Pathophysiology 5

Question 1

Islet, Alpha cell

Answer 1

glucagon

Question 2

islet, beta cell

Answer 2

insulin + amylin

Question 3

islet, delta cell

Answer 3

somatostatin

Question 4

Modifiable Causes of Diabetes

Answer 4

1) Weight/BMI
2) Central Obesity
3) Sedentary Lifestyle

Question 5

Non-modifiable Causes of Diabetes

Answer 5

1) Age
2) Ethnicity
3) Genetics

Question 6

Structure of Human Proinsulin

Answer 6

-one continuous polypeptide
1) C-peptide
2) A-chain
3) B-chain
A & B chain are insulin hormone, must be broken down to be activated

Question 7

Connecting Peptide

Answer 7

• different than C-peptide
• have 2 Arg on 1 end and 1lys 1 arg on other end
• not an active form

Question 8

What are A and B chain joined by?

Answer 8

di-sulfide bonds

Question 9

How many disulfide bonds in proinsulin?

Answer 9

3

Question 10

How active is proinsulin?

Answer 10

1/10 as active as insulin

Question 11

What converts pro insulin to insulin?

Answer 11

-protein synthesis

Question 12

Biosynthesis of Insulin

Answer 12

AAs
DNA
RNA (messenger to transfer)
then peptide

Question 13

What stimulates glucagon?

Answer 13

• amino acids

- GIP, VIP

Question 14

What stimulates insulin?

Answer 14

• glucose
• gastrin
• FFA
• secretin
• gut glucagon

Question 15

What does glucagon do?

Answer 15

-protects from hypoglycemia

Question 16

How is Blood Glucose gotten rid of?

Answer 16

• Fat synthesis
• Oxidation
• Muscle glycogen (then can go to lactic acid then hepatic glycogen)

Question 17

Gluconeogenesis

Answer 17

-production of glucose from non-carbohydrate precursor

Question 18

GLP-1

Answer 18

“glucagon like peptide”

• secreted upon the ingestion of food
• Beta cell is enhanced by glucose-dep insulin secretion
• Alpha cell: dec. postprandial glucagon secretion
• Liver: dec. glucagon reduces hepatic glucose output
• Stomach: helps regulate gastric emptying
• promotes satiety and reduces appetite*

Question 19

GLP-1 administration

Answer 19

-oral only

NOT IV

Question 20

How is diabetes diagnosed?

Answer 20

1) normally fasting blood sugar < 5.7%
2) impaired 126mg/dl 2 hr sample >200
Hem A1c >6.5%

Question 21

How many people does diabetes effect?

Answer 21

-25.8 million people
8.3% US population
7 million of 25.8 not undiagnosed

Question 22

Is diabetes related to obesity?

Answer 22

yes

Question 23

Mortality of Diabetes

Answer 23

• 72,000 in 2006 direct
• 233,000 in 2005 linked as contributing cause
• leading cause of new blindness, chronic renal failure leading to dialysis and non-traumatic amputations

Question 24

Characteristics of Type 1 DM

Answer 24

age: less than 40
~10% of all diabetes
fall and winter
-acute or subacute
-frequent metabolic ketoacidosis
-uncommon obesity
-decreased beta cells
-decreased/absent insulin
inflammatory cells in islets are present initially

Question 25

Characteristics of Type 2 DM

Answer 25

``` age: greater than 40 ~90% of all diabetes -no seasonal trend -slow or subacute -common obesity -rare metabolic ketoacidosis -absent inflammatory cells in islets -common family history -90-95% concordance in identical twins -no HLA association -uncommon to have abs to islet cells or insulin ```

Question 26

Diagnostic Criteria in Diabetic Ketoacidosis

Answer 26

-arterial pH and bicarb is distinguishing feature -pH7.25-250 -bicarb 15 - <10 positive urine/serum ketone anion gap of 10-12 alert to stupor/coma

Question 27

Typical total body defect of water and electrolytes in Diabetic Ketoacidosis (DKA)

Answer 27

-

Question 28

Diagnostic Criteria in Hyperglycemic Hyperosmolar State (HHS)

Answer 28

``` Plasma glucose >600mg/dl pH >7.3 bicarb >15 small urine/serum ketone serum osmolality >320mOsm/kg variable anion gap mental status is stupor/coma ```

Question 29

Typical total body defect of water and electrolytes in HHS

Answer 29

-

Question 30

Factors in Development of DKA

Answer 30

-infection -new-onset diabetes -discontinued insulin unknown/

Question 31

Factors in Development of HHS

Answer 31

-infection -new-onset diabetes unknown/

Question 32

Hormone of fed state

Answer 32

insulin

Question 33

Hormone of fasting state

Answer 33

counter regulatory hormone

Question 34

Serum Osmolality Calculation

Answer 34

-

Question 35

Pathophysiology of DKA

Answer 35

1) Adipose Tissue - released FFA | 2) Liver: increased ketogenesis

Question 36

Pathophysiology of HHS

Answer 36

1) Liver- increased hepatic glucose production | 2) Peripheral tissue - decreased glucose utilization