Glycemic Control in Diabetes Flashcards
How is A1C formed? What is the rate of formation proportional to?
- A series of stable, minor hmg components formed slowly and non-enzymatically from hmg and glucose
- Proportional to glucose concentration
What does A1C provide and predict? How often should it be assessed?
- Glycemic history of the previous 120 days, with the most accurate reflection of the previous 2-3 months of glycemic control
- Predicts risk for complications
- Assess every 3-6 months
What are other glycated proteins? Are they proven to be shown as an indicator of risk for complications?
- Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP)
- Not yet shown, minimal clinical relevance
A1C target for adults with T2DM to reduce risk of CKD and retinopathy if at low risk of hypoglycemia?
= 6.5%
What is the A1C target of most adults with type I or Type II diabetes?
= 7.0%
A1C target for those who are functionally dependant?
7.1-8.0%
When is an A1C target of 7.1-8.5% recommended?
- Recurrent severe hypoglycemia and/or hypoglycemia unawareness
- Limited life expectancy
- Frail elderly and/or with dementia
Why should A1C concentrations above 8.5% be avoided?
To minimize risk of symptomatic hypoglycemia and acute and chronic complications
A1C suggestion for end of life?
-A1C recommendations are not recommended, avoid symptomatic hyperglycemia and any hypoglycemia
What are the pre-prandial and 2 hour post-prandial glucose targets in most patients to reach an A1C of = 7.0%?
- Pre-prandial: 4.0-7.0
- Post-prandial: 5.0-10.0
What are the pre-prandial and 2 hour post-prandial glucose targets if A1C = 7.0% despite previous targets?
- Pre-prandial: 4.0-5.5
- Post-prandial: 5.0-8.0
(T/F) A1C values are identical to estimated mean glucose levels
False, but their are correlated
What can INCREASE A1C within the context of erythropoiesis?
- B12/Fe deficiency
- Decreased erythropoiesis
What can DECREASE A1C within the context of erythropoiesis?
- Use of EPO, Fe or B12
- Reticulocytosis
- Chronic Liver disease
What can change A1C variably within the context of altered hemoglobin?
- Fetal hemoglobin
- Hemoglobinopathies
- Methemoglobin
What can INCREASE A1C within the context of altered glycation?
- Chronic renal failure
- Decreased erythrocyte pH
What can DECREASE A1C within the context of altered glycation?
- ASA, vitamin C/E
- Hemoglobinopathies
- Increase in erythrocytes pH
What can INCREASE A1C within the context of erythrocyte destruction?
-Splenectomy
What can DECREASE A1C within the context of erythrocyte destruction?
- -Hemoglobinopathies
- Chronic renal failure
- Splenomegaly
- Rheumatoid arthiritise
What may cause falsely elevated A1C? Falsely low?
- Elevated in the context of hyperbilirubinemia
- Decreased in the context of hypertriglyceridemia
When are glycemic targets higher than the ret of the population?
Adolescent (<18 y/o)
A1C target for <18 y/o?
= 7.5%
FPG <18 y/o?
4.0-8.0
2hr PG <18 y/o?
5.0-10.0
How can we measure plasma glucose?
- Blood glucose meter
- Continuous glucose monitor
- Flash glucose monitor
What are the advantages of the CGM and flash systems?
-We will not get a singular, random measurement but rather monitor our blood glucose over time and observe trends
Why are adolescents prone to having higher glycemia and A1C levels?
- Could have difficulties managing their glycemic
- Busy lifestyle
- Social changes
- High growth hormone
- Changing from a paediatric to an adult clinic
If A1C is < 1.5% over target, what is the initial choice of therapy?
-Initiate healthy behaviour interventions and start metformin if not at target in 3 month
If A1C >/= 1.5% over target. what is the initial choice of therapy?
-Start metformin with healthy behaviour interventions AND consider second concurrent agent
what is the overarching intervention at diagnosis, and throughout treatment of Type II diabetes?
Healthy behaviour interventions (nutritional therapy, weight management, PA, with or without metformin)
What should be initiated if preliminary interventions have not achieved glycemic target and there is a risk of CVD risk?
Starts antihyperglycemic agent with demonstrated CVD benefit
What should be initiated if preliminary interventions have not achieved glycemic target and there is NO risk of CVD risk?
- Provide an additional antihyperglycemic agent best suited to the individuals based on clinical considerations, such as
- Avoidance of hypiG, weight gain
- Reduced eGFR
- Degree of hyperglycemia
- Cost/coverage
Which medications have CVD benefits?
- Empagliflozin
- Liraglutide
- Canagliflozin
What are the 4 key points in the pharmacotherapy in Type 2 Diabetes checklist?
- Choose initial therapy based on glycemia
- Start w/ metformin and +/- others
- Individualize your therapy choice based on characteristics of the person w/ diabetes and the agent
- Reach target within 3-6 months of diagnosis
Biguanides?
Metformin/glucophage
-Decrease hepatic glucoe production
a-glucosidase inhibitors?
Acarbose/Glucobay
-Delay intestinal glucose absorption
Insulin secretagogues (Meglitinide, sulfonylurea)?
- LINIDE/RIDE
- stimulate insulin secretion
- Meg is short-acting (4-7h)
- Sulf is long acting (once daily)
What are examples of incretin mimetics?
- DPP-4 inhibitors
- GLP-1 receptor agonists
DPP-4 inhibitors?
SitaglipTIN
GLP-1 receptor agonist?
ExenaTIDE
What is the mechanism of incretin mimetics?
Stimulate insulin and reduce glucagon secretion, will delay gastric emptying
Thiazolidinediones?
- ZONES
- Increase insulin sensitivity in the peripheral tissues and liver (decrease insulin resistance)
SGLT-2 Inhibitors?
- OZIN
- Decrease glucose reabsorption, increase glucose excretion
What is the first line therapy?
Biguanides (Metformin)
Key benefits of metformin
- 1 to 1.5% reduction in A1C
- Negligible risk as monotherapy
- No weight gain
- May improve CV outcomes in overweight subjects
Key risks of metformin?
- GI side effects
- Creatinine clearance (Caution if <60 ml/min)
- Lactic acidosis
- B12 deficiency
When is metformin contraindicated?
When GFR <30 ml/min or in hepatic failure
(T/F) Metformin carries a risk of hypoglycemia
F
Key insulin secretagogue benefits?
- 0.7 to 0.8% reduction in A1C
- Rapid onset of responce
- Decrease microvascular risk
When is postprandial glucose especially reduced?
Through use of meglitinides (insulin secretagogue, short-acting)
Key insulin secretagogue risks?
- **Hypoglycemia
- Weight gain
- May blunt myocardial ischemic preconditioning
- Blood sugar control is lost earlier than with Metformin
When should caution surrounding hypoG be exerted on IS?
- Kidney disease
- Liver problems
- Elderly
Which IS poses the highest risk to hypoG and weight gain?
-Glyburide (Sulfonylureas)
Key benefits of alpha-glucosidase inhibitors (AGIs)?
- 0.6% reduction in A1C
- Negligible risk as monotherapy
- Weight neutral
- Beneficial in patients with IGT
How are AGIs beneficial for patients with IGT?
- 49% reduction in CV events
- Prevention if T2DM
Key risks of AGIs?
- GI side effects
- TID dosing
- NOT recommended as initial therapy in people w/ AIC >/= 8.5%
- Ceratin contraindications
GI side effects w/ AGIs?
-Delays the absorption of glucose, therefore causing more fermentation
Significance of TID dosing of AGIs?
As they act on delaying glucose absorption, must be taken with meals
Contraindications to AGIs?
- Diabetic ketoacidosis
- IBD
Key benefits to thiazolidinediones (TZDs)?
- 0.8% risk reduction
- Negligible risk as monotherapy
- CVD benefits
CVD benefits observed with TZDs?
- Increase HDL-c
- Decrease TGs (pioglitazone)
- Decrease CVD events
Which anti-hyperG agents demonstrates a longer duration of glycemic control w/ monotherapy vs, metformin o glyburide?
-TZDs
Key risks of TZDs?
- Weight gain
- CVD
- 6-12 weeks for full glycemic effects
- Bladder cancer, macular edema (rare)
- Contraindications
CVD risks of TZDs?
- May induce edema and/or CHF
- May increase MI
- Increase LDL-c (rosiglitazone)
Contraindications to TZDs?
- Serious liver dysfunction
- Known clinical heart failure or evidence of ventricular dysfunction
Key benefits of DPP-4 inhibitors?
- 0.7% reduction in A1C
- Negligible risk as mono-therapy
- Weight neutral
- Neutral CV studies
- Well tolerated
- No risk of hypoglycemia
How does DPP-4 inhibitors impact blood glucose?
-Reduction in postprandial glycemia in combination with metformin
Key risks of DPP-4 inhibitors?
- Rare cases of pancreatitis
- Long-term safety unknown due to “new” drug
- Cardiac insufficiency if Saxagliptin
Discuss the action of GLP-1 Receptor agonists
An injection which will results in a higher level of GLP-1 being releases, and a large surge of insulin (beyond physiological levels)
Discuss the action of DPP-4 inhibitors
An oral agent which will block the DPP-4 enzyme which inhibits the release of GLP-1, therefore the drug will elicit a “normal” or physiological response of insulin
What are the impacts of DPP-4 inhibitors?
- Increase insulin secretion
- Decrease glucagon secretion
What are the impacts of GLP-1 receptor agonists?
- Decrease gastric emptying
- Increase satiety
- Decrease energy intake
- Increase nausea
- Decrease weight
- Increase insulin secretion
- Decrease glucagon secretion
Key benefits of GLP-1 receptor agonists?
- 1.0% reduction in post-prandial glycemia
- Negligible risk as mono-therapy
- Significant weight loss
- May decrease BP, CV events, mortality, kidney protection
- Potential for improved B-cell mass function
Risks of GLP-1 receptor agonists?
- Gi side effects
- Rare cases of pancreatitis
- Parafollicular cell hyperplasia
- Long-term safety unknown due to “new drug”
- nausea
- Injectable
Is there a hypoglycemic risk in GLP-1 receptor agonists?
no
Contraindication for GLP-1 receptor agonists?
-Personal/family history of medullary thyroid cancer or MEN2
Required patient education for GLP-1 receptor agonist theory?
- GI symptoms
- If on insulin, monitor for hypoG
- Delivered via pen (like insulin)
Recommendations for administering meds by pen (insulin/GLP-1 receptor agonist)?
- Refrigerate the pen prior to use
- hand wash, and inspect med for cloudiness/particulate matter
Discuss SGLT-2 inhibitors
- Both sodium and glucose co-transporters are blocked, inhibiting their reabsorption in the blood and are excreted
- Ultimately decreases glucose renal reabsorption and increases its excretion (turning symptoms into therapy)
Where is the SGTL2 channel found?
In the proximal tubule of the kidney
What is the estimated amount of glucose excreted per day on SGLT2?
77–119 g/day or 308-476 kcals/day
Discuss SGLT-2 effects on weight
-Can have significant weight-loss, however will plateau within 6-8 months (does not continue with expected weight-loss trajectory)
Discuss SGLT-2 on A1C reduction
Will act very rapidly on reducing A1C - an then there is a steady regain over about 2 years close to baseline, but still overall lower
What other impacts does SGLT2 have ?
- Will have a marked reduction in blood pressure
- Can slow the progression of kidney disease (Empagliflozin) for those w/ T2DM and high CVD risk
Empagliflozin impact on CVD death and heart failure?
-Reducing CVD death and heart failure over 4 years, where the reduction occurs quite rapidly and is relatively maintained.
SGLT-2 inhibitors key benefits?
- 0.7% A1C reduction
- Negligible risk as monotherapy
- Weight loss (~3kg)
- Decreases BP, weight, mortality, CVD death, heart failure and kidney protection
Is there hypoglycemic risk for SGLT-2 inhibitors?
No
Key risks of SGLT-2 inhibitors?
- Mycotic genital infection (most common)
- Hypovolemia
- Increased LDL-c
- Euglycemic ketoacidosis
- Long-term safety unknown
(T/F) SGLT-2 inhibitors are appropriate for both T1DM andT2DM
F, T2DM only
When should SGLT-2 be discontinued? Why?
Should insulin be stoped?
- Stop before surgery and acute illness (~3 days)
- The 1/2 life ranges from 11-13 hours, and their effects can persist for a few days after discontinuation
- Do NOT stop insulin
Which medications are not recommended to be used if eGFR is <45?
SGLT-2 and GLP-1 RA
What is euglycemic ketoacidosis?
Where there is minimal insulin secretion, but their glucose is OK -ketone body production continues and pH will still change
What are the two drugs which are not negligible risks as monotherapy?
- Insulin and IS
- Due to hypoglycemia risk
Which two drugs have the greatest potential fo weight gain?
-Insulin and TZDs
Which GLP-1RA is superior in T2DM w/ clinical CVD?
Lira
Which SGLT-2 inhibitor is superior in T2DM w/ clinical CVD?
-Cana and Empa
Which medications have the greatest potential for A1C lowering when added to metformin?
- Insulin
- SGLT-2 Inhibitors
- GLP-1RA
How many types of insulin pumps are available in Canada?
5-types
Which insulin pump does not have CGM available?
- Omnipod
- Ypsomed
What are the two kinds of insulins delivered in intensive insulin therapy?
-Bolus and Basal
Sub-types of bolus insulins?
Rapid acting and short acting
Rapid acting bolus insulin?
- Glulisine
- Lispro
- Asapart
- Faster acting asapart
Glulisine onset, peak and duration?
10-15 min
1-1.5 hr
3.5-5 hr
When should glulisine be injected?
0-15 mins before a meal
Lispro onset, peak and duration?
10-15 min
1-2h
3-4.75 hr
When should lispro be injected?
0-15 mins before meal
Aspart onset, peak and duration?
9-20 min
1-1.5h
3-5h
When should aspart be injected?
0-10 mins before the meal
Faster acting Aspart onset, peak and duration?
4min
0.5-1.5 h
3-5h
When should faster acting Aspart be injected?
0-2 mins before meal or can be administered up to 20 minutes after the start of the meal when necessary
What are sub-types of short-acting insulins?
- Insulin regular (Humulin)
- Insulin regular U-500
Insulin regular (humulin) onset, peak and duration?
30 min
2-3 h
6.5 h
When should insulin regular (humulin-R) be injected?
~30 mins before meal
Insulin regular U-500 onset, peak and duration?
15 min
4-8 h
17-24 h
When should insulin regular U-500 be injected?
~30 mins before meal
Two types of basal insulin?
- Intermediate acting
- Long-acting
Intermediate acting insulin humulin-N onset, peak and duration?
13h
5-8h
Up to 18 h
When should humulin-N be injected?
Morning and/or night
When should long acting insulin such as glargine be injected? What is its onset, peak and duration?
- Morning/Night and no less than 8h between 2 injections
- 90 min, NO PEAK and ranges from 16-42 hrs
When should premixed regular insulins be ingected? (Humulin 30/70, Novolin 30/70)
-30 mins before meal
When should premixed insulin analogues be injected? (Novomix, Humalog Mix 25)
0-10 mins before meal
0-15 mins before meal
What should insulin be titrated to achieve? What if A1C not achieved? When is a higher FPG acceptable?
- a target of fasting BG of 4.0-7.0 mmol/L
- 4.0-4.4 mmol/L
- When goal of avoiding hypoglycemia is more important
Equation to estimate A1C based on given mean BG level?
A1C % = 0.625(Mean BG) + 1.7
