Endocrine: DM Flashcards
T1 DM
cellular mediated beta cell destruction
T2 DM
insulin resistance in muscle and liver
maturity onset DM of the young
genetic disorder: impaired secretion of insulin
gestational DM
15% of pregnancies
common in 3rd tri
pre-diabetic
impaired glucose tolerance/fasting glucose
drug induced DM can be caused by which drugs?
glucocorticoids
protease inhibitors
atypical antipsychotics
screening for t1 DM is done why
if someone has relatives with T1
how is T1 DM screened for?
by measuring islet abs
T2 diabetes screening happens when
at age 45, q3 years
T2 Diabetes screening happens at what weight?
> 25kg/m2
>23kg/m2 for Asians
t2 dm may be seen with
CVD PCOS HDL < 35 TG > 250 HTN physical inactivity severe obesity
gestational DM screening
screen at 1st prenatal visit and again at 24-28 weeks with OGTT
if diagnosis of gestational DM is made,
screen for diabetes 4-12wks after delivery.
fasting plasma glucose in diabetes
> 126
random plasma glucose in diabetes
> 200
OGTT
administer 75g of glucose, obtain plasma glucose in 2 hours. if >200 and symptoms of hyperglycemia, diagnosis can be made.
A1C in diabetes
> 6.5%
one step OGTT
75g at 24-28 wks
fasting: >92
after 1 hr: >180
after 2 hr: >153
two step OGTT
50g at 24-28 weeks
after 1 hr if glucose < 140, no need for further workup
if >140, perform another OGTT using 100g.
microvascular complications of DM
retinopathy
neuropathy
nephropathy
glycemic goals of therapy:
A1C
<7%
glycemic goals of therapy:
preprandial:
70-130
glycemic goals of therapy:
postprandial
<180
BP mgmt for pt with DM
keep < 140/90
lipid mgmt for pt c DM
no specific LDL goal, use ACC/AHA guidelines.
T1 DM
insulin pump
hourly basal and bolus dosing
rapid acting insulins
requires patient education and carb counseling.
neurotransmitter dysfunction in DM
meds (3)
GLP1 receptor agonists
amylin
bronocriptine
increased lipolysis and reduced glucose uptake
meds
thiazolidinediones
dec glucose uptake meds
metformin
insulin
thiazolidinediones
decrease incretin effect
meds
metformin
alpha glucosidase inhibitors
colesevelam
increased hepatic glucose production:
meds
metformin
insulin
thiazolidinediones
increased glucagon secretion
meds
GLP1 receptor agonists
DPP 4 inhibitors
Amylin
impaired insulin secretion
meds
sulfonylurea
meglitinide
GLP1 receptor agonists
DPP 4 inhibitors
mono therapy DM
metformin
-high efficacy
-no risk hypoglycemia
weight neutral/loss
AE metformin
GI
lactic acidosis
dual therapy: DM
metformin PLUS
either
sulfonylurea, thiazolidinedione, DPP4 inhibitor, SGL2 inhibitor, GLP1 receptor agonist, or insulin
metformin plus sulfonylurea
high efficacy
moderate risk hypoglycemia
weight: gain
cost:low
dual therapies with highest efficacy and lowest costs
metformin+sulfo
metformin+thiazo
highest risk dual therapy for hypoglycemia
metformin and insulin
combination injectable therapy for DM
basal insulin + mealtime insulin + GLP-1RA
GLP1 receptor agonists
high cost
high efficacy
highest costing dual therapies
DPP4 inhibitor
SGLT2 inhibitor
GLP1 RA
highest efficacy dual therapy
sulfo
thiazo
GLP1 RA
insulin*
T2 DM pharmacotherapy
first line
metformin
DPP4 inhibitors
dipeptidyl peptidase 4 inhibitor
SGLT2
sodium glucose cotransporter 2 inhibitors
GLP1 agonists
glucose like peptide 1 agonists
diabetic pts should be started on insulin for the following parameters
A1C > 10%
glucose >300-350
MoA metformin:
reduces hepatic gluconeogenesis and can inc insulin sensitivity. can also inc uptake of glucose from blood into other tissues.
A1c reduction c metformin
1-2%
blackbox warning for metformin
lactic acidosis
dosing for metformin is based on
GFR
metformin is CI in
acute or chronic metabolic acidosis
GFR <30
onset and full effect of metformin
onset: days
full effect: 2 weeks
metabolism of metformin
not hepatic
elimination of metformin
urine, 90% unchanged.
dosing of metformin
500-100mg BID
max dose of metformin
2550 mg/day
metformin and IV contrast
avoid administration within 48 hr of contrast
pregnancy category of metformin
B
sulfonylurea examples
glipizide
glimepride
glyburide
A1c reduction of sulfonylureas
1-2%
MoA sulfonylurea
binds to receptors on pancreatic beta cells which causes the K channel to close so that K cannot leave the cell - which causes depo of the membrane. there is then an influx of calcium which stimulates insulin secretion
AE sulfos
hypoglycemia
weight gain
CI to sulfos
hypersensitivity to sulfonamides
poor renal function
pt edu for sulfos
take c food
protein binding of sulfos
high
>95%
onset of sulfo
Reduces blood glucose within hours
elimination of sulfos
hepatic
monitoring for sulfos
fasting BG
A1C
s/s hypoglycemia
CI sulfos
hepatic insufficiency
renal failure
meglitinides A1C reduction
.5 - 1.5%
meglitinide meds
repaglinide
nateglinide
MoA of meglitinides
similar to sulfos but faster
AEs of meglitinides
hypoglycemia
weight gain
URI
CI c meglitinides
hypersensitivity
use of gemfibrozil
thiazos examples
pioglitazone
rosiglitazone
MoA thiazos
decrease plasma glucose by increasing insulin sensitivity of adipose tissue, skeletal muscle, and the liver.
primary site of action of thiazos
adipose tissue
what receptor does thiazo bind to?
PPARy
thiazo A1C reduction
0.5 - 1.4 %
onset of thiazos
1-3 months
AE of thiazos
weight gain edema CHF exacerbation inc risk fractures in women myalgia headache macular edema inc LFT
protein binding of thiazo
high
>99%
Thiazo excretion
urine and feces as metabolites
CI c thiazos
NYHA class 3-4 of HF at initiation of therapy
thiazo monitoring
BG A1c LFT s/s HF bone health
DPP4 inhibitors examples
sitagliptin
saxagliptin
linagliptin
alogliptin
DPP4 A1c reduction
0.5 - 0.8%
MoA DPP4
inhibits breakdown of GLP1 during meals thus increasing insulin secretion, reducing glucagon secretion, and promoting satiety.
DPP4 inhibitors on fasting blood glucose
low impact
side effect profile for DPP4 inhibitors
minimal but monitor for s/s pancreatitis
hypoglycemia and DPP4 as monotherapy
uncommon
dose adjust DPP4 inhibitors based on
GFR
elimination and metabolism of DPP4 inhibitors
renal elimination
minor metabolism thru CYPs
SGLT2 inhibitor examples
-flozins
MoA SGLT2 inhibitors
inc urinary glucose excretion by blocking normal reabsorption in the proximal convoluted tubule
AE of SGLT2 inhibitors
inc urination
UTI
hypotension
inc risk fractures
SGLT2 inhibitors are CI in
renal impairment
alpha glucosidase inhibitor med
acarbose
MoA alpha glucosidase inhibitor
reduce absorption of glucose from intestine to bloodstream by slowing breakdown of large carbs into smaller, easier to absorb sugars
AEs of alpha glucosidase inhibitors
flatulence
diarrhea
abd pain
inc LFTs
alpha glucosidase inhibitors are CI in
IBD
colonic ulcerations
intestinal obstruction
once insulin binds,
autophosphorylations occur. CAP/Cbl protein complex and PI3 kinase facilitates glucose transporter translocation. transporter gets to membrane, pulls glucose from bloodstream (BG decreases) and glucose stored as energy.
rapid acting insulin onset
15-30 min
short acting insulin onset
30-60 min
intermediate acting insulin onset
2-4
rapid acting insulin examples
lispro
aspart
glulisine
short acting insulin examples
regular (humulin)
intermediate acting insulin example
neutral protamine hagedorn (humulin)
long acting insulin examples
lantus
levemir
rapid acting insulin peaks
.5 - 3
duration of rapid onset insulins
3-5 hr
short acting insulin, regular, peak
2-3 hr
short acting insulin, regular, duration
3-6 hr
intermediate acting insulin peak
4-6 hr
duration of intermediate acting insulin
8-12
short acting and intermediate acting insulin are typically dosed
BID
long acting insulins are typically dosed
1x a day
basal
long acting insulin onset
3-5 hr
long acting insulin peak
no peak
duration of long acting insulin
up to 24 hr.
basal dosing of insulin
either 10u daily or
.1-.2 units/kg/daily
titration of basal dose insulin
patient can do it, 2u q3 days to target A1C.
for basal insulin pt, fasting plasma glucose level should be consistent with
A1c goal
initiation of prandial dosing
appropriate if above A1c goal but basal dose is titrated and fasting is at goal
prandial dosing
start with
1 dose at largest meal
either 4u/day or 10% of total basal dose
increasing prandial dosing
1-2 units or 10-15% twice weekly.
dose insulin at _ - _ units/kg/day
0.3 to 0.6 u/kg/day
total insulin can be divided into
2/3 NPH + 1/3 regular divided in AM and PM meal
or
50% basal and 50% prandial divided in 3 meals
AE insulin
hypoglycemia
weight gain
allergy
lipoatrophy or lipohypertrophy
GLP1 analogs end in
-tide
A1C reduction of GLP1 analogs
0.5-1.5%
MoA GLP1 analogs
increases glucose dependent insulin secretion, reduction of glucagon secretion, and reduced gastric emptying
AE GLP1
N/V/D
hypoglycemia
AKI
CI GLP1
impaired renal function
monitoring for GLP1
bg a1c s/s pancreatitis hypogly weight loss
tx hypoglycemia
treat at < 70
admin 15-20 glucose, reassess in 15. if glucose still <70, admin another 15-20.
tx hypoglycemia c bg <54
admin glucagon 1mg IM or IV dextrose if no response.
DKA is more common in
T1
tx DKA
fluid replacement c 1/2NS or NS
bolus and infusion of insulin
potassium
sodium bicarb
bolus and infusion insulin rates for DKA
bolus: 0.1unit/kg
infusion: 0.1u/kg/hr
when to reduce insulin infusion in DKA
reduce by .02-.05 u/kg/hr when serum glu reaches 200
when do we give bicarb in dka?
if serum pH is <6.9
when is DKA considered resolved?
venous pH > 7.3
bicarb >15
anion gap <12
tx nephropathy in DM
screen yearly for urine album/creat ratio (normal is < 30) - if >30, use ace/arb.
obtain CrCl yearly
reduce dietary protein
retinopathy in DM
screen annually
treat extreme cases c IV steroids
neuropathy tx DM
TCAs - amitriptyline
SNRIs - duloxetine
or
anticonvulsants - gapapentin/pregabalin
