How is Diabetes Mellitus characterized?
1. Hyperglycemia with derangedd secretion of insulin
2. Thickening of basement membranes of capillaries
3. Late complications involving tissues that DO NOT require insulin for glucose uptake (retina, glomerulus, and peripheral nerves resulting in blindness, renal failure, and neuropathy)
What is the difference between Type I and Type II DM?
Type I: lack of insulin release by B-cells
Type II: Insensitivity to insulin by receptive tissue (also sometimes low insulin release)
What is the treatment for Type I DM? What are the delayed preparations?
Insulin Lispro (rapid onset, but shorter duration)
Insulin glargine (maintains glucose at around 130mg/dl for ~20hr)
Insulin Zinc extended
What are the short acting insulin preparations?
What is the treatmet for Type II diabetes?
- Diet and Exercise
- Oral hypoglycemics (& euglycemics)
- Insulin may be used
What are pharmacological treatments available to treat Type II DM? (think general groups)
What are the different sulfonylureas?
What is the MOA of sulfonylureas in treating T2 DM?
Sulfonylureas bind to the same K+ channel on membrane of pancreatic beta-cells that is regulated by glucose metabolism
--> Leads to depolarization of cells and insulin release
What are side effectsof sulfonylureas?
Prolonged and severe hypoglycemia
(May be FATAL!)
Treat with fast acting glucose:
What is reaglinide?
Not a sulfonylurea, but act just like one
--> binds to K+ channels to cause depolarization and insulin release
What is metformin? MOA?
A Biguanide used to reduce hyperglycemia
--> Reduces hepatic glucose output by inhibiting gluconeogenesis
What are adverse effects of metformin? And what is the key positive effect?
Never causes hypoglycemia
(only seen in patients with renal failure or CHF)
What is Acarbose? MOA?
An alpha-glucosidase inhibitor
--> Acts by inhibiting carbohydrate breakdown in the intestine
--> Reduces glucose uptake from intestine - reduces post-prandial spike in blood glucose
What are side effects of Acarbose?
Alone, will not cause hypoglycemia - but if taken with sulfonylurea & hypoglycemia occurs, must take glucose, not sucrose (patient should keep glucose tablets with them)
What are the thiazolidinediones? MOA?
Selective PPAR-gamma agonists (peroxisome proliferator-activated recetpor-gamma)
--> Increases insulin sensitivity
Possibly by increasing GLUT4 in muscle and adipose
--> Decreases gluconeogenesis in liver
What are some benefits of using glitazones?
No liver toxicity
Does NOT cause hypoglycemia alone
What is exenatide? MOA?
A synthetic peptide used to treat T2 DM
Mimics glucagon-like peptide-1 (GLP-1) released from the GI tract
--> Stimulates insulin release and inhibits glucagon release
What is sitagliptin? MOA?
Orally active dipeptidyl peptidase-4 inhibitor
--> prevents the breakdown of endogenouse glucagon-like peptide-1 (GLP-1)
--> GLP-1 is a potent stimulator of insulin release in a glucose-dependent manner and inhibits glucagon release
--> significantly reduces Hemoglobin A1c
What SGLT2 inhibitor is used to treat T2 DM? MOA?
Normally, in the kidney, glucose is filtered out of blood in glomerulus and 100% is reabsorbed back into the blood in the proximal tubule by the Na-glucose cotransporter-2 (SGLT2)
By inhibiting SGLT2, canagliflozin causes more glucose to be lost in urine