Diabetes Flashcards
1
Q
Diabetes Mellitus is characterized by what?
A
Presence of hyperglycemia…
2
Q
The presence of hyperglycemia can be due to what?
A
1) Defective Insulin Secretion
2) Defective Insulin Action
3) Both
3
Q
What are some medical complications that can arise from Diabetes Mellitus?
A
-CVD
-Kidney Disease
-Blindness
-Neuropathy
-Amputation
4
Q
What percentage of Diabetics die from either heart disease or stroke?
A
80%
5
Q
By how many years can unregulated Diabetes shorten one’s lifespan?
A
5-15yrs
6
Q
Three types of Islet Cells in the Pancreas? What % of total Islet Cells do they each comprise?
A
1) Delta (10%)
2) Alpha (30%)
3) Beta (60%)
7
Q
What do each of the three Islet Cell types produce?
A
Delta: Somatostatin
Alpha: Glucagon
Beta: Insulin / Amylin
8
Q
Glucagon release from Alpha Cells is stimulated by what?
A
Low blood glucose
9
Q
Insulin release from Beta Cells is stimulated by what?
A
High blood glucose
10
Q
What actions do Insulin have on the following organs / tissues:
Liver
Adipose Tissue
Skeletal Muscles
A
Liver: Increase Glycogenesis (new Glycogen production) & decrease Gluconeogenesis.
Adipose Tissue / SM: Increase Glucose uptake from blood.
11
Q
What actions does Glucagon have on the Liver?
A
Increase Glycogenolysis (Glycogen Breakdown) & increases Gluconeogenesis.
12
Q
What triggers Insulin secretion?
A
1) Increased Blood Glucose
2) Increased Serum Amino Acids
3) Increased Serum Free Fatty Acids
4) Glucagon
5) Growth Hormone
6) Cortisol
7) GIP
13
Q
What triggers Glucagon secretion?
A
1) Decreased Serum Glucose
2) Decreased Serum AA’s
3) E + NE
14
Q
What functions do Skeletal Muscles carry out when stimulated by Insulin?
A
Increased Protein Synthesis & Glycogenesis
15
Q
What function does Adipose Tissue carry out when stimulated by Insulin? By Glucagon?
A
I: Increased Lipogenesis
G: Increased Lipolysis
16
Q
How do our Adipose Tissues combat excessive carbohydrate intake?
A
-When Glycogen stores are full, convert excess carbs to Free Fatty Acids & stores them as TG’s.
17
Q
What happens to TG stores in a situation of starvation?
A
-Split into Glycerol + FFAs… FFAs are metabolized into Ketone Bodies, which themselves are used as an energy source.
18
Q
Approximately what percentage of total bodily Glucose is utilized by the Brain?
A
~20%
19
Q
How is T1DM characterized?
A
Complete lack of Insulin secretion (usually due to Beta Cell destruction)
20
Q
What types of immune destructive markers are typically seen with T1DM?
A
1) Islet Cell Antibodies
2) Insulin Antibodies
3) Glutamic Acid Decarboxylase Antibodies
21
Q
What are the peak ages of T1DM diagnoses?
A
13-14yrs (most cases take place before 25yrs)
22
Q
At what percentage of Beta Cell destruction do we see Hyperglycemia in T1DM patients?
A
80-90% destruction
23
Q
I’m a recently diagnosed T1DM patient (3wks ago). I’ve began receiving Insulin injections & my lab results show that my Insulin secretion has improved ever so slightly. What describes this phenomenon?
A
“Honeymoon Phase”… Initial improvements to Insulin secretion that occur when hyperglycemia is corrected.
24
Q
Are “Honeymoon Phase” improvements in T1DM patients permanent?
A
NO (!!!)… This is a transient period that lasts up to a couple months post-Insulin initiation & hyperglycemic correction.
25
Within what concentration (in mmol / L) would somebody be diagnosed with Impaired Fasting Glucose (IFG)?
6.1 - 6.9
26
Within what concentration (in mmol / L) would somebody be diagnosed with Impaired Glucose Tolerance (IGT)?
2hr Plasma Glucose reading of 7.8 - 11.0
27
What percent Glycolated Hemoglobin (A1C) would one have to be diagnosed with Prediabetes?
6.0 - 6.4
28
What percentage of total Diabetes Mellitus cases are T1? T2?
T1DM: 10%
T2DM: 90%
29
How does T2DM manifest?
-Initial Insulin Resistance followed by a loss of one's ability to produce Endogenous Insulin (as the body is trying to compensate for a loss of Insulin responsiveness).
30
Risk Factors for T2DM?
-Over 40yrs age
-1st degree relative with T2DM
-High Risk Population (ie. African, Arab, Asian, Indigenous)
-Obese
-History of Gestational Diabetes / Prediabetes / Large Infant birthweight
31
Other T2DM Risk Factors?
-CV / Microvascular damage
-Vascular Risk Factors (ie. Low HDL, High TG, HTN, Smoker, Obese)
-Acanthosis Nigricans / PCOS / Obstructive Sleep Apnea / HIV / Gout / Non-Alcoholic Steatohepatitis / Pancreatitis / CF / Psych Illnesses
-Certain Medications
32
What are some medications that may increase blood glucose?
-5-FU
-Beta Blockers
-Corticosteroids
-Statins
-Immunosuppressants
-Niacin
-Pasireotide
-Protease Inhibitors
-Thiazides / LDs
-Antipsychotics
33
At what organ do we see Primary Insulin Resistance?
Skeletal Muscle (as it's the primary Glucose disposal site after a meal).
34
If I'm Insulin Resistant, how does my Liver respond?
Unregulated Hepatic Glucose production (because Insulin normally suppresses the process of Gluconeogenesis).
35
If I'm Insulin Resistant, how does my Adipose Tissue respond?
Increased Lipolysis (leading to more FFAs).
36
What kinds of acute symptoms might T1DM patients present with?
-Polyuria (increased urination)
-Polyphagia (increased hunger)
-Polydipsia (increased thirst)
-Weight Loss
-Fatigue
-Blurred Vision
-Infection
37
20-40% of T1DM patients present with what after several days of experiencing acute clinical symptoms?
Diabetic Ketoacidosis
38
Symptom Onset: How do they differ between T1DM & T2DM?
T1DM: Abrupt & Symptomatic
T2DM: Gradual & often Asymptomatic
39
Weight Presentation: How do they differ between T1DM & T2DM?
T1DM: Usually thin
T2DM: > 90% Obese
40
Colton is a recently diagnosed 30yr old Diabetic patient who presents with elevated C-Peptide levels & both Diabetic Retinopathy and Diabetic Nephropathy. What form of Diabetes Mellitus does he likely have?
T2DM
-Elevated C-Peptide suggests Insulin levels being secreted are high & microvascular complications at diagnosis are present with T2DM.
41
T or F: Gestational Diabetes is more common in Indigenous women than other ethnicities.
True... 8-18% of Indigenous Women affected (vs. 4% other).
42
Between what weeks of pregnancy should women be screened for Gestational Diabetes?
24-28wks (or even earlier if risk factors are present)
43
T or F: Screening Tests used to diagnose T1DM & T2DM differ from one another.
False... The exact same tests are used to screen & diagnose.
44
What initial screening tests should be used to diagnose those who might have T2DM?
FPG or A1C
45
Carter is a 41yr old who presents with a FPG reading of 5.6mmol / L and an A1C of 5.5%. How often should he be screened for T2DM?
Every 6-12mths
-As he is considered at risk for developing T2DM with these FPG / A1C readings.
46
Adam is a 41yr old who presents with a FPG reading of 5.5mmol / L and an A1C of 5.4%. How often should he be re-screened for T2DM?
Every 3yrs
-As these FPG & A1C readings are not associated with being more at risk for T2DM development.
47
Cole is a 41yr old who presents with an FPG reading of 7.1mmol / L & an A1C of 6.6%. How often should he be re-screened for T2DM?
Doesn't need to... Those readings (above 7.0 mmol / L & 6.5%) suggest that he has T2DM!
48
An FPG above 7.0mmol / L, an A1C above 6.5%, and a 2hr PG reading [in a 75g OGTT] above what indicate a positive Diabetes diagnosis?
Above 11.1mmol / L
49
Which patient types would we want to avoid conducting A1C tests on for Diabetes Screening purposes?
-Gestational Diabetes
-Kids
-Suspected T1DM Pt's
-Anemic Pt's
-Hemoglobinopathy Pt's
50
A1C vs. FPG: Which one is better at predicting Cardiovascular Disease?
A1C
51
FPG vs. A1C vs. 2hr PG 75g OGTT tests: Which ones are costly?
A1C & 2hr PG are costly to conduct.
52
Over what length of time is A1C monitored for?
Previous 3mths
53
What exactly is A1C looking at?
% of Hemoglobin A that is irreversibly Glycosylated
54
What is a normal A1C?
4 - 6%
55
What processes tied to Erythropoiesis may raise one's A1C?
-Vit. B12 / Iron Deficiency
-Reduced Erythropoiesis
56
What processes tied to Erythropoiesis may decrease one's A1C?
-Use of Erythropoietin
-Supplementation with Iron / Vit. B12
-Chronic Liver Disease
57
Johnny is an elderly patient on low dose Aspirin for cardioprotection, as well as Vitamins C & E. How might his A1C percentage show up in lab readings (relative to normal percentages)?
DECREASED
-Vit. C & E, as well as Aspirin, contribute to a reduced A1C percentage.
58
Catherine recently underwent a surgical procedure that saw her Spleen get taken out. She is additionally Diabetic & requires regular monitoring of her A1C. She recently went in for a check-up & her Dr. noticed a spike in her A1C. In what direction (increased or decreased) would her A1C percentage likely move towards?
INCREASED
-Splenectomies can actually raise A1C counts.
59
Shivani is an elderly patient from India who was recently prescribed Dapsone (an Antibiotic) to treat a recent Leprosy diagnosis. She also presents with Rheumatoid Arthritis & is a Type II Diabetic. Her Dr. notices recent changes to her A1C in a recent checkup. How might those changes present (ie. Increased or Decreased A1C)?
DECREASED
-Dapsone usage & Rheumatoid Arthritis have shown to decrease A1C.
60
Philip is a Type II Diabetic in Palliative Care at St. Paul's. He has Chronic Kidney Failure due to old age, utilizes Fentanyl patches to mask excruciating back pain, and has recently been diagnosed with Hyperbilirubinemia due to a Gall Bladder blockade. If we compared his A1C from 15yrs ago to now, how might it present differently today?
INCREASED (GREATLY) !!!
-Hyperbilirubinemia, Chronic Opiate Use, & Chronic Renal Failure can all contribute to an elevated A1C.
61
The majority of Type I or Type II Diabetics should aim for an A1C of less than what?
< 7.0%
62
Kimmy is a 35yr old female patient who presents with Type II Diabetes. She has a currently measured A1C of 7.2 and no history of going Hypoglycemic since she was diagnosed 5yrs ago. She is about 35lbs overweight but is otherwise healthy in terms of clinically diagnosed conditions. What would be a realistic A1C target for her?
< 6.0 (as lifestyle modifications are a realistic goal of therapy and could even allow her to remiss to normoglycemia).
63
Corey is a 50yr old Type II Diabetic with an elevated A1C of 7.4. Although diagnostically rare, his mother and his brother Trevor have a history of Genetic Retinopathies. Knowing this information, what would be a realistic A1C target for Corey to try to obtain?
< 6.5 (as slightly more aggressive A1C targeting beyond 7.0 reduces the risk of CKD & Retinopathies greatly).
64
Gertrude is an elderly Type II Diabetic patient with Dementia and a history of recurrent fainting episodes due to going Hypoglycemic. What would be a realistic A1C target for her to achieve?
Between 7.1 - 8.5
65
An A1C of 5% equates to what average Blood Glucose readings?
97 mg / dL
5.4 mmol / L
66
An A1C of 6% equates to what average Blood Glucose readings?
126 mg / dL
7.0 mmol / L
67
An A1C of 7% equates to what average Blood Glucose readings?
154 mg / dL
8.6 mmol / L
68
An A1C of 8% equates to what average Blood Glucose readings?
183 mg / dL
10.2 mmol / L
69
An A1C of 9% equates to what average Blood Glucose readings?
212 mg / dL
11.8 mmol / L
70
An A1C of 10% equates to what average Blood Glucose readings?
240 mg / dL
13.4 mmol / L
71
An A1C of 11% equates to what average Blood Glucose readings?
269 mg / dL
14.9 mmol / L
72
An A1C of 12% equates to what average Blood Glucose readings?
298 mg / dL
16.5 mmol / L
73
What were the major findings of the 1993 DCCT trial for Type I Diabetics?
-Intensive targeting of an A1C of < 7.0 (via more frequented daily Insulin injections, increased Diabetes education & more frequented Dr. visits) led to a large decrease in the risk of patients experiencing Retinopathy, Neuropathy, & Microalbuminuria.
74
What were the major findings of the UKPDS Trials for Type II Diabetics?
-More aggressive A1C targeting of < 7.0% saw sustained relative risk reductions for suffering Microvascular-related complications even at 10yr follow-up.
-Obese patients on Metformin demonstrated decreased Macrovascular complication experiences.
75
What negative findings were discovered from the ACCORD Trial that caused it to be prematurely stopped at 3.5yrs?
-Further intensive targeting of an A1C of < 6% saw a substantial increase in the prevalence of all-cause death, as well as a greatly increased incidence of Hypoglycemia.
76
Propose a Self-Monitoring Blood Glucose strategy for somebody on solely NPH or Long-Acting Insulins.
-Once Daily before Breakfast (as these analogues are typically administered at bedtime).
77
Propose a Self-Monitoring Blood Glucose strategy for somebody on Premixed Insulins that are delivered prior to Breakfast & Supper (ie. BID).
-QID monitoring (ie. Prior to meals & bedtime) until Glycemic targets are met.
-Alternate BID monitoring once Glycemic targets are met.
78
Propose a Self-Monitoring Blood Glucose strategy for somebody on TID delivered RAA's or Bolus Insulins & a OD NPH or LAIA.
1) QID readings (ie. Prior to meals & bed).
2) QID readings with a focus on readings Post-Prandially.
3) Intensive Management with readings being taken prior to & after meals.
79
How do Real-Time Continuous Glucose Monitoring scanners differ from Intermittently Scanned CGM tools such as a Libra?
-Location (RTCGM on Abdomen / Upper Butt / Back of Arm... ISCGM on Back of Arm).
-Frequency of Scans (Every 5mins for RTCGM vs. Every 15mins for ISCGM).
-When to Replace Sensor (10d for Dexcom vs. 14d for Libra).
80
People with Diabetes should aim to have a "Time in Range" for approximately how many hours each day?
~17hrs (as this equates to 70% of the day spent in a desired Blood Glucose range of 3.9 - 10.0 mmol / L & is approximately equal to an A1C of 7%).
81
How does the desired "Time in Range" differ for those who are at high risk of suffering from Hypoglycemia or are elderly?
> 50% (which equates to >/= 12hrs / day spent in the desired 3.9 - 10.0 mmol / L target range).
82
If a patient presents with symptoms of DKA, is Pregnant, or is a Type I Diabetic with elevated Preprandial BG readings above 14mmol / L, what would be a more appropriate test to conduct as opposed to a BG reading?
Urine / Blood Ketone Testing
83
Examples of popular diets that can be used as lifestyle modification tools to treat Type I or Type II Diabetes include what?
-Mediterranean Diet
-Vegan / Vegetarian Diets
-Low Carb Diets
-DASH
-Intermittent Fasting
84
On average, what percentage of a typical Canadian's diet should be comprised of Carbohydrates?
45-60%
85
On average, what percentage of a typical Canadian's diet should be comprised of Proteins?
10-35%
86
On average, what percentage of a typical Canadian's diet should be comprised of Fats?
20-35%
87
For a 19-50yr old, what is the recommended DRI for Fibre intake?
W: 25g / day
M: 38g / day
88
For someone over the age of 50, what is the recommended DRI for Fibre intake?
W: 21g / day
M: 30g / day
89
Why must one subtract their Soluble Fibre from Total Carbohydrate counts?
-Because Soluble Fibre is a form of Carb that the body is unable to digest.
90
Why is it extremely important for Type I / Type II Diabetics to monitor their Alcohol consumption?
-Alcohol consumption can reduce Hepatic Glucose production & can mask Hypoglycemic symptoms.
91
How do Low-Intensity Aerobic exercises & High-Intensity Anaerobic exercises differ in terms of their effects on Blood Glucose concentrations?
Low Intensity: Reduces Blood Glucose (increases Insulin sensitivity).
High Intensity: Increases Blood Glucose (due to muscular demand increases & increased stress hormone secretion).
92
At what Blood Glucose levels should a Diabetic avoid exercising?
< 4mmol / L
93
Where was Insulin historically derived from?
Cow / Pig Pancreases
94
What was the 1st human Insulin analogue ever created ('82)?
Humulin
95
What RAIA's are commercially available?
Aspart (Brand Name = NovoRapid / Fiasp)
Glulisine (Brand Name = Apidra)
Lispro (Brand Name = Humalog)
Faster-Acting Aspart
96
What Short-Acting Insulins are commercially available?
Insulin Regular U-500 (Brand Name = Entuzity)
Insulin Regular (Brand Name = Humulin)
97
Onset, Peak & Duration of Action of Rapid Acting Insulin Analogues (RAIAs)?
O: 4-20mins
P: 0.5-2hrs
D: 3-5hrs
98
Onset, Peak & Duration of Action of Short-Acting Insulins?
O: 30mins
P: 2-3hrs
D: 6hrs
99
When should one take a Short Acting Insulin (ie. How long prior to a meal)?
30-45mins prior to meals.
100
When should one take a RAIA (ie. How long before a meal)?
0-15mins prior to meal (or within 15mins of beginning to eat).
101
What makes a RAIA better than a Short-Acting Insulin Analogue?
-Faster Onset of Action (4-20mins vs. 30mins)
102
T or F: RAIAs are more expensive than Short-Acting Insulin Analogues.
True!
103
How does Insulin Regular U-500 differ from Insulin Regular (ie. Humulin) in terms of its onset, peak, & duration of action?
O: 15mins (vs. 30mins)
P: 4-8hrs (vs. 2-3hrs)
D: 17-24hrs (vs. 6hrs)
104
How many times a day should Insulin Regular U-500 be delivered each day?
2-3x
105
The onset of action, peak, & duration of action of Intermediate-Acting Basal Insulin (ie. Insulin NPH) is what?
O: 1-3hrs
P: 5-8hrs
D: Up to 18hrs
106
The onset of action of the three Long-Acting Insulins (ie. Detemir, Glargine, Degludec) is what?
O: 90mins
107
The duration of action of U-100 Glargine is what?
D: 24hrs
108
The duration of action of U-100 Detemir is what?
D: 16-24hrs
109
The duration of action of U-300 Glargine is what?
D: >30hrs
110
The duration of action of U-100 & U-200 Degludec is what?
D: 42hrs
111
The onset, peak & duration of action of NPH Insulin is what?
O: 1-3hrs
P: 5-8hrs
D: Up to 18hrs
112
How often (per day) are NPH Insulins administered?
1-2x daily
113
Which Insulin appears cloudy?
NPH
114
What has made LAIAs more popular as of late than NPH Insulin?
-Lower risk of Hypoglycemia
-Narrowing price gap (even though LAIAs are slightly more expensive)
-Less Glucose variability
115
I'm on OD Lantus (ie. Glargine), dosed at 100U / mL. I'm planning on switching to either 300U / mL Glargine (Toujeo), 100U / mL Glargine (Basaglar), or Degludec (Tresiba). How would my dosing regimen change?
***It doesn't change!!!***
116
I'm on BID Lantus (ie. Glargine), dosed at 100U / mL. Of the following options (300U / mL Toujeo, 100U / mL Basaglar, Degludec), which one(s) require dose modifications if I switch across Insulin brands?
Switch from Lantus to Degludec: Reduce overall daily dosing by 20%...
117
What does an increasing Gauge Number mean in terms of Insulin Needle Thickness?
Larger Number = Thinner Needle... 32 Gauge will be thinner than 30 Gauge.
118
If I have an Insulin dose of
3/10 cc / mL
119
If I have an Insulin dose of 31-50U, what cc syringe should be used for injecting my Insulin?
1/2 cc / mL
120
If I have an Insulin dose of 51-100U, what cc syringe should be used for injecting my Insulin?
1 cc / mL
121
Why are Insulin Pens supplanting the previous injection technique of vials & syringes?
-Portable & more convenient to use
-Good for those who are visually impaired or lack dexterity
-More accurate dosing
122
What is the only form of Insulin that is continuously delivered via an Insulin Pump?
RAIAs
123
How often is the tubing of an Insulin Pump replaced?
Every 3d
124
What patient groups would benefit the most from utilizing an Insulin Pump?
-Poor BG ctrl with injections
-Great Glucose variability
-Frequent severe hypo episodes
-Pregnant
125
What are some of the more common Insulin side effects?
-Hypoglycemia (more frequently in those trying to achieve tight ctrl)
-Weight Gain (as it promotes Glucose uptake by cells, as well as protein & lipid synthesis)
-Local fat hypertrophy (can minimize by rotating sites)
-Initially blurred vision (can happen in 1st few wks starting)
126
What sorts of factors influence Insulin absorption?
-Exercising injection site (speeds up)
-Massaging injection site (speeds up)
-Temp (heat speeds it up)
-Hypertrophy of lipid tissues (slows it down)
-Dose itself (large = slowed down & prolonged action)
-Renal Function (Renal Failure reduces Insulin clearance so prolongs action)
-Depth of Injection (IV > IM > SC)
127
What are some examples of preferred Insulin injection sites?
-Belly / Abdomen
-Quadricep
-Tricep
-Obliques (along waistline)
128
When mixing a RAIA with an NPH Insulin, which one is drawn first?
-The RAIA is always drawn first!!!
129
Which Insulin type cannot be mixed in the same syringe as other Insulin forms?
***LAIAs***
-Short-Acting Insulins, RAIAs & Intermediate-Acting Insulins such as NPH can all be mixed together.
130
A typical initial Insulin dose for T1 Diabetics is what?
0.5 - 0.6U / kg
131
A typical Insulin dose for a T1 Diabetic who presents with either Ketosis or an Acute Illness is what?
0.5 - 1.0U / kg
132
A typical initial Insulin dose for a T2 Diabetic is what?
0.1U / kg
133
In terms of percentages, what is a typical Basal to Bolus Insulin split for somebody with T1DM?
Basal: 40-50%
Bolus: 50-60%
134
What would be considered a typical Carbohydrate to Insulin (C : I) ratio?
15 : 1 ratio
135
If my total daily dose of Insulin was 40U, what would be my estimated C : I ratio?
500 / 40
= 12.5
-Thus, (C : I) is going to be (12.5 : 1).
136
Conrad takes an average of 35U / day of Insulin. His premeal BG reading is at 11.4 mmol / L, but he desires a BG level of 5.5 mmol / L. The typical (C : I) ratio of (15 : 1) normally works for him. How many units of a RAIA would he need to take prior to a meal if he expected to eat 75g of CHO?
CF = 100 / 35 = 2.857 (this is Conrad's estimated correction factor)
[11.4mmol / L (CBG) - 5.5mmol / L (TBG)] / [2.857 (CF)] = 2.065U of RAIA
*As (15 : 1) works... (75g CHO in meal) / (15g CHO per U Insulin) = 5U baseline
*5U Baseline + 2U RAIA = 7U Total (in order to account for the CHO taken in during the meal & Conrad's CF).
137
1U of Insulin typically reduces BG by ~____ - ____ mmol / L.
2-3 mmol / L
138
Janice comes into your Pharmacy early Tuesday morning complaining of intense night sweats, a morning headache & intense appetite. Her Kroll profile states that she's a T1D patient on an Intermediate-Acting Insulin (NPH). What suggestions might you give her regarding her Insulin usage that could correct her experienced symptoms?
-Shifting Predinner Basal NPH to Bedtime (prevents Insulin peak from happening as she sleeps & shifts it to when she wakes up).
-Reducing Insulin dose.
-Could also consider taking a bedtime snack to prevent overnight blood sugar lows.
139
How does Metformin work as a diabetic medication?
-Decreases hepatic glucose production
-Enhances Insulin sensitivity
-Increases glucose utilization
-Gut microbiome effects (some AI effects)
140
I'm a diabetic patient beginning Metformin therapy. What is an appropriate starting dosage regimen?
250mg - 500mg OD
141
What is the desired usual dose for Metformin (ie. Once titration up is performed)?
850-1000mg BID (with a max dose of 850mg TID)
142
What is the brand name of extended release Metformin?
Glumetza (is for those with GI intolerances or issues)
143
We get the most "bang for our buck" at what daily dose of Metformin?
2g / day
144
Metformin reduces A1C by how many percent?
1 - 1.5% decrease
145
What additional benefits does Metformin have aside from lowering total A1C?
-Reduces TG & LDL by 8 - 15%.
-Trials have demonstrated that MI risk & total mortality decreases with its use in T2D who have obesity.
-Neutral to Modest effects on weight loss.
-Low hypo risk.
-Affordable.
146
Some important DI's with Metformin?
-***Alcohol (enhanced hypoglycemic effects)***
-Cimetidine
-Dolutegravir
-Contrast Media
147
Side effects of Metformin?
-GI upset (30% pt.'s)... Diarrhea, Nausea, Abdominal Discomfort.
-Metallic Taste (usually only a few wks).
-Vit. B12 deficiency with LT usage.
148
Explain how mechanistically Metformin can induce Lactic Acidosis.
-Inhibits the Hepatic conversion of Lactate into Glucose... Lactate accumulates in Serum & lowers arterial blood pH.
-Presents as: Weakness, Malaise, Myalgia, Labored Breathing.
149
If a patient is being put onto Metformin & has reduced eGFR, what should be done?
-Reduce the dose!!! Can become Lactic Acidosis, as Metformin is not metabolized to a different compound when it is eliminated... Reduced elimination means more drug accumulation in Serum.
150
Jean is currently on Metformin for her elevated BG. She has a recently discovered eGFR of 47mL / min & requires a dose change. What should be her new total daily intake of Metformin (provided she has no adverse GI side effects)?
1500mg / day
-eGFR of 45 - 59mL / min get a dose of 1500mg / day in divided doses.
151
Henry is currently on Metformin for his elevated BG. He has a recently discovered eGFR of 39mL / min & requires a dose change. What should be his new total daily intake of Metformin (provided he has no adverse GI side effects)?
1000mg / day
-eGFR of 30-44mL / min get a dose of 1000mg / day in divided doses.
152
If a patient on Metformin has an eGFR between 30 - 44mL / min, how often should their eGFR be checked?
Every 3 months
153
Below what eGFR would Metformin be contraindicated?
< 30mL / min
154
How do Sulfonylurea drugs work?
1) Enhance Insulin secretion by binding to SU receptors on Beta Cells.
2) K+ Channels close & Ca2+ Channels open, stimulating Insulin secretion.
155
Model Sulfonylurea drugs are...?
Glyburide
Gliclazide
Glimepiride
156
What is the usual dose of Glyburide?
5mg BID (minimal Glucose lowering effects past 10mg / day)
-Can be dosed up to 20mg / day.
157
Glyburide is CI at an eGFR of < ____ mL / min.
60mL / min
158
Usual dose of Gliclazide is what?
Regular: 80 - 160mg / day (80 = OD ; 160 = Delivered in BID div. doses)
MR: 30 - 120mg OD
159
Gliclazide is CI at an eGFR of < ____ mL / min.
30mL / min
160
Usual dose of Glimepiride is what?
1 - 8mg / day
161
Glimepiride is CI at an eGFR of < ____ mL / min.
30mL / min
162
Sulfonylurea drugs reduce A1C by how many percent?
1 - 1.5% decrease
163
Why are Sulfonylurea drugs such as Glimepiride, Glyburide & Gliclazide not as effective with progressed T2D patients?
-These drugs stimulate Insulin release... Progressed T2D's have defective responses to Insulin, as well as impairments to Insulin release from Beta Cells.
164
T or F: Sulfonylurea drugs have demonstrated cardioprotective effects.
False... Don't cause any harm but also evidence to support them as cardioprotective is inconclusive.
165
Order the three Sulfonylurea drugs (Glimepiride, Gliclazide, Glyburide) from most likely to least likely to induce hypoglycemia.
Glyburide (highest risk) > Glimepiride > Gliclazide (lowest risk)
166
If I'm a physician wanting to put an elderly patient on a Sulfonylurea drug, which one should I avoid?
Glyburide (as risk of going hypo on it is the highest of the three)
167
Aside from risk of going hypoglycemic, what other side effects can be demonstrated with those on Sulfonylurea drugs?
-Weight Gain (~2kg)
-Nausea
-Photosensitive Skin Rashes
-Cross Rxn with Sulfa Allergies (although very rare)
168
Which of the three Sulfonylurea drugs (Gliclazide, Glimepiride, Glyburide) is safe to give to pregnant women?
Glyburide (as it doesn't cross the Placenta).
-Gliclazide & Glimepiride both cross the Placenta & are thus CI!!!
169
Concurrent usage of what drugs with Sulfonylureas elevate the risk of going hypoglycemic?
-Sulfonamides
-Salicylates
-Warfarin
-Alcohol
-Cimetidine
-Clarithromycin
-Fluconazole
-NSAIDs
-Beta Blockers
-MAOIs
170
Which drugs reduce the blood sugar lowering effects of Sulfonylureas?
-Phenytoin
-Rifampin
-Colesevelam
171
Which class of drugs are sometimes referred to as Non-Sulfonylurea / Short-Acting Insulin Secretagogues?
Meglitinides
172
What is the model Meglitinde drug?
Repaglinide
173
What is the mechanism of action of Repaglinide?
-Binds sites adjacent to SU receptors, simulating Insulin secretion from Pancreas.
174
How does Repaglinide differ from Sulfonylurea drugs such as Glyburide?
-Faster OOA & Shorter DOA (reach peak levels in 1hr & 1/2 life of 1hr).
175
Repaglinide lowers A1C by how many percent?
1 - 1.5%
176
How do starting Repaglinide doses differ if:
-A1C < 8%?
-A1C > 8%?
A1C < 8%: 0.5mg before each meal + titrate up
A1C > 8%: 1-2mg before each meal + titrate up
177
Because of its short DOA, Repaglinide needs to be administered within ___ mins of a meal.
30mins
178
In terms of weight gain severity, which one has a more pronounced effect: Sulfonylureas or Meglitinides?
SU (~2kg) > Meglitinides (~0.3 - 1kg)
179
We caution Repaglinide usage in what group of patients?
Moderate Hepatic Impairment... CI in those with Severe Liver Disease.
180
Pick one statement: Carbamazepine & Rifampin (decrease / increase) levels of Repaglinide.
Decrease (!!!)
-These drugs are CYP 3A4 Inducers (so they enhance Repaglinide clearance).
181
Jennifer is on Clarithromycin for a bacterial infection & drinks a glass of grapefruit juice in the morning. She's also on Repaglinide for her diabetes management. Would the two other drugs increase or decrease her Repaglinide levels in the blood?
Increase (!!!)
-These drugs are CYP 3A4 Inhibitors (prevent Repaglinide from being cleared out of the body by the Liver).
182
Acarbose is classified as what type of a diabetic drug?
Alpha-Glucosidase Inhibitor
183
Describe the mechanism of action of Acarbose.
-Inhibits Alpha-Glucosidase enzymes in the SI... Thus, delays polysaccharide breakdown & Glucose absorption.
184
By how many percent does Acarbose typically lower A1C?
0.5 - 0.8% decrease
185
T or F: Acarbose has a pronounced effect on body weight & total lipid counts.
False (!!!)
-Has no effect on weight or lipid count.
186
Acarbose dosing should be initiated at what?
25-50mg OD
187
Once tolerance of Acarbose dosing is established, what should the dose be titrated up to?
50mg TID (max dose is 100mg TID)
188
What are the side effects of Acarbose?
-GI (Flatulence &/or Diarrhea, Bloating, Abdominal Pain)
-Can elevate ALT count
189
If we desire to correct a hypoglycemic episode for somebody on Acarbose, what sugar analogue should be given?
Glucose (as Sucrose digestion is impaired by Acarbose).
190
Acarbose is CI at an eGFR of < ___ mL / min & in those with ______ _____
________.
< 25mL / min ; Severe Liver Disease
191
We "caution" the use of Acarbose with those who have what conditions?
-IBD
-Other GI Conditions
192
The model Thiazolidinedione drugs are what?
Rosiglitazone & Pioglitazone
193
How do the Thiazolidinedione drugs work?
-Bind PPAR-Y receptors, which enhances Insulin sensitivity at muscles, fat, liver tissues.
194
Rosiglitazone & Pioglitazone lower A1C by how many percent?
1 - 1.5%
195
Rosi vs. Pioglitazone: What are their effects on Triglyceride count?
Rosi: None
Pio: Decrease by 10 - 20%
196
Rosi vs. Pioglitazone: What are their effects on LDL count?
Rosi: Increase by 5 - 15%
Pio: None
197
Rosi vs. Pioglitazone: What are their effects on HDL count?
Rosi: Increase (to some extent)
Pio: Increase (to some extent)
198
T or F: Lower dosed Pioglitazone (ie. 30mg) is just as effective as high dosed Pioglitazone (ie. 45mg) in obese patients.
False... Need high dose to see effect!
199
What do we initiate Rosiglitazone & Pioglitazone dosing at? What do we advance to once they're tolerated?
Rosi: 2-4mg OD ; 4mg BID or 8mg OD once tolerated.
Pio: 15mg OD ; 30-45mg OD once tolerated.
200
Maximum effects of Thiazolidinedione drugs is seen after how many months?
3mths
201
T or F: Thiazolidinedione drugs require dose adjustments in those who are renally impaired.
False! We caution use with eGFR < 60mL / min, but no dose adjustments required.
202
Janice is on Pioglitazone. She wants to know if the drug is eligible for EDS. What parameters must be met in order for it to be on the EDS list?
Must have tried a SU & Metformin first before it's an EDS eligible drug.
203
Gemfibrizol & TMP ______ the effects of Thiazolidinedione drugs. Rifampicin _______ the effects of Thiazolidinedione drugs.
increase (CYP 2C8 Inhibitors that reduce drug metabolism); decrease (CYP 2C8 Inducers that increase drug metabolism)
204
Why should Rosiglitazone and Pioglitazone not be used with Insulin?
-Increase risk of peripheral edema from 5% to 15%.
-Can increase risk of going hypoglycemic (as can SU combination).
205
What other side effects do the Thiazolidinedione drugs cause?
-New Onset / Worsening of Heart Failure (due to fluid retention)
-Weight gain (2.5 - 4.8kg)
-Increased distal fracture risk in postmenopausal women
206
Specific to Pioglitazone, what condition might a patient have that would require us to avoid its usage?
History of Bladder Cancer (may increase risk)
207
Due to results from a 2008 study on Rosiglitazone, what must all new diabetes medications be required to have?
-CV outcome trial (in order to demonstrate that the new drug isn't bad for the heart).
208
GLP-1 Receptor Agonists end in what?
"natide" (short-acting) or "glutide" (long-acting)
Exenatide
Lixisenatide
Liraglutide
Dulaglutide
Semaglutide
209
DPP4 Inhibitors end in what?
"gliptin"
Linagliptin
Sitagliptin
Saxagliptin
Aloglipitin
210
How do DPP4-i drugs work?
-Inhibit DPP4 enzyme, which itself is responsible for hydrolyzing Incretins. Thus, sensitivity to circulating endogenous incretins increases.
-Incretins themselves increase Insulin release & decrease Glucagon.
211
How quickly do DPP4-i drugs work?
Within wks (very quick)
212
By what A1C percentage do DPP4-i drugs drop it?
Around 0.7%
213
What are the recommended DPP4-i doses?
Sitagliptin: 100mg OD
Alogliptin: 25mg OD
Linagliptin: 5mg OD
Saxagliptin: 5mg OD
214
If a patient's eGFR falls between 30-44mL / min, how do we adjust dosing for DPP4-i drugs? If < 30mL / min?
30 - 44mL / min: Cut it in half!
< 30mL / min: Quarter it!
215
Do we need to titrate up DPP4-i doses?
Nope. Well tolerated at desired doses!
216
What are the common DPP4-i side effects?
Headache, Nasopharyngitis, URTI
217
Less common DPP4-i side effects?
-Hypersensitivity
-Bullous Pemphigoid
-Joint Pain
-Pancreatitis
218
Why do we want to avoid using DPP4-i drugs & GLP1RA's together?
Because their mechanisms of action are similar... Increases risk of Pancreatitis!
219
T or F: DPP4-i drugs are cardioprotective.
False! Have been shown that they are CV safe, but are NOT (!!!) cardioprotective.
220
Why are DPP4-i drugs favorable?
-Weight Neutral
-Low hypoglycemia risk
-Well tolerated
-OD dosing (convenient)
-No need for titration
221
Both DPP4-i drugs & GLP1RA's work similarly... What three processes do they affect?
1) Reduce Glucagon
2) Slow Gastric Emptying
3) Increase Satiety
222
Which of the GLP1RA's can you leave at room temperature for the least amount of time (14d)?
Dulaglutide & Lixisenatide
223
Which of the GLP1RA's can you leave either refrigerated or at room temperature for the longest amount of time (up to 8wks)?
Semaglutide
224
What are the short-acting GLP1RA's?
Exenatide
Lixisenatide
225
What are the long-acting GLP1RA's?
Liraglutide
Exenatide QW
Dulaglutide
Semaglutide
226
How does a Liraglutide dosing regimen differ from the other long-acting GLP1RA's?
Liraglutide: 0.6mg OD x 1wk, then 1.2 - 1.8mg OD.
-Others are dosed once weekly!!!
227
How does Exenatide dosing differ from Lixisenatide?
Exenatide: Take within 60mins of AM + PM meals.
Lixisenatide: Take 1hr prior to 1st meal of the day.
228
Why is Oral Semaglutide supposed to be taken whole (rather than split, crushed or chewed)?
-Protective SNAC encapsulation prevents stomach acid degradation from occurring.
229
By what A1C % do GLP1RA's reduce by?
1 - 1.5% (some evidence that SC Semaglutide is more potent at 1.8%)
230
Most common s/e's of GLP1RA's?
-NVD (up to 40%, with nausea being most prevalent of the three)
231
Nausea & Vomiting on GLP1RA's is generally mild and transient in nature... After how long do these symptoms typically resolve?
4-8wks
232
How do GLP1RA's affect one's weight?
-Often cause weight loss (~3kg), as heightened satiety & slowed gastric emptying lead to reduced food intake.
233
Because they slow gastric emptying, what sorts of drugs should be spaced out when one is on a GLP1RA?
Drugs requiring rapid GI absorption!
-Oral Contraceptives
-Antibiotics
-Narrow TI Drugs
234
SGLT2 Inhibitors end in what?
"gliflozin"
Dapagliflozin
Canagliflozin
Empagliflozin
235
Standard dosing of the SGLT2 Inhibitors?
Dapagliflozin: 5-10 mg OD
Empagliflozin: 10-25mg OD
Canagliflozin: 100-300mg OD
236
How do SGLT2 Inhibitor drugs work?
-Bind SGLT2 Transporters in the Kidneys, thereby reducing Glucose reabsorption & increasing urinary Glucose excretion.
237
T or F: SGLT2 Inhibitor patients have a heightened risk of going hypoglycemic.
False... No Insulin stimulation, so no hypoglycemic risk.
238
Average A1C reduction for those using SGLT2 Inhibitors as add-on therapies?
0.5 - 0.8% decrease
239
SGLT2 Inhibitors work on both ___ & ___, with effects on decreasing ___ occurring within 2wks.
FPG & PPG ; FPG
240
With what patient group would SGLT2 Inhibitors not work as well?
Those with poor renal function... Require functioning Nephrons to work!
241
SGLT2 Inhibitors cause an average of 2-3kg weight loss. However, the effects plateau at _____ wks.
26wks
242
How often are SGLT2 Inhibitors dosed?
OD
243
At an eGFR of ___ mL / min is when SGLT2 Inhibitors begin to lose effectiveness.
< 45 mL / min
244
Why can SGLT2 Inhibitors be continued down to Dialysis levels at their standard doses?
Because they infer cardio-renal protection to patients on them!
245
Most common side effects of SGLT2 Inhibitors?
-Increased urination & thirst
-Mycotic Genital Infections (more in Females)
-UTIs (high dose Dapagliflozin only)
-DKA
246
SGLT2 Inhibitors can also cause _________ ___________, as drops can reach 3-5mm Hg & 2mmHg.
Postural Hypotension
247
As there is a potential for inducing dehydration on SGLT2 Inhibitors, what sorts of patients should we caution their use with?
-Elderly
-Loop Diuretics / ACEi / ARBs
-Low SBP
-CKD
248
If a patient demonstrates DKA symptoms (ie. Breathing Difficulties, Thirst, NV, Confusion, Abdominal Discomfort), what should we do about SGLT2 use?
-Hold its use & check Ketone levels (irrespective of BG values).
249
Does Canagliflozin increase risk of amputations or bone fractures?
-Probably not, but we still caution their use in those with microvascular issues, amputative history, and in those with heightened fracture or fall risk.
250
How do SGLT2 Inhibitors exert Cardioprotective & Renal Benefits?
-Natriuresis & Glucosuria (which lowers pre-load & decreases pulmonary congestion / systemic edema).
-BP reductions.
-Stimulates renal erythropoietin secretion (which leads to new RBC production & improved O2 delivery).
-Reduce oxidative stress & local inflammation.
251
What is the one SGLT2 Inhibitor covered by the Sask Formulary that is indicated for Class II / III Heart Failure treatment?
Dapagliflozin
252
What is the initiating Basal Insulin dose given to T2DM patients beginning Insulin therapy?
10U hs
253
How might a T2D patient titrate up their Insulin dose in order to reach a FBG of 4-7mmmol / L?
1U hs or 1-2U q2-3 days until the target FBG of 4-7mmol / L is reached.
254
What sorts of events would suggest that Basal Insulin has reached its ceiling effect & a T2D patient requires additional drug therapies?
-Require > 0.5U / kg / day
-FBG is at target & A1C is still high
-2hr PPG > 3mmol / L higher than pre-meal reading
-Bedtime BG > 3mmol / L higher than morning FBG reading
255
New diabetes drug that acts as both a GIP and GLP1 dual Agonist?
Tirzepatide
256
How does Tirzepatide work?
-Enhances Insulin secretion in response to food & reduces Glucagon.
257
What is the standard initiating dose of Tirzepatide? What do we titrate up to?
I: 2.5mg SQ injection once weekly
T: Increments q4wks to max dose of 15mg once weekly
258
Common side effects of Tirzepatide?
-NVD
-Dyspepsia, Constipation, Abdominal Pain
-Increased hypo risk when added to SUs or Basal Insulins
259
Other considerations for somebody initiating Tirzepatide?
-On meds requiring immediate absorption (ie. OC's)?
-Pancreatitis / Pancreatic Cancer history? Gallbladder dx?
-HF patient? This drug can increase HR by 2-4bpm...
-Fainting history or hypovolemia? This drug can decrease SBP & DBP...
260
For women with Preexisting Diabetes who wish to become pregnant, what A1C should be targeted prior to conception?
< 7.0% (but push for < 6.5% if safe)
261
For women who are currently pregnant & have Preexisting Diabetes, what A1C percentage should be targeted?
< 6.5% (push for < 6.1% if safe)
262
What Antihyperglycemic medications would a pregnant T2D patient be safe to continually take in the 1st Trimester? Which agents (that are often part of diabetes medication therapies) should be discontinued?
C: Metformin, Glyburide, Insulin
D/C: ACEi / ARBS, Statins
263
What is the DOC for pregnant, preexisting T1 / T2DM patients?
Insulin! Metformin & Glyburide are alternatives for those unwilling to use Insulin.
264
How do the FPG & PPG readings differ between elderly T2DM patients who are functionally independent, functionally dependent, & those who are frail &/or have dementia?
Func Indep: 4-7mmol / L FPG ; 5-10mmol / L PPG
Fund Depen: 5-8mmol / L FPG ; < 12mmol / L PPG
Frail / Dementia: 6-9mmol / L FPG ; < 14mmol / L PPG
265
How do hypoglycemic symptoms present at BG levels < 4.0mmol / L?
-Trembling
-Palpitations
-Sweating
-Anxiety
-Hunger
-Nausea
-Tingling
266
How do hypoglycemic symptoms present at BG levels < 2.8mmol / L?
-Difficulty Concentrating
-Confusion
-Weakness
-Drowsiness
-Vision Changes
-Difficulty Speaking
-Headache
-Dizziness
267
How do we address hypoglycemia in order to prevent progression into severe hypoglycemia?
1) Recognition of autonomic or neuroglycopenic symptoms.
2) Confirm BG (ie. CBG, FGM, CGM).
3) Treat with fast sugars (15g fast-acting CHO).
4) Retest in 15mins to ensure BG > 4.0mmol / L (& retreat if necessary).
5) Eat within the hour (either meal or snack that includes starch & protein).
268
Treating hypoglycemic episodes with 15g of fast-acting CHO's raises BG by approximately ____ mmol / L within 20mins of treatment.
2mmol / L
269
What does the "5 to Drive" rule mean?
Waiting until BG > 5mmol / L before driving.
270
What are some examples of fast-acting CHO's (15g equivalents) that can be used to treat acute hypoglycemic episodes?
-4 Glucose tabs
-15mL sugar dissolved in water
-2/3 cup juice or pop
-6 LifeSavers
-15mL Honey
271
For somebody in a state of severe hypoglycemia (ie. < 2.8mmol / L BG), how many grams of CHO's should they be treated with?
20g Oral CHO (raises BG by ~3.5mmol / L over 45mins)
272
If a patient is unconscious & in a state of severe hypoglycemia, what must be done?
1) Treat with Glucagon (1mg IM or IV ; 3mg Nasal Spray)
2) Call 911
3) Roll patient into recovery position and eat when safe to do so
273
Metabolic Acidosis can often accompany DKA. How does it present clinically?
-NV / Abdominal Pain
-Air Hunger
-Fruity Acetone Breath
-Hyperventilation
-Confusion
274
How do we correct DKA?
1) Fluid Replacement (IV NaCl)
2) K+ Replacement (if < 5.5mmol / L) once Diuresis starts
3) Correcting Metabolic Acidosis (SAI admin)
4) Addition of NaHCO3 if in shock or pH < 7
275
What should be done if somebody comes in for DKA treatment & has K+ levels of < 3.3mmol / L?
Halt giving Insulin until levels exceed this concentration.
276
If a patient presents very high blood sugar, intense dehydration & minimal ketoacidosis, what condition might they have?
Hyperosmolar Hyperglycemic Syndrome (HHS)
277
DKA is considered to be an _______ Insulin Deficiency, whereas HHS is considered to be a ______ Insulin Deficiency.
Absolute ; Relative
278
A typical BG range of somebody with DKA is ___ mmol / L, whereas a typical BG range of somebody with HHS is ___ mmol / L.
14mmol / L (or higher) ; 34mmol / L (or higher)
279
T or F: Blood pH of somebody with HHS is abnormally low.
False! Ketones are unaffected, so no changes to blood pH.
280
DKA presents more commonly in T_DM patients, whereas HHS presents more commonly in T_DM patients.
1 ; 2
281
HHS symptoms last around _ days, whereas DKA symptoms last around _ days.
5 days ; 2 days
282
Regarding sick day management, how should diabetic patients alter their course of self-treatment?
-Potential increase in Total Daily Insulin (10-20%)
-Extra Glucose Free Fluids (to combat dehydration)
-Monitor BG more frequently (every 2-4hrs) & check for Ketones
283
What pneumonic is used in order to remember the drugs that should be held from sick day management?
SADMANS
284
BP target of Diabetic patients?
< 130 / 80
285
1st line drugs for hypertensive diabetic patients with CV risk factors?
ACEi / ARBs
286
What diabetic patient types are indicated to be on Statins?
-Over 40yrs
-Over 30yrs & DM duration over 15yrs
-Microvascular Disease
287
LDL-C target for Diabetics?
< 2.0mmol / L or > 50% reduction in LDL from current levels
288
1st line Dyslipidemia drug for Diabetics?
Statins (Atorvastatin 10-20mg ; Rosuvastatin 5-10mg)
-High Dose Statin (ie. Atorvastatin 40-80mg ; Rosuvastatin 20-40mg) if > 50yrs & multiple ASCVD risk factors.
289
Add-on therapies for Dyslipidemia when high dose Statin doesn't regulate LDL-C?
Ezetimibe
PCSK9 Inhibitor
290
Why is low dose Aspirin not recommended as a primary prevention measure for ASCVD?
Risk of Bleed >>> Modest CV Benefits
291
What are some risk factors of diabetic nephropathy?
-Longer duration Diabetes
-Poor BG / BP / Lipid Ctrl
-Obese
-Smoker
292
T or F: Retinopathic damage (unlike Nephropathic or Neuropathic damage) is reversible if caught early.
True!
