Therapy of Diabetes Flashcards
1
Q
What is the leading cause of blindness and end-stage renal disease?
A
Diabetes Mellitus
2
Q
What is the etiology of Type 1 Diabetes?
A
Autoimmune destruction of pancreatic β-cells
3
Q
What is the etiology of Type 2 Diabetes?
A
Insulin resistance. with inadequate β-cell function to compensate
4
Q
Insulin levels in Type 1 Diabetes?
A
Absent or negligible
5
Q
Insulin levels in Type 2 Diabetes?
A
Higher than normal
6
Q
Insulin action in Type 1 Diabetes?
A
Absent or negligible
7
Q
Insulin action in Type 2 Diabetes?
A
Decreased
8
Q
Is there insulin resistance in Type 1 Diabetes?
A
May be present if patient is obese
9
Q
Age of onset in Type 1 Diabetes?
A
<30 years
10
Q
Age of onset in Type 2 Diabetes?
A
> 40 years
11
Q
Acute complications of Type 1 Diabetes?
A
1) Ketoacidosis
2) Wasting
12
Q
Acute complications of Type 2 Diabetes?
A
Hyperglycemia =
1) Hyperosmotic seizures
2) Coma
13
Q
Chronic complications of Type 1 Diabetes?
A
1) Neuropathy
2) Retinopathy
3) Nephropathy
4) Peripheral vascular disease
5) Coronary artery disease
14
Q
Chronic complications of Type 2 Diabetes?
A
1) Neuropathy
2) Retinopathy
3) Nephropathy
4) Peripheral vascular disease
5) Coronary artery disease
15
Q
Pharmacological intervention for Type 1 Diabetes?
A
Insulin
16
Q
Which drugs can cause diabetes?
A
1) Pyriminil (Vacor) (rodenticide)
2) Pentamidine
3) Nicotinic acid (Niacin) (B3)
4) Glucocorticoids
5) Thyroid hormones
6) Growth hormone
7) Diazoxide
8) β-adrenergic agonists
9) Thiazides
10) Interferon
11) Chronic alcoholism
12) Cyclosporine
13) HIV protease inhibitors
14) Atypical antipsychotics (clozapine and olanzapine)
15) Megestrol acetate
17
Q
How does Pyriminil cause diabetes?
A
Loss of pancreatic β-cells
18
Q
How does Pentamidine cause diabetes?
A
Cytotoxic effect on pancreatic β-cells (type 1)
19
Q
How does Nicotinic acid (Niacin) cause diabetes?
A
Insulin resistance
20
Q
How do Glucocorticoids cause diabetes?
A
1) Metabolic effects
2) Insulin antagonism
21
Q
How do Thyroid hormones cause diabetes?
A
Increase hepatic glucose production
22
Q
How does Growth hormone cause diabetes?
A
Reduces insulin sensitivity =
1) Mild hyperinsulinemia
2) Increased blood glucose levels
23
Q
How does Diazoxide cause diabetes?
A
Inhibition of insulin secretion
24
Q
How do β-adrenergic agonists cause diabetes?
A
1) Glycogenolysis
2) Gluconeogenesis
25
How do Thiazides cause diabetes?
Hypokalemia-induced inhibition of insulin release
26
How does Interferon cause diabetes?
β-cell destruction (type 1)
27
How does chronic alcoholism cause diabetes?
1) Insulin insensitivity
2) Pancreatic β-cell dysfunction
28
How does Cyclosporine cause diabetes?
1) Suppresses insulin production and release
2) Insulin resistance
29
How do HIV protease inhibitors cause diabetes?
Insulin resistance with insulin deficiency relative to hyperglucagonemia
30
How do Atypical antipsychotics (clozapine and olanzapine) cause diabetes?
1) Weight gain
2) Insulin resistance
31
How does Megestrol acetate cause diabetes?
Insulin resistance
32
The primary goals of DM management are:
1) To reduce the risk of microvascular and macrovascular disease complications
2) To ameliorate symptoms
3) To reduce mortality
4) To improve quality of life
5) To minimize weight gain and hypoglycemia
33
Early diagnosis and treatment to near normoglycemia reduces the risk of developing:
Microvascular disease complications
34
Retinopathy, nephropathy, and neuropathy are ___(macro/micro)-vascular complications.
Microvascular
35
What should you do to reduce the risk of developing macrovascular disease?
Aggressive management of cardiovascular risk factors:
1) Smoking cessation
2) Treatment of dyslipidemia
3) Intensive blood pressure control
4) Antiplatelet therapy
36
Ischemic heart disease, peripheral vascular disease, and cerebrovascular disease are ___(macro/micro)-vascular complications.
Macrovascular
37
How does hyperglycemia contribute to poor wound healing?
By compromising white blood cell function and altering capillary function
38
Which severe manifestations of poor diabetes control always require hospitalization?
1) Diabetic ketoacidosis (DKA)
2) Hyperosmolar hyperglycemic state (HHS)
39
HbA1c goal for males and non-pregnant females?
<7% or <6.5% without significant
hypoglycemia
40
Critically ill (Hospital) glucose goal?
140-180 mg/dL, or down to 110-140mg/dL (without hypoglycemia)
41
____ is recommended for all insulin resistant, overweight or obese individuals.
Weight reduction
42
What plans are available for medical nutrition therapy?
1) Low-carbohydrate, low-fat, calorie-restricted diets
2) Mediterranean diets rich in
mono-unsaturated fatty acids (olive oil)
3) Healthier eating behaviors
43
In individuals with type 2 diabetes, ingested
protein appears to __(decrease/increase) insulin response without __(decreasing/increasing) plasma glucose concentrations.
Increase; Increasing
44
Should carbohydrate sources high in protein be used to treat or prevent hypoglycemia?
NO
45
Saturated fat should be ___ of total calories.
<7%
46
Avoid a high-protein diet in patients with:
Nephropathy
47
How should physical activity goals be carried out?
At least 150min/wk of moderate intensity exercise spread over at least 3 days/week with no more than 2 days off between activities.
48
Resistance/Strength training is recommended at least 2 times a week in patients without:
1) Proliferative diabetic retinopathy
2) Ischemic heart disease
49
It is NOT appropriate to give patients with DM:
Brief instructions and a few pamphlets
50
When should diabetes education occur?
1) At initial diagnosis
2) At ongoing intervals over a life-time
51
You should emphasize that diabetic complications can be prevented or minimized with:
1) Good glycemic control
2) Managing risk factors for CVD
52
Blood pressure goals in diabetics?
<140/<90
53
Initial drug therapy for hypertension in diabetics should be with:
ACEi or Angiotensin-receptor blocker (ARB)
54
What lifestyle modifications should be done for dyslipidemia?
1) Reduction of saturated fat and cholesterol intake
2) Increasing omega-3 fatty acids intake
3) Use of viscous fiber and plant sterols
4) Weight loss
5) Increased physical activity
6) Statins (according to risk)
55
Use __ for secondary
cardioprotection in diabetics.
Aspirin
56
How should insulin be given to critically ill (hospitalized) diabetics?
IV insulin
57
How should insulin be given to non-critically ill diabetics?
Scheduled subcutaneous insulin with basal, nutritional, and correction coverage.
58
The aim of prevention of type 1 DM is:
To slow or stop its progression
59
What is Teplizumab?
A humanized monoclonal antibody to CD3 on T cells
60
Teplizumab is the first FDA approved drug that:
Mildly delays the onset of type 1 DM in patients 8 years of age or older with preclinical disease.
61
The “4 life-style pillars” for the prevention of type 2 diabetes are to:
1) Decrease weight
2) Increase aerobic exercise
3) Increase fiber in diet
4) Decrease fat intake
62
Which drugs are used for preventing Diabetes Mellitus?
1) Metformin
2) Rosiglitazone
3) Acarbose
4) Liraglutide
63
Which drug reduces the RISK of
developing type 2 DM?
Metformin
64
Which drug reduces the INCIDENCE of developing type 2 DM?
Rosiglitazone
65
Which drugs reduce the PROGRESSION of developing type 2 DM?
1) Acarbose
2) Liraglutide
66
Which DM patients always require insulin?
Type 1
67
Which insulin drugs are rapid acting?
1) Aspart
2) Lispro
3) Glulisine
4) Technosphere
68
Which insulin drugs are short acting?
Regular insulin
69
Which insulin drugs are intermediate acting?
NPH
70
Which insulin drugs are long acting?
1) Detemir
2) Glargine
3) Degludec
71
The simplest regimens that can approximate physiologic insulin release use:
“Split-mixed” injections
72
What do “Split-mixed” injections consist of?
1) A morning dose of an intermediate-acting insulin (NPH)
2) A “bolus” rapid-acting insulin or regular insulin prior to the morning and evening meals
73
In "Split-mixed” injections, the morning intermediate-acting insulin dose provides:
1) Basal insulin during the day
2) Prandial coverage for the midday meal
74
In "Split-mixed” injections, morning intermediate-acting insulin dose provides:
Basal insulin throughout the evening and overnight
75
When are "split-mixed" injections acceptable?
When patients have fixed timing of meals and carbohydrate intake.
76
"Split-mixed" injections may NOT achieve good glycemic control overnight without causing:
Nocturnal hypoglycemia
77
How can we reduce nocturnal hypoglycemia in "Split-mixed" injections?
Moving the evening NPH dose to bedtime
78
Bolus or prandial insulin can be provided by either:
1) Regular insulin
2) Rapid-acting insulin analogs
79
The rapid onset and short duration of action of ___ more closely replicate normal physiology than does ___.
The rapid-acting insulin analogs; Regular insulin
80
Regular insulin is ___ insulin (____ insulin)
Soluble ;Crystalline zink
81
What is the most sophisticated and precise method for insulin delivery?
Continuous subcutaneous insulin infusion (CS-II) or insulin pumps using a rapid-acting insulin
82
Advantages of pairing Insulin pump therapy with Continuous glucose monitoring (CGM)?
1) Allows calculation of a correct insulin dose
2) Alerts the patient to hypoglycemia and hyperglycemia
83
Insulin pump therapy may also be paired to ___.
Continuous glucose monitoring (CGM)
84
Insulin pumps require ____ and ____ than does a basal-bolus multiple daily injections regimen.
Greater attention to details; More frequent self-monitored blood glucose (SMBG)
85
Patients need ___ on how to use and maintain their Insulin pump.
Extensive training
86
All patients treated with insulin should be instructed how to recognize and treat ___.
Hypoglycemia
87
At each visit, patients with type 1 DM should be evaluated for __ including:
Hypoglycemia; The frequency and severity of hypoglycemic episodes
88
Hypoglycemic unawareness may result from:
1) Autonomic neuropathy
2) Frequent episodes of hypoglycemia
89
____ is a relative contraindication to continued intensive therapy.
The loss of warning signs of hypoglycemia
90
Patients who have ___ despite proper insulin dose may benefit from addition of the
amylinomimetic pramlintide.
Erratic postprandial glycemic control
91
___ suppresses endogenous production of glucose in the liver.
Amylin
92
Is Pramlintide a substitute for bolus insulin?
NO
93
Patients who have erratic postprandial glycemic control despite proper insulin dose may benefit from addition of the amylinomimetic ___.
Pramlintide
94
Pramlintide __(can/can't) be mixed with insulin.
Can't
95
When pramlintide is initiated, the dose of prandial insulin should be ____ to prevent hypoglycemia.
Reduced by 30 - 50%
96
Effects of Pramlintide?
1) Slows gastric emptying mediated by the vagus nerve
2) Reduces glucagon secretion
3) Promotes satiety or reduces appetite - centrally
4) Produces moderate weight loss
97
Slowed gastric emptying from Pramlintide is mediated by which nerve?
Vagus
98
Adverse effects of Pramlintide?
1) Hypoglycemia
2) GIT disturbances
a) Nausea & Vomiting
b) Anorexia
99
Patients with HbA1c ≤ 7.5% are usually treated with:
Metformin
100
All patients with DM Type 2 should be treated with:
Therapeutic life-style modification
101
Symptomatic DM Type 2 patients may initially require treatment with:
Insulin or combination therapy
102
Patients with HbA1c > 7.5% but < 8.5% could be initially treated with:
1) A single agent
OR
2) Combination therapy
103
Patients with > 8.5% HbA1c will require:
1) Two agents
OR
2) Insulin
104
Obese patients without contraindications are often started on:
Metformin
105
Contraindications to Metformin?
1) Renal dysfunction
2) Congestive cardiac failure
3) Metabolic acidosis
4) Impaired hepatic function
106
Non-obese patients with Type 2 DM are more likely to be:
Insulinopenic
107
Non-obese patients with Type 2 DM need medications that do what?
Increase insulin secretion
108
Which medications are insulin secretagogues?
Sulfonylureas
109
Sulfonylureas have several potential drawbacks, including:
1) Weight gain
2) Hypoglycemia
110
Sulfonylureas may not be taken in patients with:
1) Liver disease
2) Kidney disease
111
Do Sulfonylureas produce a durable glycemic response?
NO
112
Which Sulfonylurea alternatives are better?
1) Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)
2) GLP-1 receptor agonists
113
Do Thiazolidinediones (TZDs) produce a durable glycemic response?
Yes
114
Why is Thiazolidinedione (TZDs) use limited?
Because they can cause:
1) Weight gain
2) Osteoporosis
3) Fluid retention
4) Risk of new onset heart failure
115
Duration of action of Sulfonylureas?
24 hours (Give once daily)
116
Duration of action of Non-sulfonyureas secretagogues?
2-3 hours
117
Duration of action of Biguanides (Metformin)?
6-12 hours (Give 3 times)
118
When do we reach the max effect of Thiazolidinediones?
4 weeks
119
Duration of action of GLP-1 receptor agonists / Incretin mimetics?
10 hours or 24 hours (Depending on the drug)
120
Duration of action of DPP-4 inhibitors?
24 hours (Once daily)
121
Treatment selection for DM Type 2 should be based on multiple factors:
1) A patient who has had diabetes for several years, due to progressive failure of β-cell
function, is more likely to require insulin therapy
2) Multiple co-morbidities
3) If the patient’s fasting blood glucose readings are consistently elevated or only fluctuate postprandially.
4) Adverse effect profile
5) Contraindications
6) Hypoglycemia potential
7) Effect on body weight
8) Tolerability by the patient
9) Cost
10) Motivation
11) Resources
12) Potential difficulties with adherence
13) Older age
122
What should you do if the patient’s postprandial blood glucose readings are the primary reason for poor control?
Pick a medication that addresses postprandial blood glucose fluctuations
123
Which drugs are best for postprandial blood glucose regulation?
1) Glinides
2) α-glucosidase inhibitors
124
Which combination therapy will help arrest β-cell failure?
Thiazolidinediones (TZDs) + GLP-1 receptor agonists
(Metformin + Pioglitazone + Exenatide)
125
How do Thiazolidinediones help arrest β-cell failure?
By reducing apoptosis of β-cells
126
How do GLP-1 receptor agonists help arrest β-cell failure?
By augmenting pancreatic function
127
What does GLP-1 do?
1) Enhances insulin release in response to an ingested meal
2) Suppresses glucagon secretion
3) Delays gastric emptying
4) Decreases appetite
128
What degrades GLP-1?
Dipeptidyl peptidase-4 (DPP-4)
129
Which drugs are Glucagon-like peptide-1 agonists?
1) Exenatide
2) Liraglutide
3) Semaglutide
130
Which GLP-1 agonist can be given orally?
Semaglutide
131
What are Dual Agonists?
Drugs that activate both the Glucose-dependent Insulinotropic polypeptide (GIP) and GLP-1 receptors
132
Which drug is a Dual Agonist?
Tirzepatide
133
Which initial therapy is best for T2 DM with or at high risk for atherosclerotic cardiovascular disease?
GLP-1 receptor agonists, with or without metformin
134
Which initial therapy is best for T2 DM without atherosclerotic cardiovascular disease?
Metformin
135
Which is used as second or third line therapy for T2 DM without atherosclerotic cardiovascular disease?
GLP-1 receptor agonists
136
Another use for GLP-1 receptor agonists and GIP/GLP-1 dual agonists?
Weight loss
137
What are the most common adverse reactions to GLP-1 receptor agonists?
GI side effects
138
Exenatide effects?
1) Delays gastric emptying
2) Suppresses postprandial glucagon release
3) Increases insulin secretion in a glucose dependent manner
4) Increases beta-cell mass, from decreased beta-cell apoptosis
5) May increase beta-cell formation
6) Suppresses appetite
7) Weight loss
139
All adverse effects of Exenatide?
1) Nausea, vomiting, diarrhea
2) Acute pancreatitis
3) Renal impairment and acute renal injury
140
Major adverse effect of Exenatide?
Nausea
141
Is Exenatide's major side effect dose or time dependent?
Dose-dependent
142
Can Exenatide cause hypoglycemia?
No, unless combined with other drugs.
143
How should insulinopenic patients with T2 DM be given meds?
1) Insulin injections at bedtime (intermediate- or long-acting basal insulin)
2) Oral agents or GLP-1 receptor agonists for control during the day
144
Modification of therapy for insulinopenic T2 DM patients should depend on:
1) Fasting and posprandial glucose monitoring
2) HbA1c monitoring
3) Times of development of hypoglycemia
145
DPP-4 are enzymes that degrade:
Incretin hormones
146
Effects of DPP-4 Inhibitors?
1) Prolong the half-life of endogenous GLP-1
2) Decrease postprandial glucose levels
3) Decrease glucagon concentration
4) Increase circulating GLP-1 and GIP and thus, insulin concentrations in a glucose-dependent manner
147
Which drugs are DPP-4 Inhibitors?
1) Sitagliptin
2) Saxagliptin
3) Linagliptin
4) Alogliptin
148
Are DPP-4 Inhibitors given IV or orally?
Orally
149
DPP-4 Inhibitors' dosage should be reduced in patients with:
Impaired renal function
150
Do DPP-4 Inhibitors reduce weight?
NO
151
Adverse effects of DPP-4 Inhibitors?
1) Nasopharyngitis
2) URTIs
3) Headaches
4) Hypoglycemia when combined with insulin secretagogues or insulin.
5) Acute pancreatitis
6) Allergic reactions (Angioedema)
7) GIT: Nausea, diarrhea, and abdominal pain.
152
What is the FDA warning on DPP-4 Inhibitors?
Increased heart failure risk and severe joint pain
153
What is SGLT2?
The main transporter for glucose reabsorption in the proximal tubules (90%).
154
Which drugs are SGLT2 Inhibitors?
1) Canagliflozin
2) Dapagliflozin
155
How do SGLT2 Inhibitors decrease blood glucose levels?
By increasing urinary glucose loss
156
SGLT2 inhibitors benefits?
1) Protects kidneys
2) Reduce risk of heart disease
157
Mild adverse effects of SGLT2 inhibitors?
1) Thirst
2) Polyuria
158
Severe adverse effects of SGLT2 inhibitors?
1) Increased incidence of UGS infections
2) Intravascular volume contraction and hypotension = osmotic diuresis
3) Decreased bone mineral density at the lumbar spine and the hip
4) Fractures due to osteoporosis and/or falls secondary to hypotension.
159
What is the FDA warning on SGLT2 Inhibitors?
Increased incidence of UGS infections
160
SGLT2 Inhibitors should not be used in patients prone to:
Diabetic ketoacidosis
161
When T2DM adolescents' glycemic goals can NOT be achieved or maintained with metformin and sulfonylurea, what should you give them?
Insulin
162
Elderly patients may have an altered presentation of hypoglycemia because of:
Loss of autonomic nerve function with age
163
Which drugs are best for T2 DM in the elderly?
1) DPP-4 inhibitors (Sitagliptin)
2) Shorter-acting insulin secretagogues (rapaglinide)
3) Low-dose sulfonylureas
4) α-glucosidase inhibitors
164
DPP-4 inhibitors or α-glucosidase inhibitors have __(high/low) risk of hypoglycemia.
Low
165
How should you treat Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States?
Insulin given by continuous IV infusion
166
It is important to stop which drug in all patients who arrive in acute care settings?
Metformin
167
Metformin should be discontinued temporarily after any major surgery until it is clear that the patient:
1) Is hemodynamically stable
2) Has normal renal function
