Pharmacology & Exercise in Diabetes Flashcards
Key points in PA checklist?
- Minimum of 150 mins of moderate-vigorous aerobic exercise/week
- Include resistance training > 2 times/week
- Set PA goals, involve multi-disciplinary team if available
- Minimize uninterrupted sedentary time
What should be assessed pre-exercise?
Conditions that can predispose to injury
What conditions may predispose to injury?
- Neuropathy
- Coronary artery disease
- Peripheral artery disease
How could coronary artery disease be assessed pre-exercise?
Resting ECG, potential stress test
What are the 3 steps in the PA Interactive decision tool?
1) Pre-Activity screening
2) PA level and participation
3) PA Program recommendation
Give recommendations for aerobic exercise
- Walk at comfortable pace for 5-15 mins, then progress over 12 weeks to walk for 50 mins/session.
- Alternatively, try shorter bouts of exercise - such as 10 mins 3x/day after meals
Give recommendations for resistance exercise
-Choose 6-8 exercises targeting arms, chest, back, legs, abdomen and work on increasing resistance.
How should resistance training be increased over time?
Increase resistance until you can only perform 3 ets of 8-12 reps, with 1-2 mins between each set
What’s important when beginning resistance exercise?
Receive instruction and periodic supervision by a qualifies exercise specialist to maximize benefits and minimize risk of injury.
Give recommendations for interval exercise
- alternate between high and low intensity
- will shorten total exercise duration while increasing fitness gains and variety
What is intensity interval training?
Example: Alternating between 30 seconds at very high intensity and 90 seconds at low intensity
Exercise in ___ can have similar benefits as other forms of exercise and will help minimize barriers from conditions such as osteoarthritis
water
What are 2 additional pieces of exercise advice?
1) Use pedometers/accelerometers
2) Break up sedentary time - try getting up briefly every 20-30 mins
List the ABCDESSS of Diabetes care
A1C - optimal glycemic control BP control Cholesterol - reach LDL targets Drugs to protect heart Exercise and Healthy eating Screening for complications Smoking cessation Self-management, stress, other barriers
A1C target?
= 7%
BP target?
<130/80
LDL target?
<2.0 mmol/L or >50% reduction
Drugs to protect heart? (4)
ACEi or ARV
Statin
ASA
SGLT2/GLP-1 RA
When is SGLT2 or GLP-1 RA recommended?
T2DM with CVD and A1C not at target
Intensive insulin therapies T1DM
- basal-bolus injection therapy
- continuous subcutaneous insulin infusion
Discuss basal-bolus injection therapy
- Bolus insulin at meal times + basal insulin 1-2x/day
- covers the insulin required at each meal
What does basal-bolus injection therapy simulate?
Normal physiological response to meals, but required multiple injections (~1/meal + basal)
Discuss continuous subcutaneous insulin infusion
-“insulin pump therapy” infusion via catheter and will cover the amount of insulin needed throughout the day and into the night
When is conventional Tx used?
-Elderly, 2 injections/day
Describe the normal BG curve
Low in mornings (~5 mmol/L) where BG will peak at each peak, almost superimposed with insulin secretion
What is the goal of insulin therapy in T1DM?
Mimic the physiological secretion of insulin in response to meals
Why do we need basal insulin?
Since we never have 0 insulin in our system
What are the two types of insulin?
Human insulin and insulin analogs (synthesized from AA)
What takes care of the spikes of blood glucose in response to meals? What takes care of the baseline insulin?
- Bolus insulin
- Basal insulin
Describe the effects of Human basal insulin
-Require 1 injection/day and works to cover insulin levels slightly higher than our basal needs, peaking in the middle of the day
Describe the effects of Analogue basal insulin
Maintains basal insulin levels closer to normal physiology - avoids peaking in middle of the day
Analogue insulin > ___
Human insulin
Describe the effects of human bolus insul
-Requires 3 injections/day and results in insulin peaks slightly lower, and delayed, compared to glucose levels
Describe the effects of analogue bolus insulin
3 injections/day - and better matching with spikes in blood glucose compared to human bolus
What is conventional insulin Tx? When is it recommended?
Premixed insulin which mixes long and short-acting, aims to “average” out the peaks of glucose during the day.
-NOT recommended or preferred, but OK for those who have to limit injections, or low education/independence
Effects of human premixed injection?
Will partially cover 3 meals/day
Effects of analogue premixed insulin
Will cover quite well breakfast and lunch, and skip entirely the lunch
Disadvantages of conventional/premixed?
Does NOT match physiological blood glucose, meaning that there will be repeated times during the day where the patient experiences episodes of hyper and hypoglycemia
Bolus insulin can be both ____
short and fast acting
Example of fast acting bolus insulin?
Lispro/Humalog
Example of short acting bolus insulin?
Regular/Humulin-R
Intermediate acting basal insulin?
NPH/Humulin-N
Long-acting basal insulin?
Glargine/Lantus
Remixed insulin?
30/70 or Humulin (30/70)
Advantage of long-acting basal insulin?
Duration is 20-24 hours, which means that the patient will only require 1 injection/day and could inject at night –> more convenient
What is to be considered with insulin tx?
Its ability to mimic physiological insulin response, and ease of administration
Humalog onset? Peak ? duration?
Onset: 10-15 min
Peak:1-2 hr
Duration: 3-5 hr
Humulin-R onset? peak? duration?
Onset: 30 mins
Peak: 2-3 hr
DurationL 6.5 hr
Humulin-N onset? peak? duration?
Onset: 1-3 hr
Peak: 5-8 hr
Duration: 10-18 hr
Lantus onset? peak? duration?
Onset 90 min
Peak: no peak
Duration: 20-24hr
Humulin 30/70 onset? peak? duration?
Onset: 30-60 min
Peak: dual
Duration: 10-16 hr
What does conventional Tx consist of?
Premixed or fixed insulin plans
Considerations in conventional Tx?
- insulin injections 1-3/day
- Strict meal plans, CHO and meals should not be skipped
- PA may lead to hypoglycemia
When in intensive Tx recommended?
For better control, more freedom with food intake
Considerations in intensive Tx?
-Multiple daily injections (>/=3/day) or continuous insulin infusion via insulin pumps
What does intensive Tx consist of?
Basal insulin combined with bolus injections of rapid insulin before meals will mimic normal physiology
Pros of intensive Tx?
- More flexible in timing/content of meals can adjust insulin)
- Delays onset and slows progression of complications
- Will improve quality of life
- Can adjust to execise
Cons of intensive Tx?
- Must learn carb counting
- SMBG frequent
- Requires more injections/day and calculations
- Must be educated and functionally independent
How will intensive Tx reduce progression and complications of DM over 10 years?
Stuies show that A1C will reduce to normal levels (<7%) and stay consistent over 10 years
How will intensive Tx reduce progression and complications of DM over 20 years?
Reduced the risk of non-fatal MI, stroke or death from CVD (recall that heart disease = +++ risk in diabetics)
Name 5 ways insulin could be delivered
- Syringe
- Pen
- Insulin pump
- Continuous glucose sensor
- Glucose sensor (Wifi_
Insulin delivery with syringe?
Pt can fill syringe w/ amount of insulin, then perform subcutaneous injection
Insulin deliver w/ pen?
Can “scroll”to adjust amount of insulin, delivered with quick prick and less pain
Insulin delivery w/ insulin pump?
Installed w/ needle, into skin and must be changed every 2-3 wks – can control release of bolus and basal insulin with NO injections
Insulin delivery w/ continuous glucose sensor?
Will read BG and adjust insulin accordingly, where the pt will then self-administer the insulin (not automatic)
Why no automatic glucose injections?
Liabilities, but do exist
Explain the advantage of CONTINOUS glucose monitoring
If we only monitor at random times during the days, we could miss major episodes of hypo and/or hyperglycemia, and could have the false impression that our BG is normal
What is used in the management of T1DM? T2DM?
T1: Intensive/conventional Tx
T2: Antihyperglycemic agents
First-line medication T2DM?
Metformin (glucophage), a biguanide
Mechanism of metformin?
Two actions: Liver and periphery
- Decr. gluconeogenesis and increase haptic glucose uptake
- Incr. insulin sensitivity and glucose uptake
Safety of metformin?
Common, no hypoG, help w/ weight control
Side effects of metformin?
GI, transient.
May limit satiety, could help w/ weight loss of 5% and increase insulin sensitivity, B12 deficiency
What should be monitored annually for patients on metformin?
B12 and folate levels
Contraindications to metformin?
- renal insufficiency
- liver or heart failure
Name the 4 classes of anti-hyperG agents (AI-IT)
a-glucosidase inhibitors
insulin secretogogues
incretin mimetics
thiazolidinediones
a-glucosidase inhibtor examples?
Acobase/Glucobay
insulin secretogogues examples?
- Meglitinide/Repaglinide/Prandin
- Sulfonylurea/Glyburide/Diabteta
Action of a-glucosidase inhibitors?
(Pill) operates in the intestine to delay intestinal glucose absorption
Recommendation for a-glucosidase?
Take with meals to maximize the interaction between acarbose and glucose
Action of Insulin Sectretogogues ?
Will stimulate the secretion of insulin, short or long-action
Recommendations for Insulin Sectretogogues ?
May pose risk of hyoglycemia, but not as much as pure insulin injections
Action of insulin mimetics?
Stimulate insulin release an reduce glucagon secretion, play on GLP-1 and delay gastric emptying
Action of TZDs?
Increase insulin sensitivity in peripheral tissues and liver (HAM)
Examples of incretin mimetics?
DPP-4 inhibitors or GLP-1 receptor agonists
Action of DPP-4 inhibitor (incretin mimetic)
Usually, GLP-1 will be degraded by the DPP-4 enzyme. DPP-4 inhibitor will block these actions, thus promoting the survival of GLP-1
Action of GLP-1? (Gut-peptide)
- Stimulate insulin release
- Inhibit glucagon release
- Slow gastric emptying
- Increase satiety
Which anti hyperG medications may induce 5% weight loss which can improve insulin sensitivity?
Incretin mimetics and metformin
Action of GLP-1R agonist? (Incretin mimetic)
Enhance actions of GLP-1
How does GLP-1 lower blood glucose?
- Stimulate insulin release
- Inhibit glucagon release
- Slow gastric emptying
How does GLP-1 allow for better weight control?
Increasing satiety
Mechanism of SGLT-2 inhibitors?
Will block glucose transport on the proximal renal tubule, promoting glycosuria which will lower blood pressure
How does SGLT2 also act to control HTN?
Osmotic action will cause the loss of water, as well as the loss of sodium alongside glucose
When ___ is added to metformin, there is better efficacy on lowering A1C
SGLT2
Advantages of SGLT2?
Rare hypoG, lower BP, raise HDL
Contraindications of SGLT2?
Renal failure, loop diuretics, T1DM
Side effects of SGLT2?
Risk of UTI, infections, hypotension, diabetic ketoacidosis, elevate LDL transiently
SGLT2 and CVD risk?
Reduce, HTN
What is always the foundation of treatment? What may be added based on A1C?
Lifestyle and behaviour interventions, metformin
If A1C <1.5% below target?
Continue lifestyle, then add metformin if target not reached
If A1C >1.5% above target?
Immediate metformin, and consider adding 2nd anti-hyperG
If symptomatic hyperG and/or metabolic decompensation?
Initiate insulin immediately with or without metformin
All targets are evaluated every ____ months, where the decision regarding treatment of further unmet glycemic targets will be based on ____
3
Clinical CVD
Presence of clinical CVD and glycemic targets not met?
Recommend starting additional anti hyperG w/ CVD benefits
Anti-hyperGs with CVD benefit? (CLE)
- Canagliflozin
- Liraglutide
- Empagliflozin
NO presence of CVD but glycemic targets not met?
Recommend starting additional anti hyperG that considers the individuals clinical considerations
Anti hyperG agents recommended for those with no CVD but unmet targets?
Incretin mimetics
SGLT2 inhibitors
Clinical considerations for those with no CVD but un-met targets?
- Avoidance of hypoglycemia, weight-gain
- Reduced kidney function
- CVD risk factors
- Degree of hyperG
- Patient preference
Essentially, what is the goal of anti hyperG medications?
Lower A1c
What is the best therapy to reduce hyperG?
Insulin, but may cause weight gain
Difference between insulin from our own pancreas and insulin secretions? how does this impact weight gain?
Insulin from our pancreas will be released directly into portal vein, and we will need less of it to accomplish its function. Injected insulin (from subcutaneous) must pass through periphery and exert it actions, thus we require more exogenous insulin to reach the same effects on BG where we know more insulin leads to more weight gain.
Bottom line on endogenous vs. exogenous insulin and weight gain?
MORE exogenous insulin must be injected to reach the same response, where this excess amount of insulin may lead to weight gain and pose a risk of hypoglycemia
Anti hyperG w/ reduced CVD outcomes?
GLP-IR
SGLT2
Anti hyperG w/ neutral CVD outcomes?
DPP-4 inhibitors
Insulin
TZDs
Anti hyperG w/ rare incidence of hypoG? ( GSD-TAW)
GLP-1R SGLT2 DPP-4 inhibitors TZDs a-glucosidase inhibitor Weight loss agent (orlistat)
Anti hyperG w/ risk of hypoG?(II)
Insulin Insulin secretagogues (meglitinide, sulfonylurea)
Anti hyperG w/ moderate decrease in weight?
GLP-1R
SGLT2
Anti hyperG w/ mild decrease in weight?
Weight loss agent (orlistat)
Anti hyperG w/ mild increase in weight?
Insulin secretagogues (meglitinide, sulfonylurea)
Anti hyperG w/ moderate increase in weight?
Insulin, TZDs
Anti hyper G w/ neutral weight gain?
DPP-4 inhibitors
a-glucosidase inhibitors
Most effective anti hyperG in lowering A1C when added w/ metformin?
Insulin
Highly effective anti hyperG in lowering A1C when added w/ metformin?
GLP-1R
SGLT2
Moderate effective antihyperG in lowering A1C when added w/ metformin?
DPP-4 inhibitors
TZDs
Insulin secretagogues
Mildly effective antihyperG in lowering A1C when added w/ metformin?
a-glucosidase inhibitor
Weight loss agent (orlisat)
Drug-nutrient interaction w/ biguanides? Metformin)
Reduce folate and B12 absorption, take w/ meals
Drug-nutrient interaction w/ a-glucosidase inhibitors?
take w/ first bite of meal, limit alcohol
Drug-nutrient interaction w/ insulin secretagogues?
Avoid alcohol, as alcohol can mask symptoms of hypoG (recall that IS can induce hypoG)
Drug-nutrient interaction w/ incretin mimetics?
Caution w/ alcohol (side effects - do not cause hypoG) , GI side effects, heartburn
Drug-nutrient interaction w/ TZDs?
None
Pharmacotherapy for HTN in patients w/ diabetes WITH CKD or CVD?
ACE inhibitor or ARB
Pharmacotherapy for HTN in patients w/ diabetes WITHOUT CKD or CVD?
ACE inhibitor or ARB OR
DHP-CCB OR
Thiazide diuretic
What should be checked 1-2 weeks after initiation of ACEi or ARB?
Serum K+ and creatinine at baseline
(T/F) Combinations of agents that block the AAS should be used
False
How should most people w/ diabetes be treated in initial management? Later on?
Standard-dose monotherapy, but more than 3 drugs may be needed to reach target values for those w/ diabetes
(T/F) Diabetic pts must present with high LDL to be put on statin
False, do not need to present with high LDL as CVD risk already so high
Diabetic person with CVD disease and greater than 40 - statin?
Yes
Diabetic with DM >15 years, and >30 y/o - statin?
Yes
Contraindications to statin therapy?
Women of childbearing potential
