Endocrinology

Diabetes – Insulin

Ready – Set – Inject – Love

Rapid – Short – Intermediate – Long

Insulin types:
1. Rapid-Acting Insulin: RAPID doesn’t L-A-G
- L= Lispro (Humalog, Admelog)
- A= Aspart (Novolog, Fiasp)
- G= Glulisine (Apidra)
o *Also LAG = LOG (HumaLOG and NovoLOG) – both end in LOG
Onset: 15 min, peak: 1 hour, duration 3 hours
*less hypoglycemia than other insulins, take right before eating

Regular or short-acting insulin

Regular = Regular
- Insulin Regular (Novolin R, Humilin R, Novolin ge Toronto, Entuzity)
Onset: 30 min, peak 2 hours, duration: 3 hours
Take 30 min prior to eating
*Entuzity – super concentrated, for pts that are inulin resistant.

Intermediate acting insulin

Intermediate = “N”termediate
- NPH (Novolin N, Humilin N)
Onset: 2 hours, peak 8 hours and duration 16 hours [would you rather work “2” “8” hour shifts
or “16” hour shift
- cloudy appearance
- Given at bedtime or BID

Long-Acting insulin
“It takes a “LONG” time to pay back “LARGE DEBT”
- Insulin gLARGine (Lantus, Basaglar)
- Insulin DETemir (Levemir)
- Ultra long acting – Degludec (Tresiba)
o Also L for long acting and both lantus and Levemir start with “L”
Onset 2 hours, peak: NONE, duration: 24 hours
- Usually once a day HS. Detemir is shorter acting, may be given BID at low doses.

*All insulins are clear except intermediate acting ones.

Insulin Switching:
Always a 1:1 conversion. Know the instances when it is not:
- Rapid acting to short acting: reduce dose by 10-20%
- Intermediate to long acting: reduce by 20%, change from BID to OD
- Long acting to intermediate: 20% dose reduction
- Don’t switch entuzity to other insulins (usually on it for insulin resistance)

Pharmacheive – Diabetes Questions Review

- SGLT2i – may increase the risk of euglycemic diabetic ketoacidosis and may not be
appropriate in a pt with a history of DKA
- Pt presents to emerg with DKA. K= 3.5 (3.5-5.0); Na: 135 and Cl 97 (all normal)
- what would you do: optimize volume status with IV fluids and potassium
supplementation then administer IV insulin as soon as possible
o supplemental potassium is advised if levels <5.0 before administering insulin

- T1DM – required rapid acting and basal insulin

- 55 year old, taking saxagliptin. Recently diagnosed with a fungal infection, prescribed
ketoconazole. Which is most likely to result with co-administeraton:
o Increased likelihood of nasopharyngitis, headaches from saxagliptin
- Mild-mod. hypoglycemia episode – treat with 15g CHO
- GDM and diabetes in pregnancy= GDM is defined as any female with an onset of
diabetes or glucose intolerance during pregnancy (regardless of whether it resolves after
giving birth)
- Metformin AE: GI side effects (Diarrhea, N/V). Long term use may cause B12 deficiency
which can present with anemia, jaundice, neurologic changes (tingling, numbing, of
extremities). Lactic acidosis is a rare but serious AE. ]
- T1DM – has a stomach infection (sick day management) – has diarrhea and cannot
tolerate food
o Ensure she is adequately hydrated
o Should check her urine ketones every 3-4 hours at bedtime
o Should continue taking her basal insulin but not bolus
 ACRONYM “SICK”
 S= sugar – measure BG more frequent (q3-4h and at bedtime)
 I= insulin – always take basal, only use bolus in BG elevated
 C= Carbs – maintain fluids (with minimal sugar), mineral and CHO
intake. Limit caffeine
 K= ketones – check q3-4h and at bedtime
- Basal insulin starting dose: 0.1-0.2unit/kg

Drug induces causes of dysglycemia:

- BB, corticosteroids, immunosuppressants (tacrolimus), isoniazid, niacin, protease I
(ritonavir), thiazide and loop diuretics, Second gen AP;s.
- SSRIs do not cause dysglycemia
 - Which agent is most likely to cause hypoglycemia? glyburide
o Sulfonylureas – associated with hypoglycemia + weight gain
o Repaglinide – can also cause hypoglycemia + weight gain
o DPP4i – weight neutral s/e: cold sxs (stuffy or runny nose), headache
o Acarbose – s/e: flatulence, diarrhea (not hypoglycemia when used on its own)
o GLP1-RA – not linked to hypoglycemia when used on their own
Which agent is most likely to help with wt loss?
1. Repaglinide, 2. rosiglitazone 3. dapagliflozin 4. acarbose
- To manage elevated BG levels in the AM (FBG)
- Inc bedtime insulin dose
- Should eat dinner earlier
- Some light exercise at bedtime

In pts with ASCVD – GLP1 agonists and SGLT2i (empa, cana) may reduce MACE

Which can slow the progression of nephropathy in pts with ASCVD? Empagliflozin

*Pts should not hold their basal insulin for sick day management due to risk of DKA
CV Protection in diabetes:
- Smoking cessation is encourages
- Statins should be considered with microvascular pathologies (nephropathy, retinopathy,
neuropathy)
- ASA is recommended in pts with T2DM and heart attack history
- Antihypertensives should be initiated in type 2 diabetic pts if they develop hypertension
or if they present with microvascular complications
o ACEi/ARBS are initiated in pts regardless of BP if they present with microvascular
complications
68 year old female, T2DM, chronic UTIs. Current on ASA daily, bisoprolol 2.5mg, rosu 40mg,
candesartan 8mg, HCTZ 12.5mg, sitagliptin/metformin 50/1000mg BID and nitro 100mg HS
prophylaxis for UTI.
BP= 145/95 and A1c= 7.8% (everything else is normal, CrCl= 70ml/min)
Options: 1. switch sita/metformin to metformin alone
2. Add empa 10mg
3. Insulin glargine 10 units HS – she has chronic UTIs so no empa
4. Add risoglitazone 4mg – TZDs are not rly used due to significant AE (edema, CHF, potential MI
risk for rosiglitazone)

How would you normalize BP?

1. Increase bisoprolol to 5mg daily – giver her age, BBs would only exert a modest effect on BP,
with a higher risk of bradycardia
2. Add diltiazem ER 120 mg once daily
3. Amlodipine 5mg once daily
4. Spironolacone 12.5mg once daily

First line: ACEi/ARB then can add on dhp-CCB, thiazide diuretics.

The addition of amlodipine to an ACEi has led to the reduction of a composite CV outcome in
high risk pts
- BBs have a modest BP lowering effect, esp in elderly and can cause dysglycemia and
bradycardia
- Do not use non-dhp CCBs in HTN with diabetes

- Reduce his bedtime insulin dose to

10 units to avoid hypoglycemia
 - the patients A1c is in the target range and requires optimization of the current regimen
and correction of hypoglycemia first

Diabetic peripheral neuropathy – first line agents: anticonvulsants, gabapentin, pregabalin,

valproate, and antidepressants: amitriptyline, duloxetine and venlafaxine.
- opioids (tramadol, tapentadol, morphine, oxycodone) are not recommended first line
due to risk of dependence

- Repaglinide and rosiglitazone should be avoided in pts with T2DM who are overweight
as they can cause weight gain

Wt gain agents – insulin, insulin secretagogues and TZDs (avoid in overweight or obese)
Metformin, acorbose and DPP4i are weight neutral
GLP1R-a and SGLT2i can cause weight loss

*Orlistat, liraglutide, and semaglutide – are approved medications for chronic weight
management in Canada

Treatment of diabetes in pregnant women:

- metformin is considered safe to use in pregnant women with diabetes
*Also – glyburide is now known to exhibit teratogenic activity

Women of child bearing age with diabetes – to minimize risk to fetus and mother:
1. Start folic acid supplement: 1mg daily 3 mos prior to conception and continue at least 12
weeks gestation to prevent congenital anomalies
2. Screen for retinopathy before conception, during first trimester and regularly until the first
year postpartum
3. Screen for CVD and CKD prior to conception and throughout pregnancy
4. Before pregnancy, women should aim for A1c <7 (or <6.5 if safe)
5. Discontinue teratogenic meds like ACEi, ARBs, statins.

Pregnancy targets: A1c <6.5 (6.1 if safe); FBG <5.3 and 1h PPG <7.8

Canagliflozin s/e: UTI, hypotension, candida balantitis (NOT urinary retention)

Which agent is not associated with CV benefits? rosiglitazone

Atypical antipsychotics such as quetiapine can worsen hyperglycemia.

A1c >1.5% out of target – start combo tx (i.e. metformin + empa)

- Target FBG: 4-7 and 2h post prandial BG: 5-10
- concomitant use of empa and furosemide may increase the risk of hypotension
Which med can you start for vascular protection? Statins – should be started for individuals
over the age of 40 with T2DM.

Next Section: Hyperthyroidism / Hypothyroidism

Meds that can induce hypo: lithium, amiodarone, interleukin 2, interferol alpha TKA
- Lithium can cause both hypo and hyper

Levo should be administered at least 30-60min before meals as food reduces the bioavailability

Monitoring for hypothyroidism

Which pt should be approached with caution when initiating thyroid supplementation? 50 year
old pt with 1 year history of ACS - - levo can precipitate sxs of angina, therefore the doses
should be titrated slowly.

Methimazole (MMI – is first line due to its favorable side effect profile + safety
Treatment with thioamides may be life long – pts are often treated until they are euthyroid for
at least 12-18 months

Juandice is a rare but serious side effect of MMI – seek medical attention immediately if sxs
appear
Lower starting doses of levo are often required in elderly pts and pts with cardiac disease

Monitoring for TSH – 4-6 weeks before measuring TSH again and increasing levo dose

Methimazole must be stopped 5 days before a thyroid scan

RAI:
- wait 2-3 days after stopping MMI to start RAI
- RAI therapy may lead to hypo requiring life long levo therapy
- A negative pregnancy test is required to receive RAI tx
- RAI tx has been associated with an inc risk of orbitopathy (Graves ophthalmopathy)

Women already on levo supplementation prior to conception are advised to inc their dose by 2
extra tablets a week immediately upon discovering a positive pregnancy test and TSH should be
monitored 4 weeks later

In the postpartum period, thyroid hormone requireemnts are expected to return to pre-
pregnancy levels. Hypothyroidism should be managed in BF women the same as non-BF
women. {ANS: Return levo dose to the pre-pregnancy dose now that she is no longer pregnant}

If taking levo on an empty stomach is not possible, pts can take their med at bedtime or with
meals, provided they consistently take it this way.

Biotin can interfere with thyroid tests resultin in false positive and should be stopped 2 days
prior.

Myxedema coma - Levo must be administered in an IV form and switched to po once back to
baseline
- Empiric IV corticosteroids should be initiated and administered before levo
- Supportive care should also be implemented to target hypothermia, volume depletion,
hypoglycemia, hyponatremia, hypothermia and hypoventilation.

Sulfonylureas – can inc risk of hypothyroidism

Acet is the antipyretic of choice for thyroid storm (avoid NSAIDs)

Thyroid surgery:
- thyroid replacement may be required due to resulting hypothyroidism following surgery
- ATD (antithyroid drugs) pre treatment should be used to create a euthyroid state prior
to thyroid surgery
- BBs may be used short term until a euthyroid state is achieved prior to surgery
Acute sickness (i.e. HF exacerbation_ may falsely indicate thyroid disorder and therapy might
not be required at this time. At a risk of receiving unnecessary drug therapy due to euthyroid
sick syndrome and should have thyroid levels retested in 4 weeks.

- At high doses, some BB can block the conversion of T4 to T3 (propranolol and nadolol
may inhibit the conversion of T4 to T3)

- No non-pharm exists for hypothyroidism – requires exogenous thyroid hormone

supplementation
s
- RAI will induce hypothyroidism and pts may need lifelong supplementation with levo

- Methimazole is safe to use during breastfeeding