back 82

1) Glucokinase (MODY2)
2) Two hepatocyte nuclear transx factors that regulate beta cell growth/death
3) Insulin promoter factor

Front 83

What is a possible cause of gestational diabetes?

Back 83

The hormones during pregnancy increase insulin resistance and therefore increases insulin secretion to compensate.
May unmask some genetic predisoposition

Front 84

What % of women with gestation diabetes will develop Type 2 DM later in life?

Back 84

50%

Front 85

What FBG & 2hPG values are normal?

Back 85

FBG = <6 mmol/L
2hPG = <7.8 mmol/L

Front 86

What FBG and 2hPG values indicate impaired glucose tolerance?

Back 86

FBG = 6-7 mmol/L
2hPG = 7.8-11 mmol/L

Front 87

What FBG and 2hPG values indicate diabetes?

Back 87

FBS = >7 mmol/L
2hPG = > 11.1 mmol/L
The test must be done at least twice if no symptoms.

Front 88

What are some macrovascular complications related to diabetes?

Back 88

1) Stroke
2) Heart disease/CAD
3) HTN
4) Peripheral vascular disease

Front 89

What are some microvascular complications related to diabetes?

Back 89

1) retinopathy
2) Neuropathy
3) Nephropathy

Front 90

Why is it important to have good glycemic control in a diabetic?

Back 90

Good glycemic control indicates decreased glycosylation of proteins and therefore will reduce the complications associated with diabetes.

Front 91

What are the "optimal" HbA1C, FBG and postprandial glucose levels of diabetic?

Back 91

HbA1C= <7%
FBG = 4 - 7 mmol/L
Postprandial = 5 - 10 mmol/L

Front 92

What is the pathophysiology behind the progression of Type 2 DM?

Back 92

Type 2 is strongly associated with obesity. Increased obesity = increased insulin resistance.
As insulin resistance increases, the beta cells compensate by producing more insulin.
After a while the beta cells become exhausted and insulin secretion diminishes.
With both increases resistance and insulin secretion, glucose levels will rise.

Front 93

What has more on an affect on reduction of Type 2 DM disease progression; lifestyle changes or drugs?

Back 93

Lifestyle changes (ie. diet, exercise) can reduce your risk by almost 60% compared to 30% with metformin alone.

Front 94

What lifestyle changes are important for someone at risk for diabetes?

Back 94

Diet - caloric restriction and regular physical activity.

Front 95

What weight loss goal is ideal for lifestyle changes in a diabetic?

Back 95

5-10% of your weight over 6 months.
If you reduce your calorie intake by 500kcal/day you will loss ~1-2lbs/week.

Front 96

How much physical activity is recommended for someone with diabetes?

Back 96

As long as there are no health restriction, accumulate 150 minutes of aerobic activity per week, spread over 3 non-consecutive days of the week.
Goal is to increase it to 4 hours or more per week.
Encourage resistance exercises in addition to aerobics.

Front 97

How often should blood glucose levels and HbA1C be checked in a diabetic?

Back 97

HbA1C should be monitored every 3 months.
Blood glucose levels should be self monitored before and after each meal.

Front 98

Why can't oral hyopglycemic agents not be given to treat Type 1 DM?

Back 98

Oral glycemic agents act mostly on insulin and/its pathway of secretion which is not available (or very low) in Type 1 DM due to autimmune destruction.

Front 99

What is the MOA of sulfonylureas?

Back 99

SU bind to SUR and close K+ATP pump, depolarizing the cell, increasing iCa+2 and therefore increasing insulin secretion

Sulfonylureas bind to the SU receptor located adjacent to the K+ATP channel on the beta cell.
The sulfonylurea causes the pump to close, thereby increasing the amount of K+ in the cell and thereby making it more negative then outside the cell causing the beta cell to depolarize.
This intracellular change will cause Ca+2 to enter the beta cell and increase intracellular calcium inducing insulin secretion.

Front 100

What overall affect does sulfonylureas have on glucose?

Back 100

Sulfonylurea will increase insulin secretion and therefore decrease serum glucose levels, improving hyperglycemia and reducing glucotoxicity.

Front 101

What are some side effects of sulfonylureas?

Back 101

1) Weight gain
2) Hypoglycemia - because their action is glucose-independent there is nothing regulating it beyond the dose - long acting

Front 102

What are some of the sulfonylurea drugs used?

Back 102

1) Glyburide
2) Gliclazide - shorting acting therefore decreased risk of hypoglycemia
3) Glimepiride
4) Chlorpropamide - long acting

Front 103

What is the MOA of meglitinides?

Back 103

Meglitinides act very similar to sulfonylurea except it binds to a different receptor on the K+ATP pump. It increases insulin secretion.

Front 104

What are some pros and cons of meglitinides?

Back 104

1) Glucose stimulated release therefore minimal effect when fasting - take with meals.
2) Short acting therefore attenuates postprandial hyperglycemia
3) B/c it is short acting, has a decreased risk of hypoglycemia

Front 105

What are two meglitinide drugs?

Back 105

1) Repaglinide
2) Nateglinide

Front 106

What is the MOA of alpha-glucosidase inhibitors?

Back 106

Competiviely inhibit pancreatic alpha amylase and intestinal membrane-bound alpha glucosidase.
This enzyme breaks down complex CHO into simple monosaccharide CHO therefore reducing the amount of postprandial CHO available to cause hyperglycemia

Front 107

What are some disadvantages/side effects of alpha-glucosidase inhibitors?

Back 107

1) They are meal dependent
2) With no breakdown of complex CHO you increase the energy available for bacterial growth and therefore cause gut discomfort (bloating, diarrhea, flatulence)

Front 108

What is the MOA of biguanides?

Back 108

1) Decrease hepatic gluconeogensis
2) Increases insulin stimulated glucose transport at the muscles by 10-40%
3) Decreases FA oxidation by 20%

Front 109

What are three pros of biguanides?

Back 109

1) Weight loss
2) Less hypoglycemia
3) Reduces Triglycerides, LDL, and cholesterol while increasing HDL.

Front 110

What is the prototype biguanide drugs?

Back 110

Metformin

Front 111

What are some side effects of biguanides?

Back 111

Diarrhea, nausea, vomiting, flatulence and metallic taste.

Front 112

What is the MOA of Thiazolidinediones (TZD)?

Back 112

TZD are insulin-sensitizing agents.
TZD bind to peroxisome proliferator-activated receptors (PPAR) inside the nucleus, activating the transcription of a bunch of genes that do the following:
1) Liver - decreases insulin resistance and hepatic glucose production and fat.
2) Pancreas - decreases demand for insulin secretion
and increases beta cell insulin content
3) Muscle - decreases insulin resistance and increases glucose uptake

Front 113

What are some side effects of TZD?

Back 113

1) Weight gain
2) Fluid retention - increases risk of macula edema and fractures

Front 114

Why was troglitazone TZD taken off the market?

Back 114

Hepatoxicity

Front 115

What is the overall effect of TZD?

Back 115

Enhances responsiveness and efficiency of beta cells.

Front 116

When shouldn't you use TZD?

Back 116

Class II or higher CHFdue to the fluid retention.

Front 117

What are two type of TZD drugs being used?

Back 117

1) Rosiglitazone
2) Pioglitazone

Front 118

What are 2 new drugs in development that aren't available in Canada?

Back 118

1) Amylin analogs - suppress endogenous glucagon production
2) Glitazars - PPAR agonists that are insulin sensitizing agents.

Front 119

What are incretins and what role do they play in treating diabetes?

Back 119

Incretins are hormones released by the gut in response to food ingestion. GLP and GIP stimulate insulin secretion in the presence of glucose.

Front 120

What MOA does GLP-1 have on decreasing blood glucose levels?

Back 120

1) Increases insulin secretion
2) Decreases glucagon secretion
3) Slows gastric emptying
4) Reduces food intake
5) Improves insulin sensitivity.

Front 121

What are some of the problems being encountered with the GLP-1 analogs?

Back 121

They are rapidly broken down therefore they don't last very long.

Front 122

How can you increase the lifespan of the GLP-1 analog drugs?

Back 122

1) GLP-1 agonist - increases the amount and slightly different therefore digested slower
2) Dipeptidy peptidase -IV inhibitors - blocks the enzyme that degrades GLP-1

Front 123

What are the 6 various oral hypoglycemic agents used to treat Type 2 DM?

Back 123

1) Sulfonylurea
2) Meglitinides
3) Alpha-glucosidase inhibitors
4) Biguanides
5) Thiazolidinediones (TZD)
6) Incretins

Front 124

Whom is insulin used to treat?

Back 124

Type 1 DM because they lack insulin production.
Type 2 DM can also need insulin injections if there disease is so severe that insulin production is low.

Front 125

What are the 2 types of insulin?

Back 125

Short and long acting.
Short = mimics short & 2nd phase insulin during meals
Long = basal line insulin.

Front 126

What are the two common types of short insulin and how long do they usually last for?

Back 126

1) Humalog - onset in 5-15 minutes and lasts 4-6 hours total
2) Novorapid - same as humalog

Front 127

What are the 4 common long acting insulin drugs?

Back 127

1) NPH
2) Lente
3) Ultralente
4) Glargine/determir

Front 128

What is the disadvantage of NPH long acting insulin? What is the advantage of glargine?

Back 128

NPH peaks between 4-10 hours therefore you need to make sure that you have food intake around this time otherwise you become hypoglycemic.
Glargine has no peak therefore no need to worry about food intake = baseline insulin.

Front 129

What is the short insulin used for?

Back 129

To prevent postprandial hyperglycemia.

Front 130

What is the long acting insulin used for?

Back 130

To maintain euglycemia during fasting.
To decrease hepatic gluconeogenesis.

Front 131

If you have are a DM with a unpredicatable lifestyle what insulin injection pattern would be best to maintain euglycemia?

Back 131

Intenstive Insulin regime.
- Take short acting before every meal
- Take long acting NPH twice a day to keep baseline insulin levels up
- Also add glargine to maintain a peakless baseline.

Front 132

What is a handy way to administer diabetic drugs, especially in children?

Back 132

Pulsatile pump therapy

Front 133

What are some disadvantages of insulin treatment?

Back 133

1) Weight gain
2) Hypoglycemia
3) Variability in insulin kinetics and compatibility.

Front 134

Besides monitoring blood glucose levels, what other things should be monitored (complications)?

Back 134

1) Lipids
- LDL <2
- HDL/TAG ratio <4
2) Monitor for CAD and CVD
3) Antiplatelet therapy
4) Regular eye exams
5) ACEi or ARBs for renal protection against renal disease, monitor for proteinuria
6) BP = <130/80
7) Regular foot exams (neurological), ED and gastric emptying evaluation.
8) Monitor HbA1C

Front 135

What are some chronic complications that diabetics encounter?

Back 135

1) MI
2) peripheral vascular disease
3) limb amputation
4) Leading cause of blindness and renal failure
5) pregnancy complications
6) neuropathy
7) Infections
8) Peridontal disease
9) HTN

Front 136

What must be tightly controlled in diabetics to delay long term complications?

Back 136

1) Blood glucose levels (HbA1C <7)
2) BP (130/80)
3) Lipids (LDL <2)

Front 137

What are the 5 current classifications of diabetes?

Back 137

1) Type 1
2) Type 2
3) Gestational
4) Impaired fasting glucose (impaired glucose tolerance)
5) Other - infection, drugs, endocrinopathies, genetic defects, pancreatic disorders, etc.

Front 138

Compare and contrast Type 1 and Type 2 DM?

Back 138

1) Type 1 - early onset, autoimmune destruction of beta-cells which may be triggered by genetics and/or environment (virus causing molecular mimicry)
2) Type 2 - presents later in life and procresses slowly.
-associated with obesity or increased intra-abdominal fat ,
- increased insulin resistance (due to fat) and decreased insulin secretion.

Front 139

What are the 3 main anatomical changes that occur to cause Type 2 DM?

Back 139

1) Increased insulin resistance
2) Decreased insulin secretion
3) Increased glucose production.

Front 140

Why is Type 1 DM associated with weight loss and ketone-prone?

Back 140

Type 1 DM there is reduced or no insulin secreted therefore no glucose will be pulled into the cell. The patient will be peeing out glucose, taking a lot of its calories with them = lean.
In the absense of insulin, lipolysis increases releasing glycerol and FFA. Without glucose the brain dies therefore FFA are made into ketones in the absence of insulin to provide E for the brain

Front 141

What HLA mutations are usually associated with Type 1 DM?

Back 141

HLA-DR3 and DR4.

Front 142

What are some classic symptoms of diabetes that occur with acute metabolic complications?

Back 142

1) Polyuria
2) Polydyspia
3) Weight loss or gain
4) dehydrated
5) confused, dizzy, seizures, coma
6) extreme fatigue
7) blurred vision
8) recurring infections
9) slow to heal
10) tingling/numbness
11) ED

Front 143

How do you determine the diagnosis of diabetes?

Back 143

Fasting blood glucose greater or equal to 7 (normal is <6.1 mmol/L) on two seperate occasions or once with symptoms

Front 144

If the patient has trouble fasting and you suspect diabetes, what test beside FBG could preformed?

Back 144

2hr postglucose load >11.1 on two seperate occasions or once with symptoms.

Front 145

What are the normal and diabetic ranges for FBG and 2hPG readings?

Back 145

1) Normal
- FBG = <6
- 2hrPG = <7.8

2) Diabetic
-FBG >7mmol/L
- 2hrPG - >11.1 mmol/L

Front 146

What are the values for impaired glucose tolerance test (FBG and 2hrPG)?

Back 146

FBG - 6.1 - 7 mmol/L
2hrPG - 7.8-11.2 mmol/L

Front 147

When is the gestational screen for diabetes usually done?

Back 147

24-28 weeks of gestation.

Front 148

How could you determine if an adult had Type 1 or type 2 DM?

Back 148

- Symtpoms - type 1 may have weight loss, ketones
-Check for autoantibodies against insulin or glutamic acid decarboxylase (GAD)).
- Check the level of C-peptide...if high then endogenous insulin is being produced just your body is resistant (Type 2)

Front 149

When should screening for DM of an asymptomatic patient occur?

Back 149

- >40yo
- repeat every 3 years
- Can perform screen at younger age if their are risks.

Front 150

When should testing for DM be done earlier then 40yo?

Back 150

1) Overweight (BMI>27)
2) Family Hx of DM (first degree)
3) Member of a high risk ethnic group (Asians, hispanic, aboriginal or african
4) Low HDL or high LDL
5) HTN
6) Dx with gestational DM
7) Previous testing had impaired fasting glucose
8) Polycystic ovary syndrome
9) Dx with schizophrenia (drugs)
10) complications associated with DM.

Front 151

If a person presents in coma, what is the first test you should run?

Back 151

Blood glucose.
If high blood glucose then look for ketoacidosis.
If low, treat the hypoglycemia (i.e. glucose bolus)

Front 152

What are some acute complications of DM?

Back 152

1) Hypoglycemia
2) Infections
3) MI
4) Stroke
5) Diabetic ketoacidosis
6) Hyperosmolar non-ketotic hyperglycemia

Front 153

What are some clinical features of diabetic ketoacidosis (DKA)?

Back 153

DKA could present with:
a) thirsty
b) polyuria
c) dehydrated
d) hypotensive
e) ketosis (acetone on the breath)
f) hyperventilating (due to metabolic acidosis)
g) vomiting - electrolyte imbalance
h) Drowisness / Coma
i) abdominal pain

Front 154

What are some metabolic features of diabetic ketoacidosis (DKA?

Back 154

1) Hyperglycemia
2) Glucosuria
3) Ketonemia
4) Metabolic acidosis
5) Hyperkalemia (need insulin to pull K+ in to the cells)
6) Uremia
7) Hypertriglyceridemia
8) Hemoconcentration.

Front 155

What is the pathogenesis to why the lack of insulin causes the metabolic features associated with DKA?

Back 155

- Insulin deficiency leads to gluconeogenesis and glcyogenolysis while at the same time glucose uptake into the cell is reduced = hyperglycemia
- The excess glucose osmoles in the ECFV leads intracellular dehydration and to osmotic diuresis accompanied by a loss of electrolytes
- The absence of insulin, increases glucagon which stimulates lipolysis and ketogenesis, raising the amount of ketones in the blood.
- Accumulation of ketones and the lack of insulin leads to metabolic acidosis compensated for by respiratory alkalosis (hyperventilating)
- In the absence of insulin and the presence of acidosis, K+ moves out of the cell into the ECFV and then can be loss with urine.

Front 156

What are the three types of ketones that form during fatty acid beta-oxidation?

Back 156

1) Beta-hydroxybutyrate *
2) Acetoacetate
3) Acetone

Front 157

If you suspect DKA, what lab tests should be ordered?

Back 157

1) blood glucose
2) ketones
3) blood gases
4) electrolytes (E7)
5) phosphates
6) CBC
7) ECG
8) urinanalysis
9) Chest X-ray
6) urea, creatinine

Front 158

How do you treat someone with DKA?

Back 158

1) First start to replenish their ECFV with isotonic saline
2) Give insulin to decrease the hyperglycemia and stop lipolysis and ketogenesis. Do this slowly as to not drop glucose levels to quickly.
3) Monitor electrolytes, especially K+ and PO4- very closley

Front 159

Why does DKA cause a pseudohyponatremia?

Back 159

The hyperglycemia (and high levels of ketones) cause increases osmoles in the ECFV. This will cause fluid to move out of the ICFV and into the ECFV therefore causing dilutional hyponatremia.
Also, the osmoles will cause osmotic diuresis which will pull the Na+ out with the glucose.

Front 160

Why must potassium levels be closely monitored in someone with DKA?

Back 160

Initially they can be hyperkalemic due to K+ flux out of the cell (lack of insulin and acidosis). Also the patient is volume depleted therefore it may be a dilution effect and when volumes return to normal they may become hypoK+.
- Also, when insulin is administered, it pulls K+ into the cell with it therefore reducing the K+ in the blood.

Front 161

What are some side effects is DKA is not managed appropriately?

Back 161

- Cerebral edema - due to too fast of a glucose drop and excess fluids.
- Severe metabolic compensation
- Hypokalemia - heart problems
- permanent neurological injury.

Front 162

What is hyperosmolar non-ketotic hyperglycemia?

Back 162

- Occurs in the elderly in with Type 2 DM.
- Extreme dehydration due to hyperglycemia osmotic diuresis
- Because of residual insulin activity, lipolysis and ketogenesis is not activated.

Front 163

What happens to the sodium levels in someone with hyperosmolar non-ketotic hyperglycemia?

Back 163

Initially they may appear hyponatremic due to osmotic effects pulling fluid out of the ICFV into the ECFV but as they become more dehydrated they become hypernatremic

Front 164

Why is lactic acidosis high in patients with hyperosmolar non-ketotic hyperglycemia?

Back 164

Volume contraction and decreased delivery of oxygen to tissues results in increased anaerboic metabolism.

Front 165

What usually precipitates hyperosmolar non-ketotic hyperglycemia?

Back 165

Increased insulin resistance secondary to stress or illness or drug complications.

Front 166

What lab tests would confirm a hyperosmolar non-ketotic hyperglycemia?

Back 166

- High blood glucose
- Negative for ketones
- Increased osmolality (>340mOsm/kg)
- Hypo or hypernatremia depending on dehydration state
- pH is normal (unless severe lactic acidosis)

Front 167

In hyperosmolar non-ketotic hyerglycemia, what is the conscious state reflective of?

Back 167

Proportional to the increase in serum osmolarity.
The higher the osmoles in the blood, the more confused the patient.

Front 168

What is the equation to determine osmolality?

Back 168

Osmolality = 2[Na+] + urea + glucose.

Front 169

Why does hyperglycemia cause vascular problems?

Back 169

Hyperglycemia causing increased glycosylation of proteins in the vessel walls. Glycosylated proteins don't function the same as normal.
This causes basement membrane thickening and vascular complications.

Front 170

In the doctor's office, what must be monitored regularly to prevent long term diabetic complications?

Back 170

1) Blood glucose - HbA1C, glucose meter (for the patient)
2) Renal function - microalbuminemia, urea, creatitine
3) P/E - BP, cardiac, neurological, opthamological
4) Lipids

Front 171

Why is HbA1C used to monitor long term glucose control in DM?

Back 171

Hb becomes glycosylated when glucose levels are high. This chemical transformation is irreversible.
The amount of stable HbA1C is directly proportional to the average glucose concentration over the previous 6 weeks.
The long lifespan of RBC allows the HbA1C to accumulate.
Gives physicians a window into how their glucose levels have been.
More glycosylation = worse glucose control.

Front 172

How often should the HbA1C be measured and what is the target reading?

Back 172

Every 3 months
Target is <7%
For every 1% rise in HbA1C there is a 2 mmol/L increase in average glucose concentration.

Front 173

Why are high glucose levels bad?

Back 173

Glucose causes glycosylation of proteins (irreversible) which changes their function.
This contributes to the long term complications that occur with DM

Front 174

What can be done to prevent microalbuminuria (nephropathy) from occurring in DM?

Back 174

1) Monitor BP (<130/80)
2) ACEi or ARB - renal protective.

Front 175

What must be monitor and how often for a patient with diabetes?

Back 175

1) HbA1C - 4x per year (<7%)
2) BP at every visit (<130/80)
3) Lipids once a year (LDL <2, total cholesterol:HDL ratio <4)
4) Annual urine albumin/creatinine ratio
5) Annual cardiovascular, foot, neurological and retinal exam.
6) Monitor BMI / Lifestyle changes
7) ASA and ACEi/ARB
8) Glucose readings before and after meals.

Front 176

In general terms, what chronic complications dominate DM?

Back 176

1) vasculature
2) eye disease
3) renal disease
4) neurological disease
5) skin disease
6) infection

Front 177

Why is hyperglycemia dangerous? What is the pathogenesis of DM?

Back 177

1) non-enzymatic glycosylation of protein amino groups
2) Intracellular hyperglycemia causes osmotic load

Front 178

What are the 3 stages of glycosylation of amino end of a protein?

Back 178

1) Schiff base formation (reversible)
2) Amadori production formation (reversible)
3) Advanced glycosylated end product formation (AGEs) (irreversible)

Front 179

How does glycosylation cause the chronic complications observed in DM?

Back 179

1) AGE occur on proteins, lipids and nucleic acids, altering their function
2) The accumulation of AGEs causes the pathology to occur

Front 180

How does intracellular hyperglycemia cause chronic complications?

Back 180

- Glucose enters cells that don't require insulin for uptake (nerves, lens, kidney, blood vessel)
- Glucose is metabolized to sorbitol and fructose which create an osmotic load
- Pathology occurs due to osmotic cell injury.

Front 181

What type of vascular diseases are observed in DM?

Back 181

1) Microvascular
- microangiopathy
- hyaline arteriolosclerosis
2) Macrovascular
- accelerated atherosclerosis

Front 182

What is diabetic microangiopathy?

Back 182

- Accumulation of AGEs causing thickening of the basement membrane of blood vessels.
- The thickening alters the structural integrity of the wall therefore weakening it and causing leaky vessels and microaneurysms

Front 183

How does hyaline arteriosclerosis occur?

Back 183

Arteriole wall thickened with hyaline, narrowing the lumen

Front 184

What are 3 common sites where accelerated macrovascular atherosclerosis occurs in DM?

Back 184

1) Coronary arteries
2) Cerebrovascular
3) Peripheral vascular - obstruction below the knee = amputation, impotence

Front 185

What renal diseases commonly occur in DM?

Back 185

1) Progressive glomerulosclerosis (nodular vs. diffuse)
2) Vascular changes - arteriolosclerosis (renal artery) and athreosclerosis (afferent and efferent)
3) Infection - pylenephritis
4) Papillary necrosis
5) Autonomic neuropathy - function obstruction of bladder

Front 186

What are the two types of glomerulosclerosis that occurs in DM and what is the difference between the two?

Back 186

1) Diffuse - increase in mesangial matrix diffusely through the glomerulus (glomeruli BM thickening)
2) Nodular - ball-like deposits of mesangial matrix; located in the largely in the periphery,

Front 187

What renal disease is pathoneumonic for diabetes?

Back 187

Nodular glomerulosclerosis.

Front 188

What is papillary necrosis (AKA Necrotizing papillitis)?

Back 188

Ischemic necrosis of the medullary papillary - infarction, necrosis.
Cells slough off and block the ureter from draining.

Front 189

What are some common eye diseases that occur in DM?

Back 189

1) Cataracts
2) Glaucoma
3) Diabetic retinopathy
4) Ocular palsies

Front 190

What are the 3 types of diabetic retinopathy that can form?

Back 190

1) Background (non-proliferative) - increased vasculature permeability and retinal ischemia
2) Pre-proliferative - increased caliber and beading of retinal veins
3) Poliferative - ischemia and hypoxia of retina results in neovascularization.

Front 191

What vessels features will you see with background (non-poliferative) diabetic retinopathy?

Back 191

Microaneurysms (spots)
Hemorrhages (blots)
Hemorrhage into nerve fibers (flames shape)

Front 192

What vessels features will you see with pre-poliferative diabetic retinopathy?

Back 192

Venous beading (sausages)
Cotton wool spots (microinfarct of nerve fiber layer with fuzzy edge)

Front 193

What type of vessels will you see in someone with proliferation diabetes retinopathy?

Back 193

Increase in vessel # - but very fragile
Retinal detachment

Front 194

How does glaucoma occur in someone with diabetes?

Back 194

New vessel formation blocks drainage of the aqueous humor increasing occular pressure and causing glaucoma.

Front 195

What nerve usually gets paralyzed in ocular palsy?

Back 195

CN III infarct but also CNIV and CNVI

Front 196

Which 4 neurological diseases are associated with diabetic complications?

Back 196

1) Distal symmetric sensori-motor neuropathy - glove & stocking loss of sensation
2) Autonomic neuropathy (ANS)
3) Diabetic polyradiculopathy (nerve roots)
4) mononeuropathy or mononeuropathy multiplex (CNS and PN)

Front 197

What organ dysfunctions may occur in someone with autonomic neuropathy?

Back 197

1) ED
2) Bowel dysfunction

Front 198

What is diabetic polyradiculopathy?

Back 198

Axon loss at the level of the nerve root (L2-4, maybe L5)
- rapid development of pain and weakness of upper legs
- muscle wasting because nerve is no longer supplying a particular muscle therefore no movement.

Front 199

What causes mononeuropathy and how would distinguish it from distal sensori-motor polyneuropathy?

Back 199

Mononeuropathy develops when the nerve gets compressed, entraped or infarcted.
It will cause a asymetric loss rather then symmetric as seen is distal sensor-motor polyneuropathy.

Front 200

What are 5 skin diseases commonly associated with complications of DM?

Back 200

1) Ulcers
2) Recurrent infections - candida
3) Granuloma annulare - lesions with raised annular border on dorsum of hand/arm
4) Injection site lipodystrophy
5) Necrobiosis lipoidica diabeticorum - shiny, non-scaling plaque on shin with yellowish skin and telangietasia.

Front 201

What are some common infections seen in DM?

Back 201

1) Malignant otitis externa (pseudomonas)
2) Rhinocerebral mucormycosis - mucor fungal infection of the sinus that can invade the wall, into the CNS and invade the brain
3) Mucocutaneous candidal infection (mouth and vagina)
4) Emphysematous cholecystisis (gallbladder)
5) Emphysematous pyelonephritis/papillary necrosis
6) Soft tissue infection (diabetic foot)

Front 202

What is the "diabetic foot"?

Back 202

Neruopathic loss of sensation results in altered forces being placed on the foot.
-Development of ulcers, hematomas, and calluses
- fail to sense injury or presence of foreign body

Front 203

What are the 4 hormones responsible for the glucose counter regulatory response system?

Back 203

Glucagon
Epinephrine
Growth hormone
cortisol (GC)
All raise blood glucose levels - oppose the effects of insulin.

Front 204

What organs are involved in sensing changes in glucose levels?

Back 204

1) Brain - transporters and sensors in the ventromedial hypothalamus that releases pituitary hormones (ACTH and GH)
2) Pancreatic islets - glucose receptors
3) Liver (and kidney slight) - respond to signals and alter metabolism.

Front 205

During hypoglycemia, what hormones are rapid acting?

Back 205

1) Glucagon is the most important - it release is dependent on the rate of drop in glucose and the absense of insulin
- increases hepatic GLUCONEOGENESIS, glycogenolysis and permit ketogenesis
2) Epinephrine - back up role and has a multi organ effect.
- increases gluconeogenesisi in both the liver and the muscle, inhibits peripheral glucose use and stimulates lipolysis.

Front 206

During hypoglycemia, what hormones are slow acting?

Back 206

GH and cortisol take 3-4 hours to kick in
1) Growth hormone increases lipolysis therefore providing glycerol for gluconeogenesis and FFA for E
2) Cortisol - increases gluconeogenesis, lipolysis and protein catabolism

Front 207

Why is lipolysis so important?

Back 207

1) Liberates FFA which are used as an alternate energy source for a number of tissues
2) Liberated glycerol is a gluconeogenesis substrate to make glucose
3) FFA beta-oxidization in the liver supplies the energy for gluconeogenesis
4) FFA can't cross the BBB however ketones generated from FA metabolism in the liver is an alternate fuel source for the brain.

Front 208

What are some adrenergic symptoms of hypoglycemia?

Back 208

"fight or flight response"
- tachycardia, palpitations, pounding heart
- sweating
- tremors
- anxiety / nervousness
- feeling cold.

Front 209

What are some neuroglycopenic symptoms of hypoglycemia?

Back 209

- tiredness
- confusion / disorientated
- decreased level of consciousness
- blurred vision
- behavioral changes
- dizziness / incoordination
- slurred speech
- hunger/headache
- paresthesias (tingly, numbness

Front 210

What is the normal glucose range?

Back 210

3.8 - 6 mmol/L

Front 211

What order do the various hypoglycemic symptoms arise and at what blood glucose level?

Back 211

1) Hypoglyemic symptoms arise around <3.7
2) Adrenergic symptoms arise around 3.3
3) Neuroglycopenic symptoms arise around 2.8
- Coma occurs at <1.6

Front 212

What is Whipple's triad?

Back 212

1) Symptoms of hypoglycemia
2) Lab confirmation of hypoglycemia (<2.5mmol/L)
3) Relief of symptoms following rapid administration of glucose

Front 213

If someone presents with hypoglycemia what is the initial treatment?

Back 213

Bolus of glucose - 20-50mL of 50% in 1-3 minutes.
Hypoglycemia is a medical emergency.
Following treatment will depend on the cause of the hypoglycemia.

Front 214

How do you classify hypoglycemia?

Back 214

Fasting vs. Reactive (AKA function or postprandial)
Hyperinsulinism vs. Non-hyperinsulinism
Ill vs. Non-ill loooking

Front 215

What is the main cause of reactive hypoglycemia?

Back 215

Reoccurent episodes of hyoglycemia following 2-4 hours after a meal:
Too much insulin
Or not enough or too slow of a counter-regulatory response (glucagon, E, GH or cortisol)

Front 216

What are some other causes of reactive hypoglycemia?

Back 216

1) Post-gastrectomy
2) Alcohol indigestion
3) Galactosemia
4) Heriditary fructose intolerace
5) Insulin and sulfonylurea (both reactive and fasting)

Front 217

What are some causes of fasting hypoglycemia?

Back 217

1) Insulin or sulfonylurea overuse
2) Insulinoma
3) Endocrine disorders (adrenal, hypopituitary)
4) Heptatic or renal disease
5) Various inborn or neonatal disorders
6) Septicemia
7) Other drugs (EtOH, salicylate, quinine)

Front 218

When should a person be tested if you suspect they are hypoglycemic?

Back 218

You must test when the patient is hypoglycemic, at the time they have symptoms.
You may need the patient to do a 72 hour fast to get them hypoglycemic again.

Front 219

What lab tests should you order when someone is hypoglycemic?

Back 219

1) blood glucose
2) Insulin levels
3) C-peptide levels
4) ketones
5) pituitary, adrenal, liver and kidney functions
6) drug screen for ethanol, sulfonylurea

Front 220

What results would you suspect with regards to symptoms, glucose, insulin, C-peptide and ketone levels in someone with a insulinoma? What about factitious insulin (exogenous)?

Back 220

a) Insulinoma = hypoglyemia symptoms, elevated insulin and C-peptide (endogenous) and decreases ketones because insulin inhibits lipolysis.
b) Factitous = + symptoms, elevated insulin but decreased C-peptide because it is exogenous and decreased ketones.

Front 221

What results would you suspect with regards to symptoms, glucose, insulin, C-peptide and ketone levels in someone with excess sulfonylurea intake? What about IGF-2 secreting tumor?

Back 221

a) Sulfonylurea = + symptoms, increased insulin and C-peptide, decreased ketones
b) IGF-2 tumor = + symptoms, low insulin and C-peptide (like normal) but low ketones (because IGF-2 acts like insulin, it is just isn't insulin.

Front 222

What results would you suspect with regards to symptoms, glucose, insulin, C-peptide and ketone levels in someone with a non-insulin hypoglycemia (i.e pit or adrenal gland?

Back 222

+ve symptoms, decreased (normal) insulin and C-peptide, increased ketones.

Front 223

What results would you suspect with regards to symptoms, glucose, insulin, C-peptide and ketone levels in someone with non-hypoglycemic disorder (have symptoms like hypoglycemia but it isn't hypoglycemia)?

Back 223

+ve symptoms, decreased (normal) insulin and C-peptide, increasd ketones however glucose levels will no be in the hypogllycemic range.

Front 224

Beta cells expand in response to increased demand. What causes an increase in insulin demand?

Back 224

Obesity
Pregnancy
Insulin resistance (type 2 DM)

Front 225

How can beta cell mass increase?

Back 225

1) Hypertrophy (increase in size)
2) Hyperplasia (increase in #)
3) Decreased apoptosis.

Front 226

With increase demand, beta cells poliferate. Where in the pancreas are the new cells created?

Back 226

On ductal cells.

Front 227

What happens to the beta cells during gestational diabetes?

Back 227

Islet cell hyperplasia
Loss of islet cell architeture.

Front 228

What changes are observed in the pancreas of someone with Type 1 DM?

Back 228

Type 1 is autoimmune disease.
Infiltration and destruction of beta cells by T cells (CD4+ and CD8+)
Increased replication of beta cells is observed to try and compensate for the destruction.

Front 229

What happens to the space that was occupied by beta cells, following their destruction in a Type 1 DM?

Back 229

The space is filled in by non-beta cells such as alpha and delta cells. Therefore these cells are no longer just located in the periphery.
Plus the hyperplasia of these cells to fill the space may cause hyperglycemia due to increased glucagon.

Front 230

How is beta cell mass decreased in Type 2 DM?

Back 230

1) glucotoxicity
2) glucolipotoxicity
3) ER?
4) Overuse trying to compensate for insulin resistance.

Front 231

What role does IAPP play in type 2 DM?

Back 231

IAPP is released from beta cells with insulin.
IAPP can form amyloid fibers that become toxic to the beta cell and induce apoptosis.

Front 232

How does cystic fibrosis cause diabetes?

Back 232

The mucus clogs the pancreatic duct, blcoking exocrine secretion of digestive enzymes which causes pancreatis which damages the beta cells.