Diabetes and Insulin Flashcards
Endogenously insulin is produced in
the beta cells
Endogenously glucagon is produced in
the alpha cells
Insulin promotes
storage of glucose, fatty acids, and amino acids
daily insulin secreted is equivalent
to 40-50 units
Activation of Na+/K+ ATPase in cell membranes by insulin
moves K+ into cells and decreases concentration of K+ in plasma
The primary source of endogenous glucose production following glycogenolysis and gluconeogenesis is
the liver
How is insulin secretion regulated?
via negative feedback effect of the blood glucose concentration in the pancreas
Glycogenesis is
glycogen formation
Glycogenolysis is
glycogen breakdown
The body will not secrete insulin when
blood glucose levels <50 mg/dL
The body secretes maximum insulin at concentrations of
> 300 mg/dL
Blood glucose concentrations are
maintained within a narrow range
____ glucose is more effective than ____ glucose in evoking the release of insulin
Oral, IV
Insulin receptor expression is
highest in the tissues
promotes use of carbohydrates for energy
Relationship between glucagon and insulin
They are reciprocally secreted
glucagon acts to mobilize glucose, fatty acids, and amino acids into systemic circulation
Glucagon secretion occurs
during hypoglycemia
Glucagon acts by
activating adenylate cyclase for cAMP formation
exogenous administration can lead to enhanced myocardial contractility
Diabetes mellitus can affect vascular system because
it impairs vasodilation–> chronic proinflammatory, prothrombic and proatherogenic state–> vascular complications
Goals of therapy for diabetes
prevent adverse consequences of hypo/hyperglycemia
avoid weight gain
reduce micro/macrovascular complications
HbA1c <6-7% associated with fewer microvascular complications
symptoms often resolve when blood glucose < 200 mg/dL
Diagnosis of diabetes is based on
elevated fasting plasma glucose greater than 126 mg/dL or hemoglobin of 6.5% or greater
Long term complications of diabetes include
retinopathy, kidney disease, HTN, CAD, peripheral/cerebral vascular disease, and peripheral/autonomic neuropathies
T1DM diagnosis is based on
random glucose >200 mg/dL + HbA1C >7%
Hypoglycemia treatment
each 1 mL of 50% glucose will increase blood glucose of 70 kg patient by 2 mg/dL
Hyperosmolar nonketotic coma is due to
dehydration/hyperosmolality
DKA is
decreased insulin activity allows catabolism of free fatty acids into ketone bodies leading to accumulation
infection is a common precipitating factor
Treatment: correct hypovolemia, hyperglycemia and total body potassium deficit
The treatment for type 1 DM
insulin therapy (necessary for survival)
Circulating insulin levels are altered more by
renal dysfunction than hepatic disease
The duration of action of insulin is
30-60 minutes after IV administration
Alpha-adrenergic stimulation will
decrease basal secretion of insulin
Beta-adrenergic or parasympathetic nervous system will
increase basal secretion of insulin
Insulin response to glucose is greater after
oral ingestion than IV infusion
Type 1 DM need
at least two daily SQ injections of intermediate or long-acting insulin + rapid acting insulin following meals
The basic principle of insulin administration is to
provide slow, long-acting, continuous supply of insulin that mimics basal secretion
Insulin formulations include:
basal insulin-intermediate acting & long acting
short acting- meal time
rapid acting- meal time (preferred for prandial coverage)
The most commonly used commercial preparation of insulin is
U-100 (100 U/mL)
Typical daily exogenous dose for T1Dm is around
0.5 to 1 U/kg/day
Insulin requirements can be increased dramatically by
stress, sepsis, or trauma
Rapid acting insulins include:
lispro, insulin aspart, and glulisine
The onset, peak and duration for rapid acting insulin is
onset: 5-15 minutes, peak 45-75 minutes, duration 2-4 hours
Intermediate acting insulins include
NPH
The onset, peak, and duration for intermediate acting insulin is
2 hours, peak 4-12 hours, duration 18-28 hours
Short acting insulin includes
regular insulin
The onset, peak, and duration for short acting insulin
onset: 30 minutes, peak 2-4 hours, duration 6-8 hr
Long acting insulins include
glargine and detemir (have a similar onset, peak, and duration to intermediate acting insulins)
What preparations are used in continuous subcutaneous insulin infusions?
short acting (regular) or rapid acting (lispro, aspart, glulisine)
CSII or continuous subcutaneous insulin infusion pumps
are smart and deliver basal infusion and bolus doses before meals, can accommodate nocturnal basal requirements, pumps are very smart and can alter infusion during exercise, surgery, etc.
Type, onset, peak, and duration of action of lispro
Lispro or humalog is rapid acting, has an onset of 15 minutes, peak of action of 45-75 minutes, duration of 2-4 hours
Benefits of lispro include
decrease in postprandial hyperglycemia and less risk of hypoglycemia
Lispro has a lysine/proline switch that prevents hexamer formaiton and
the monomer is rapidly absorbed
(insulin has 6 molecules that associate with zinc molecules to form hexamers–> must dissociate to monomers before absorption from SQ site)
Type, onset, peak, and duration duration of action of insulin aspart and glulisine
rapid acting insulin
onset: 10-15 minutes
peak: 45-75 minutes
Duration: 2-4 hours
Regular insulin is a
short acting insulin (fast-acting preparation) and can only be given IV and subcutaneous
Regular insulin also goes by
humulin R, Novolin R, ReliOn R
What is the preferred treatment for abrupt onset of hyperglycemia or ketoacidosis?
regular insulin
What is the onset, peak, and duration of action of regular insulin?
onset: 30 minutes
peak: 2-4 hours after SQ injection b/c of insulin hexamers
duration: 6-8 hours
periop dosage is 1-5 U or infusion (0.5-2.0 U/hr)
What is neutral protamine hagedorn (NPH) and the onset, peak, and duration?
intermediate acting
onset: 2 hour
peak: 4-12 hours
duration 18-28 hours
What is the onset, peak, and duration of detemir (levemir)?
long-acting insulin analogue for basal replacement
onset: 2 hours
peak: 3-9 hours
duration: 6-24 hours
can be administered as single bedtime injection to provide basal insulin for 24 hours with less nocturnal hypoglycemia
cannot be mixed with rapid acting insulin
What is the onset, peak, and duration of glargine (lantus)?
long-acting insulin onset: 90 minutes peak: none duration: 20-24+ hours less pronounced peaks
What is the onset, peak, and duration of degludec (Tresiba)?
long-acting insulin onset: 2 hours Peak: none duration: > 40 hours can be used in hepatic/renal impairment
For mixed insulins, the first number is
long acting and the second is the short/rapid acting insulin
always dosed before breakfast and evening meal
What are the five main side effects of insulin?
hypoglycemia, allergic reactions, lipodystrophy, insulin resistance, and drug interactions
The most serious side effect of insulin is
hypoglycemia
first symptoms are compensatory effects of increased epinephrine secretion: diaphoresis, tachycardia, HTN, rebound hyperglycemia caused by SNS activation may mask diagnosis (Somogyi effect)
What is the Somogyi effect?
when there is rebound hyperglycemia caused by SNS activation during a period of hypoglycemia
Why do we have severe CNS effects with hypoglycemia & what are they?
mental confusion, seizures, and coma because brain depends on glucose for metabolism
Prolonged hypoglycemia can cause
irreversible brain damage
What is lipodystrophy?
fat atrophies at site of SQ injection
Insulin resistance is
when a patient requires more than 100 units of insulin daily
acute insulin resistance is associated with trauma from infection/surgery
It is necessary to be mindful of allergic reactions with
NPH & heparin b/c protamine could be administered IV to antagonize anticoagulant effects of heparin and cause large allergic reaction to protamine
What are the four major classes of oral antidiabetic drugs?
secretagogues, biguanides, thiazolidinediones or glitazones, and alpha-glucosidase inhibitors
Secretagogues include
sulfonylureas and meglitinides and increase insulin availability
Biguanides include
metformin and suppress excessive hepatic glucose release
Thiazolidinediones or glitazones include
rosiglitazone, pioglitazone and improve insulin sensitivity
Alpha-glucosidase inhibitors include
acarbose, miglitol and delay GI glucose absorption
Metformin is
an oral biguanide
rarely causes hypoglycemia & can be used in combination with insulin and sulfonylureas
Contraindications of metformin include
lactic acidosis, AKI, GI intolerance, acute hepatic disease
caution in patients with renal dysfunction d/t dependence on renal clearance
Where is metformin metabolized?
it is not; it is excreted by the kidneys
Metformin can also be used
in PCOS, nonalcoholic fatty liver, premature puberty
The elimination half-time of metformin is
2 to 4 hours
The dosage of metformin is
TID 500-1000 mg w/ meals
The mechanism of action of metformin is
activates adenosine monophosphate activated protein kinase to suppress hepatic glucose production
Metformin should not be administered in patients with
hepatic dysfunction, renal insufficiency (creatinine >1.5 mg/dL), IV contrast dye, acute MI, CHF, arterial hypoxemia, and sepsis b/c it can cause lactic acidosis
Metformin should be discontinued
48 hours before elective surgery because of its ability to cause lactic acidosis
Sulfonylureas should not be administered to
patients with sulfa allergies
The mechanism of action of sulfonylureas are
to act on sulfonylurea receptors on pancreatic and cardiac cells; inhibit adenosine triphosphate sensitive K+ channels on pancreatic beta cells resulting in Ca2+ influx and simulation of insulin resistance
Sulfonylureas produce
hypoglycemia that is infrequent but is more often prolonged and more dangerous than hypoglycemia from insulin
Sulfonylureas have a cardioprotective mechanism through
close K-ATPase channels and inhibit ischemic preconditioning
Glyburide is considered a ____ and it’s mechanism of action is
sulfonylurea and it increases insulin sensitivity and inhibits liver production of glucose
What is the dose, peak plasma level, DOA, elimination half-time of glyburide?
dose: 2.5-20 mg daily (Qd/BID)
Peak plasma: 3 hours
DOA: 18-24 hours
Elimination half-time: 4.6-12 hours
Where is glyburide metabolized?
liver
What is the dosage, duration of action, and elimination half-time of glipizide?
sulfonylurea
dose: 5-40 mg daily
duration of action: 12-24 hours
elimination half-time: 4-7 hours
What is the dosage, duration of action, and elimination half-time for glimepiride?
sulfonylurea
dose: 2-4 mg daily
duration of action: 24+ hours
elimination half-time: 5-8 hours
Meglitinides include
repaglinide and nateglinide and are secretagogues
A concern with nateglinide (Starlix) includes
accumulation of active metabolites may cause hypoglycemia
The mechanism of action of meglitinides include
stimulation of release of insulin from the pancreas
Alpha-glucosidase inhibitors include
acarbose and miglitol and work by decreasing carbohydrate digestion and absorption of disaccharides by interfering with intestinal glucosidase activity
Thiazolidinediones include
rosiglitazone and pioglitazone and they act at skeletal muscle, liver, and adipose tissue via peroxisome proliferator activator receptor-gamma to decrease insulin resistance and hepatic glucose production and to increase use of glucose by the liver
glucagon like peptide-1 receptors agonists include
exenatide and liraglutide and they bind to receptors in the pancreas, GI tract, and brain to increase insulin secretion from beta cells (glucose dependent), decrease glucagon production from alpha cells and reduce gastric emptying
Dipeptidyl-peptidase- 4 inhibitors include
Saxagliptin, sitagliptin, linagliptin, alogliptin, and vildagliptin and increase insulin secretion from alpha cells (glucose dependent) and reduce pancreatic alpha cell secretion of glucagon
Amylin agonists include
pramlintide and it does not alter insulin levels
it suppresses gastric emptying, inhibits glucagon release and reduces HbA1c levels
Colesevalam acts as
a bile acid sequestrant and lowers glucose levels and decreases HbA1C (MOA unclear)
Bromocriptine mesylate is
a dopamine receptor agonist and it lowers glucose levels and decreases HbA1c (MOA unclear)
What are the aims of combination therapy?
target two or more causes of hyperglycemia simultaneously
Primary aim: decrease HbA1c
Secondary aim: decrease in daily insulin dose
Diabetic autonomic neuropathy is
a decreased ability to compensate/risk of CV instability/sudden cardiac death
patients with DM and HTN have 50% likelihood
Patients with diabetes are at risk for aspiration due to
autonomic dysfunction–> delayed gastric emptying–> premedicate with antacid and metoclopramide
Perioperative morbidity in diabetic patients is
related to their preexisting end-organ damage
Glucose should be kept at
<180 intraop
Patients with T1DM may have difficult intubations because
of temporomandibular joint and spine mobility should be assessed preoperatively to assess for glycosylation of tissue proteins and limited mobility of joints
Hyperglycemia is associated with:
hyperosmolarity, infection, poor wound healing, increased mortality
severe hyperglycemia–> worse neurological outcomes following ischemia
Plasma glucose levels should be
monitored q30-1 hour intraop with insulin infusions and diabetic patients in general
____ & ____ should be held prior to surgery
sulfonylureas and metformin have long half-lives and should be discontinued 24-48 hours before surgery
One unit of regular insulin lowers plasma glucose by
25-30 mg/dL
Regular insulin-units per hour=
plasma glucose/150 (this is so dumb to memorize)
AM dose of regular insulin
should be held the day of surgery
