Virtual DiabetesEd Session 7 · risk factors in people with diabetes Develop a treatment plan to reduce ASCVD risk in a person with diabetes Alice is a 56yo AAF presenting for follow-up

Diabetes Education Services© 1998-2020 www.DiabetesEd.net Page 1

Virtual DiabetesEd Session 7 CV Risk Management & Intensive Insulin

Diana Isaacs, PharmD, BCPS, BC-ADM, BCACP, CDCES

Diana Isaacs, PharmD, BCPS, BC-ADM, CDCES

Clinical Pharmacy Specialist

CGM Program Coordinator

Cleveland Clinic Diabetes Center

� Diana Isaacs, PharmD, BCPS, BC-ADM, BCACP, CDCES is a consultant or speaker for the following companies: Lifescan, Companion Medical, Dexcom, Xeris Pharmaceuticals, Novo Nordisk

� Dr. Isaacs also serves as a member of the NCBDE Credentialing committee

� This program is not endorsed by NCBDE

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� Define atherosclerotic cardiovascular disease (ASCVD) risk factors

� Describe optimal approaches to treat ASCVD risk factors in people with diabetes

� Develop a treatment plan to reduce ASCVD risk in a person with diabetes

Alice is a 56yo AAF presenting for follow-up for type 2 diabetes. Alice reports that her blood pressure has been higher lately. Denies s/sx of hypoglycemia.

� PMH

� Type 2 diabetes x5 years

� HTN x 5 years

� Depression

� Meds

� Metformin1000mg PO bid

� Glipizide 10mg PO qam

� Chlorthalidone 25mg PO daily

� Escitalopram 10mg PO daily

� PE

� Ht: 5’3” Wt: 185lbs , BMI:32.8kg/m2

� BP: 140/88mmHg

� A1c=6.9%, K: 4.5mEq/L, Scr:0.8mg/dL, ACR 32 mg/g

� Tchol=204mg/dL, HDL=34mg/dL, LDL=120mg/dL, TG=250mg/dL

� Social history

� (+)Alcohol: 1-2 drinks/week

� (+) Tobacco use: 1/2ppd

� Exercise: walks 15 min twice/week

� Occ: receptionist

� Home monitoring

� FBG and pre-meal: 110-1130mg/dL

� BP: 140-150/80-90mmHg

� What are Alice’s blood pressure, cholesterol and glucose targets?

� What lifestyle changes should be advised to reduce cardiovascular risk?

� Is Alice a candidate for aspirin?

� What changes should be made to optimize Alice’s medication regimen?

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� Endorsed by the American College of Cardiology

� ASCVD is defined as:

� Coronary heart disease

� Cerebrovascular disease

� Peripheral arterial disease

� The leading cause of morbidity and mortality in people with diabetes

� Largest contributor to direct and indirect costs

� $37.7 billion/year

� Rates of heart failure hospitalization are 2x higher in people with diabetes

Make sure people with diabetes know the signs and seek immediate help.

People with diabetes may not experience intense chest or jaw pain during heart attack due to neuropathy.

Heart Attack

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� Smoking

� Overweight and obesity

� Physical inactivity

� Diabetes

� Hypertension

� Dyslipidemia

� Family history of premature coronary disease

� Chronic kidney disease

� Presence of albuminuria

***Assess risk factors at least annually***

CVD risk

Insulin resistance

Hypertension

Dyslipidemia

Endothelial dysfunction

Inflammation

Procoagulantfactors

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BP Category SBP DBP

Normal <120 mmHg And <80mmHg

Elevated 120-120mmHg And <80mmHg

Hypertension

Stage 1 130-139 mmHg Or 80-89mmHg

Stage 2 ≥140mmHg Or ≥90mmHg

Whelton et al. 2017 High Blood Pressure Clinical Practice Guideline

Individuals with SBP and DBP in 2 categories should be designated to the higher BP category

Taking an accurate Blood Pressure

� Assess BP at every office visit

� If BP >120/80 mmHg

� Encourage lifestyle changes to reduce BP

� Lifestyle changes

� Weight loss

� DASH Style diet (fresh fruit, veggies, whole grains, reducing sodium and increasing potassium intake)

� Moderation of alcohol intake

� Increased physical activity

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� BP goal <140/90mmHg if 10 year ASCVD risk <15% (ADA)

� BP goal <130/80mmHg (AACE, ACC/AHA)

� if ASCVD risk ≥15% (ADA)

� BP target based on individual assessment and shared decision making that addresses CV risk and potential adverse effects of BP meds.

Prompt initiation of drug therapy when BP is above target

�No albuminuria – Use any of 4 classes of meds

Includes ACE Inhibitors, ARBs, thiazide-like diuretics or calcium channel blockers

�With albuminuria – Start ACE Inhibitor or ARB

� (Avoid ACEi and ARB at same time)

� Multiple Drug Therapy often required

� If BP≥160/100 start 2 drug combo

Alice is a 56yo AAF presenting for follow-up for type 2 diabetes. Alice reports that her blood pressure has been higher lately. Denies s/sx of hypoglycemia.

� PMH

� Type 2 diabetes x5 years

� HTN x 5 years

� Depression

� Meds





� PE

� Ht: 5’3” Wt: 185lbs , BMI:32.8kg/m2

� BP: 140/88mmHg

� A1c=6.9%, K: 4.5mEq/L, Scr:0.8mg/dL, ACR 32 mg/g

� Tchol=204mg/dL, HDL=34mg/dL, LDL=120mg/dL, TG=250mg/dL

� Social history

� (+)Alcohol: 1-2 drinks/week

� (+) Tobacco use: 1/2ppd

� Exercise: walks 15 min twice/week

� Occ: receptionist

� Home monitoring


� BP: 140-150/80-90mmHg

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� http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/

� 42% risk of a cardiovascular event in the next years

� This puts Alice at HIGH risk

A. BP<120/80 mmHg

B. BP<130/80 mmHg

C. BP<140/80 mmHg

D. BP<140/90 mmHg

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� Albumin to Creatinine ratio (ACR)= 32 mg/g

YES

Recommendations for the

treatment of confirmed

hypertension in people with

diabetes.

*An ACEi or ARB is

suggested to treat

hypertension for patients

with UACR 30–299 mg/g

creatinine and strongly

recommended for patients

with UACR ≥300 mg/g

creatinine.

**Thiazide-like diuretic; long-

acting agents shown to

reduce cardiovascular

events, such as

chlorthalidone and

indapamide, are preferred.

***Dihydropyridine calcium

channel blocker.

Initial dose adjustment may be needed for renal dysfunction or elderly

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Initial dose adjustment may be needed for renal dysfunction or elderly

• Adverse effects– Dry cough with ACEI

– Caused by inhibition of bradykinin breakdown

– Hyperkalemia– Angioedema (< 1%)

• Occurs 2-4x more frequently in African Americans– Bump in SCr

• Up to 30% is acceptable

– Orthostatic hypotension (initial dose)– Skin rash (captopril)

• Contraindications– Pregnancy – Bilateral renal artery stenosis

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� Not meeting BP targets on 3 classes of antihypertensive meds (including a diuretic) at optimal doses

� Consider mineralcorticoid receptor antagonist

� Spironolactone (Adlactone®) 25-100mg daily

� Eplerenone (Inspira®) 50-100mg daily

� Monitor serum creatinine, potassium

� Use in recurrent MI, heart failure

� Side effects: depression, sexual dysfunction, exercise intolerance, sedation, dizziness

� Monitor BP, lipids, heart rate, glucose

� When stopping, taper dose gradually

� Can elevate glucose and mask adrenergic symptoms of hypoglycemia (ex. tachycardia)

� Sweating will still occur (cholinergic mediated)

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� Direct renin inhibitors (Alsikiren, Tekturna®)

� Similar side effects to ACEi/ARB, rarely used in clinical practice

� Combined alpha and beta blockers (ex. Carvedilol)

� Similar precautions as beta blockers

� Loop diuretics (ex. Furosmedie)

� Use when eGFR<30 or if greater diuresis is needed, monitor electrolytes

� Potassium sparing diuretics (ex. Amiloride, triamterene)

� Use in combination with thiazide to retain potassium, minimal effect on BP

� Alpha 1 blockers (ex. Doxazosin)

� Vasodilator, risk of orthostatic hypotension

� Often used for people with DM + benign prostatic hypertropthy (BPH)

� Alpha 2 agonists (ex. Clonidine)

� Centrally acting

� Administer with a diuretic

� Side effects: sedation, dry mouth, orthostatic hypotension, impotence

� Avoid abrupt discontinuation

A. Add lisinopril

B. Replace chlorthalidone with lisinopril

C. Add amlodipine

D. Replace chlorthalidone with amlodipine

Assume all choices include lifestyle modifications

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� Obtain a lipid panel at time of diagnosis and every 5 years after if under 40 years old (if not taking lipid lowering therapy)

� Obtain a lipid panel at initiation of therapy, 4-12 weeks after or a change in dose and annual thereafter

� Intensify lifestyle therapy and optimize glycemic control in patients with elevated TG ≥150mg/dL) and/or low HDL (<40mg/dL mean, <50mg/dL women)

�All ages – DM + ASCVD 10 year risk >20%

�Under age 40 with CV Risk Factors

�Age 40-75 without CV Disease

�High intensity statin

�Consider moderate intensity statin

�Consider moderate intensity statin

ASCVD Risk include: LDL >100, HTN,

Smoke, CKD, albuminuria, family hx ACSVD

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High Intensity:

Lowers LDL ≥50%

Moderate Intensity:

Lower LDL 30-<50%

� Lipitor (atorvastatin)

40-80mg

� Crestor (rosuvastatin)

20-40mg

� Lipitor (atorvastatin)

10-20mg

� Crestor (rosuvastatin)

5-10mg

� Zocor (Simvastatin)

20-40mg

� Pravachol (pravastatin)

40 – 80mg

� Mevacor (lovastatin) 40 mg

� Lescol (fluvastatin) XL 80mg

� Livalo (pitavastatin)

2-4mg

***If person can’t tolerate

intended statin dose, use

maximally tolerated dose

�Meta-analysis of data from 18,000 patients with diabetes from 14 randomized statin trials (mean follow-up 4.3 years)

�Each 38 mg/dl LDL reduction reduces relative risk of death and CVD by 9-13%.

Kearney PM et al. Lancet 2008;371:117–125, ADA Standards of Care 2020

� Consider fibrates or fish oil when TG>500mg/dLand definitely when TG>1000mg/dL

� High TG puts people at increased pancreatitis risk

� Rule out secondary causes

� In People with ASCVD on a statin with controlled LDL but elevated TG (135-499mg/dL), adding icosapent ethyl can be considered to reduce CV risk (REDUCE-IT trial)

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� Alice’s lipid panel is as follows:

� Total cholesterol: 204mg/dL

� LDL: 120mg/dL

� HDL: 34mg/dL

� Triglycerides: 250mg/dL

� Which ASCVD risk factors does Alice have? Low HDL, smoker, overweight, high BP, albuminuria

� 10 year ASCVD risk=42%

A. Optimize lifestyle modifications only

B. Lifestyle + initiate a moderate intensity statin

C. Lifestyle + initiate a high intensity statin

D. Lifestyle + initiate statin + icosapent ethyl

E. Lifestyle + initiate a statin + fibrate

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� Consider aspirin therapy (75-162 mg/day) for most men or women w DM age ≥ 50 years, with 1 additional CVD risk factor and not at increased risk of bleeding

� Caution in patients over 70 (higher bleeding risk)

� In pts who can’t tolerate, use Plavix, (clopidogrel)

CVD risk factors: family history of premature ASCVD, hypertension, smoking, dyslipidemia, CKD/albuminuria

� Use aspirin (75-162mg/day) in those with diabetes and a history of ASCVD

� Dual antiplatelet therapy with a P2Y12 inhibitor for 1 year after acute coronary syndrome and may have benefits beyond

� With known CVD and HTN, use:

� Aspirin

� Statin� B/P Med

If prior MI, continue Beta Blockers for at least 2 years after the event

� Don’t use Actos or Avandia with CHF� Diabetes Meds that decrease CV events:

SGLT2 Inhibitors – empagliflozin ,canagliflozin, dapagliflozin

GLP-1 RAs – liraglutide, dulaglutide, semaglutide

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� Consider independently of baseline A1C or individualized A1C target

HF or CKD predominates: SGLT2i

Established ASCVD or indicator of high ASCVD risk: GLP1 RA or SGLT2i

A. Yes

B. No

� Current meds





� Home monitoring


� Denies s/sx hypoglycemia.

� A1C=6.9%

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A. No changes since A1C is at target

B. Add empagliflozin

C. Add dulaglutide

D. Add linagliptin

If you add an agent, would you stop or decrease any of the others?

Category Recommendations

Nutrition • Maintain optimal weight• Calorie restriction• Plant based diet-high in polyunsaturated and

monounsaturated fats • Avoid trans fats, limit saturated fats• Consider DASH/Mediterranean meal plans• Increase omega-3 fatty acids, viscous fiber, plant

stanols/sterols (lipids)

Physical Activity • 150 minutes/week moderate exertion• Strength training

Sleep 6-8 hours per night

Alcohol • 2 drinks/day for men• 1 drink/day for women

Tobacco Cessation Avoid tobacco products

Salt Intake <2300mg/day

Diabetes Care 2020;43(Suppl. 1):S111-134ENDOCRINE PRACTICE Vol 26 No. 1 January 2020

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A. Tobacco cessation

B. Weight loss

C. Increase physical activity

D. Reduce alcohol intake

E. Reduce salt intake

Select all that apply

�Social history

�(+)Alcohol: 1-2 drinks/week

�(+) Tobacco use: 1/2ppd

�Exercise: walks 15 min twice/week

�Occ: receptionist

�BMI:32.8kg/m2

�A1C and aspirin� A1C less than 7% for most (avg 2-3 month BG)

Pre-meal BG 80-130 Post meal BG <180

� Aspirin: previous CVD event or ages 50-70 with CVD risk factors

�Blood Pressure < 140/90 or 130/80 based on risk assessment

�Cholesterol � Eval if statin therapy indicated

Diana Isaacs, PharmD, BCPS, BC-ADM, CDCES

Clinical Pharmacy SpecialistCGM Program Coordinator

Cleveland Clinic Diabetes Center

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� Review types of insulin and action profiles

� Discuss strategies to determine and fine-tune insulin settings for insulin pumps and connected pens

� Discuss how to fine-tune bolus rates including coverage for carbs and hyperglycemia

Meal Meal Meal

Insulin bolus occurs in the first 10 minutes after eating

Basal insulin is released every 12 minutes

Blood glucose– goes up after eating

InsulinBlood glucose

Basal insulin

• Regular insulin• Novolin R, Humulin R

• Neutral protamine hagedorn (NPH) insulin

• Novolin N, Humulin N

• Long-acting insulin• Glargine (Lantus®, Basaglar®),

Detemir (Levemir®), Degludec(Tresiba®)

• Rapid-acting insulin• Lispro (Humalog®, Admeolog®),

Aspart (Novolog®), Glulisine(Apidra®)

• Pre-mixed insulin • Lispro 50/50, 75/25, Aspart 70/30

• Ultra-rapid• Insulin aspart (Fiasp)

• Inhaled insulin• Afrezza®

• Concentrated insulin• Humulin R U-500

• Glargine U-300 (Toujeo®)

• Degludec U-200 (Tresiba®)

• Lispro U-200 (Humalog®)

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Freeman. The Journal of the American Osteopathic Association, January 2009, Vol. 109, 26-36.

Fast enough to

match the

absorption of

carbohydrates

Insulin Release:1st phase: peak 1-2 minutes, duration 10 minutes, suppresses hepatic glucose production2nd phase: duration 1-2 hours

AspartLispro

U-100

Inhaled

Lispro

U-200

Faster Aspart

Glulisine

Regular1.

2.

3.1. Slowest onset/longest duration

2. Rapid-acting, similar onset/duration3. Fastest onset, inhaled is quickest

NPH

Levemir

Glargine U-300

DelgudecU-100

Glargine

DegludecU-200

1. Shortest duration2. Medium duration3. Longest duration

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2.

3

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Cost

Onset of Action

Volume per injection

Technology

Hypoglycemia

Adherence Formulary

Duration of Action

Patient Preference

A. Insulin glargine (Lantus®)

B. Insulin lispro (Humalog®)

C. Insulin degludec (Tresiba®)

D. Novolin N

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� Streamlines pathway for integration with digitally connected devices (e.g., pumps, pens, automated insulin dosing (AID) systems)

� iCGM

� iController

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� Utilize bolus calculator similar to insulin pumps (enter BG and/or CHO intake) for dose calculations

� Customized settings for insulin calculators

� Monitor insulin on board (IOB)

� Dosing reminders

� Improved data aggregation linked to glucose or CGM

� Monitor insulin viability (temperature and expiration)

� Reduced diabetes burden

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� Works with lispro(Humalog), aspart (Novolog, Fiasp) 3.0 mL pre-filled cartridges � Doses: ½ - 30 units

� Bluetooth connects to an app in smartphone� Works with Android and Apple products

� Dose calculator (up to 4 timed settings throughout the day), tracks IOB, insulin dose reminders

� Non-rechargeable battery (1 year use)

� Glooko and Dexcom Clarity integration

� Monitors insulin temperature

� Requires rx to pharmacy, $35

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https://www.companionmedical.com/InPen

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1https://www.companionmedical.com/InPen

� Fiasp

� Humalog

� Tresiba

� Novolog

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� Insulin dose recording including date/time of injection

� Attaches on the main insulin pens on the market (Sanofi, Lilly, Novo)

� Transmits insulin information via bluetooth to smartphone

� Uses a lithium cell battery (non rechargeable), lasts 1800 injections

http://diabnext.com/

�Durable (non-disposable) pen

�Records last dose & time since last injection

�Dosing in half-unit increments

�Available in two colors

�Compatible with insulin aspart3mL cartridges

�FDA cleared

� Durable pen

� Takes 3mL cartidges of Toujeo, Tresiba, Novolog, Fiasp

� Doses in ½ units

� Displays last dose, time since last dose, insulin on board

� 800 dose memory

� Near field communication (scan) to App for downloading

� Not FDA cleared, launched in Europe 2019

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� Basal rate - a continuous 24-hour delivery of insulin, “background” insulin

� Bolus dose – used for carbohydrate and correction doses

� Insulin-to-carb ratio – how many grams of carbs will be covered by 1 unit of insulin

� Insulin sensitivity factor (aka correction bolus or ISF) – how much 1 unit of insulin is expected to lower glucose

� Target – the goal glucose level

� Insulin-on-board (aka active insulin time or IOB) – a pump feature that keeps track of a previous bolus

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� Weight: 72kg

� Weight based dosing

� 72*0.5=36 units

� Basal=36/2=18 units

� If using injections, plan for a basal of 18 units daily

� If using a pump, start at 18/24=0.75 units/hour

� Rule of 450 for insulin to carb ratio

� 450/36=12.5

� What does this mean? 1 unit of insulin is expected to cover 12.5 grams of

carbohydrate

� Rule of 1700 for sensitivity factor

� 1700/36=47

� What does this mean? 1 unit of insulin is expected to lower glucose by 47

points

� Current insulin regimen� Insulin degludec 40 units daily

� Insulin aspart 12 units TID a.c. + sensitivity: 25

� Estimated total daily dose 80 units

� She plans to start insulin pump therapy� Weight: 100kg

� 100*0.5=50 units

� 80 units*0.75=60 units

� Average 60+50/2=55 units/day (TDD)

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A. 8

B. 10

C. 12

D. 15

Hint: Use the rule of 450

� Rule of 450 for insulin to carb ratio

� 450/55=8.18

� What does this mean? 1 unit of insulin is expected to cover 8.18 grams of

carbohydrate

Would round to 8 or 8.2

A. 20

B. 30

C. 40

D. 50

Hint: Use the rule of 1700

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� Rule of 1700 for sensitivity factor

� 1700/55=30.9

� What does this mean? 1 unit of insulin is expected to lower glucose by 30.9

points

Would likely round to 30

� Use calculations as a starting point

� Fix fasting first

� Begin with basal rate testing

� Multiple patterns can be set throughout the day

� Alternative basal patterns can be set for sick days, menstruation, etc

� Once basal at goal, focus on bolus settings

BasalBolus

� Start with glucose 80-180mg/dL with last bolus > 4 hours

� Wear CGM or check glucose every 2 hours

� Glucose should not change by more than 30mg/dL if basal is effective

� Avoid physical activity, stress, and high fat meals before test

� Start with overnight, and then work on the rest of the day in smaller segments

� If >30mg/dL rise or fall, make basal rate adjustment, 10-20% increments

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Do you see any problems?

� Temporarily increase or decrease basal settings

� A great option for high stress, sick days, steroid bursts, exercise, etc.

� Start the temp basal 1-2 hours prior to exercise or activity requiring the change

� If patient is using a lot of temp basals, it’s more difficult to make adjustments

� Not apparent on some pump reports

� Medtronic 670G: temp target option of 150 vs usual target of 120 in auto mode

� Control IQ Exercise mode (target of 140-160)

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� TDD=49 units

� Rule of 1700

� 1700/49=35

� Current sensitivity is 40

The calculation is slightly different from the current sensitivity. Look at the glucose data to determine if the sensitivity should be decreased.

� TDD=49 units

� Rule of 450

� 450/49=12.9

� Current carb ratio is 15

The calculation is different from the current carb ratio. Look at the glucose data to determine if the carb ratio should be decreased.

� Does glucose go low after a correction dose? � May need a higher

sensitivity� Ex. 1:60 instead of 1:50

� Does glucose remain high after a correction dose? � May need a lower

sensitivity� Ex. 1:50 instead of 1:60

� Often people are more sensitive overnight (less insulin needed)

� Does the person spike high after eating?� Is the person bolusing BEFORE the

meal� Counting carbs correctly? � May need a more intensive carb

ratio� Ex. 1:8 instead of 1:10

� Does the person go low after eating? � Counting carbs correctly? � May need a less intensive carb ratio� Ex. 1:10 instead of 1:8

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� Compare pre-meal BG to 2 hour post-meal BG

� Goal post-meal BG should be 30-60mg/dLhigher than pre-meal BG

� If the 2 hour PPG is >60mg/dL above pre-meal

� Decrease carb ratio by 10-20%

� If the 2 hour PPG is <30mg/dL above pre-meal

� Increase the carb ratio by 10-20%

� When BG is above target and correction dose is taken (without food), does glucose return to target within 3-4 hours?

� If BG is low at 3-4 hours, the ISF is likely too strong

� Increase by 10-20%

� Example: 5055 or 60

� If BG is high after 3-4 hours, the ISF is too weak

� Decrease by 10-20%

� Example: 5045 or 40

� Is basal staying constant overnight?

� Are carbs entered for boluses?

� Is glucose under 180, 2 hours after meals and returning to 80-130, 4 hours after meals?

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� Use formulas as a starting point for insulin calculations

� Keep in mind the type of insulin and duration of action

� Fine tune insulin settings based on glucose data

� Connected devices (smart pens, pumps) may tracking insulin dosing and delivery much easier

� Consensus Statement by AACE/ACE Insulin Pump Management Task Force

� https://journals.aace.com/doi/pdf/10.4158/EP.16.5.746

� Companion Medical: Determining SIP settings

� https://www.companionmedical.com/virtual-conference/

Thank You� Please email us with any

questions.

� [email protected]

� www.diabetesed.net

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Documents

Virtual DiabetesEd Session 7 · risk factors in people with diabetes Develop a treatment plan to reduce ASCVD risk in a person with diabetes Alice is a 56yo AAF presenting for follow-up