Lec 17 Diabetes type I and Hypoglycemia Flashcards
What are the 3 cardinal signs of diabetes mellitus?
- polyuria
- polydipsia
- weight loss
What is pathophys of type 1 diabetes vs type 2 diabetes?
type 1 = absolute insulin deficiency
type 2 = insulin resistance with relatively insulin deficiency
What are mechs of action of glucagon?
- stimulates glucose production in liver
- stimulates glycogenolysis
- lipolysis and ketone production
What are normal actions of insulin?
anabolic
- glycogen synthesis in liver
- triglyceride synthesis in adipose
- protein synthesis in muscles
- Na retention
- glucose transport in skeletal muscle and adipose tissue
In the fasting state what are the major organs of glucose utilization?
50% to brain
25% to muscle/fat
25% to GI/splanchnic
What is level of insulin in periods of fasting state?
low insulin in fasting state
What is the major stimulus for insulin release?
glucose entering B cell and converted to G-6-P –> increase ATP –> closes K-ATP channel –> increased intracellular Ca –> exocytosis of insulin
What is action of GLP-1/GIP on insulin level?
stimulate insulin release via increase in cAMP
What are the 2 major immediate effects of glucose release?
- inhibits hepatic glucose production
- stimulates muscle/fat cell glucose uptake via GLUT-4 receptor
Which glucose transporter is insulin-dependent? where is it located?
GLUT-4
located in adipose tissue and skeletal muscle
What is mech of diabetes causing dehydration/thirst?
have hyperglycemia that overloads renal threshold –> glucose excreted = osmotic so leads to water diuresis –> dehydration and thirst
What is effect of insulin deficiency on glucose metabolism?
leads to increase blood glucose due to uninhibited hepatic glucose production AND lack of glucose entering muscle and fat
What is effect of insulin deficiency on carbs/fats/proteins?
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
What is the etiology/pathogenesis of juvenile onset type 1 DM?
- 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
What are signs of diabetic ketoacidosis?
- kussmaul respirations [rapid/deep breathing]
- N/V/ab pain
- psychosis/delirium
- dehydration
- fruity breath odor due to exhaled acetone
can lead to coma
What type of diabetes primarily associated with diabetic ketoacidosis?
type 1 insulin-dependent DM
What is pathogenesis of diabetic ketoacidosis?
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
What lab changes in diabetic ketoacidosis?
- 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
What happens to K level in diabetic ketoacidosis?
hyperkalemia but depleted intracellular K due to transcellular shift from decreased insulin
What is treatment for diabetic ketoacidosis?
rehydration
replace electrolytes
IV insulin and K
glucose if necessary to prevent hypoglycemia
What is the biochemistry of ketoacidosis?
fatty acids are oxidized to acetyl CoA –> excess acetyl CoA goes to ketoacids –> decrease serum pH, kussmaul breathing
What are precipitating causes of diabetic ketoacidosis?
- undiagnosed type 1 DM
- infection
- inadequate insulin therapy
- trauma
- MI
- pregnancy
What is difference between age of onset/ peak age/weight in type 1 vs type 2 diabetes?
type 1: < 40 yo; peak = 10-14 yo
usually thin
type 2: >40 yo; peak = 60-70 yo usually overweight
What are symptoms of hypolgycemia?
sweating, tremor, tachycardia, hunger, anxiety, difficulty concentrating, irritability, confusion, lethargy, coma
What is effect of stress hormones [catecholamines, cortisol] on glucose control?
may contribute to diabetic state; may suppress insulin release from beta cells
What is action/time frame of glucagon?
in minutes
increases liver glucose output
What is action/time frame of epi/norepi?
in minutes
increase liver glucose output; decrease muscle glucose uptake
What is action/time frame of cortisol/GH?
in hours
increase liver glucose output
decrease muscle glucose uptake
What is whipple’s triad for hypoglycemia?
- symptoms of hypoglycemia
- documented low blood glucose (<70 mg/dl)
- relief of symptoms with food/glucose
What are causes of hypoglycemia?
- excess insulin
- decreased hepatic glucose production
- decreased counter-regulatory hormomes
- tumor-induced hypoglycemia
What is minimal daily glucose utilization?
180 g = mainly by the brain
