Diabetes (Rahhal) Flashcards
What hormones do each of the following cells produce? Beta cells:______ Alpha cells:_____ Delta cells:_____
Beta cells: insulin Alpha cells: glucagon Delta cells: somatostatin
How does insulin work in regards to the protein GLUT4?
the pancreas releases insulin where it travels to find its receptor on various tissues. When insulin binds to its receptor, a cascade of events occurs, one of which is the expression of the protein GLUT4. GLUT4 gets inserted into the cell membrane to allow for the passage of Glc into the cell.
What are the 3 anabolic actions of insulin with regard to the following tissues? Adipose tissue:_______ Muscle:___________ Liver:_____________
Adipose tissue: increase glc uptake and lipogenesis, decrease lipolysis Muscle: increase glc uptake, glycogen synthesis and protein synthesis Liver: increase glc synthesis and lipogenesis, decrease gluconeogenesis
type ___ diabetes is a defect first of insulin action and second secretion, whereas type ____ diabetes is purely a defect of insulin secretion.
II; I
type I diabetes is mostlly caused by an autoimmune response in which antibodies are made to various types of cells or antigens in the pancreas - one of the most common antibodies in type I diabetes is against this enzyme
glutamic acid decarboxylase
what is the most common environmental trigger that turns on type II diabetes?
obesity; thought to be due to the excess circulation of free fatty acids and inflammatory cytokines that impair the insulin receptor, causing resistance, and that are toxic to beta cells
what is a hemoglobin A1c, and why is it measured as an average over several months?
it is a percentage that represents that amound of glucose that is attached to red blood cells. should be <5.7%
diabetes leads to complications such as _______ disease, which is the leading cause of end stage renal disease, adult onset blindness, and nontraumatic lower extremity amputations
microvascular
this disease is seen an ~20-30% of patients with DM, which presents initially with microalbuminemia that progresses to heavy albuneuria and proteinuria
diabetic kidney disease (nephropathy)
what is the leading cause of death in diabetics?
cardiovascular disease
Is diabetes good or bad?
BAD (you’re ready for the wards!)
what non-pharmacological approaches are appropriate for a type I diabetic? Type II?
Type 1: control carb intake Type 2: lose weight and control carbs
these diabetes managment drugs inhibit the enzymes that break down complex sugars, which then slows the absorption of glucose
alpha glucosidase inhibitors
this alpha glucosidase inhibitor decreases the absorption of glucose, does not affect insulin secretion so do not cause hypoglycemia, and main side effect includes flatulence and diarrhrea
acarbose
what are the 3 types of insulin “secretagogues”?
sulfonylureas/meglitinides, GLP-1 agonists, DPP-IV inhibitors
this class of drugs binds to their own receptors on the ATP-sensitive K+ channels in the pancreatic islet cells which starts a chain reaction that ultimately leads to the influx of calcium into the cell, and glucose-independent secretion of insulin
sulfonylureas (ie, glipizide, glimepiride, glyburide) and meglitinides
where is endogenous GLP-1 made, and how do GLP-1 agonists work?
GLP-1 is made endogenously in the L-cells of the small intestine. GLP-1 agonists work by binding the GLP-1 receptor on the islet cells to enhance the production of insulin. It is glucose-dependent, so the main benefit is they do not cause hypoglycemia. They do not work unless glucose is already present.
What are the 2 main side effects of GLP-1 agonists (ie, exenatide, liraglutide)?
nausea, some cases of pancreatitis
contraindications of this drug include patients with heart or renal failure, becuse of the excess amount of lactic acid that is produced
metformin
Which class of insulin secretagogues would you want to give to help a patient jump start their weight loss?
GLP-1 agonists
what is the main side effect of sufonylureas and meglitinides?
hypoglycemia
main side effects of this class of drugs includes weight gain, fluid retention, and increased risk of CV disease/death
TZDs (ie, rosiglitazone)
don’t use in patients with edema or CHF
what two classes of drugs work by improving insulin sensitivity?
biguanides (metformin) and TZD
how do DPP-IV inhibitors work?
they help GLP-1 last longer by preventing its breakdown by the DPP-IV enzyme.
*same side effects as GLP-1 agonists - may cause pancreatitis in some individuals with a history and do NOT cause hypoglycemia because they are glucose-dependent drugs.
this drug works on the liver only to decrease gluconeogenesis; side effects include diarrhea, nausea, bloating and abdominal pain
metformin
This class of drugs works by promoting insulin sensitivity, increasing glucose uptake in the skeletal muscle and increasing fatty acid uptake in adipose tissue
TZDs (PPAR gamma agonists)
class of drugs that prevents the reabsorption of glucose, increasing its excretion in the proximal tubule of the kidneys
SGLT-2 inhibitors (ie, canagliflozin)
side effects of this class of drugs includes vulvovaginal candidiasis and UTIs
SGLT-2 inhibitors
why do we use both long-acting and short-acting treatments to control secretion of insulin?
becuase this mimics the body’s natural secretion of insulin. long-acting for basal maintenance of insulin levels (ie, to prevent gluconeogenesis from happening all the time) and short-acting to accommodate the burst of insulin needed to handle a bolus of food.
what is the first line treatment of a type II diabetic, after diet and exercise?
metformin to improve insulin sensitivity, then can add other classes as needed. evetually type II diabetics will need insulin because the pancreas will get tired.
what is the treatment for type I diabetes?
insulin only
what is the maximum effect of all drugs (besides injectable insulin) on HbA1c?
at maximum dose, drugs reduce HbA1c by 1% each
what is the goal of diabetes therapy for microvascular disease?
HbA1c < 7%
what is the best way to reduce a diabetic patient’s macrovascular (ie cardiovascular) disease risk?
control blood pressure, reduce lipids, and smoking cessation
