Therapy of Diabetes Flashcards
What is the leading cause of blindness and end-stage renal disease?
Diabetes Mellitus
What is the etiology of Type 1 Diabetes?
Autoimmune destruction of pancreatic β-cells
What is the etiology of Type 2 Diabetes?
Insulin resistance. with inadequate β-cell function to compensate
Insulin levels in Type 1 Diabetes?
Absent or negligible
Insulin levels in Type 2 Diabetes?
Higher than normal
Insulin action in Type 1 Diabetes?
Absent or negligible
Insulin action in Type 2 Diabetes?
Decreased
Is there insulin resistance in Type 1 Diabetes?
May be present if patient is obese
Age of onset in Type 1 Diabetes?
<30 years
Age of onset in Type 2 Diabetes?
> 40 years
Acute complications of Type 1 Diabetes?
1) Ketoacidosis
2) Wasting
Acute complications of Type 2 Diabetes?
Hyperglycemia =
1) Hyperosmotic seizures
2) Coma
Chronic complications of Type 1 Diabetes?
1) Neuropathy
2) Retinopathy
3) Nephropathy
4) Peripheral vascular disease
5) Coronary artery disease
Chronic complications of Type 2 Diabetes?
1) Neuropathy
2) Retinopathy
3) Nephropathy
4) Peripheral vascular disease
5) Coronary artery disease
Pharmacological intervention for Type 1 Diabetes?
Insulin
Which drugs can cause diabetes?
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
How does Pyriminil cause diabetes?
Loss of pancreatic β-cells
How does Pentamidine cause diabetes?
Cytotoxic effect on pancreatic β-cells (type 1)
How does Nicotinic acid (Niacin) cause diabetes?
Insulin resistance
How do Glucocorticoids cause diabetes?
1) Metabolic effects
2) Insulin antagonism
How do Thyroid hormones cause diabetes?
Increase hepatic glucose production
How does Growth hormone cause diabetes?
Reduces insulin sensitivity =
1) Mild hyperinsulinemia
2) Increased blood glucose levels
How does Diazoxide cause diabetes?
Inhibition of insulin secretion
How do β-adrenergic agonists cause diabetes?
1) Glycogenolysis
2) Gluconeogenesis
How do Thiazides cause diabetes?
Hypokalemia-induced inhibition of insulin release
How does Interferon cause diabetes?
β-cell destruction (type 1)
How does chronic alcoholism cause diabetes?
1) Insulin insensitivity
2) Pancreatic β-cell dysfunction
How does Cyclosporine cause diabetes?
1) Suppresses insulin production and release
2) Insulin resistance
How do HIV protease inhibitors cause diabetes?
Insulin resistance with insulin deficiency relative to hyperglucagonemia
How do Atypical antipsychotics (clozapine and olanzapine) cause diabetes?
1) Weight gain
2) Insulin resistance
How does Megestrol acetate cause diabetes?
Insulin resistance
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
Early diagnosis and treatment to near normoglycemia reduces the risk of developing:
Microvascular disease complications
Retinopathy, nephropathy, and neuropathy are ___(macro/micro)-vascular complications.
Microvascular
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
Ischemic heart disease, peripheral vascular disease, and cerebrovascular disease are ___(macro/micro)-vascular complications.
Macrovascular
How does hyperglycemia contribute to poor wound healing?
By compromising white blood cell function and altering capillary function
Which severe manifestations of poor diabetes control always require hospitalization?
1) Diabetic ketoacidosis (DKA)
2) Hyperosmolar hyperglycemic state (HHS)
HbA1c goal for males and non-pregnant females?
<7% or <6.5% without significant
hypoglycemia
Critically ill (Hospital) glucose goal?
140-180 mg/dL, or down to 110-140mg/dL (without hypoglycemia)
____ is recommended for all insulin resistant, overweight or obese individuals.
Weight reduction
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
In individuals with type 2 diabetes, ingested
protein appears to __(decrease/increase) insulin response without __(decreasing/increasing) plasma glucose concentrations.
Increase; Increasing
Should carbohydrate sources high in protein be used to treat or prevent hypoglycemia?
NO
Saturated fat should be ___ of total calories.
<7%
Avoid a high-protein diet in patients with:
Nephropathy
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.
Resistance/Strength training is recommended at least 2 times a week in patients without:
1) Proliferative diabetic retinopathy
2) Ischemic heart disease
It is NOT appropriate to give patients with DM:
Brief instructions and a few pamphlets
When should diabetes education occur?
1) At initial diagnosis
2) At ongoing intervals over a life-time
You should emphasize that diabetic complications can be prevented or minimized with:
1) Good glycemic control
2) Managing risk factors for CVD
Blood pressure goals in diabetics?
<140/<90
Initial drug therapy for hypertension in diabetics should be with:
ACEi or Angiotensin-receptor blocker (ARB)
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)
Use __ for secondary
cardioprotection in diabetics.
Aspirin
How should insulin be given to critically ill (hospitalized) diabetics?
IV insulin
How should insulin be given to non-critically ill diabetics?
Scheduled subcutaneous insulin with basal, nutritional, and correction coverage.
The aim of prevention of type 1 DM is:
To slow or stop its progression
What is Teplizumab?
A humanized monoclonal antibody to CD3 on T cells
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.
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
Which drugs are used for preventing Diabetes Mellitus?
1) Metformin
2) Rosiglitazone
3) Acarbose
4) Liraglutide
Which drug reduces the RISK of
developing type 2 DM?
Metformin
Which drug reduces the INCIDENCE of developing type 2 DM?
Rosiglitazone
Which drugs reduce the PROGRESSION of developing type 2 DM?
1) Acarbose
2) Liraglutide
Which DM patients always require insulin?
Type 1
Which insulin drugs are rapid acting?
1) Aspart
2) Lispro
3) Glulisine
4) Technosphere
Which insulin drugs are short acting?
Regular insulin
Which insulin drugs are intermediate acting?
NPH
Which insulin drugs are long acting?
1) Detemir
2) Glargine
3) Degludec
The simplest regimens that can approximate physiologic insulin release use:
“Split-mixed” injections
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
In “Split-mixed” injections, the morning intermediate-acting insulin dose provides:
1) Basal insulin during the day
2) Prandial coverage for the midday meal
In “Split-mixed” injections, morning intermediate-acting insulin dose provides:
Basal insulin throughout the evening and overnight
When are “split-mixed” injections acceptable?
When patients have fixed timing of meals and carbohydrate intake.
“Split-mixed” injections may NOT achieve good glycemic control overnight without causing:
Nocturnal hypoglycemia
How can we reduce nocturnal hypoglycemia in “Split-mixed” injections?
Moving the evening NPH dose to bedtime
Bolus or prandial insulin can be provided by either:
1) Regular insulin
2) Rapid-acting insulin analogs
The rapid onset and short duration of action of ___ more closely replicate normal physiology than does ___.
The rapid-acting insulin analogs; Regular insulin
Regular insulin is ___ insulin (____ insulin)
Soluble ;Crystalline zink
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
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
Insulin pump therapy may also be paired to ___.
Continuous glucose monitoring (CGM)
Insulin pumps require ____ and ____ than does a basal-bolus multiple daily injections regimen.
Greater attention to details; More frequent self-monitored blood glucose (SMBG)
Patients need ___ on how to use and maintain their Insulin pump.
Extensive training
All patients treated with insulin should be instructed how to recognize and treat ___.
Hypoglycemia
At each visit, patients with type 1 DM should be evaluated for __ including:
Hypoglycemia; The frequency and severity of hypoglycemic episodes
Hypoglycemic unawareness may result from:
1) Autonomic neuropathy
2) Frequent episodes of hypoglycemia
____ is a relative contraindication to continued intensive therapy.
The loss of warning signs of hypoglycemia
Patients who have ___ despite proper insulin dose may benefit from addition of the
amylinomimetic pramlintide.
Erratic postprandial glycemic control
___ suppresses endogenous production of glucose in the liver.
Amylin
Is Pramlintide a substitute for bolus insulin?
NO
Patients who have erratic postprandial glycemic control despite proper insulin dose may benefit from addition of the amylinomimetic ___.
Pramlintide
Pramlintide __(can/can’t) be mixed with insulin.
Can’t
When pramlintide is initiated, the dose of prandial insulin should be ____ to prevent hypoglycemia.
Reduced by 30 - 50%
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
Slowed gastric emptying from Pramlintide is mediated by which nerve?
Vagus
Adverse effects of Pramlintide?
1) Hypoglycemia
2) GIT disturbances
a) Nausea & Vomiting
b) Anorexia
Patients with HbA1c ≤ 7.5% are usually treated with:
Metformin
All patients with DM Type 2 should be treated with:
Therapeutic life-style modification
Symptomatic DM Type 2 patients may initially require treatment with:
Insulin or combination therapy
Patients with HbA1c > 7.5% but < 8.5% could be initially treated with:
1) A single agent
OR
2) Combination therapy
Patients with > 8.5% HbA1c will require:
1) Two agents
OR
2) Insulin
Obese patients without contraindications are often started on:
Metformin
Contraindications to Metformin?
1) Renal dysfunction
2) Congestive cardiac failure
3) Metabolic acidosis
4) Impaired hepatic function
Non-obese patients with Type 2 DM are more likely to be:
Insulinopenic
Non-obese patients with Type 2 DM need medications that do what?
Increase insulin secretion
Which medications are insulin secretagogues?
Sulfonylureas
Sulfonylureas have several potential drawbacks, including:
1) Weight gain
2) Hypoglycemia
Sulfonylureas may not be taken in patients with:
1) Liver disease
2) Kidney disease
Do Sulfonylureas produce a durable glycemic response?
NO
Which Sulfonylurea alternatives are better?
1) Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)
2) GLP-1 receptor agonists
Do Thiazolidinediones (TZDs) produce a durable glycemic response?
Yes
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
Duration of action of Sulfonylureas?
24 hours (Give once daily)
Duration of action of Non-sulfonyureas secretagogues?
2-3 hours
Duration of action of Biguanides (Metformin)?
6-12 hours (Give 3 times)
When do we reach the max effect of Thiazolidinediones?
4 weeks
Duration of action of GLP-1 receptor agonists / Incretin mimetics?
10 hours or 24 hours (Depending on the drug)
Duration of action of DPP-4 inhibitors?
24 hours (Once daily)
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
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
Which drugs are best for postprandial blood glucose regulation?
1) Glinides
2) α-glucosidase inhibitors
Which combination therapy will help arrest β-cell failure?
Thiazolidinediones (TZDs) + GLP-1 receptor agonists
(Metformin + Pioglitazone + Exenatide)
How do Thiazolidinediones help arrest β-cell failure?
By reducing apoptosis of β-cells
How do GLP-1 receptor agonists help arrest β-cell failure?
By augmenting pancreatic function
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
What degrades GLP-1?
Dipeptidyl peptidase-4 (DPP-4)
Which drugs are Glucagon-like peptide-1 agonists?
1) Exenatide
2) Liraglutide
3) Semaglutide
Which GLP-1 agonist can be given orally?
Semaglutide
What are Dual Agonists?
Drugs that activate both the Glucose-dependent Insulinotropic polypeptide (GIP) and GLP-1 receptors
Which drug is a Dual Agonist?
Tirzepatide
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
Which initial therapy is best for T2 DM without atherosclerotic cardiovascular disease?
Metformin
Which is used as second or third line therapy for T2 DM without atherosclerotic cardiovascular disease?
GLP-1 receptor agonists
Another use for GLP-1 receptor agonists and GIP/GLP-1 dual agonists?
Weight loss
What are the most common adverse reactions to GLP-1 receptor agonists?
GI side effects
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
All adverse effects of Exenatide?
1) Nausea, vomiting, diarrhea
2) Acute pancreatitis
3) Renal impairment and acute renal injury
Major adverse effect of Exenatide?
Nausea
Is Exenatide’s major side effect dose or time dependent?
Dose-dependent
Can Exenatide cause hypoglycemia?
No, unless combined with other drugs.
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
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
DPP-4 are enzymes that degrade:
Incretin hormones
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
Which drugs are DPP-4 Inhibitors?
1) Sitagliptin
2) Saxagliptin
3) Linagliptin
4) Alogliptin
Are DPP-4 Inhibitors given IV or orally?
Orally
DPP-4 Inhibitors’ dosage should be reduced in patients with:
Impaired renal function
Do DPP-4 Inhibitors reduce weight?
NO
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.
What is the FDA warning on DPP-4 Inhibitors?
Increased heart failure risk and severe joint pain
What is SGLT2?
The main transporter for glucose reabsorption in the proximal tubules (90%).
Which drugs are SGLT2 Inhibitors?
1) Canagliflozin
2) Dapagliflozin
How do SGLT2 Inhibitors decrease blood glucose levels?
By increasing urinary glucose loss
SGLT2 inhibitors benefits?
1) Protects kidneys
2) Reduce risk of heart disease
Mild adverse effects of SGLT2 inhibitors?
1) Thirst
2) Polyuria
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.
What is the FDA warning on SGLT2 Inhibitors?
Increased incidence of UGS infections
SGLT2 Inhibitors should not be used in patients prone to:
Diabetic ketoacidosis
When T2DM adolescents’ glycemic goals can NOT be achieved or maintained with metformin and sulfonylurea, what should you give them?
Insulin
Elderly patients may have an altered presentation of hypoglycemia because of:
Loss of autonomic nerve function with age
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
DPP-4 inhibitors or α-glucosidase inhibitors have __(high/low) risk of hypoglycemia.
Low
How should you treat Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States?
Insulin given by continuous IV infusion
It is important to stop which drug in all patients who arrive in acute care settings?
Metformin
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
