Diabetes Mellitus

Question 1

Pancreatic Hormones

Answer 1

α - cells = Glucagon
β - cells = Insulin, Amylin
δ - cells = Somatostatin

Produced in Islets of Langerhams

Question 2

Insulin Hormones

Answer 2

Storage Hormone
Promotes glucose uptake, Glucose usage
Results to Glycogenesis?
Type 3 receptor (enzyme-linked) - tyrosine kinase

Question 3

Glucagon

Answer 3

Increase hepatic glucose input
Results to Glycogenolysis

Question 4

Type 1 DM

Answer 4

Absolute deficiency on insulin due to β-cells destruction

Insulin-Dependent DM

Question 5

Type II DM

Answer 5

Inadequate secretion of insulin for β-cells
Insulin resistance (decrease sensitivity of insulin receptors)

Question 6

Goals of Therapy for DM

Answer 6

• Control hyperglycemia
• Inc. insulin secretion
• Enhance insulin action
• Delay carbohydrate absorption
• Enhance excretion of glucose

Question 7

Secretagogues

Answer 7

A. Insulin
B. Sulfonylurea Drugs (OHAs)
C. Meglitinides

Question 8

Insulin

Answer 8

Rapid-Acting
* Insulin Lispro
* Insulin Aspart
* Insulin Glulisine

Short-Acting
* Regular Insulin (Humulin-R®)
* Semi-Lente

Intermediate-Acting
* Neutral Potamine Hagedorn (Isophane Insulin)
* Lente (30% semilente, 70% ultralente)

Long-Acting
* Insulin Glargine
* Insulin Detemir
* Insulin Levemir
* Insulin Degludec
* Ultralente

Question 9

Rapid-Acting Insulin

Answer 9

SQ
5 min before meals
Rapid onset of action in 5-15 minutes

Question 10

Short-Acting Insulin

Answer 10

SQ/IV; 20 min before meals
USES:To prevent Postprandial Hyperglycemia

Question 11

Intermediate-acting insulin:

Answer 11

AM - 2/3 of the dose
PM - 1/3 of the dose

Question 12

Long-acting insulin

Answer 12

SQ, OD

Insulin Glargine (peak-less insulin) - has a character release pattern that shows no peak & a plateau serum insulin level that is maintained for about 24 hours

Question 13

Sulfonylureas (OHAs)

Answer 13

First Generation:
* Chlorpropamide - longest t1/2
* Tolbutamide - most cardiotoxic
* Acetahexamide
* Tolazamide - safest for elderly

Less Potent, More side effects
SE: Disulfiram-like reaction

2nd generation
* Glibenclamide (Euglucon®)
* Glipizide (Minidiab®)
* Gliclazide (Diamicron®)
* Glimepiride (Solosa®)

More potent
Once daily dosing

Question 14

MOA of Sulfonylureas

Answer 14

Block potassium channels (ATP-sensitive channels), resulting to β-cell depolarization and insulin release

A/E: Weight Gain, Hypoglycemia

Question 15

Meglitinides

Answer 15

Repaglitide (Prandin®, Novonorm®)
Nateglitide (Starlix®)

Question 16

Controls postprandial glycemia (taken before meals)

Answer 16

Meglitinides
* Repaglinide
* Nateglinide

Question 17

MOA of Meglitinides

Answer 17

Inhibiting ATP-Sensitive Potassium Channels

Question 18

Insulin Sensitizers

Answer 18

Biguanides
* Metformin

Thiazolidinedione - must not be given to patient w/ CHF (ClassIII-IV)
* Rosiglitazone (Avandia®) - risk of cardiovascular mortality
* Pioglitazone (Actos®) - bladder cancer
* Troglitazone

Question 19

1st line initial treatment of type 2 DM esp. among obese patients

Answer 19

Metformin

Only biguanide type of oral antidiabetic

Question 20

MOA of Metformin

Answer 20

Liver: Reduce Hepatic Gluconeogenesis
Adipose Tissue & Muscle: Increase Glucose Uptake/usage

Question 21

A/Es of Metformin

Answer 21

Weight loss
Diarrhea
Lactic acidosis (Rare)

Advantage: Less hypoglycemia

CI: Chronic Alcoholics, Renal Failure, Hepatitis

Question 22

MOA of Thiazolidinediones

Answer 22

Regulates gene expression by binding to PPAR- γ
Activate PPAR ( Peroxisome Proliferator-acting receptor ) , Gamma → Increases transcription of insulin-responsive genes

Adjunct only, not first line

Question 23

Adverse effects of Thiazolidinediones

-glitazone

Answer 23

Edema (Contraindicated to CHF)
Weight Gain
Hepatotoxicity

Question 24

Alpha-glucosidase Inhibitors

Answer 24

Acarbose (Glucobay®, Gluconase®)
Voglibose (Basen®)
Miglitol (Glyset®)

Question 25

MOA of α-glucosidase Inhibitors

Answer 25

Inhibit intestinal α-glucosidases responsible for the breakdown of complex polysaccharides & sucrose into asbsorbable monosaccharides

May be given to Type 1 DM patients as a combination therapy with Insulin

Question 26

S/E of α-glucosidase Inhibitors

Answer 26

Diarrhea
Flatulence
Abdominal Bloating

Question 27

Glucose Reabsorption Inhibitors

Answer 27

Canagliflozin
Dapaglifozin
Empaglifozin

Question 28

MOA of Glucose Reabsorption Inh

-gliflozin

Answer 28

Blocks Sodium Glucose Cotransporter 2 Inhibitor (SGLT2) → reabsorption of glucose from the kidney is decreased, renal excretion of glucose is increased, and blood glucose levels are lowered

Question 29

Adverse Effects of Glucose Reabsorption Inhibitors

Answer 29

UTI
Dehydration
Genital yeast infection

Question 30

Incretin Hormone

Answer 30

t50 = 2 mins
Degraded by peptidyl dipeptidase 4 (DPP 4)

Question 31

Actions of Incretin

Answer 31

Increase Insulin Secretions, glucose uptake
Decrease glucagon secretions, Gastric emptying

Question 32

GLP-1 analogue (Glucagon-like peptide-1)

Answer 32

Exenatide (Byetta®)
Liraglutide

A/E: Weight loss, Nausea, Risk of pancreatitis in px with high VLDL

Question 33

DPP-4 inhibitor (Dipeptide peptidase IV)

Answer 33

Sitagliptin (Januvia®)
Alogliptin

A/E: Less weight loss, suited for older patients

Question 34

DPP-4 inhibitor (Dipeptide peptidase IV)

Answer 34

Co-secreted with insulin by pacreatic β-cells in response to elevated blood glucose levels

Dec. gastric emptying, suppression of glucagon secretion, dec. appetite

Question 35

Amylin mimetic

Answer 35

Pramlintide acetate
Synthetic analog of human amylin

Question 36

Pramlintide acetate

Answer 36

Slows the rate at which food is delivered from stomach to intestine
A/E: Anorexia, Wt. loss, Inc risk of hypoglycemia

Question 37

Dopamine Agonist

Answer 37

Bromocriptine

Question 38

Treatment of hyperprolactinemia and Parkinson’s Disease

Answer 38

Dopamine Agonist
Bromocriptine (Cycloset)

Taken within 2 hrs after wakiing in the morning
Taken w/ food