GI/ENDO unit tree

Diabetes ABCs

• A1c 

  • < 7% ADA goal

• Blood pressure 

  • < 130/80

• Cholesterol 

  • LDL < 70 mg/dL or < 55 mg/dL for those with ASCVD

  • HDL-C > 40 mg/dL, > 50 mg/dL in women 

  • TG’s < 150 mg/dL

• Smoking Cessation

ADA Type 1 Diabetes…

• Autoimmune beta-cell destruction 

• Patients REQUIRE insulin for survival 

• Teplizumab (Tzield) = T1DM prevention possible

ADA Type 2 Diabetes…

the most prevalent form of diabetes

• Progressive insulin secretory defect/insulin resistance 

• Disease patho = ominous octet

• Screening should begin at age 35.

Drugs that decrease blood sugar

• Alcohol 

• Colesevelam 

• Ranolazine 

• Beta-blockers - may mask hypoglycemic symptoms

Drugs that increase blood sugar

• Glucocorticoids 

• Sympathommimetics 

• Atypical Antipsychotics 

• High-dose thiazide 

• Immune checkpoint inhibitors

Insulin vs Glucagon Overview…

Role of insulin: released post-prandial…

• Anabolism 

• GLUT 4 translocation 

• Glucose uptake into cells 

• Glycogen synthesis (storage) 

Role of glucagon: release in the fasting state 

• Goal of increasing blood glucose 

• Catabolism 

• Liver and adipose tissue release glucose via glycogen 

Symptomatic Hypoglycemia

 (too low blood sugar, acute disease state)

1. Autonomic Nervous System (SNS)

   1. Diaphoresis, palpitations, shaking, dizziness, hunger 

2. Neuroglycopenic Symptoms (CNS)

   1. Confusion

   2. Drowsiness

   3. Speech difficulty 

How do we diagnose diabetes?

→ 2 abnormal test results; can be the SAME two tests or two different tests…

• A1C DM > 6.5%

• Fasting plasma glucose > 126 mg/dL

• 2 hr plasma glucose > 200 mg/dL

• Random glucose > 200 mg/dL

What is A1C? 

Glucose bound to hemoglobin shows average blood sugar levels over the past 90 days

• An A1C of 7% reflects a blood sugar of 154 mg/dL

Type 2 DM Pathophysiology…

• Decreased…

  •  insulin production from B-cells

  • Incretin effects

  • Muscle glucose uptake

• Increased…

  • Liver gluconeogenesis 

  • Fat lipolysis  

  • Glucagon secretion 

  • Insulin resistance

TX associated with hypoglycemia?

• Meglitinide 

• Sulfonylurea 

• Insulin

Class: SGLT2 Inhibitors

• MOA: inhibit SGLT-2 from reabsorbing glucose back into body from urine

  • Proximal convoluted tube

    • Glucose, Na loss, osmotic diuresis (water loss) 

  • Lowers glucose levels, weight loss, blood pressure reduction 

  • Decreases adverse cardiovascular events

  • REDUCE hospitalization for heart failure

  • REDUCTION of kidney failure

Canagliflozin (Invokana) Dosing: 

• 100 mg once a day, may increase to 300 mg 

Dapagliflozin (Farxiga) Dosing: 

• 5 mg once daily, may increase to 10 mg 

Empagliflozin (Jardiance) Dosing:

• 10 mg once daily, may increase to 25 mg 

Ertugliflozin (Steglatro) Dosing: 

• 5 mg once daily, may increase to 15 mg 

Bexagliflozin (Brensavvy) Dosing: 

• 20 mg once daily 

SGLT-2 Inhibitors Adverse Effects…

1. Genitourinary tract infections/Urinary tract infections 

2. Polyuria initially

3. Hypotension, hypovolemia due to osmotic diuresis (water loss)

4. Initial decrease in GFR may occur

5. Euglycemic ketoacidosis 

6. Fractures → canagliflozin  

7. Necrotizing fasciitis

SGLT-2 Inhibitor Contraindications…

• Severe renal impairment (End-stage renal disease/on dialysis)

• History of hypersensitivity 

• Temporary dc before scheduled surgery to avoid ketoacidosis (stress)

SGLT2 Inhibitors and ASCVD…

• Empagliflozin 

• Canagliflozin

SGLT2 Inhibitors and Heart Failure…

• Empagliflozin 

• Dapagliflozin 

• Canagliflozin 

• Ertugliflozin

SLGT2 Inhibits and CKD…

• Empagliflozin 

• Dapagliflozin 

• Canagliflozin

Canagliflozin renal dosing 

• GFR 30 - 60 

  • Dose adjusted to 100 mg daily 

The Incretin Effect

• Insulin secretory response is GREATER to oral glucose than IV glucose due to incretins

• Incretin effect is diminished in type 2 diabetes

  • Incretin response is impaired in T2DM

    • Decreased response to GIP

    • Decreased secretion of GLP-1

Incretin Mimetics…

• MOA: synthetic analog of human GLP-1 resistant to DPP-4 

• supraphysiologic incretin levels

Exenatide, Liraglutide, Dulaglutide, Lixisenatide, Semaglutide…

• Glucose-dependent insulin production 

• Satiety 

• Weight loss

• Slows gastric emptying

GLP-1 RA and Cardiovascular Benefits:

• Liraglutide 

• Semaglutide

• Oral Semaglutide 

• Dulaglutide

Incretin Mimetics Adverse Effects:

1. GI: nausea, vomiting, diarrhea, abdominal pain 

2. Headache 

3. Rare renal dysfunction, pancreatitis 

Warnings/Cautions

1. Creatine Clearance < 30 mL/min for Exenatide

Incretin Mimetic Contraindications: 

• Medullary thyroid cancer, personal or family history 

• Multiple endocrine neoplasia syndrome type 2