DM and Metabolic Syndrome

Question 1

Know BP goals for diabetics.

Answer 1

<130/80 mmHg

Question 2

Biguanides

Answer 2

Metformin (Gluocphage®, Glucophage XR®, Fortamet®, Glumetza®)

Question 3

Mechanism of Action of Biguanides:

Answer 3

-> FBG, 1-2% A1c reduction
•	↓ hepatic glucose production (major)
•	↑ peripheral uptake by muscle (minor)
•	↓ GI glucose absorption (minor)
•	Requires insulin for efficacy, but does not stimulate insulin release

Question 4

What is Considered first-line therapy for DM II?

Answer 4

Metformin

Question 5

v

Answer 5

Based on cost, beneficial effects on lipid profile, weight “neutral,” and may reduce CV events
• ↓ TGs, TC and LDL, and ↑ HDL (slightly)

Question 6

Sulfonylureas

Answer 6

Glipizide (Glucotrol®, Glutrol XL®), glyburide (Diabeta®, Micronase®), glimepiride (Amaryl®)

Question 7

Mechanism of Action of Sulfonylureas:

Answer 7

-> FBG, 1-2% A1c reduction
• ↑ insulin secretion from functioning β-cells and enhance β-cell sensitivity (major)
• ↓ hepatic glucose production (minor)
• ↑ insulin receptor sensitivity &/or number (minor)

Question 8

Meglitinides:

Answer 8

Repaglinide (Prandin®), nateglinide (Starlix®)

Question 9

Mechanism of Action of Meglitinides:

Answer 9

Stimulate release of insulin from functioning β-cells

Glucose-dependent (effect diminished at low serum glucose concentrations)

Question 10

v

Answer 10

Short duration of action leads to more effects on PPBG vs. FBG

A1c reduction 0.5-1.9% (repag > nate)

Question 11

α-Glucosidase Inhibitors

Answer 11

Acarbose (Precose), miglitol (Glyset)

Question 12

Mechanism of action of α-Glucosidase Inhibitors:

Answer 12

Delays carbohydrate absorption (starches and sucrose)

Reduces the postprandial spike in glucose

Does not affect absorption of lactose, fructose or glucose

Question 13

v

Answer 13

Patient should be consuming a diet high in complex carbohydrates (50% or more)

Does not ↑ insulin levels or cause hypoglycemia when used alone

Neutral or slight benefit in LDL, HDL, and TG

Question 14

Thiazolidinediones (TZDs)

Answer 14

Rosiglitazone (Avandia), pioglitazone (Actos)

Question 15

Mechanism of Action:

Answer 15

Stimulate the peroxisome proliferator-activated receptor-gamma (PPAR-γ)
• ↑ insulin sensitivity (major)
• ↓ hepatic glucose production (minor)
• ↓ plasma insulin levels (minor)

Question 16

v

Answer 16

Requires presence of insulin to be effective

Question 17

SGLT2 Inhibitor

Answer 17

Canagliflozin (Invokana®)

Question 18

Mechanism of Action:

Answer 18

Inhibits glucose reabsorption in the kidney to increase the amount of glucose excreted in the urine

• A1c reduced by about 1%
• Beneficial AE profile
• Limited potential for hypoglycemia and often leads to weight loss
• Increased risk for UTIs and genital mycotic infections
• Diuretic effects – caution for hypovolemia

Question 19

Incretin Mimetics

Answer 19

DPP-IV Inhibitors

Sitagliptin (Januvia®), Saxagliptin (Onglyza®), Linagliptin (Tradjenta®), Alogliptin (Nesina®)

Question 20

Mechanism of Action:

Answer 20

-> 0.5-0.8% A1c Reduction
o Prevent enzymatic inactivation of GLP-1 and GIP. Binding of active GLP-1 and GIP to incretin receptors of pancreatic β-cells potentiates insulin secretion and inhibits glucagon secretion

Question 21

GLP-1 Receptor Agonists Mechanism of Action

Answer 21

o Induces insulin release even before blood glucose levels are elevated
o Causes increase in beta cell mass
o Increases insulin secretory capacity

Question 22

Components of MetS Syndrome:

Answer 22

Abdominal obesity
TG >150
HDL 130/85
Fasting Glucose >100

Question 23

Pathophysiology of MetS

Answer 23

Environmental (Obesity, sedentary lifestyle, atherogenic diet, high alcohol intake, smoking)

Insulin resistance (Central obesity, genetics, age, drugs)

Inflammation (Leading to endothelial dysfunction)

Question 24

Orlistat Mechanism of action

Answer 24

Reduce fat absorption by interfering with gastric and pancreatic lipases in the stomach and small intestine

Question 25

Associated symptoms of Orlistat

Answer 25

Flatulence with discharge, fecal urgency, fecal incontinence, steatorrhea, oily spotting/evacuation; generally mild to moderate

Will also reduce absorption of fat-soluble vitamins
Recommended to take supplement (A, D, E, K)

Question 26

Anorexants Mechanism of action

Answer 26

Sympathomimetic amine: inhibits reuptake of NE and increases release of NE from nerve terminals
Thought to have a stimulatory effect on the satiety regions of the brain, leading to appetite suppression

Question 27

Associated symptoms of Anorexants

Answer 27

USE ONLY SHORT TERM!

Sympathomimetic effects (increased BP/HR, palpitations, insomnia, irritability, anxiety, ECG changes, etc.)
Effects are similar to amphetamines, although less pronounced
Use cautiously in those with uncontrolled cardiovascular disease

Question 28

Diabetes:

Answer 28

order characterized by elevated glucose caused by impaired insulin production and/or insulin activity

Question 29

Diagnostic Criteria for diabetes:

Answer 29

FBG > 126 mg/dL
A1c > 6.5%
OGTT (rarely performed)
Random glucose > 200 mg/dL + symptoms

Question 30

Symptoms of diabetes:

Answer 30

Classic – “3 Ps” – polydipsia, polyuria, polyphagia
Blurred vision
UTI, Yeast infections
Dry, itchy skin
Numbness, tingling in extremities
Fatigue
Unexplained weight loss

Question 31

Insulin therapy may be needed early in the disease, how do we give insulin?

Answer 31

Start with basal and add bolus as needed