Glucose Metabolism

Front 1

normal range for Blood Glucose?

Back 1

3.5 - 8 mmol/L

Front 2

At what blood glucose level does major CNS dysfunction occur?

Back 2

1 mmol/L

Front 3

What does glucose do?

Back 3

Stimulate insulin release from beta islet cells in the panreas

Front 4

What substrate does not directly maintain glucose levels?

Back 4

fatty acids

Front 5

Function of insulin?

Back 5

Regulates fat disposition and usage of fuels

Front 6

When glucose enters the beta islet cell how does it stimulate insulin release?

Back 6

increase ATP which blocks K channels and K doesnt leave cell = depolarization = Ca channel open and get influx of Ca = release insulin

Front 7

What drug classes block K channels so you increase insulin secretion?

Back 7

1. Meglitinide

2. Sulfonylurea

Front 8

3 sites insulin targets

Back 8

Muscle, liver, adipose

Front 9

FED STATE: what will increased levels of insulin do?

Back 9

Increase uptake of glucose into cells and generate ATP (increase uptake of glucose in muscle, liver and adipocytes)

Front 10

FED STATE: What is suppressed?

Back 10

1. Liver synthesis of glucose or release of glucose into blood.

2. Fat cell lipolysis and release of free FA

Front 11

FED STATE: What is synthesized and stored?

Back 11

Glycogen, Triglycerides, protein

Front 12

NON-FED STATE: what does decreased insulin do?

Back 12

signals to brain --> liver --> breakdown of glyogen to increase glucose levels

Front 13

NON-FED STATE: What is promoted?

Back 13

1. making and releasing glucose

2. Free fatty acids used

Front 14

Define Diabetes Mellitus?

Back 14

deficiency of circulating insulin leading to impaired use of glucose

Front 15

What are characteristics of hyperglycemia?

Back 15

disordered carbohydrate, fat, and protein metabolism

Front 16

What is diabetes the leading cause of?

Back 16

Blindness, end stage renal disease, lower limb amputtion, CV disease

Front 17

How much does diabetes shorten life expectancy?

Back 17

10-15 years

Front 18

What is the most common way to diagnose diabetes?

Back 18

8HR fasting glucose > 7 mmol/L

Front 19

What is the normal level of 8HR fasting glucose test?

Back 19

<6mmol/L

Front 20

What is a borderline response toHR fasting glucose test?

Back 20

between 6-7 mmol/L

Front 21

What is the diagnosis for diabetes using the casual blood glucose test?

Back 21

>11.1 mmol/L + symptoms (polyuria, polydipsia - excessive thirst, unexplained weight loss)

Front 22

What is the diagnosis for diabetes using the 2HR blood glucose in a 75g oral glucose tolerance test?

Back 22

>11.1 mmol/L

Front 23

What is the normal level in a 75g oral glucose tolerance test?

Back 23

< 7.8 mmol/L

Front 24

Which testis no longer routinely recommended by ADA?

Back 24

2hr blood glucose in a 75g OGTT

Front 25

Which diabetes has absolute insulin deficiency?

Back 25

Type 1

Front 26

Why is Type 2 Diabetes a Heterogeneous disorder?

Back 26

insulin resistance + decrease in beta cell secretion

Front 27

Which diabetes has relative insulin deficiency?

Back 27

Type 2

Front 28

What is Gestational Diabetes?

Back 28

Type 3: glucose intolerance

Front 29

How much of the beta islet cells are destroyed in Type 1 at the time of clinical symptoms?

Back 29

60-80%

Front 30

What is Insulitis?

Back 30

mononuclear and cytotoxic T cells clustering around islets = inflammation of Beta cells

Front 31

What are patient with Type 1 diabetes prone to?

Back 31

diabetic ketoacidosis

Front 32

What is diabetic ketoacidosis?

Back 32

when you decrease insulin levels the signal to adipocytes is lost (which stops mobilization of FA when glucose is high). So instead you are pouring out FA to liver to make ketoacids which leads to acidic intermediates

Front 33

What is the Tx for Type 1?

Back 33

Exogenous insulin and blood glucose monitoring

Front 34

What are the 3 mechanisms responsible for Type 1 Diabetes?

Back 34

1. Genetic susceptibility

2. Autoimmunity

3. Environmental Triggers

Front 35

What is 90% of genetic risk of Type 1 linked to?

Back 35

MHC polymorphism

Front 36

What is the concordance for identical twins in Type 1 diabetes?

Back 36

70%

Front 37

What are future Tx for Type 1?

Back 37

1. Cadaveric islet transplants

2. Cultured islet (Stem cell) = BEST

3. Immunemodulation (stopping T-cells from killing)

4. Vaccine (turn T cells into tolerant T cells)

Front 38

For Type 2 what is the greatest population: diagnosed, undiagnosed, glucose intolerant?

Back 38

Glucose Intolerant

Front 39

Where is Type 2 prevalent in?

Back 39

Aging population.

Obese individuals

Front 40

What has a strong impact of incidence rate on Type 2?

Back 40

If parents had Type 2 diabetes (more so than siblings type 2)

Front 41

Which type of diabetes does family history have a stronger impact?

Back 41

Type 2

Front 42

What is the Tx for Type 2?

Back 42

Diet, exercise and drug therapy

Front 43

What are metabolic consequences of Type 2?

Back 43

1. Peripheral insulin resistance in muscle and fat

2. Decreased uptake of glucose = increased hepatic glucose output

3. decreased panreatic insulin secretion

4. increase lipolysis and decreased triglyceride uptake = Maldistribution of fat and increased circulating FFA

Front 44

What are the consequences of increased lipolysis and decreased triglyceride uptake in Type 2?

Back 44

Maldistribution of fat and increased circulating FFA

Front 45

What is the best predictor whether someone will become diabetic?

Back 45

insulin resistance

Front 46

When does insulin resistance occur?

Back 46

10-20 years before onset of disease

Front 47

What does insulin resistance mean?

Back 47

Too much fasting response, too little fed response

Front 48

What happens to triglyceride uptake for insulin resistance?

Back 48

they decrease which increases circulating FFA

Front 49

What kind of far is related to insulin resistance?

Back 49

Brown fat

Front 50

What is the relationship between FFA and insulin sensitivity?

Back 50

too much FA can lead to decrease in insulin sensitivity

Front 51

What drugs target glucose production in liver for TYPE 2?

Back 51

Biguanides

Thiazolidinediones

Front 52

What drugs target peripheral glucose uptake and insulin resistance in muscle and adipose tissue?

Back 52

Biguanides

Thiazolidinediones

Front 53

What drugs target pancreas insulin secretion?

Back 53

Sulfonylureas

Meglitinides

Dipeptidyl pepidase-4 inhibitors

GLP-1 analogue [exenatide]

Insulin

Front 54

What drugs target glucose absorption in intestine?

Back 54

Alpha-glucosidase inhibitors