DM-1 Flashcards
Defn of Diabetes
hyperglycemia resulting from defects in insulin secretion, insulin action, or both that leads to the failure of various organs
Morbidity of DM
blindless
end-stage renal disease
non-traumatic amputations
Type 1:
percent
cause
age
clinical presentation
body type
treatment
other
percent: 5%
cause: auto-immune
age: children
clinical presentation: acute, life-threatening polydipsia, polyphagia, weight loss, DKA
body type: thin
treatment: insulin
other: predisposed to other types of auto-immune disorders
Type 2:
percent
cause
age
clinical presentation
body type
treatment
other
percent: 95%
cause: lifestyle, insulin resistance, genetic
age: adult >40
clinical presentation: gradual, subtle sx., fatigue, polydipsia, polyuria
body type: overweight/obese
treatment: lifestyle, non-insulin injections, orals, insulin
other: have metabolic syndrome
If a patient has C-peptide what type of DM does it indicate
Type 2
(type 1 has zero)
If a patient has islet cell antibodies what type of DM does it indicate
Type 1
If a patient has antibodies to insulin what type of DM does it indicate
Type 1
Risk factors for T2DM
lifestyle
FH
HTN
Dyslipidemia
gestational DM or giving birth >9 lb baby
Race (Hispanic, Native, AA, Pacific)
Genetic defects in B-Cell function
can resent like type 1 or type 2 (more type 1)
usually insulin dependent
MODY (maturity-onset diabetes of youth)
LADA (latent autoimmune diabetes in adults)
Secondary causes of DM
Pancreatic disease (pancreatitis, cystic fibrosis)
Endocrinopathies (acromegaly, cushings, hyperthyroidism)
Most prevalent drug induced diabetes
steroids
atypical antipsychotics
protease inhibitors
statins
Imparied fasting glucose
> 100 mg/dl but <126 mg/dl
Imparied glucose tolerance
2 hour OGTT >140 mg/dl but <200 mg/dl
HgbA1C between what is pre-diabetes
5.7% and 6.4%
Oral Glucose Tolerance Test (OGTT)
75 gm glucose load
BS check q30 min x 2 hours
level peak at 1 hr, remain below 200 throughout return to fasting at 2 hrs
Diagnosis of DM
symptoms of DM + any glucose >200
Fasting plasma glucose >126
Plasma glucose >200 after 2 hrs of OGTT
HgbA1C >6.5%
Fasting BG range: normal, pre DM, DM
normal: <100
pre DM: 100-126
DM: >126
2hr PP BG range: normal, pre DM, DM
normal: <140
Pre DM: 140-200
DM: >200
A1C range: normal, pre DM, DM
normal: <5.7
Pre DM: <5.7-6.4
DM: >6.4
What stores glucose
adipose tissue
glycogen
triglycerides
How much insulin is secreted a day and how much can your body store
secreted: 25-50 units
store: 200 units
Epi stimulates what
glycogenolysis
Glucocorticosteriods stimulate what
gluconeogenesis
GLP-1 secreted from the small intestine after a meal, increases _________ secretion, inhibits _________ secretion, signals satiety in CNS, and delays gastric emptying
insulin
glucagon
BS normal range and CNS normal range of glucose homeostasis
BS: 70-130
CNS: >40-60
T1DM pre-clinical stage
immune markers are present but no symptoms present (B-cell destruction occurs here)
T1DM initial hyperglycemia
80-90% destruction of B-cells
T1DM honeymoon phase
days to weeks after diagnosis
last for few months
BS decrease and decrease in insulin requirements
T1DM total destruction of b-cells
complete full clinical disease
T2DM defect in the secretion and function of hormones that regulate ____________ metabolism
carbohydrate
T2DM starts as insulin resistance and progresses to insulin _________
deficienct
Insulin resistance defn
excess body fat and excess glucose load cause cells to not properly recognize insulin and utilize it effectively
What does this describe:
-higher amounts of insulin are required to maintain euglycemia
-insulin promotes the storage of glucose as fat and results in weight gain
-pancreas is unable to keep up with demand and hyperglycemia occurs
insulin resistance cycle
Insulin suppresses glycogenolysis and gluconeogenesis in the _______
liver
Insulin __________ in hepatocytes causes the insulin suppression to be inhibited
resistance
Patho of pancreas, muscle, fat, liver, GI
pancreas: defective b-cell secretion
muscle: reduce glucose uptake and utilization
fat: inappropriate lipolysis
liver: excess glucose production, hepatocyte insulin resistance
GI: decreased incretin effect
What is fasting
no food for 8 hours or more
Post-prandial
1-2 hours after meal
Pre-prandial
right before a meal regard less of the time since last food
Goals for fasting, post-prandial, and pre-prandial
fasting: <130
post-prandial: <180
pre-prandial: no goal
What are continuous glucose monitors
-Device with filament inserted under the skin
-monitors blood sugars at specified intervals
-send to a smart phone
-sensor changed out every. 10-14 days
TIR (time in range) goal
aim for 70% or greater
TBR (time below range) goal
Low: <4% (<70)
Very Low: <1% (<54)
Who should use a CGM
-patients on intensive insulin therapy
-patients prone to hypoglycemia
-children as young as 2
-insurance coverage patients
How often should a fingerstick be if a patient is on non-insulin therapy only
3x/wk up to 2x qd
How often should a fingerstick be if a patient is on insulin therapy
qd up to 4x qd
How often should a fingerstick be if a patient has multiple daily injection insulin
4-6x qd
What is hemoglobin A1C
-represents percentage of total hemoglobin that has been glycosylated
-estimated average glucose over 3 months
How often to check a patient’s A1C if they are at goal compared to not at goal
goal: 6 months
not: 3 months
Limitation of A1C
-does not reflect change in blood sugar
-impacted by anything that impacts erythrocyte turnover
-does not show full tory regarding glucose excursions
Alternative glucose goals who fits this criteria
-patient w/ limited life expectancy and significant functional and cognitive impairments (A1C <8%)
-Young children
-Pregnant patients
-Patient w/ significant hypoglycemia - TIR >50%, TBR <1%
What is diabetic ketoacidosis (DKA)
life-threatening state resulting from a relative or absolute deficiency of insulin (mainly Type 1)
What is the triad in DKA
hyperglycemia
anion gap metabolic acidosis
ketosis
Pathophysiology of DKA
Insulin deficit with increased levels of stress hormones and a precipitating factor
-Stress hormones: glucagon, cortisol, epi, growth
-Precipitating factors: insulin deficiency, undiagnosed DM1, non-compliances, stress
What are the 5 results of insulin deficiency results
hyperglycemia
glycogen catabolism
glycogen depletion
lipolyis
ketosis
What is the main result of hyperglycemia
polydipsia*
polyuria*
weight loss*
volume depletion
electrolyte depletion
renal hypoperfusion
hypotension
What are the 4 ketosis results
anion gap metabolic acidosis
compensatory alkalosis
hypotension
shock
What are the diabetic ketoacidosis clinical course effects
hyperglycemia
polydipsia, polyuria dehydration
anorexia, ab pain, acidosis
Kussmaul breathing
altered consciousness
coma, death
Diagnostic criteria for DKA
BS > 250
pH <7.3
Bicarb <15
Ketonuria or ketonemia
Treatment of DKA
-IV Regular Insulin 0.1 u/k bolus or 0.1 u/kg/hr infusion (MONITOR potassium before starting)
-IV fluids 0.9% NS id corrected NA+ <135 or 0.45% NS if corrected NA >135
-IV potassium supplementation: K+ will be elevated then when IV given K+ returns to intracellular space and serum K+ will be low
Before IV regular insulin is given for DKA what level does the serum K+ have to be
> 3.3
When to give dextrose in DKA treatment
blood glucose falls <250 replace dextrose but continue IV insulin until ketones are undetectable
When to use bicarb in DKA treatment
not recommended
could use when pH <6.9
What is hyperglycemia hyperosmolar syndrome (HHS)
life-threatening emergency resulting from severe dehydration and hyperglycemia in Type 2 DM
-serum osmol elevates and severe dehydration occurs as result of osmotic diuresis
HHS diagnostic criteria
BG: >600 mg/dl
pH >7.3
Bicarb >18 mEq/l
Serum Osmol: >320 mOsmo/L
Treatment for HHS
IV fluids ~9L
IV regular insulin infusion
Electrolytes (K+, Mg)
Treat precipitating event
DKA:
age
duration of symptoms
glucose level
potassium conc
bicab conc
ketone bodies
pH
serum osmolarity
prognosis
age: <40
duration of symptoms: <2 days
glucose level: <600
potassium conc: low
bicab conc: <18
ketone bodies: yes
pH: <7.3
serum osmolarity: <350
prognosis: 3-10% mortality
HHS:
age
duration of symptoms
glucose level
potassium conc
bicab conc
ketone bodies
pH
serum osmolarity
prognosis
age: >60
duration of symptoms: >5 days
glucose level: >800
potassium conc: variable
bicab conc: normal
ketone bodies: no
pH: normal
serum osmolarity: >350
prognosis: 1-20% mortality
Primary problems in DKA and HHS
DKA: acidosis
HHS: dehydration
Key things to look for in DKA and HHS
DKA: acidosis, ketones
HHS: glucose, no ketones, no acidosis, high osmols
Primary treatment strategies for DKA and HHS
IV fluids, IV insulin, IV potassium
Monitoring for DKA and HHS
DKA: glucose, pH, ketones, e-lytes
HHS: glucose, osmol, e-lytes, fluid/urine output
What is the correct sodium equation
Measured Na + (1.6*glucose -100)/100
Difference between hyperglycemia and hypoglycemia
hyper: not enough insulin, too much glucagon
hypo: not enough glucagon, too much insulin
Risk factors for hypoglycemia
increased age
skip meals
exercise/weight loss
illness
alcohol ingestion
CKD
dementia
Medications that cause hypoglycemia
insulin
sulfonylureas (glyburide mainly)
beta-blockers
fluoroquinolone antibiotics (cipro, levofloxacin)
Difference between level 1 and level 2 hypoglycemia
Level 1: BG <70
Level 2: BG <54
Signs and symptoms of hypoglycemia
hunger
paleness
fatigue
rapid heartbeat
irritability
sweating/shaking
Severe hypoglycemia
loss of consciousness
seizures
coma
death
Beta blockers can mask hypoglycemia except for what symptom
sweating
(they inhibit hepatic glucose production and reduce glycogenolysis)
Relative hypoglycemia
-person w/ diabetes has symptoms of hypoglycemia despite >70 BG
-occur in chronic elevated BG
-hard to achieve optimal glucose control
-no harm to patient
-treat like hypoglycemia due to discomfort
Prevention of hypoglycemia
patient education
setting patient-specific glycemic targets
frequent monitoring of glucose levels
flexible and rational regimens for insulin and other drugs
How to treat inpatient conscious and inpatient unconscious hypoglycemia
inpatient conscious: oral meds
inpatient unconscious: IV access
Outpatient conscious rule of 15 (hypoglycemia)
15 g fast acting carbs
check BS after 15 min
If <70 repeat step 1 and 2
once >70 eat a meal with protein or fiber
Examples of 15 g of fast-acting carbs
4 oz of regular pop
hard candies
1 tbsp sugar
1 dose glucose gel
3-4 glucose tablets
Outpatient unconscious treatment
intranasal 3 mg
prefilled syringe 1 mg
reconstituted powder kit 1 mg
call 911 or drive them to hospital
Inpatient unable to take oral with and without IV access treatments
no IV: glucagon
IV: 25 g of 50% dextrose IV
What is the first phase of glucose homeostasis
lasts few minutes -> small readily releasable pool of ganules
release in response to nutrients and non-nutrients secretagogues
What is the second phase of glucose homeostasis
sustained second phase -> exclusive by nutrients
When you eat what happens to your glucose levels
rapid burst of insulin at mealtimes and then it slowly falls back to basal levels (basal insulin between meals)
Insulin secretion by exocytosis
-glucose transport by beta cells by GLUT transporter
-glucose metabolism -> produce ATP -> K+ channels close
-depolarization of beta cells -> increase Ca2+ and activate exocytosis (insulin secreted)
What are the positive effects of insulin
glycogenesis
lipogenesis
active transport of glucose in muscle and adipose cells
glycolysis
protein synthesis
What are the negative effects of insulin
lipolysis
gluconeogenesis
protein catabolism
glycogenolysis
What are the three target tissues of insulin
liver
skeletal muscle
adipose tissue
What are the main effects of insulin
decrease glucose production and increase glucose uptake and utilization by tissues
Insulin replacement
-mimic secretory pattern of nondiabetic pancreas
-control basal and postprandial glucose levels
-minimize risk of hypoglycemia
Insulin preparations differ by what
amino acid sequence
onset of action
peak for max impact
duration of action
solubility
Insulin routes of administration
intramuscularly, IV, nasally
long term subQ or infusion
no oral (low bioavailability)
Factors affecting absorption of insulin
site of injection
type of insulin
SubQ blood flow
regional muscular activity
insulin volume and concentration
Recombinant human insulin has a ____ ______ of 30-60 minutes
30-60
Since regular insulin levels are peaks are later than normal insulin made by the body there is elevated insulin after glucose has decreased causing what
delayed hypoglycemia
Insulin ______ are biologically active
monomers
(delate in absorption triggers the development of insulin analogs, zinc takes dimers and forms hexamers)
Human insulin analogs are made to provide a more _________ insulin profile and reduce the risk of ____________
physiologic
hypoglycemia
Modifications of insulin are made to prevent _______ formation or dissociate ______ faster causing a faster onset and shorted duraction of action
hexamer
hexamer
What are the 3 rapid insulins that decrease self association (decrease hexamer formation)
lispro (humalog)
aspart (novolog)
gluisine (aprida)
Rapid acting insulin analogs
-rapid onset
-short duration of action -> decrease hypoglycemia risk
-lyumjev is the fastest
-control of blood glucose during meals and snacks
Intermediate acting insulin analogs
-NPH = neutral protamine hagedorn
-onset delayed by combining native insulin with protamine (tissue enzyme degrades this) and zinc
-dissolves more slowly causing slow absorption and long duration
-can control glucose overnight, fasting, and meals, combo with short-acting insulin
Long acting insulin analogs
-mimic basal insulin release -> no peak
-prolonged absorption
-need combo with something else
What does lantus and tresiba do (long acting insulin)
tresiba -> bind to albumin through lipid additions slow distributions to peripheral tissues
lantus aggregates are neutral pH -> do not mix w/ short acting, stabilization of hexamers
Adverse effects of insulin
common: hypoglycemia and weight gain
rare:
-hypertrophy (lipoatrophy)
-hypersensitivity reactions (swelling, heat, allergy to insulin, immune resistance causing circulation of anti-insulin antibodies)
Decreased hypoglycemic effect of insulin
albuterol, diuretics, diltiazem, epi, estrogen, corticosteroids, terbutaline, thyroid estrogen
Increase hypoglycemic effect of insulin
oral diabetic agents, beta-blockers, sulfonamides, clonidine, fluoxetine, alcohol, anabolic steroids
Insulin binding to the receptor causes a cascade of events including PI3K or PKB resulting in the release of _________
GLUT 4
How many amino acids is in the A and B chain of insulin
A has 21
B had 30
The disulfide linkages in insulin provide chemical _________ to the structure
stability
The biosynthesis of insulin occurs in the _____ cells of the pancreas from preproinsulin
beta
Proinsulin is more ______ than insulin with the addition of amino acids arg, arg, lys, and arg
basic
What enzyme catalyzes the cleavage of a dipeptide segment of the amino acid connector C-chain in proinsulin
prohormone convertases PC 1and 2
Only the insulin ______ is able to react with the insulin receptors and is the only readily absorbable form
monomer
True or False: Zinc takes dimers and creates hexamers
true (store insulin in beta cells)
Insulin molecules can form dimers due to _______ bonding
hydrogen
Storage of insulin at neutral pH leads to __________ reaction
deamidation
Insulin analogues are classified according to their what two factors
rate of onset
duration of action
Modifications of rapid-acting insulin analogues do not form ______ in solution and dissociate immediately into ______ producing a very quick onset of action
dimers
monomers
Intermediate-acting insulin is prepared by combining regular insulin and zine in an ______ buffer
acetate
The isoelectric point of insulin glargine is 7 causing an _____ precipitation on SC and decreased absorption rate
increase
Insulin degludec has a long duration of action due to what two things
formation f soluble multihexamer
hexadecanoic acid side chain binding to albumin
Insulin Glargine is more ________ causing it to be soluble in acidic formation but ________ solubility at physiological pH
acidic
decrease
What are the indications of temporary use of insulin therapy
pregnancy
stress/surgery/hospitalization
short term steroids
When is basal and bolus insulin doses
basal: once daily except for NPH
bolus: meals and bedtime
(all type 1 patients need both)
How often do you change an insulin pump
q3 days
When to use insulin therapy in Type 2 patients
when NI’s are no longer effective
use in combo with NIs to simplify and max treatment (add basal first)
How to dose new start and insulin only patients
0.5 units for low BMI or Type 1
1 unit for high BMI, Type 2, illness, ketosis, stress, growth
70% basal and 30% bolus
divide bolus by meals a day
How to dose new start and basal added to NI
start low, go slow
20% of body weight (kg)
1700 rule defn
gives number of mg/dl your BS will drop with 1 unit of SHORT acting insulin
How to calculate 1700 rule
1700/TDD = ISF
(Current BS - Target BS) / ISF = units needed
On average 1 unit short acting insulin covers how many carbs
15 grams
How to calculate carb counting for insulin
500/TDD = # of gm of CHO covered by 1 unit of insulin
Common adverse effects of biguanides
diarrhea
GI upset
What are the biguanides generic and brand names
Metformin (glucophase, fortamet)
Common adverse effects of sulfonyureas
hypoglycemia and weight gain
What are the sulfonylureas generic and brand names
Glipizide (glucotrol)
Glimepiride (amaryl)
Glyburide (micronase, diabeta)
Common adverse effects of GLP-1 RAs
nausea
What are the GLP-1 RA generic and brand names
Liraglutide (victoza, saxenda)
Semaglutide (ozempic, rybelsus, wegovy)
Dulaglutide (trulicity)
Tirzepatide (mounjaro)
Common adverse effects of DPP-IV I
not really anything maybe upper respiratory tract infections
What are the DPP-IV I generic and brand names
Sitagliptin (januvia)
Saxagliptin (onglyza)
Linagliptin (tradjenta)
Alogliptin (nisena)
Common adverse effects of SGLT-2 I
genitourinary infections
What are the SGLT-2 generic and brand names
Canagliflozin (invokana)
Dapagliflozin (farxiga)
Empaglifozin (jardiance)
Ertuglifozin (steglatro)
Bexagliflozin (brenzavvy)
What are the basal insulins
lantus
basaglar
toujeo
semglee
tresiba
NPH
What are the bolus insulins
regular
humalog
novolog
apidra
fiasp
