26 - Diabetes Flashcards
Fasting blood glucose target for adults
4-7
Fasting blood glucose target for children
- 4-8
- Consider target of 6-10 in children who have had severe or excessive hypoglycemia
2h post-prandial BG for aduts
5-10
2h post-prandial BG for children
5-10 (same as adults)
What can happen from BG levels that are too high?
- Diabetic ketoacidosis
- Body can’t take up glucose that is there b/c not enough insulin => high BG levels
- Levels of 13-13.5 mmol/L causes body to start producing ketones, which are then filtered through kidneys and appear in urine
Why is it important to keep BG and A1c in recommended levels?
- Can become symptomatic on day-to-day basis
- Can cause microvascular complications
Describe the possible microvascular complications of diabetes
- Nephropathy (kidney damage)
- Retinopathy = leading cause of blindness in Canada
- Neuropathy (lack of sensation in extremities)
What are the most common neuropathies of diabetes?
- Diabetic gastroparesis = neuropathy in GI tract so normal movement is impaired (feeling of food being stuck when swallowing)
- Erectile dysfunction
What is the RRR for glucose control for microvascular complications?
- 60% of nephropathy and retinopathy
- 45% of neuropathies
___ is a major complication of type 1 diabetes
Diabetic ketoacidosis
Major causes of diabetic ketoacidosis
- Failing to take insulin
- Poor sick day management
Do you still need to take insulin on sick days?
Cold or flu causes stress that causes hormone release (norepinephrine, cortisol, and glucagon) that causes blood glucose to increase
Risk factors for diabetic ketoacidosis in children
- Children w/ poor control or previous episodes of DKA
- Peripubertal and adolescent girls (insulin causes weight gain)
- Children on pumps or long-acting insulin
- Children w/ psychiatric disorders
- Those w/ difficult family considerations
What is A1C?
Glycated hemoglobin
What are the various A1C targets?
- 6.5% or less in adults w/ T2DM who are at low risk of hypoglycemia to reduce risk of CKD & retinopathy
- 7.0% or less in most adult’s w/ type 1 or 2 DM
- 7.1-8% = functionally dependent
- Goal 7.1-8.5% in px w/ recurrent severe hypoglycemia and/or hypoglycemia unawareness, limited life expectancy, or frail elderly and/or w/ dementia
What are the A1C targets for children and why?
- A1c targets more relaxed for children b/c being too stringent increases risk of hypoglycemia (has been shown to cause more learning difficulties and cognitive difficulties in children following a tight glucose control)
- < 18 y/o A1c = 7.5% or less
Is a 2% change in A1C a big deal?
- YES!!
- Going from 7% to 9% is huge and has much greater risk of complications
What is the initial dosing range of insulin for type 1 diabetes?
0.5-1 U/kg/day
When may insulin dosing decrease?
- Dose may decrease during a “honeymoon phase” (when insulin causes body to increase insulin production) which can last weeks to months after the initial diagnosis
- 0.2-0.5 U/kg/day
When may insulin dosing increase?
- Dose may increase for children as they enter puberty
- 0.5-1.5 U/kg/day
What should the ratio be for long-acting and rapid-acting insulin?
Typically dosing is approx. 50% basal and 50% rapid-acting split between 3 meals
of insulin units are adjusted based on ____
- BG readings
- Amount of carbs consumed at each meal
- Expected exercise
- Presence of illness
- Changes in age and weight over time
Who requires a basal amount of insulin?
Everyone
What is basal insulin? Give examples
- Long-acting (detemir, glargine; should be clear, throw away if cloudy)
- Intermediate-acting (NPH; should be cloudy)
- Both are given 1-2 times/day
Onset and duration of long-acting insulin
- Onset 90 min
- Duration 16-24 h (detemir) or 24 h (glargine)
- Gives a small amount of insulin for 24 h, doesn’t have a peak
- Glargine is pH dependent (formulated at pH 4)
When should detemir insulin be given and why?
At bed time and in the morning b/c doesn’t last until next bedtime dose if only given at bedtime
Onset and duration of intermediate-acting insulin
- Onset 1-3 h
- Duration < 18 h
Which insulin therapy is preferred for adults and type 1 diabetics?
Basal-bolus insulin therapies (multiple daily injections or continuous subcutaneous insulin infusion)
When should a continuous subcutaneous insulin infusion be considered?
If glycemic targets not met w/ optimized multiple daily injections
What is prandial insulin? Give examples
- Rapid-acting (aspart, glulisine, lispro)
- Short-acting (Humulin/Toronto)
Onset and duration of rapid-acting insulin
- Onset < 20 min
- Duration 3-5 h
Onset and duration of short-acting (Toronto) insulin
- Onset 30 min
- Duration 6.5 h (about 2x as long as rapid-acting)
What is the advantage of rapid-acting insulin over short-acting?
- Better for unpredictable eating schedules (ex: don’t know how much a child will eat, so can give insulin right when they start eating)
- Rapid causes less late morning/afternoon hypoglycemia (short acting lasts longer so will push glucose levels down for more time) know this
What is important to know about mixing insulin?
- Can’t mix lispro and glargine, will change the PK profile
- Can mix Humalog w/ NPH
Pediatric diabetic ketoacidosis causes increased risk for _____
Cerebral edema
Describe proper insulin administration techniques
- Rotate injection spots at the same site (not rotating will affect absorption and leave lumps under skin)
- Inject into abdomen/stomach, outer thigh, or back of arm
- Don’t inject into muscles that are going to be active (will increase absorption)
What are some sx of hyperglycemia?
- Polyuria (b/c high blood glucose makes the body want to pee it out, and water follows glucose)
- Polydipsia (excessive thirst)
- Weight loss (losing water weight)
What is the proper management of hyperglycemia?
- Monitor for trends in elevated BG and adjust when blood glucose results are consistently elevated; typically, don’t adjust insulin causing a single elevated BG reading
- Adjust only 1 insulin at a time, unless the adjustment will cause low BG readings to occur later in the day
- In most cases, insulin adjustments should approximate a 10% change to the insulin causing the effect (ex: originally using 4 U at breakfast, increase to 4.5 U)
What are some drugs that can increase blood glucose?
- Thiazides (only at higher doses; ex: HCTZ 12.5 mg isn’t concerning, but > 25 mg would require monitoring)
- Prednisone (must monitor in first 1-3 weeks after starting)
- Atypical antipsychotics
- Niacin (doses > 1 g/day)
When is a correction factor used?
When pt is very hyperglycemic
Describe the correction factor/ insulin sensitivity factor
- For rapid-acting insulin (aspart, glulisine, or lispro) divide 100 by the person’s total daily dose (TDD); result will estimate the reduction in BG for 1 U of insulin (ex: TDD = 33 U, 100 / 33 = 3 mmol/L approx.)
- For short-acting insulin (Humulin R, Novolin ge Toronto) divide 85 by TDD; result will estimate the reduction in BG for 1 U of short-acting insulin (ex: TDD = 33 U, 85 / 33 = 2.6 mmol/L)
Describe the insulin to carbohydrate ratio (ICR)
- ICR = total grams of carbs consumed per day / total daily dose of insulin units (ex: 450 g / 33 U = 13.6 g -> 1 U of insulin required for every 13.6 g of carbs consumed)
- Children = 450 g carbs
- Adults = 500 g carbs
- Can find out how many carbs are in different foods directly from “nutrition facts” labels (*don’t include fiber)
What is hypoglycemia? What are some sx?
- BG < 4 mmol/L
- Sx = sweaty and generally feeling unwell
What is the tx for hypoglycemia?
- Treat immediately w/ carbs and figure out the cause (ex: exercise, skipped meal, skipped insulin)
- For children < 15 kg = 5 g carbs
- For children 15-30 kg = 10 g carbs
- For anyone > 30 kg = 15 g carbs (ex: 4 glucose tablets, 175 mL of juice or regular soft drink)
What is a good option in regards to exercise and T1DM?
Decrease insulin if doing regularly scheduled exercise b/c too much insulin during activity may cause hypoglycemia and can prevent body from burning fat efficiently
At what BG level should a person not exercise?
> 14 mmol/L w/ ketones or > 16.7 mmol/L
What can cause hyperglycemia following cessation of high intensity exercise?
- Insulin deficiency
- Stress response
When does delayed hypoglycemia following moderate or strenuous activity generally occur?
- 6-15 h following activity
- Can be responsible for hypoglycemia > 24 h later
What are the general recommendations for people w/ diabetes and exercise?
- Good idea to bring sugar tablets and snacks w/ you
- Know sx of hypoglycemia and what to do to treat them
- Monitoring BG before starting exercise and after; if exercise is long, check BG during
- Stay hydrated
Describe the recommendations for glycemic management of type 2 diabetes in adults
- In the absence of metabolic decompensation, metformin should be initial agent of choice in people w/ newly diagnosed T2DM, unless contraindicated
- Metabolic decompensation = marker hyperglycemia, ketosis, or unintentional weight loss
- Contraindications to metformin = class 4 or 5 chronic kidney disease (CrCl < 30 mL/min) and hepatic failure
- Initial use of combinations of submaximal doses of anti-hyperglycemic agents produces more rapid and improved glycemic control and fewer side effects compared to monotherapy at maximal doses
What is the recommendation for insulin use in T2DM?
- 3rd line behind metformin and gliclazide??
- May be started on insulin at beginning, used to get them down to normal then started on oral meds to maintain
- Still make insulin, so don’t have to worry about exact insulin injection amounts to account for carbs and stuff like that in type 2 diabetics
How often should blood glucose and A1c be measured?
- If using insulin pump, SMBG (self-monitoring of blood glucose) = 4 or more times/day
- If using basal insulin, SMBG = at least as often as insulin is being given (ex: NPH/long-acting given at bedtime, SMBG before breakfast)
- Daily SMBG not usually required if px has prediabetes or has diabetes and is being treated w/ behaviour interventions and is meeting glycemic targets
- *People w/ type 1 diabetes should measure blood glucose about 4 times/day
- Type 2 DM can measure once a day or less (depending on control)
- A1c should be measured every 3 months
Metformin – advantages, max dose, major SE, CI
- One of the best agents to lower A1C
- Also decreases microvascular complications & decrease CV events
- Max dose = around 2500 mg/day; greater than that can cause lactic acidosis, which is 50% fatal
- Major SE = nausea, diarrhea, stomach upset
- Get concerned when CrCl < 40 mL/min b/c absolutely contraindicated in < 30 mL/min
Sulfonylureas - CI, MOA, SE
- Can increase weight, so avoid use in obese px
- Glyburide stimulates release of insulin from pancreas (gliclazide very similar)
- Don’t show decrease in CV events
- SE = hypoglycemia & weight gain
Acarbose - MOA, dose, efficacy, SE, monitoring
- Blocks alpha-glucosidase (breaks long carbs into smaller carbs) in GI tract & pancreatic alpha-amylase, so delays carb digestion
- Dose – 50 mg once to start, titrate up to 100 mg TID w/ meals; increase dose every 1-2 months
- Takes about 8 weeks for maximal effect
- Efficacy – commonly decreases A1c approx. 0.7-0.8%
- Weight neutral or slight weight loss
- Low risk of hypoglycemia when used alone
- *Associated w/ significant GI effects (flatulence > 40%, diarrhea ~ 30%, abdominal pain)
- Monitor liver function tests (AST, ALT) every 3 months for first year & reassess frequency
Thiazolidinediones - example, indication, dose, efficacy, CI, SE, monitoring
- Pioglitazone
- Indicated for type 2 diabetes on high dose insulin (over 2 U/kg) & on maximally tolerated metformin who aren’t achieving optimal control
- Helps increase sensitivity of cells to insulin so they can recognize glucose & uptake it
- Delayed onset of 4 weeks, max effect in 8-16 weeks
- Dose = typically 15-30 mg once daily
- Efficacy – commonly decreases A1c ~ 0.8-0.9%
- Weight gain (approx. 2.5-5 kg) b/c increased glucose uptake in cells
- Minimal risk of hypoglycemia when used alone
- Contraindicated in any amount of heart failure b/c worsens HF
- Not indicated for use w/ insulin due to increased risk of HF
- Edema 5%; rare = mild anemia
- Increased incidence of fractures
- Requires monitoring of liver function (ALT, AST) at baseline
- Monitor for blood in urine & dysuria (rarely associated w/ bladder cancer)
DPP-4 inhibitors - example, indication, dose, efficacy, SE
- Sitagliptin
- Indicated in type 2 diabetics who aren’t adequately controlled on or are intolerant to metformin & a sulfonylurea, and for whom insulin isn’t an option
- Dose = typically 100 mg once daily (decrease dose in renal dysfunction)
- Delayed onset < 4 weeks, max effect ~ 18 weeks
- Efficacy = commonly decreases A1c ~ 0.5-0.7%
- Weight neutral or slight weight loss (approx. 1-2 kg)
- Minimal risk of hypoglycemia when used alone
- Doesn’t appear to have beneficial CV outcomes (does have benefit for microvascular complications)
- Caution w/ use in HR (especially saxagliptin)
- Reports of arthralgias, joint pain
GLP-1 receptor agonists - example, administration, indication, efficacy, SE, dose, CI, disadvantage
- Liraglutide/ victoza
- Subcut injectable (supplied as 6 mg/mL solution)
- Indicated in combination w/ metformin, or metformin & a sulfonylurea, or metformin & basal insulin
- Efficacy – commonly decreases A1c ~ 1%
- CV benefit – for every 100 px w/ T2DM and high CV risk, tx w/ liraglutide for ~ 4 years will result in 2 less CV events, 2 less cases of nephropathy, but 1 extra case of acute gallbladder disease, and 2 extra cases of discontinuation due to adverse effects (ex: nausea, vomiting, diarrhea)
- Studied in px that had a CV event and trying to control BG to prevent a second one
- Increased incidence of nausea (39%), headache, diarrhea (21%), hives
- Titrate dose upward; 0.6 mg subcut once daily x 1 week, then 1.2 mg subcut once daily, may increase to 1.8 mg subcut once daily
- Weight neutral or slight weight loss (up to 3 kg)
- Lower risk of hypoglycemia when used alone
- Associated w/ medullary thyroid cancer & multiple endocrine neoplasia syndrome (rare); CI if personal or family hx; can still use in hypothyroidism
- Very expensive!
SGLT2 inhibitors - example, indication, efficacy, CV benefits, dose, CI, SE
- Empagliflozin/ jardiance
- Produces increased urinary glucose excretion (blocks re-uptake of glucose in kidneys so it stays in urine)
- CV benefits & adverse effects aren’t consistent in this class of drugs
- Indicated for:
- Monotherapy (if CI/intolerance to metformin)
- Combination w/ metformin
- Combination w/ metformin or sulfonylurea
- Combination w/ pioglitazone (alone or w/ metformin)
- Combination w/ insulin (basal or prandial)
- Efficacy = decreases A1c ~ 0.4-0.7%
- CV benefits – reduced risk of composite major CV events and all cause death (why its increasing in popularity for T2DM)
- Recommended for px w/ previous CV events
- 10 mg daily dose provided virtually same benefit as 25 mg dose
- Dose typically 10 mg daily w/ 1st meal of the day
- CI in renally impaired px (eGFR < 45 mL/min) b/c drug is less effective
- Weight neutral or weight loss (approx. 4 kg)
- SE = UTI, 3-4-fold increased risk of genital fungal infections, rare DKA; canagliflozin associated w/ increased fractures & greater risk of lower limb amputation
- Empagliflozin is a good option as long as pt doesn’t have recurrent UTI’s (b/c increases glucose in urine, which induces growth of bacteria)
- Increased risk of Fourneir’s gangrene (necrotizing fasciitis) around perineum (very rare; inform pt to get checked if experiencing redness, swelling, or pain b/c not a normal UTI; tx = debridement) – not a reason to stop recommending
- Reduced doubling of sCr, initiation of renal replacement therapy, or death due to renal disease
- In adults w/ T2DM w/ clinical CKD in whom glycemic targets aren’t achieved w/ existing anti-hyperglycemic medications and w/ eGFR > 30, SGLT2 inhibitors w/ proven renal benefit may be considered to reduce risk of progression of nephropathy
Which meds should be stopped on sick days if pt can’t stay hydrated?
SAD MANS = sulfonylureas, ACE inhibitors, diuretics/direct renin inhibitors, metformin, ARBs, NSAIDs, SGLT2 inhibitors
What is the objective of sick day management in insulin-managed diabetes?
- Minimize metabolic imbalance
- Avoid severe hypoglycemia
- Prevent hyperglycemia and ketosis leading to DKA
What are 2 diabetes emergencies w/ similar qualities?
DKA (diabetic ketoacidosis) and HHS (hyperosmolar hyperglycemic state)
Is DKA or HHS more common in T2DM
HHS b/c ketones aren’t present
Why do BG and ketones increase on sick days?
- Illness and infection allow the body to release counter-regulatory hormones that oppose the action of insulin; this allows circulating levels of glucose to rise quickly along w/ increase in circulating fat cells
- W/ lower insulin levels, higher glucose levels, and increasing fat cells, blood becomes more acidic and ketone bodies increase
When is ketone testing recommended?
- All px w/ T1DM during periods of acute illness accompanied by elevated BG
- Measured every 2-4 h around the clock as long as
Should insulin be omitted on sick days?
- Never
- Supplemental rapid-acting or short-acting may be needed for hyperglycemia and ketosis
- Can safely be given every 3-4 h w/o discussion w/ physician
What is the target for BG and ketones during brief illness?
- BG < 14 mmol/L
- Ketones negative
What should be done if pt is having trouble eating and drinking?
- 10-15 g of carbs should be taken every 1-2 h to prevent hypoglycemia
- 250 mL an hour while awake can be recommended to prevent dehydration
When should pharmacotherapy be initiated w/ gestational diabetes?
If pt doesn’t achieve BG targets w/in 2 weeks of initiation of nutritional therapy and exercise
Which anti-hyperglycemics are safe in pregnancy?
- Use of insulin to achieve glycemic targets has been shown to decrease fetal & maternal morbidity
- Multiple daily injections are most effective
- Metformin shown to be safe in pregnancy
- In women w/ GDM who decline insulin & don’t tolerate or are inadequately controlled on metformin, glyburide may be used (glyburide = 3rd line after insulin & metformin)
Why should gestational diabetes be diagnosed and treated?
- Macrosomia (large baby)
- Shoulder dystocia & nerve injury (during birth, babies’ shoulder is dislocated b/c is so big)
- Neonatal hypoglycemia
- Preterm delivery
- Hyperbilirubinemia
- C section
- Offspring obesity
- Offspring diabetes
What are the targets for GDM?
- Fasting & preprandial BG < 5.3 mmol/L
- 1h postprandial BG < 7.8 mmol/L
- 2h postprandial BG < 6.7 mmol/L
Describe the recommendation for ASA use in diabetics?
- ASA not routinely recommended for primary prevention of CVD among diabetics
- Insufficient evidence to support use of ASA for primary prevention (weighing risk of bleeding vs. CVD protection = no benefit)
