Tx of Diabetes

Question 1

Type 1 DM

Answer 1

AI disease
Lack of endogenous insulin

replace insulin

Question 2

Type 2 DM

Answer 2

Noninsulin dependent diabetes
b cells desensitized to glucose challenge
peripheral tissues resistant to insulin actions

improve insulin sensitivity at early stages and replace insulin in later stages

Question 3

Type 3 DM

Answer 3

non pancreatic causes

Drugs impair glucose tolerance- corticosteroids, thiazides, oral contraceptives

Question 4

Type 4 DM

Answer 4

gestational

Question 5

Goals of treatment of DM

Answer 5

Treat hyperglycemia to avoid long term complications
-fasting glucose 90-120 mg/dl
2 hr post prandial- below 150 mg/dl
HbA1c- below 7%

Question 6

Insulin

Answer 6

51 AA peptide
Two peptide chains linked by disulfied bond
Preproinsulin>proinsulin> insulin + free C peptide

Acts in liver, muscle, and adipose tissues to decrease blood glucose levels and shift from energy use to storage
-Acts through stimulation of tyrosine kinase receptor

Question 7

Insulin secretion and effects

Answer 7

Stimulated by increase ATP/ADP ratio which is modulated by glucose, AA, FA, parasympathetic activity

Glucose causes Increase in ATP which closes the K+ channel in the islet cell, stopping K efflux and depolarizing the cell (glucose is low, cell is hyperpolarized). Depolarizing cell will signal Ca++ influx which causes exocytosis of insulin

Question 8

Sulfonyl urea drugs

Answer 8

Block K+ channels and depolarize islet cells, causing Ca++ influx and insulin vesicle release

Question 9

Exogenous insulin

Answer 9

Subq administration- allowing for slower absorption
Tailored to pts activity and diet
AE: hypoglycemia, insulin allergy, lipoatrophy, weight gain, insulin edema

Question 10

Rapid acting insulin

Answer 10

insulin lispro, insulin aspart, insulin glulisine

Question 11

Short acting insulin

Answer 11

novolin R, humulin R

regular length insulin
-8 hrs

Question 12

Intmdt acting insulin

Answer 12

Humulin N

Novolin N

Question 13

Long acting insulin

Answer 13

insulin detemir, insulin glargine (levemir and lantus)

lasts 24 hrs

Question 14

Tx of DKA

Answer 14

IV infusion of regular insulin at low rate

-administer glucose along to prevent hypoglycemia and fluid and electrolytes

Question 15

Sulfonylureas

Answer 15

secretagogues

• inhibit activity of K+ channel on islet cell
• activate residual b cells to release insulin by binding to and activating SUR1 (subunit of the K/ATP channel)
• some pts may be allergic
• decrease hepatic clerance of insulin and decrease serum glucagon by stimulating somatostatin release
• can cause weight gain because using more glucose, hypoglycemia
• orally available, metabolized by liver, metabolites excreted in urine

Question 16

First generation sulfonylureas

Answer 16

Tolbutamide, tolazamide, chlorpropamide

for those prone to hypoglycemic episodes

Question 17

Second gen sulfonylureas

Answer 17

binds to SUR1 with higher affinity, lower dose req’d

Glyburide, glipizide, glimepiride

Question 18

Contraindications of sulfonylureas

Answer 18

type 1 DM
pregnancy
lactation
significant hepatic or renal insufficiency

Question 19

Meglitinides

Answer 19

Secretagogues

• similar MOA to sulfonylurea
• Repaglinide, nateglinide (more rapid)
• cleared by liver (not for those with hepatic insufficiency)
• hypoglycemia AE

Question 20

Biguanides

Answer 20

Metformin
Insulin sensitizers
Euglycemic effect- helps maintain normal blood glucose levels without producing hypoglycemia

Question 21

MOA of Metformin

Answer 21

• inhibits gluconeogenesis in the liver, helpful in maintaining normal blood glucose level
• inc peripheral insulin sensitivity
• actings AMP-activated protein kinase
• Inhibits mTOR-C1

Question 22

Clinical use of metformin

Answer 22

1st line for type 2 DM
Taken with food
also used for PCOS or fatty liver disease

Question 23

Metformin toxicity

Answer 23

Lactic acidosis- impair hepatic metabolism of lactic acid, but rare

Most AE are GI related- diarrhea, abd discomfort, nausea, metabollic taste, reduced B12 absorption

Question 24

Thiazolidinediones (TZDs)

Answer 24

Rosiglitazone and Pioglitazone
-PPARy agonists with PPARa agonist activity
(rosiglitazine 10x ppary affinity than pioglitazone)

Question 25

MOA of TZD

Answer 25

IN adipose tissue, PPARy activators promote transport of serum lipids to adipose tissue - may activate ppary in other tissues to promote insulin sensitivity- dec hepatic gluconeogenesis, enhance uptake of glucose by skeletal muscle cells - reduce glucose and triglycerides metabolized by liver, so can cause hepatic toxicity chf, weight gain

Question 26

alpha-glucosidase inhibitors

Answer 26

Inhibitor of intestinal glucose absorption | -competitive and reversible inhibitors of pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes

Question 27

Acarbose and miglitol

Answer 27

a-glucosidase inhibitors -inhibits intestinal glucose absorption -reduces fasting glucose, a1c and post prandial glucose no risk for hypoglycemia can cause flatulence, bloating, diarrhea not recommended for pts with ibd

Question 28

Incretins

Answer 28

glucagon like peptide1 (GLP1) and glucose dependent insulinotropic peptide (GIP) Released by cells in ileum, which is stimulated by nutrients entering the gut -increase insulin secretion, decrease glucagon secretion, delay gastric emptying, decrease appetite

Question 29

GLP1

Answer 29

Exenatide, liraglutide (victoza), albiglutide, duraglutide (tide ending) -increase insulin secretion, decrease glucagon secretion, delay gastric emptying, decrease appetite - low risk of hypoglycemia, AE- nausea, vomiting, diarrhea - promote weight loss

Question 30

DDP4- Inhibitors of Dipeptidyl peptidase 4

Answer 30

Inhibitor of enzyme that degrades endogenous incretins (GLP-1 and GIP) - increase level of endogenous incretins - Sitagliptin, Saxagliptin, Linagliptin, Alogliptin - Monotherapy or in combo with metformin (not with GLP1 analogs)

Question 31

SGLT2 inhibitors

Answer 31

-Canagliflozin, dapagliflozin, empagliflozin - Glucose reabsorbed in proximal tubules by sodium glucose transporter (SGLTs) - Inhibition causes glycosuria and lowers glucose levels - Efficacy reduced in chronic kidney disease Side effects- inc incidence of genital infections and UTI - manageable with better hygiene - can also lead to intravascular volume contraction and hypotension -SGLT2 inhibition promotes weight loss

Question 32

Pramlintide

Answer 32

Amylin analog - increase insulin secretion, decrease glucagon secretion, delay gastric emptying, decrease appetite, decreases appetite (hypothalamus) - preprandial as adjunct to insulin improves post prandial glucose control AE: hypoglycemia and GI symptoms

Question 33

Covesevalam

Answer 33

Bile acid sequestrant, cholesterol lowering drug -Can reduce glucose absorption via decreasing FXR nuclear receptor activation may exacerbate hypertriglyceridemia

Question 34

Bromocriptine

Answer 34

Dopamine agonist -lowers glucose levels AE- nausea, fatigue, dizziness, vomiting, headache

Question 35

Combo therapy of diabetes

Answer 35

different MOA target diff proteins Begin with monotherapy with metformin, GLP1 mimic, SGLT2 inh, GPP-4 inh Sulfonylureas and TZDs are second choice Add additional agents as needed Add insulin therapy to other agents