Exam 3

Question 1

What are the signs and symptoms of diabetes and how are they related to the pathophysiology of diabetes? (polys, weight loss, fatigue, UTIs/infections, ketoacidosis, blurred vision)

Answer 1

Polyuria - Increased urination due to osmotic diuresis from glucose in urine

Polydipsia - Thirst due to the polyuria

Polyphagia - Increased hunger because the body tissues are “starving” without getting the glucose-dependent uptake

Weight loss - Due to excretion of glucose in urine, body fat and protein stores broken down for fuel

Fatigue - Due to hyperglycemia after a meal

UTIs, respiratory infections, etc - Glucose is great for bacteria growth

Ketoacidosis - Due to body making ketones for fuel because it doesn’t absorb enough glucose

Blurred vision - Osmotic-induced changes in the lens of the eye

Question 2

What are the long-term complications of diabetes on the kidneys, eyes, peripheral nervous system, and cardiovascular system?

Answer 2

Diabetic kidney disease - There’s persistent proteinuria, a decreased eGPR, and increased arterial BP. This is a major cause of death in Type 1 patients. Do annual urinalysis tests (for microalbuminuria). Limit protein intake to 0.8mg/kg/day, conisder ACE-i or ARB if UACR is high (300)/GFR is low (60)

Retinopathy - Most common complication and most common cause of blindness.
- Glaucoma also common
- Optimize glycemic control, have eye exam every 1-2 years if no evidence of retinopathy

Peripheral neuropathy - Best treatment is to get blood sugars down. Do annual monofilament testing. Pregabalin, duloxetine, or gabapentin for treatment.

GI neuropathies - Gastroparesis, diarrhea/constipation, fecal incontinence

Atherosclerotic cardiovascular disease (ASCVD) - leading cause of morbidity and mortality. SGLT-2Is, and GLP-1RAs are preferred in these patients. Assess CV risk factors annually.
- Also heart failure, stroke, peripheral vascular disease

Diabetic kidney disease - Microalbuminuria tests annually
Retinopathy/glaucoma - Eye exam annually
Peripheral neuropathy - Monofilament testing annually
ASCVD & others - Asses CV risk annually,
- BP goal for T2DM + ASCVD ≥ 15% = <130/80
- BP goal for T2DM + ASCVD < 15% = <140/80

Question 3

What are the goals of therapy in the treatment of type 1 and type 2 diabetes? How should the patient be monitored to establish whether these goals have been met or not?

Answer 3

Goals of therapy - Keep patient asymptomatic, prevent long-term complications, maintain euglycemia (no low/high values), achieve/maintain appropriate body weight, maintain normal growth in children, enhance patient education/self-reliance, minimize cardiovascular risk factors

• Blood glucose tests: Fasting target is 80-130, random/PPD is <180, HS goal is 90-150.
• A1c: Goal is <7% (maybe <6% in individual patients + pregnant women); A1c of 7% ~150; PPG impacts A1c more at lower A1c ranges, fastings impact A1c more at higher A1c ranges

Question 4

What is the onset, peak, duration of action, and adverse effects of aspart, lispro, and glulisine?

Answer 4

All have onset of 10-20 mins, peak at 30-90 minutes, and have a duration of 3-5 hours. Compatible when mixed with NPH.

Aspart - Fiasp may have <10min onset and duration up to 7 hours, but that’s the only exception.

Question 5

What is the onset, peak, duration of action of insulin regular and NPH?

Answer 5

Regular - Onset of 30-60 minutes, peak at 2-4 hours, duration of 5-8 hours. Compatible with NPH

NPH - Onset of 2-4 hours, peak at 4-10 hours, duration of 8-12 hours. Compatible with regular, lispro, aspart, and glulisine.

Question 6

What is the duration of action of Humulin-R U500, Degludec U300, Glargine U300, and Lispro U200?

Answer 6

Humulin-R U500 - 6-10 hours; Has best A1c reduction, but most weight gain

Degludec U200 - 42 hours

Glargine U300 - >30 hours

Lispro U200 - 3-5 hours

• Change to concentrated when TDD is 200-300units/day

Question 7

What is the onset, peak, duration of action of glargine, detemir, and degludec?

Answer 7

Glargine - Onset of 2-4 hours, no peak, lasts 20-24 hours.

Detemir - Onset of 1.5-4 hours, peak is 6-14 hours, lasts 16-20 hours.

Degludec - Onset of 1 hour, no peak, lasts ~42 hours.

Question 8

What are key points we need to think about when designing an initial insulin regimen? What are the recommended starting ranges for Type 1 and 2 patients?

Answer 8

Type 1 patients: More sensitive than Type 2 patients.
- Avg. daily dose is 0.5-0.6u/kg/day
- Honeymoon phase for new diagnosed patients 0.1-0.4u/kg/day
- Should test BG 4x/day
- Basal-bolus dosing: 50-70% of insulin as basal, the last 30-50% as bolus.
- NPH + short-acting: 2/3 of dose in the morning injection, 1/3 in the PM; R/N-0-R/N-0
- Also R/N-0-R-N and using insulin pre-mixes
- Pumps are the goal to get best flexibility. Here we use rapid acting to cover the basal and prandial needs.

Type 2 patients:
- Starting dose is 0.1-0.2u/kg/day or 10 u/day
- Start with basal
- Increase dose every 2-4 days until goals are met, target FBS first

Question 9

How do we adjust doses of insulin for diabetes patients (type 1 or 2) based on their blood glucose readings?

Answer 9

Type 1: Doses are adjusted based on patient response. Prandial doses can be adjusted based on carb content (ex. 1 unit per 15g carbs). Remember type 1 pts are usually much more sensitive.
- Empiric: increase by 2u decreases by ~50

Type 2: Increase dose by 2 units every 3 days to reach FBS goal.
- For patients on more then 0.5u/kg/day of basal, consider adding bolus to avoid over basalization. Start with 0.1u/kg or 10% basal dose or 4-5 units of bolus.
- Empiric: increase by 4u decreases by ~50

Insulin-to-carb ratio: Average is 1 unit per 10-15g carbs (adult and 20-30g carbs (kids). Assess the carbs eaten over a 3 day period and divide that number per meal by the amount of bolus given.
- Rule of 500: 500/ daily dose of insulin (TDD) = number of grams of carbs per 1 unit of insulin. Ex. 500/40u = 12.5g carb per 1 unit.

Correction Factor: 2:50 > 150
- Rule of 1800: 1800/TDD = # of mg/dL change of BG per 1 unit. Ex. 1800/90 = 20mg/dL drop per 1 unit.
- Rule of 1500: Use if pt is on regular insulin.

Question 10

What are the typical signs and symptoms of hypoglycemia? What are some predisposing factors for hypoglycemia (including drugs)? What are the available treatment options for hypoglycemia?

Answer 10

Hypoglycemia: Level 1: BG < 70; Level 2: BG < 54
Causes: Increased insulin doses, decreased caloric intake, increased muscle utilization, excessive alcohol

Signs and symptoms: tremors, diaphoresis, anxiety, dizziness, hunger, tachycardia, blurred vision, weakness/drowsiness, headache, irritability, confusion, slurred speech

Treatment: Rule of 15s. 15g of fast-acting carbohydrates unless BS is <50, then use 30g. Then, wait 15 mins and check again. If BG is not > 79, then repeat 15g carbs.
- 4oz OJ, 6 oz cola, 5-6 life savers, 2 tsp sugar, 1tsp honey, 3-4 glucose tabs

Question 11

What are the advantages and disadvantages of these drug classes for treatment of diabetes: insulin, metformin, SGLT-2s

Answer 11

Ultra rapid insulins:
- Pros: Decreases PPD hypoglycemia and PPD lowering of BS, less nocturnal hypoglycemia, greater flexibility
- Cons: Risk of hypoglycemia is no meal within 15 mins of dose, will need to combine with longer acting for best BS control

Long acting insulins:
- Pros: 24+ hour coverage with constant absorption pattern, no pronounced peak, good for pts with nocturnal hypoglycemic episodes
- Cons: Can’t be mixed with other insulin

Metformin:
- Pros: Decreases hepatic production of glucose, increases glucose utilization, increases GLP-1 secretion; Reduces risk of mortality and CV death, decreases risk of stroke and other heart problems, minimal hypoglycemia, positive/neutral effects on weight, cheap
- Cons: May cause lactic acidosis

SGLT2Is:
- Pros: Improved CV benefits from decreasing weight, decreasing BO, and osmotic diuresis, renoprotective (reduce worsening in renal function)
- Cons: Canagliflozin in particular has warnings for bone fractures, AKIs, leg/foot amputations, and serious genital infections

Question 12

What are the advantages and disadvantages of these drug classes for treatment of diabetes: GLP-1s, GLP + GIPs, DPP-4s, TZDs, sulfonylureas

Answer 12

GLP-1s -
- Pros: also inhibits glucagon secretion, delays gastric emptying, decreases appetite, decreases weight, CV and renal benefits
- Cons: Expensive, mostly injections

GLP + GIPs -
- Pros: weight loss, really good decrease of A1c
- Cons: Expensive, injection

DPP-4s -
- Pros: Increases glucose-dependent insulin secretion, weight neutral
- Cons: need to adjust doses for renal functions (except linagliptin)

TZDs -
- Pros: Decreases triglycerides, increases HDLs
- Cons: hepatotoxicity, exacerbates HF

Sulfonylureas -
- Pros: Cheap, effective
- Cons: Hypoglycemia, secondary failure pretty common esp. after 5 years

Question 13

Metformin: Adverse events, monitoring parameters to follow, generic names, usual doses (1, + dosing in renal insufficiency)

Answer 13

Adverse events - GI effects like diarrhea, flatulence, nausea/vomiting, vitamin B12 malabsorption or deficiency

Monitoring - SCr at least annually, Vit B12 annually

Generic - Metformin

Doses - initial is 500mg BID or 850 daily, max dose is 1000mg BID.
- If eGFR is above 60, then normal initial dose. Monitor SCr annually.
- eGRF between 45 and 60, then normal initial dose, but monitor SCr every 3-6 months.
- eGFR between 30 and 45, then don’t start metformin, and reduce by 50% if already taking, monitor SCr every 3 months.
-eGFR less than 30, stop taking metformin and don’t start.

Question 14

SGLT2 inibitors: Adverse events, monitoring parameters to follow, generic names, usual doses (4, + when they should stop with renal insufficiency)

Answer 14

Adverse events - UTIs, female/male genital fungal infections, increased urination, hypotension, hyperkalemia, increased cholesterol (also FDA risk of leg/foot amputations, bone fracture, AKIs)

Monitoring parameters - Renal function (eGFR)

Generic names - Canagliflozin, empagliflozin, dapagliflozin, ertugliflozin

Usual doses -
Canagliflozin: 100mg (max 300mg daily); Don’t start in eGFR less than 30, but may stay on 100mg if they are already taking it and albuminuria is > 300mg/d
Dapagliflozin: 5mg daily (max 10mg daily); don’t start is eGFR less than 25, if already taking just monitor
Empagliflozin: 10mg daily (max 25mg daily); don’t use in eGFR less than 30
Ertugliflozin: 5mg daily (max 15mg daily); don’t start if eGFR less than 60 (monitor if already on)

Question 15

GLP-1 agonists: Adverse events, monitoring parameters to follow, generic names, usual doses (7)

Answer 15

Adverse events - Nausea, vomiting, diarrhea, acute pancreatitis, gallbladder disease

Monitoring parameters - retinopathy

Generic names - Liraglutide, dulaglutide, semaglutide, exenatide, lixisenatide

Usual doses -
Dulaglutide/Trulicity: 0.75mg -> 4mg once weekly (caution ESRD)
Semaglutide/Ozempic: 0.25mg x4 weeks -> 0.5mg-2mg once weekly
Liraglutide/Victoza: 0.6mg x7 days, then 1.2mg -> 1.8mg daily
Exenatide/Byetta: 5mcg x1 month, then 10 mcg BID (avoid CrCL < 30)
Exenatide/Bydureon: 2mg once weekly (avoid CrCL < 30)
Lixisenatide/Adylyxin: 10mcg x10 days, then 20mcg daily (avoid eGFR <15)

Oral semaglutide (Rybelsus): 3mg PO daily x30 days, then 7mg daily -> 14mg

Question 16

GLP-1 + GIP agonists: Adverse events, monitoring parameters to follow, generic names, usual doses (1)

Answer 16

Adverse events - Nausea, vomiting, diarrhea, warnings for pancreatic thyroid tumors and gallbladder disease, tachycardia

Monitoring - Retinopathy

Generics - Tirzepatide

Doses - 2.5mg SQ weekly, increase by 2.5mg/week -> 15mg

Question 17

DPP4 inhibitors: Adverse events, monitoring parameters to follow, generic names, usual doses (4)

Answer 17

Adverse events - Nasopharyngitis, URIs, headache, some pancreatitis, joint pain, heart failure risk

Monitoring - Renal function

Generic - sitagliptin, saxagliptin, linagliptin, alogliptin

Doses -
Sitagliptin: 100mg daily, CrCL 30-50 decrease to 50mg, CrCL less than 30 decrease to 25mg (same if ESRD with dialysis)
Saxaglipin: 2.5-5mg daily, CrCL < 50 then 2.5mg daily
Linagliptin: 5mg once daily
Alogliptin: 25mg daily, CrCL 30-60 decrease to 12.5mg, CrCL <30 then 6.25mg (same if ESRD and dialysis)

Question 18

Sulfonylureas (2nd gen): Adverse events, monitoring parameters to follow, generic names, usual doses (5)

Answer 18

Adverse events - Hypoglycemia (d/c if starting insulin), weight gain, hematologic, allergy

Monitoring -

Generic - Glyburide, Glipizide, Glimepiride

Doses - Start low and increase dose every 1-2 weeks until max dosage.
Glimeperide - 1-2mg daily -> 8mg
Glipizide - 2.5-5mg daily -> 40mg
Glipizide XL - 2.5-5mg daily -> 20mg
Glyburide - 1.25-5 daily -> 20mg
Glyburide micronized - 1.5-3mg daily -> 12mg

Question 19

Thiazolidinediones: Adverse events, monitoring parameters to follow, generic names, usual doses (2)

Answer 19

Adverse events - Hepatotoxicity, resumption of ovulation, exacerbations of HF, edema, fracture risk

Monitoring - LFTs (don’t start if 2.5x normal), n/v, abdominal pain, anorexia, dark urine, fatigue

Generic - Pioglitazone, Rosiglitazone

Dosing -
Pioglitazone: 15, 30mg -> 30-45mg daily max
Rosiglitazone: 4mg -> 8mg daily max
- Titrate up every 12 weeks

Question 20

Pramlintide: Adverse events, monitoring parameters to follow, generic names, usual doses

Answer 20

Adverse effects - Severe hypoglycemia with concomitant insulin admin, N/V, anorexia

Monitoring -

Generics - pramlintide (symlin)

Dosing -
- Type 1 patients: 15mcg and titrate up by 15mcg to 30-60mcg (may also decrease insulin needs)
- Type 2 patients: 60mcg and titrate up to 120mcg (may also decrease insulin needs)

Question 21

Meglitinides: Adverse events, monitoring parameters to follow, generic names, usual doses

Answer 21

Adverse events - Hypoglycemia (less than sulfonylureas), weight gain

Monitoring - watch closely for hypoglycemia

Generics - Repaglinide (Prandin), nateglinide (starlix)

Doses -
A1c < 8%, then start 0.5mg repaglinide or 60mg nateglinide w/ meals
A1c > 8%, then start 1-2mg or 120mg nateglinide w/ meals
- repaglinide max is 16mg/day
- nateglinide max is 360mg/day
Adjust doses weekly, skip dose if skip meal, add dose if add meal

Question 22

α-glucosidase inhibitors: Adverse events, monitoring parameters to follow, generic names, usual doses

Answer 22

Adverse events - GI issues like flatulence, diarrhea, abdominal pain/cramping, rashes, LFTs

Monitoring -

Generic - acarbose, miglitol

Dosing -
- start at 25mg daily with meals fro 7-14 days, then 25mg BID, for 14days, then 25mg TID for 6 weeks, then 50 TID (max if <50kg), then 100mg TID (max if >50mg) if tolerated

Question 23

What were the key clinical outcomes for these trials about anti-hyperglycemic agents: EMPAG-Reg, DAPA-HG, CANVAS, LEADER, SUSTAIN-6

Answer 23

EMPAG-Reg: Empagliflozin improves CV risk and shows renoprotective characteristics.

DAPA-HG: Dapagliflozin improves CV risk.

CANVAS-R: Canagliflozin improves CV risk.

LEADER: Less CV death in liraglutide group than placebo. Liraglutide shows renal benefits.

SUSTAIN-6: Semaglutide has less CV death than placebo. Same with nonfatal MI and stroke. Semaglutide also has renal benefits

Question 24

What were the key clinical outcomes for these trials about anti-hyperglycemic agents: REWIND, SAVOR-TIMI, EXAMINE, TECOS

Answer 24

REWIND - showed that dulaglutide has renal benefits

SAVOR-TIMI - Saxagliptin causes more HF hospitilizations than placebo, but no difference in CV death, MI or stroke

EXAMINE - Alogliptin caused more HF hospitalizations than placebo

TECOS - No increased risk for CV events or HF hospitalizations with sitagliptin

Question 25

What are the appropriate recommended uses and contraindications/precautions for insulin, metformin, SGLT2 inhibitors?

Answer 25

Insulin - Start if A1c is > 10% or if blood glucose readings are above 300

Metformin - Used as an adjunct to diet in uncontrolled type 2 patients, in combo with insulin and other non-insulin products. Use for all type 2 patients (if tolerated and not contraindicated).
- Contraindications: Renal dysfunction, unstable HF patients, heavy alcoholics, pts at risk for lactic acidosis (post MI, shock, COPD, hepatic failure, surgery/radiologic procedure)

SGLT2 inhibitors - Adjunct to diet and exercise, use with or without metformin as initial treatment for type 2 pts or if they are at high risk for atherosclerotic cardiovascular disease, HR, or CKD
- Hold SGLT2 for 3 days before surgery due to risk of DKA
- Risk of bone fractures, AKI, leg/food amputations, serious genital infections (these mostly with canagliflozin)

Question 26

What are the appropriate recommended uses and contraindications/precautions for GLP-1 agonists, GIP+GLP-1 agonists, DPP-4 inihibitors?

Answer 26

GLP-1 agonists - Use with or without metformin as an appropriate initial therapy or if they are at high risk for ASCVD, HF, or CKD. For T2, GLP-1 is preferred to insulin when possible (if they can afford it and tolerate it). If insulin is used, combo therapy with GLP-1 is recommended
- Contraindications: severe renal disease, pts with chronic pancreatitis, history of medullary thyroid carcinoma, gallbladder disease, gastroparesis,

GLP-1 + GIP - Being marketed especially for weight loss

DPP-4 inhibitors - Monotherapy and add-on therapy with metformin or TZDs in T2 pts, also combo therapy with SUs.
- Contraindicated with GLP-1 agonist, increases digoxin concentrations, durgs like ketoconazole, clarithromycin, rifampin, etc. decrease saxagliptin AUC.

Question 27

What are the appropriate recommended uses and contraindications/precautions for 2nd gen sulfonylureas, thiazolidinediones, pramlintide, meglitinides, and α-glucosidase inhibitors?

Answer 27

Sulfonylureas - Adjunct to diet and exercise for type 2 patients, used in combo with insulin and other agents. Best for type 2, short duration of diabetes so far, FBS of less than 250, high fasting C-peptide levels.
- Contraindicated with drugs that increase or decrease hypoglycemic effect; Caution if elderly, irregular dietary intake, alcoholics, taking other hypoglycemic agents.

Thiazolidinediones - Use pioglitazone first. Use as adjunct to diet and exercise, and can be in combo with SUs, DPP-4, metformin, or insulin
- Contraindications: Causes with NYHA class III and IV.

Pramlintide - Use in type 1 and 2 patients, also used for weight loss. Use when they are already on insulin but not achieving adequate control.

Meglitinides - Use adjunct to diet and exercise for uncontrolled T2DM or in combo with metformin
- Contraindications: Don’t use with SUs. Caution in elderly and patientst with hypatic/renal dysfunction

α-glucosidase inhibitors - Adjunct to diet and exercise and in combo with other agents
- Contraindications: DKA, inflammatory bowel disease, colonic ulceration, intestinal obstruction, hypersensitivity

Question 28

What are the contraindicated drugs for diabetes patients with kidney disease, cardiovascular disease, and obesity?

Answer 28

Kidney disease -
- all are neutral (except SGLT-2s and GLP-1s have benefit)
- at eGFR <30, no metformin

Cardiovascular disease -
- ASCVD: SUs may have risk
- HF: TZDs have risk, saxagliptin and alogliptin are potential risk

Obesity -
- TZDs, SUs cause weight gain

Question 29

What is the optimal treatment for diabetes patients with concomitant hypertension, kidney disease, hyperlipidemia, obesity?

Answer 29

Kidney disease - SGLT2i or if that’s not tolerated, then GLP1RA (liraglutide)

Cardiovascular disease - SGLT2 for heart failure, GLP-1 (dulaglutide) or SGLT2 for ASCVD, maybe TZD later down the road

Obesity - SGLT2s, GLP1s, and metformin cause weight loss

Question 30

How do we treat diabetes patients who is pregnant? (type 1, type 2, gestational)

Answer 30

Pregnant - Our goals during pregnancy is FBS of 70-95, 1h PPD 110-140, 2h PPD 100-120, A1c <6%.
- Type 1: Increased risk of hypoglycemia in first trimester, increased DKA risk, so prescribe ketone strips, insulin requirements drop after birth
- Type 2: Risk for co-morbidities is higher, control weight, insulin requirements drop after birth
- Gestational: Insulin preferred starting at 0.7-1u/kg/day divided in basal and bolus doses, use metformin if can’t take insulin

Avoid glyburide/glipizide, minimal data on the other agents. Usually we just go with insulin

Question 31

How do we treat pediatric diabetes patients?

Answer 31

Pediatrics - Determine if type 1 or 2. Goal is A1c <7%
- Type 1: Insulin (pump is preferred), important to think of psychosocial aspects/school system
- Type 2: Focus on weight reduction. If <8.5% do metformin only, if >8.5% do basal insulin + metformin; if those don’t work, at GLP-1 (liraglutide or exenatide); then add bolus insulin/pump

Question 32

How do we treat diabetes patients who are older adults?

Answer 32

Healthy: goal A1c 7-7.5%, fasting 80-130, HS 80-180, <140/90

Complex/intermediate health: goal A1c <8%, fasting 90-150, HS 100-180, <140/90

Poor health/end-stage: no goal A1c, fasting 100-180, HS 110-200, <150/90

Question 33

How do we treat diabetes patients who are hospitalized?

Answer 33

• Hyperglycemic patients have much higher risk of infection
• Perform A1c test if none taken within 3 months

If glucose > 180, then start insulin with target of 140-180, maybe 110-140 if no increased hypoglycemia.

• Terminally ill pts use insulin if glucose >250

Monitoring: Check pre-prandial if patient is eating, check q4-6 hours if not eating, if IV insulin check q30min-2h. Beware of hypoglycemia

Treatment: Basal-bolus is preferred if not critically ill, use IV if critical

**short-acting glucocorticoids raise BG throughout the day, longer-acting may cause for insulin adjustment.

Metformin and SGLT2s should be held 3-4 days before surgery, all other oral glucose lowering meds held day of surgery. Give 1/2 of NPH or 75% long-acting morning of surgery.

Question 34

How do we change between U-100 therapies? How do we change U100 to concentrated insulin (5 types of conversions)?

Answer 34

Between U100 therapies: If NPH -> long-acting, then keep dose the same; If BID NPH -> long-acting, then decrease the dose by 20%.

Changing U100 to concentrated:
- BID NPH -> U300 glargine, then decrease the dose by 20%
- If daily glargine/detemir -> daily concentrated glargine, then it’s a 1:1 conversion
- Basal insulin -> U-200 degludec is a 1:1
- Lispro U100 -> Lispro U200 is a 1:1
- U100 basal-bolus regimen -> U500 regimen may need 20% dose reduction from total insulin. U500 replaces basal and bolus. If A1c > 8%, then 1:1; if A1c < 8%, then 20% reduction.

Question 35

What is the basic pathophysiology of DKA and HHS?

Answer 35

DKA - A precipitating factor (like non-adherence, infection, or new diagnosis) causes an increased stress response that increases catecholamines/cortisol/GH that oppose insulin. This causes an increase of hepatic glucose production and decreased peripheral insulin sensitivity, all leading to a lack of peripheral glucose uptake and an increase in adipose tissue. Triglycerides are then broken down to glycerol and FFAs. These FFAs are broken down into ketones that are used for fuel.

HHS - Insulin deficiency or resistance leads to reduced glucose utilization that leads to increased hepatic glucose output due to excess glucagon secretion. There’s lot of glucose in urine which leads to increased water loss and dehydration which can cause acute kidney injury, leading to decreased ability to clear excess blood glucose. This leads to hyperosmolality, potentially leading to mental confusion, coma, and seizures.

Question 36

What is the DKA triad and how is it different from the laboratory presentation of HHS?

Answer 36

DKA:
- Hyperglycemia
- Hyperketonemia
- Metabolic acidosis

HHS: no/few ketones, normal pH, extremely high glucose, high serum osm
- Severe hyperglycemia
- Hyperosmolality!!
- Severe fluid depletion

Question 37

What is the formula for corrected sodium, anion gap, and osmolality?

Answer 37

Corrected sodium: Measured Na + 1.6[(glucose - 100)/100]

Anion gap: Na - (Cl + Bicarb)

Osmolality: (Na x 2) + BUN/2.8 + Glucose/18

Question 38

What are the common laboratory abnormalities that happen in patients with DKA or HHS?

Answer 38

DKA: Low blood pH (<7), low bicarb (<10), more than 3 β-HB, more than 12 anion gap

HHS: no ketones, HIGH blood sugar, normal pH, BUN > 100mg/dL, serum osm > 320

Question 39

What treatment options are there for DKA?

Answer 39

1. Restore circulatory volume (fluids)
   - Give 0.9% NaCl (NS) at 500-1000mL/hr for the first 1-4 hours
   - at 2-4 hours, evaluate the corrected Na
   - If Na is corrected, change to 1/2 NS and decrease the rate by 50%; If Na is low, continue NS but still decrease the rate by 50%.
   - Once BS is 200, change to D5W with 1/2 NS until ketoacidosis resolves.
2. Inhibit ketogenesis and return of normal glucose metabolism (insulin)
   - After fluids have been initialed, start IV insulin and monitor BG every hour.
   - Start 0.1u/kg/hour (+/- bolus of 0.1u/kg); check every hour and adjust dose to maintain glucose of 200-250
   - Once anion gap closes, we can change to SubQ and maintain glucose of 150-200
   - When transitioning, overlap IV and SubQ by 2-4 hours to prevent rebound ketoacidosis or hyperglycemia. Start at 0.1u/kg q2h and adjust prn; Also could add up rate from drip and divide it into q2h
   - When initiating SubQ (for moderate DKA), start 0.2u/kg q2h to maintain BG of 200-250. Once anion gap closes, maintain glucose at 150-200.
3. Correct electrolyte imbalances (supplement electrolytes)
   - Potassium: Want to maintain K of 4-5 mmol/L
   - Because we are already starting insulin, want to add KCl supplementation. If K 4-5, add 20mEq/L KCl. If K 3-4, add 40mEq/L KCl. If K < 3, at 10-20 mEq/hr until K > 3, then add 40mEq/L
   - Sodium: Keep monitoring corrected sodium, but we are managing this through the fluids we are giving.
   - Phosphate: If phos is less than 1mg/dL and there are comorbidities, then we may supplement phos
   - Bicarb: Only if pH is less than 6.9 do we give bicarb. In that case, give 50-100 mmol bicarb q1-2h until pH is above 7.

Question 40

What treatment options are there for HHS?

Answer 40

1. Restore circulatory volume (fluids)
   - Start with 1/2 NS (or NS) at 500-1000mL/hr for the first 1-4 hours
   - Evaluate corrected Na at 2-4 hours
   - If Na normal/high, reduce the fluid rate; If Na is low, consider NS
   - When blood sugar is 300, change to D5W w/ 1/2 NS until HHS is resolved
2. Restore urine output to 50mL/hour or more (fluids)
3. Return blood glucose to normal (fluids + insulin)
   - Start IV insulin at 0.1u/kg/hr (+/1 bolus)
   - Check glucose every hour with goal of 300
   - Once at 300, decrease infusion to 0.02-0.05u/kg/hour to maintain glucose of 200-300 until pt is mentally alert
   - Once mentally alert, can change to SubQ (with 2-4h overlap)

**hypo-K is not as big of an issue here, but maybe supplement 10mEq/L while on insulin if needed.
*Only supplement phos if <1mg/dL

Question 41

What are the minor differences in the treatment of DKA and HHS?

Answer 41

• The blood sugar goals are different. DKA goal is 150-200, but HHS goal is 300.
• More emphasis on potassium with DKA
• DKA starts with NS, HHS starts with 1/2 NS. DKA reduces NS to 1/2 NS and reduces rate by 50% once Na is corrected, but HHS only reduces rate.

Question 42

How do we read needle/syringe markings, and what is the difference between needle length and gauge?

Answer 42

Needle/syringe markings - labeled with units; U500 syringes go by 5s. You’ll chose the length and gauge depending on the thickness of the SQ tissue.

Gauge - diameter of the needle, the larger number means smaller needle

Needle length - from 12.7mm to 4mm

Question 43

What are the general storage guidelines for insulin?

Answer 43

Unused insulin should be stored in refrigerator and it’s good until the expiration date on the bottle.

Used insulin should be stored at room temperature and is good for about 1 month. Same with insulin cartridges.
- Most of the mixes are only good for 10-14 days after being opened (except Novolin 70/30 and ReliOn)
- Ultra long acting Tresiba is good for 56 days
- Other exceptions too

Question 44

What are good counseling points for patients using insulin, insulin pens, needles/syringes, and injection devices?

Answer 44

Insulin pens:
- Remove the needles and replace the pen cap before storing
- Never store electronic pens in the fridge

Needle/Syringe:
- Use one syringe with one type of insulin
- Don’t wipe the needle with alcohol and don’t let it touch anything but clean skin and insulin bottle topper
- Make sure to recap syringe
- Dispose into sharps bin after use

Question 45

What are contraindications for inhaled insulin and non-insulin injectables?

Answer 45

Inhaled - chronic lung disease (asthma/COPD)

Non-insulin injectables -
- GLP-1s: Type 1 diabetes, history of throid tumors, history of pancreatitis
- Amylinomimetic:

Question 46

What are barriers that could prevent a patient from using proper glucose monitoring?

Answer 46

• Discomfort or fear of finger sticks
• Elevated readings
• Reminder of disease
• Cost
• Inconvenience
• Social stigma
• Lack of understanding

Question 47

What are the components of insulin pumps?

Answer 47

Insulin - the fuel, rapid acting only
Reservoir - the gas tank, inserts into the pump for use
Insulin Pump - the engine, controls how much insulin is used
Infusion set - the tires, delivers the insulin to the body

Question 48

All insulin pens are primed with 2 units before every administration except for what 3 pens?

Answer 48

Humulin U500 -> 5 units
Toujeo Max SoloStar U300 -> 4 units
Toujeo Solostar U300 -> 3 units

Question 49

Out of Trulicity, Victoza, Adlyxin, Bydureon BCuse, Byetta, Ozempic, and Mounjaro, which are dosed daily vs. weekly?

Answer 49

Daily:
- Byetta (exenatide IR is BID)
- Victoza (liraglutide)
- Adlyxin (lixisenatide)

Weekly:
- Trulicity (dulagluide)
- Ozempic (semaglutide)
- Bydureon BCise (exenatide ER)
- Mounjaro (tirzepatide)

Question 50

What non-insulin injectables require pen needles, have pen needles included, or are auto-injectors? (ozempic, bydureon BCise, victoza, adlyxin, symlinPen, trulicity, mounjaro, soliqua, xultophy)

Answer 50

Require pen needles:
- Victoza, adlyxin
- SymlinPen
- Soliqua
- Xultophy

Pen needles included:
- Ozempic

Auto-injector:
- Trulicity
- Bydureon BCise
- Mounjaro