diabetes Flashcards
how would you explain what diabetes is
a metabolic disorder characterized by the resistance to action of insulin, insufficient insulin secretion or both
differentiate between T1DM and T2DM
T1DM
- absolute deficiency of pancreatic beta cells
- no C peptide level
- abrupt onset
- onset usually <30yo
- thin
- positive Ab
- frequent proneness to ketosis
T2DM
- progressive loss of adequate insulin secretion by pancreatic beta cells on the background of insulin secretion
- normal or abnormal C peptide level
- onset >40yo
- gradual onset
- often overweight
- less prone to ketosis
what is insulin resistance
in presence of insulin, glucose utilisation is impaired and hepatic glucose output increased at early stage
what are the signs and symptoms of hyperglycemia
- polyphagia, polyuria, polydypsia
- dry skin
- blurred vision
- drowsiness
- decreased healing
what are the signs and symptoms of hypoglycemia
- shaking
- fast heartbeat
- sweating
- dizziness
- anxious
- impaired vision
- weakness
- fatigue
- HA
- irritable
how can blood glucose be measured
1, FBG
- no caloric intake in ≥8hrs
- random/ casual blood glucose
- taken at any time of the day, regardless of meal intake - PPG
- usually 2hrs after a meal
- or OGTT 75g - HbA1c
- measures the average amount of glucose in a person’s body over 3m (lifespan of a RBC)
what contributes to a high HbA1c
FBG often contributes much more to high HbA1c as compared to PPG
how to diagnose DM
if HbA1c
≤6.0 –> no further tests needed, No DM
6.1-6.9 –> FBG/OGTT
if
(i) FBG ≤6.0 or OGTT <7.8 –> no DM
(ii) FBG 6.1-6.9 or OGTT 7.9-11.0 –> pre-DM
(iii) FBG ≥7.0 or OGTT >11.8 –> DM
≥ 7.0 –> no further tests needed, DM
what are the risk factors of DM
- genetics (asian)
- environment (stress level, poor health literacy, language barrier)
- diet (carb heavy, stir fry, binge eating, fast food)
what are the key medication changes to the medications during ramadan fasting
- TDS to BD
- reduce medications with high hypoglycemia risk (SU, insulin)
- evening dose > than morning dose as sunset meals tend to be heavier
what are the risk factors of a diabetic foot
- poor glycemic control
- peripheral artery disease
- peripheral neuropathy
- visual impairment
- smoking
what are the bacteria strains that are of concern regarding diabetic foots
mild-moderate infections by gram pos cocci (esp staph and strep)
chronic and severe infections by mixed gram pos cocci and gram neg bacilli w/wo anaerobes
what are the key patient education pointers for diabetic foot management
- maximise blood glucose control, reduce risk factors for diabetic foot
- self-examination of the foot (for cracks, wounds, dryness)
- proper nail and foot care and hygiene (wash feet everyday and make sure to dry between toes, cut nails straight across, can moisturise but not in between toes)
- foot protection (never go barefooted, wear nicely fitted socks and shoes)
- annual foot examination by podiatrist
what are the types of complications for DM
microvascular
- neuropathy
- retinopathy
- nephropathy
macrovascular
- increased risk of CVD
others
- decrease in life expectancy
what are the monitoring parameters and frequency of monitoring for DM
- HbA1c
- generally target <7.0
- q3m, q6m if stable - BP
- generally <130/80
- every visit - lipids
- <2.6 / <1.8 if high risk ASCVD
- q3-6m, q12m if stable - eye and foot exam
- q12m at clinic
- self examination of foot every day - albuminuria and renal function
- q6m, q12m if no presence of albuminuria
what are the non-pharmacological management for DM
- smoking cessation
- limiting alcohol intake
- weight management (target BMI 18.5-22.9)
- physical activity (≥150mins/w, at least 3d a week of moderate intensity exercise)
- dietary management using “My Healthy Plate’s Quarter” (restrict simple carb, limit sugary beverages, consume: fruits and vege, legumes, grains, cereals, skinless poultry, lean meats, fish, low fat dairy products)
- improve mental well-being and managing stress
what are foods of simple carbs
- white bread
- white rice
- pasta
- sweetened beverages and cereals
- candy and sweets
- fruit juices
what is the general treatment algorithm for DM
- start with assessing patient’s overall health status
- age and frailty
- comorbidities and concurrent medications
- life expectancy and QoL
- risk of ADR to treatment
- recent changes to health
- cognitive ability, wellbeing and social support - determine need for glycemic control and also for cardiorenal risk reduction
- CVD risk factors (HTN, DM, dyslipidemia, obesity, FHx, CKD, smoking, presence of albuminuria)
- CKD risk factors (HTN, CVD, obesity, smoking, FHx, hx of AKI, CKD, age esp ≥65yo) - agree on management with patient with additional considerations
- safety concerns (risk of hypoglycemia, c/i and caution)
- cost and affordability
- impact on weight
- route of administration
- dosing frequency - monitor and review response to treatment
what are the options for pharmacological management of DM
biguanides
- metformin
sulfonylureas
- glipizide (second gen)
- gliclazide (second gen)
- glibenclamide (second gen)
- glimepiride (third gen)
- tolbutamide (first gen)
thaizolidinediones
- pioglitazone
- rosiglitazone
alpha-glucosidase inhbitors
- acarbose
GLP1 receptor agonist
- liraglutide
- semaglutide
DPP4 inhibitors
- sitagliptin
- linagliptin
SGLT2 inhibitors
- empagliflozin
- dapagliflozin
- canagliflozin
insulin
- rapid acting (aspart, lispro, glulisine)
- short acting (normal insulin)
- intermediate acting (NPH)
- long acting (detemir, glargine U100)
- ultra long acting (degludec, glargine U300)
what is the moa of metformin
- decrease hepatic glucose production
- (secondary) increase peripheral/ muscle glucose uptake and utilization
what is the place of therapy for metformin in DM (incl pk, c/i, s/e, ddi)
- first line for T2DM and gestational DM
- reduces HbA1c by 1.5% up to 2.0%
- onset within days, renally excreted as 90% unchanged
- c/i in CrCl <30 (half dose for CrCl <45), hypoxic states
- ddi with alcohol, cationic drugs like digoxin and iodine contrast
- s/e commonly GI, anorexia, transient metallic taste –> take with or after food (long term: decrease vitB12)
what is lactic acidosis
lactic acidosis refers to an accumulation of lactate, leading to acidosis, usually due to anaerobic metabolism
glucose is converted into energy (in form of ATP) by the body which forms pyruvate which subsequently forms lactate, in the absence of O2
what are the symptoms of lactic acidosis
- nausea
- shallow or labored breathing
- mental confusion
what is the moa for sulfonylureas
- primarily to increase insulin secretion by pancreatic beta cells through blockade of K+ channel
- (secondary) decrease hepatic glucose output and increase insulin sensitivity
what is the place in therapy for sulfonylureas in DM (incl pk, c/i, s/e, ddi)
- HbA1c reduction of 1.5%
- rapid onset –> taken 15-30mins before meals
- tolbutamide is 95% H metabolism, glipizide is 90% H metabolism –> both preferred in R impairment
- gliclazide is 50% R and 50% H elimination
- glibenclamide is 70% R elimination –> avoid in CrCl <50
- s/e include hypoglycemia (esp in elderly and esp for R excreted SU), weight gain
- ddi with BB as BB can mask hypoglycemia sx like fast HR and tremors (though not sweating)
what is the moa of TZD
- works as a peroxisome proliferator activated receptor agonist to promote glucose uptake into target cells to decrease insulin resistance and increase insulin sensitivity
what is the place in therapy for TZD in DM
- HbA1c reduction of 0.5-1.4%
- onset in months
- eliminated in liver
- c/i in acute liver disease (ALT >3x ULN) and NYHA III/IV (caution in NYHA I and II
- s/e of hepatotoxicity, edema, fracture risk, weight gain
what is the moa of alpha-glucosidase inhibitors
- competitively inhibit brush border alpha-glucosidase enzymes to delay glucose absorption and decrease PPG since enzyme required for breakdown of complex carbs
- complex carbs stay in the gut and is not absorbed thus no increase in PPG
what is the place in therapy of alpha-glucosidase inhibitors for DM
- HbA1c reduction of 0.5-0.8%
- onset rapid with each meal –> useful for carb-rich meals
- eliminated 50% in feces
- s/e include GI (flatulence, abdominal pain, diarrhea), elevated LFTs
- c/i in GI diseases
- ddi with intestinal adsorbents and enzyme preparations as may reduce effectiveness of drug
what is glucagon and why is it important to manage levels of glucagon
glucagon is a hormone produced by alpha cells in pancreas and works in opposition to insulin, acting to mobilise glucose when blood glucose levels are too low
what is the moa of GLP1 receptor agonists
- works to act as endogenous GLP1 (incretin) to bind to GLP1 receptor to cause delayed gastric emptying and reduced food intake, decreased glucagon, improved beta cell function, increase glucose-dependent insulin secretion
what is the place in therapy of GLP1 receptor agonists for DM
- reduces HbA1c by 0.7-1.5%
- lower risk of hypoglycemia than SU as the increase in insulin secretion is only when BG levels are elevated
- not renally cleared
- s/e include N/V
- first line injectable over insulin if greater blood glucose lowering effect required
what is the moa of DPP4 inhibitors
- works by inhibiting DPP4 enzyme to prevent conversion of active GLP1 into inactive metabolite, to increase concentrations of endogenous incretin
- delay gastric emptying and decrease food intake, increase glucose-dependent insulin secretion, decrease glucagon and improve beta cell function
what is the place in therapy of DPP4 inhibitors
- reduces HbA1c by 0.5-0.95%
- Linagliptin is a good choice for CKD
- Sitagliptin associated with pancreatitis, counsel on s/sx including N/V, abdominal pain, fever
- generally very mild s/e, except for rare severe joint pain
- dose of Sitagliptin should be adjusted in renal impairment (50mg OD for 30≤CrCl<50 and 25mg OD for CrCl <30 or ESRD)
- s/e of sitagliptin are acute pancreatitis, N/V, abdominal pain, skin reaction, angioedema
- s/e is linagliptin are nasopharyngitis
what is the moa of SGLT2i
- inhibits SGLT2 which is a protein found in proximal convoluted tubule in the kidneys in order to increase excretion of glucose and lower blood glucose levels
- SGLT2 is responsible for reabsorption of glucose in the kidneys
what is the place in therapy for SGLT2i
- reduces HbA1c by 0.8-1.0%
- recommended for T2DM with CKD (given that eGFR ≥30)
- do not initiate if eGFR ≤30 for canagliflozin, if eGFR ≤45 for dapagliflozin and empagliflozin
- s/e for all SGLT2i are hypotension, hypoglycemia, urinary frequency and urgency, increased risk of mycotic infections or UTI, renal impairment, increased risk for DKA
- cost is a limitation
what is DKA
diabetic ketoacidosis is when the body produces high levels of ketones due to severe insulin deficiency leading to high levels of circulating fatty acids and a state of ketosis –> drop in blood pH –> metabolic acidosis –> disrupts normal cellular functions and can lead to severe complications if left untreated
what are the key hall marks and s/sx of DKA
key hallmarks
- hyperglycemia
- metabolic acidosis
- ketosis
s/sx
- fruity breath
- N/V
- abdominal pain
- fatigue
- confusion
- frequent urination
- excessive thirst
why might SGLT2i increase the risk of DKA
SGLT2i can lead to a fluid loss and electrolyte imbalance –> relative hyperglycemia and insulin deficiency
what is the moa of insulin
insulin regulates carbohydrates, fats and protein
- facilitates glucose uptake into adipose and muscle tissues and inhibit hepatic insulin output
- enhances fat storage by promoting formation of fat (TG) from fatty acids (fatty acids in circulation can interfere with insulin action and contribute to insulin resistance) and also restricts fat mobilization for lipolysis for energy (will breakdown into fatty acids and glycerol)
- promotes protein synthesis (to build and repatir tissue and overall metabolic function) and inhibit proteolysis (to preserve lean body mass and ensure adequate AA stores for other essential metabolic processes)
what is the role in therapy of insulin
- for all types of DM
- drug of choice in pregnant women
- HbA1c greatest reduction of by up to 2.5%
- response is variable in diff individuals and depends on route of administration
- s/e are inj site rxn (redness, swelling and itching), hypoglycemia, weight gain, lipodystrophy (lipoatrophy or lipohypertrophy*)
*more common
what are the pk characteristics of insulin
- onset depends on route of administration (IV>IM>SQ)
- rate limiting step is formation of SQ depot
- upon administration, immediately absorbed into blood stream
- exogenous insulin eliminated by kidneys (endogenous by liver)
what are the injection sites for insulin and how does it affect rate of absorption
- abdomen (2 inch circle around the belly button, rotate sites to prevent lipohypertrophy)
- top and outer thighs (avoid bony area above knees)
- outer upper arms (areas where fatty tissues present)
- buttocks
rate of absorption in decreasing order: abdomen > upper arms > thigh > buttock
what are the available pre-mixes
- NOVOMIX30 (30% aspart 70% aspart protamine)
- HUMALOG 25/75 (25% lispro, 75% lispro protamine)
- MIXTARD 30/70 (30% regular 70% NPH)
- MIXTARD 50/50 (50% NPH 50% regular)
what is the range of pen needles, needles for vials and gauge sizes
pen needles: 4-12.7mm
needles for vials: 6-12.7mm
28-32 (thicker = lower gauge)
what is the max volume and increment for each of the following: (i) 1cc (ii) 1/2cc (iii) 1/3cc
1cc max dosage is 100mL, increments is 2u
1/2 cc max dosage is 50mL, increments is 1u
1/3cc max dosage is 30mL, increments is 1u
what is the usual size of each vial
10mL
how does storage conditions affect insulin stability
- if unopened and refrigerated, until exp date
- if unopened and not refrigerated, 28 days
- if opened, regardless of refrigeration, 28 days
what is the administration steps for insulin
prepping vials
1. check insulin label for insulin type and exp date
2. visually inspect vial is clear (look for white clumps or color change)
3. for cloudy insulins, gently roll vial back and forth between hands
4. wipe the top of vial and injection site with an alcohol swab
5. remove protecting covering over the plunger and needle
6. draw up air equal to insulin dose to be administered into the syringe
7. inject the air into the insulin vial
8. with syringe still inserted, invert the vial and withdraw the insulin dose (using bunny ears technique)
9. if bubbles are present, gently tap the syringe and remove syringe from vial
SQ injection technique
10. pinch area to be injected
11. insert needle at a 90deg angle to the skin in the center of the pinched area
12. release the pinch
13. press the plunger to inject the insulin
14. hold the syringe in place for 5-10sec to ensure full delivery of insulin (pulling out immediately may cause insulin to leak out)
15. remove syringe or device
what are some factors that can affect insulin absorption
- temperature (increasing T increases A)
- massage (increases A)
- exercise (increases A)
- lipohypertrophy (decreases A due to bulging of adipose tissue)
- lipoatrophy (increases A due to concavity or pitting of adipose tissue)
what should patients be counselled on regarding hypoglycemia when on pharmacological management for DM
- s/sx include fast HR, tremor, palpitation, sweating, dizziness, hunger, anxiety, shaking, weakness and fatigue, irritability, blurry vision, confusion
- manage by 15/15/15 rule (15g of fast acting carbs, wait 15mins then remeasure BG levels if still <4.0 then take another 15g of fast acting carbs)
- fast acting carbs include half cup (250mL) of fruit juice, regular sweetened beverages, 1tbsp of sugar, 1tbsp of honey, 5-6 pieces of hard candy, glucose tablet or gel
how to manage if patient is on insulin and is at risk of hypoglycemia
- decrease current insulin dose by 20%
what are some dosing conversions for insulin
- decrease 20% if NPH BD to detemir or glargine U100 OD
- decrease 20% if glargine U300 to any other basal alternatives
what are the considerations to oral therapies upon initiating insulin
- continue metformin
- discontinue or reduce 50% for SU if basal insulin, discontinue if mealtime insulin
- continue SGLT2i
- discontinue or reduce TZD
- discontinue DPP4i if GLP1RA initiated
what if patient has high risk or established ASCVD, HF or CKD
ASCVD: add GLP1RA or SGLT2i
HF: add SGLT2i
CKD: SGLT2i>GLP1RA
if need additional BG lowering after metformin first line
if additionally want weight loss: SGLT2i, GLP1RA
if financial difficulties: SU > TZD > DPP4i
if need further BG lowering after metformin and another antiDM agent already
add GLP1RA before insulin unless sx of hyperglycemia or >10%
if A1c still above goal but basal dose >0.5IU/kg or FPG at goal
add prandial coverage with either rapid or regular insulin
if on bedtime NPH already, consider splitting dose into 2/3 morning 1/3 evening
what is somogyi effect vs dawn phenomenon
somogyi effect is release of cortisol in waking hours that causes BG to rise sharply
dawn phenomenon is BG levels drop sharply at night and body responds by releasing glucagon causing BG to increase
what are the pharmacological management in preventing DM complications
- aspirin if high risk ASCVD
- BP
- lipids
- vaccines (influenza, pneumococcal)
what are the ASCVD risk factors
- LDL ≥2.6
- high BP
- smoking
- CKD
- albuminuria
- FHx
