Lec 17 Diabetes type I and Hypoglycemia

Question 1

What are the 3 cardinal signs of diabetes mellitus?

Answer 1

• polyuria
• polydipsia
• weight loss

Question 2

What is pathophys of type 1 diabetes vs type 2 diabetes?

Answer 2

type 1 = absolute insulin deficiency

type 2 = insulin resistance with relatively insulin deficiency

Question 3

What are mechs of action of glucagon?

Answer 3

• stimulates glucose production in liver
• stimulates glycogenolysis
• lipolysis and ketone production

Question 4

What are normal actions of insulin?

Answer 4

anabolic

• glycogen synthesis in liver
• triglyceride synthesis in adipose
• protein synthesis in muscles
• Na retention
• glucose transport in skeletal muscle and adipose tissue

Question 5

In the fasting state what are the major organs of glucose utilization?

Answer 5

50% to brain
25% to muscle/fat
25% to GI/splanchnic

Question 6

What is level of insulin in periods of fasting state?

Answer 6

low insulin in fasting state

Question 7

What is the major stimulus for insulin release?

Answer 7

glucose entering B cell and converted to G-6-P –> increase ATP –> closes K-ATP channel –> increased intracellular Ca –> exocytosis of insulin

Question 8

What is action of GLP-1/GIP on insulin level?

Answer 8

stimulate insulin release via increase in cAMP

Question 9

What are the 2 major immediate effects of glucose release?

Answer 9

• inhibits hepatic glucose production

- stimulates muscle/fat cell glucose uptake via GLUT-4 receptor

Question 10

Which glucose transporter is insulin-dependent? where is it located?

Answer 10

GLUT-4

located in adipose tissue and skeletal muscle

Question 11

What is mech of diabetes causing dehydration/thirst?

Answer 11

have hyperglycemia that overloads renal threshold –> glucose excreted = osmotic so leads to water diuresis –> dehydration and thirst

Question 12

What is effect of insulin deficiency on glucose metabolism?

Answer 12

leads to increase blood glucose due to uninhibited hepatic glucose production AND lack of glucose entering muscle and fat

Question 13

What is effect of insulin deficiency on carbs/fats/proteins?

Answer 13

insulin inhibits lipolysis so lack of insulin –> lipolysis –> rise in fatty acids in blood stream –> ketogenesis by liver

also lack of insulin –> proteolysis and loss of muscle mass

Question 14

What is the etiology/pathogenesis of juvenile onset type 1 DM?

Answer 14

• autoimmune attack on B cells by T cells due to antibodies against glutamic acid decarboxylase [GAD], insulin, or the islet cells themselves

combo of genetic and environmental factors/triggers

Question 15

What are signs of diabetic ketoacidosis?

Answer 15

• kussmaul respirations [rapid/deep breathing]
• N/V/ab pain
• psychosis/delirium
• dehydration
• fruity breath odor due to exhaled acetone

can lead to coma

Question 16

What type of diabetes primarily associated with diabetic ketoacidosis?

Answer 16

type 1 insulin-dependent DM

Question 17

What is pathogenesis of diabetic ketoacidosis?

Answer 17

lack of insulin causes high glucose in blood –> goes to urine and drags h2O and electrolytes out leading to dehydration

lipolysis eventually leads to ketone body formation and acidosis

Question 18

What lab changes in diabetic ketoacidosis?

Answer 18

• hyperglycemia
• anion gap metabolic acidosis
• high H; low HCO3
• high blood ketone levels
• leukocytosis
• hyperkalemia but depleted intracellular K due to transcellular shift from decreased insulin

Question 19

What happens to K level in diabetic ketoacidosis?

Answer 19

hyperkalemia but depleted intracellular K due to transcellular shift from decreased insulin

Question 20

What is treatment for diabetic ketoacidosis?

Answer 20

rehydration
replace electrolytes
IV insulin and K
glucose if necessary to prevent hypoglycemia

Question 21

What is the biochemistry of ketoacidosis?

Answer 21

fatty acids are oxidized to acetyl CoA –> excess acetyl CoA goes to ketoacids –> decrease serum pH, kussmaul breathing

Question 22

What are precipitating causes of diabetic ketoacidosis?

Answer 22

• undiagnosed type 1 DM
• infection
• inadequate insulin therapy
• trauma
• MI
• pregnancy

Question 23

What is difference between age of onset/ peak age/weight in type 1 vs type 2 diabetes?

Answer 23

type 1: < 40 yo; peak = 10-14 yo
usually thin

type 2: >40 yo; peak = 60-70 yo usually overweight

Question 24

What are symptoms of hypolgycemia?

Answer 24

sweating, tremor, tachycardia, hunger, anxiety, difficulty concentrating, irritability, confusion, lethargy, coma

Question 25

What is effect of stress hormones [catecholamines, cortisol] on glucose control?

Answer 25

may contribute to diabetic state; may suppress insulin release from beta cells

Question 26

What is action/time frame of glucagon?

Answer 26

in minutes

increases liver glucose output

Question 27

What is action/time frame of epi/norepi?

Answer 27

in minutes

increase liver glucose output; decrease muscle glucose uptake

Question 28

What is action/time frame of cortisol/GH?

Answer 28

in hours
increase liver glucose output
decrease muscle glucose uptake

Question 29

What is whipple’s triad for hypoglycemia?

Answer 29

• symptoms of hypoglycemia
• documented low blood glucose (<70 mg/dl)
• relief of symptoms with food/glucose

Question 30

What are causes of hypoglycemia?

Answer 30

• excess insulin
• decreased hepatic glucose production
• decreased counter-regulatory hormomes
• tumor-induced hypoglycemia

Question 31

What is minimal daily glucose utilization?

Answer 31

180 g = mainly by the brain