Endocrine Flashcards
Diabetes screening
- 5
- 6
- 8
1) screen by fasting plasma glucose (FPG) and / or HbA1C
FPG < 5.6 and HbA1C <5.5 = normal (repeat screen q3y)
FPG 5.6-6 or HbA1C is 5.5-5.9%
= if no risk factors patient is at risk and screening repeated yearly
= if > 1 risk factor go to OGTT
FPG 6.1-6.9 or HbA1C 6-6.4% = Go to OGTT
FPG >7 or HbA1C >6.5% = diagnosed with Type 2 diabetes
2) Secondary OGTT
FPG <6.1 and 2h blood glucose <7.8 = do HbA1C
= <6 patient is at risk and requires yearly screening
= 6-6.4 then patient diagnosed with pre-diabetes
2h blood glucose 7.8-11.0 = diagnosed with IGT (form of prediabetes)
FPG 6.1-6.9 = diagnosed with impaired fasting glucose
FPG >7 or 2h blood glucose is >11 = diagnosed with diabetes
What are variations of autonomic neuropathy?
Cardiovascular - exercise intolerance, sustained heart rate, syncope, dizziness, lightheadedness, balance
GI - dysphagia, bloating, N/V/D, constipation, loss of bowel control
GU - loss of bladder control, UTI, urinary frequency/dribbling, erectile dysfunction, loss of libido, dyspareunia
Sudomotor (sweat glands) - pruritus, dry skin, lib hair loss, calluses, reddened areas
What should be included in a diabetes physical exam?
- CVD assessment
- metabolic risk factors (height, weight, WC, BMI)
- complete CV and peripheral vascular exam
- blood pressure - Retinopathy assessment
- fundoscopy - Peripheral neuropathy assessment
- 10g Semmes-Weinstein monofilament or tuning fork
- Screening x 4 each big toe
- If positive screening complete multi site testing - Foot exam including insufficiency, pulses
- Thyroid, abdominal exam
What is considered microalbumineria and macroalbumineria
Urine ACR
Micro
Male 2-20
Female 3-28
Macro <20 in male and >30 in female
When should you screen for kidney function in diabetes
Type 1 diabetes - annually in postpubertal individuals with duration of diabetes 5+ years
Type 2 diabetes - at diagnosis and annually thereafter
What kidney function tests should be used to monitor kidney function in diabetes
Random urine ACR and serum creatinine for eGFR
What pharmacological agents can be used for vascular protection in diabetes and what are the indications for each?
Statins if any of:
a) 40+ years
b) Macrovascular damage
C) age <40 years with 1 of the following
i) age >30 years and diabetes duration >15 years
ii) microvascular complication: retinopathy, nephropathy iii) other risk factors acceding to Canadian cardiovascular guidelines
high risk (FRS >20%): start statin
intermediate risk (FRS 10-19%): start statin if LDL >3.5 or apoprotein B >1.2 or non-HDL cholesterol >4.3
low risk (FRS <10%): start statin if LDL >5 or familial hypercholesterolemia
ACEi/ARB even in the absence of HTN if any of
a) 55 years +
b) Macrovascular end organ damage (CAD, MI, stroke, PVD)
c) <55 years and microvascular end organ damage (nephropathy, neuropathy, retinopathy)
How frequently should a patient with diabetes have eye exam done?
Type 2 - at time of diagnosis and then every 1-2 years thereafter if no or minimal retinopathy
What patients with diabetes should have a baseline resting ECG completed?
> 40 years
Duration of diabetes >15 years and age >30 years
End organ damage (any micro or macro)
Cardiac risk factors
How often should an ECG be performed in patients with diabetes?
q2 years
Exercise ECG stress testing is recommended for diabetc patients with:
Typical or atypical cardiac symptoms
Symptoms or signs of associated diseases (abnormal ABI, carotid bruit, TIA, stroke)
Resting ECG abnormalities such as Q waves
How often should lipid profile be completed in patient with diabetes
At time of diagnosis and then repeated yearly
What are the classes of diabetes drugs and the types of drugs in each?
- Insulin sensitizers
- Biguanides, thiazolinedidiones - Insulin secretagogues
- Sulfonylureas, meglitindes - Carbohydrate absorption inhibitors
- Alpha glucosidase inhibitor - Incretin agents
- GLP-1 agonists and DDP4 inhibitors - Weight loss agents
- Lipase inhibitor
What is the only class of diabetes medication associated with significant risk of hypoglycemia
Secretagogues
Which antihyperglycemic agents are usually okay to use in end stage renal failure
Thiazolinedidiones and DPP-4 inhibitors
What antihyperglycemic agents are weight negative or weight neutral
Metformin
Alpha glucosidase inhibitor (acarbose)
Thiazolinedidiones
GLP 1 agents
What is an example biguanide medication
Metformin
What is the MOA of biguanides
Inhibit glucose production and output by liver by activation of AMP activated protein kinase
Enhance peripheral glucose uptake
What is the only oral anti hyperglycemic agent proven to decrease mortality by lowering CVD risk
Metformin
What are common and serious side effects of metformin
Common: diarrhea, B12/folate deficiency/anemia
Serious - lactic acidosis
What are contraindications to using metformin
Severe kidney, liver or heart failure
What are examples of drugs that are thiazolidinediones
End in glitazone (pioglytazone, rosiglitazone)
MOA of thiazolidinediones
PPAR gammaagonist resulting in
Decreased glucose production in liver
Increased glucose uptake
Indication for TZDs
ALMOST NEVER USED DUE TO SERIOUS SIDE EFFECTS
Adverse effects of TZDs
Common - weight gain
Serious - increased risk of CVD, CHF, osteoporosis, bladder cancer, anemia
Examples of drugs that are sulfonylureas
Names start with gli (glybride, gliclazide, glimepiride)
Sulfonylureas MOA
Activate sulfonylurea receptor on beta cell to stimulate endogenous insulin secretion
Indication for sulfonylureas
Usually 2nd line to add to metformin
Sulfonylureas adverse effects
Associated with hypoglycemia!!
Can lose its effectiveness over time
Common - weight gain, hypoglyemia
Meglitinides drugs
end with glinide (repaglinide)
Meglitinide MOA
bind to a different domain of sulfonylurea receptor on beta cell to stimulate endogenous insulin secretion
Meglitindes adverse effect
Hypoglycemia
What is an incretin
peptides released by intestines in response to meal
Drug examples of GLP1 agonists
end with “tide” exenatide, liraglutide
MOA of GLP1 agonists
activation of GLP-1 receptor in beta cells to stimulate release of insulin, increasing beta cell response
inhibition of gastric emptying to decrease beta cell workload
GLP1 agonists adverse effects
common: nausea and vomiting, significant weight loss
serious: pancreatitis (rare)
DDP4 inhibitors names of drugs
end with “lipton”
sitagliptin (Januvia) saxagliptin (Onglyza) linagliptin (Tradjenta)
DDP 4 inhibitors MOA
block DPP-4 degradation of GLP, thereby increasing GLP effect and incretin pathway (same mechanism of GLP-1 thereafter)
DDP4 inhibitors adverse effects
common: GI upset, edema
serious: pancreatitis (rare)
Alpha glucosidase inhibitor drug names
acarbose (Prandase, Glucobay)
Alpha glucosidase inhibitor MOA
slow absorption of starch and sucrose in gut on brush border of small intestine
Alpha glucosidase indication
Usually used as adjunt therapy
Alpha glucosidase adverse effects
common: flatulence, diarrhea
Lipase inhibitor drug example
Orlistat
Lipase inhibitor MOA
inhibit gastric and intestine lipase to prevent breakdown and absorption of dietary fat, thereby reducing calorie intake and weight
Lipase inhibitor adverse effects
steatorrhea and flatulence
Blood pressure pharmacological management in patients with diabetes
1st line = ACEI, ARB for diabetic and hypertensive patients with cardiovascular risk factors, cardiovascular disease or kidney disease
2nd line = dihydropyridine calcium channel blocker, then hydrochlorothiazide as adjunt to first line
Anti platelet therapy in patients with diabetes
aspirin as primary prevention in diabetics without coronary artery disease is NOT currently recommended, because it does not reduces coronary artery disease events and increases GI bleed
aspirin 75mg to 162mg daily as secondary prevention in diabetics with history of coronary artery disease is currently recommended due to reduction in future coronary artery disease events
clopidogrel 75mg may be used in people unable to tolerate aspirin
Treatment for serum triglyceride >10 mmol/L
Fibrate should be used to reduce risk of pancreatitis
How big of an impact can nutrition therapy have on HbA1C?
Reduce by 1-2%
Blood glucose targets
- HbA1C <7%
if possible with low risk of hypoglycaemia, can decrease target to HbA1C <6.5 to lower risk of nephropathy
target HbA1C should be above 6% (below is associated with increased mortality) - fasting / pre-prandial blood glucose 4-7
- 2hr post prandial blood glucose 5-10
Note: if PPG 5-10 cannot achieve HbA1C <7%, than aim for PPG of 5-8
to assess response to meal, blood glucose should increase by <3 at 2hr post prandial reading
Indications for Orlistat
- diabetic patients with BMI >30 with no comorbidities or risk factors
- diabetic patients with BMI >27 with obesity related comorbidities or risk factors
Indications for bariatric surgery
when other interventions have failed:
- diabetic patients with class 3 obesity (BMI>40)
- diabetic patients with class 2 obesity (BMI 35 - 40) with comorbidities
Indications for less stringent HbA1C control
less stringent HbA1C (7-8.5%) if patient have any of following:
limited life expectancy
high level of functional dependency
coronary artery disease with high risk of ischemic event
multiple comorbidities
history of recurrent severe hypoglycemia
hypoglycemia unawareness
longstanding diabetes that is difficult to control
Approach to antihyperglycemic therapy
1st line = Metformin, especially if patient is overweight
2nd line = sulfonylurea: Glyburide (Diabeta), Gliclazide (Diamicron), Glimepiride (Amaryl)
3rd line =
DPP-4 inhibitor: Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta)
alpha-glucosidase inhibitor: Acarbose
4th line = insulin usually
insulin is added as last line agent after multiple agents (usually after 2 or 3 oral agents) or if symptomatic hyperglycemia with HHS
if insulin, first start as basal (preferably long acting), then add bolus if diabetes is still uncontrolled
if bolus insulin is used, discontinue insulin secretagogues (e.g. Sulfonylurea) whereas metformin can be continued (insulin will control sugars, but metformin still has decreased mortality effect)
What is HHS
Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis.
Symptoms include signs of dehydration, weakness, leg cramps, vision problems, and an altered level of consciousness. Onset is typically over days to weeks.
What is HONK
Hyperglycaemic Hyperosmolar Nonketotic Coma (HONK)
HONK is a dangerous condition brought on by very high blood glucose levels in type 2 diabetes (above 33 mmol/L).
Suggested times to check blood glucose
before breakfast, which is best estimate of fasting blood glucose
before meal
2hr after meal, which is best estimate of post-prandial glucose
before bed
overnight occasionally
Insulin MOA
endogenous insulin is synthesized and released by beta cells in islet of Langerhans of pancreas in response to increased blood glucose
insulin binds to tyrosine kinase insulin receptors on mainly myocytes in muscle, hepatocytes in liver and adipocytes in adipose tissue, activating PI3K -> PIP3 -> PDK&Akt signalling pathway
insulin elicits cell response to decrease blood glucose including
increased glycogenesis, lipogenesis, tracylglyceride synthesis overall
decreased lipolysis, glycogenolysis, ketogenesis in all tissue cells
increased glucose uptake from blood in liver and muscle cell
increased glycogenesis and protein synthesis in adipocytes
inhibition of lipolysis
Rapid acting bolus insulin examples
Humalog
Novorapid
Apidra
Rapid acting insulin onset of action, peak of dose response, duration
10-15 min
1-1.5 h
4-5 h
Short acting bolus insulin examples
Humulin R
Novolin
Toronto
Short acting insulin onset of action, peak of dose response and duration
0.5-1h
2-4h
5-8h
Intermediate acting basal insulin examples
HumulinN
Novolin NPH
Intermediate acting basal insulin onset of action, peak and duration
1-3 h
5-8 h
18 h
Extended long acting basal insulin examples
Lantus
Levemir
Extended long acting basal insulin onset of action, peak and duration
1.5 h
No peak
24 h
Preferred bolus and basal insulin types
Rapid acting because fast peak and shorter acting
Extended long acting because longer acting and no peak, reducing the risk of hypoglycemia
Premixed insulin examples
Humulin 30/70
Novolin 30/70
Humalog mix 25
NovoMix 30
Premixed insulin onset of action, peak and duration
10-30 min
Mix of short and intermediate
18 h
Methods of insulin therapy
Premixed insulin regimen vs intensive therapy (preferred)
Intensive therapy methods:
- MDI basal bolus analogue intensive therapy with basal insulin, bolus insulin (before meal according to carb counting) and high blood glucose correction (bolus)
insulin - Insulin pump intensive therapy same concept as MDI with basal insulin, bolus insulin and high blood glucose correction (bolus) insulin with pump, there is automatic continuous instantaneous injection of basal insulin, bolus insulin is manually added and adjusted by user based on carbohydrate counting of meal or blood glucose level
Approach to starting basal and bolus insulin
1) Basal QHS to bring blood glucose reading before breakfast to 4-7
a) start with 5-10 units QHS SC and then titrate by increasing 10% every 3-4 days until blood glucose before breakfast is at target of 4-7
b) intermediate acting insulin usually need to be split into 2 doses one at breakfast and one at night
if hypoglycaemia event, then
a) switch to Lantus or Levemir; or
b) fix by splitting dose into BID dosing (one in morning, one at night)
2) post-prandial blood glucose (2 hours post breakfast, lunch and dinner)
a) start with 5 units with meals and titrate by increasing by 10% of current dose every 3-4 days until 2 hour post prandial blood glucose is at target of 5-10
b) aim for dose of 40% basal and 60% prandial
Approach to starting premixed insulin
pre-mixed insulin usually only used to decrease number of injections, usually for poor glycemic control compared to basal + bolus insulin given separately
Usually start 5-10 U daily or BID before breakfast and / or dinner
if converting from basal + bolus insulin regimen: total amount of basal and bolus units daily divided in 2/3 - 1/3 over 2 equal doses in morning and night
