Diabetes Mellitus - Christian Flashcards
What do alpha cells do?
a. elevate insulin in the blood
b. elevate glucose in the blood
c. secrete glucagon
d. cause liver and kidney to secrete/retain glucose
b. elevate glucose in the blood
c. secrete glucagon
d. cause liver and kidney to secrete/retain glucose
Beta cells secrete which of the following?
a. insulin
b. C-peptide
c. amylin
d. all of the above
d. all of the above
What is the basic pathophysiology of Type 1 Diabetes?
Rapid onset of Autoimmune Beta-cell destruction => leading to absolute insulin deficiency (nearly 50-80% of Beta-cell function is lost by the time of Dx)
**Antibodies to glutamic acid decarboxylase (GAD)-65 are frequently present.
What is the basic pathophysiology of Type 2 Diabetes?
Insidious/slow PROGRESSIVE insulin secretory defect on the background of insulin resistance
(more tissue => secrete more insulin => cells stop “listening” to insulin)
***Nearly 50-80% of Beta-cell function is lost by the time of Dx
What therapies can cause Drug Induced Hyperglycemia?
***glucocorticoids
oral contraceptives
cyclosporine, tacrolimus, sirolimus
niacin
HIV protease inhibitors
thiazide diuretics
statins
gonadotropin releasing hormone agonists
other — beta blockers, beta agonists, megasterol, alcohol…
What type of diabetes is diagnosed by glucose tolerance test?
Gestational diabetes:
(first a one hour challenge – if >140 mg/dL, another 3 hour test will be performed, checking sugar every hour and if 2 reads are high => gestational DM)
Who should we screen for diabetes?
Screen all overweight adults (BMI >25) with > 1 risk factor:
- physical inactivity
- 1st degree relative with DM
- High risk race/ethnicity
- Women with a baby >9 lbs or Hx of GDM
- HTN
- HDL 250 mg/dL
- Women with PCOS
- A1c > 5.7%, IGT or impaired fasting glucose on previous testing
- Obesity, acanthosis nigricans, and other conditions associated with DM
- History of CVD
Dx of DM
fasting plasma glucose of 126 mg/dL on 2 separate occasions
random plasma glucose of 200 mg/dL with symptoms (polyuria, polydipsia, weight loss)
plasma glucose >200 mg/dL 2 hours after a 75-g oral glucose load (pregnancy)
glycosylated hemoglobin >6.4% (A1c)
What is the HbA1c for pre-diabetes? Diabetes?
Prediabetes = 5.7%-6.4%
Diabetes = >6.5%
How often do you retest HbA1c?
Every 3 months. It takes 3 months to regenerate RBCs.
What are important areas to focus on when performing a physical exam on pts with DM?
Vitals - Height, weight, BP
HEENT - pupillary reaction to light, dilated retinal exam
Neck - thyroid gland
Heart and lung exam, blood flow (pulse) in arms, legs, feet and neck (carotid) arteries
Skin - vitiligo, acanthosis nigricans, ulcers
Feet for sores, injuries, and decreased sensation (monofilament exam annually).
Reflexes and sensation (neuro).
What are the microvascular complications of DM?
retinopathy (annual eye exam)
neuropathy (annual monofilament exam)
nephropathy (annual microalbumin screen)
What are the macrovascular complications of DM?
class 1A indication for aspirin daily => both primary and secondary prevention
What laboratory tests are important to check in pts with DM?
glucose (fasting or random)
A1c
Lipids
renal panel
microalbumin
TSH
hepatic panel
***Test annually!
What are the currently incentivized laboratory evaluations and management strategies for patient with DM?
measure hemoglobin A1c every 6 months
maintain hemoglobin A12c at individual targets of less than 7%/less than 8%
measure LDL annually => maintain LDL cholesterol to less than 100 mg/dL or at level achieved by high dose statin
BP
What is the recommended treatment strategy for Type 1 DM?
Intensive therapy allows the use of insulin in a way that mimics the pancreas (short [prandial] plus long [basal] vs pump)
short (regular, lispro, aspart, glulisine) + long (glargine, detemir)
What is the list of current drugs used for treatment of Type 2 DM?
Biguanides (metformin)
Sulfonylureas (insulin secretagogues)
Alpha-glucosidase inhibitors
Thiazolinediones
Amylinomimetics
Incretin modulators: GLP-1 mimetics (glucagon-like peptide),
DPP-IV inhibitors (dipeptidyl peptidase-IV)
What is the 5-part Tx/therapy strategy for Type 2 DM?
diet (calorie consumption)
exercise
education
medications
self monitoring
What diabetic therapies work by increasing satiety?
Amylin Analogs and GLP-1 Agonists
What diabetic therapies work by decreasing glucose absorption and decreasing gastric emptying?
↓ Glucose absorption
Alpha-glucosidase inhibitors
↓Gastric Emptying
GLP-1 Agonists
DPP-IV Inhibitors
Amylin Anologs
What diabetic therapies work by decreasing glucose production?
Metformin and TZDs
What diabetic therapies work by increasing insulin secretion and decreasing glucagon?
↑ Insulin Secretion Sulfonylureas GLP-1 Agonists DPP-IV Inhibitors Meglitinides
↓ Glucagon Secretion
GLP-1 Agonists
DPP-IV Inhibitors
Amylin Analogs
What diabetic therapies work by increasing peripheral glucose uptake?
Metformin and TZDs
What diabetic therapies work by decreasing glucose reabsorption?
SGLT2 Inhibitors
Why is Metformin a good/bad initial drug monotherapy for treatment of DMII?
high efficacy => decreases HbA1c
lipid lowering, decreases macrovascular complications
low risk for hypoglycemia
weight neutral (maybe loss)
side effects of GI upset and ***lactic acidosis
low cost!
Which patients can you allow to have a HbA1c of 7?
older than 70
problems with hypoglycemia
may not live for another 10 years
Who should not take Metformin?
renal impairment (Cr >1.5 men, >1.4 women)
cardiac, resp insuf, sepsis leading to hypoxia or reduced tissue perfusion (cellular strain, possibly metabolic acidosis, might lead to lactic acidosis)
lactic acidosis
liver disease, alcohol abuse
radiographic contrast agents
What are the pros/cons of using Sulfonylureas for DMII Tx?
bind to sulfonylurea receptor on beta cells, stimulate insulin release
hypoglycemia, weight gain, potential impairment of cardiac ischemic preconditioning
What are the pros/cons of using Thiazolidinediones (TZDs) for DMII Tx?
Increases the amount of glucose taken up by muscle cells and keeps the liver from overproducing glucose
addresses primary defect of T2D, no hypoglycemia, lipid lowering, decreased macrovascular complications
SE - edema, could precipitate CHF, increased fx risk in women, increased? MI with rosiglitazone (Avandia – now off market)
$$expensive$$
What are the pros/cons of using GLP-1 agonists (incretin mimetics) and DPP-IV inhibitors for DMII Tx?
activate GLP-1 receptors, increase glucose-dependent insulin secretion, decrease glucagon secretion, delay gastric emptying
DPP-IV inhibits degradation of GLP-1 and GIP (gastric inhibitory peptide)
no hypoglycemia, potential weight loss
SE - nausea, vomiting, pancreatitis (rare), no long term studies
expensive
Don’t decrease HbA1c THAT much… not worth cost!
What is the role of Incretins (GLP-1 Receptor Agonist)?
- Increase insulin production
- Speeds insulin release
- Decreases glucagon production
- Slows gastric emptying
- Promotes satiety
What is the MOA of GLP-1 Receptor Agonists?
MOA: incretin (GLP-1) analog => increased insulin synthesis and release (β cells), decreased glucagon secretion (α cells), and decreased hepatic glucose production
Additional benefit of satiety promotion
What is the MOA of DPP-IV Inhibitors?
MOA: blocks the degradation of incretin by inhibiting the DPP-IV enzyme => increased insulin synthesis and release (β cells), decreased glucagon secretion (α cells), and decreased hepatic glucose production
What patients should avoid GLP-1 Receptors Agonists?
Use is contraindicated in patients with or a family history of medullary thyroid cancer and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2).
What are the 3 rapid acting human insulins?
Lispro (Humalog)
Aspart (Novolog)
Glulisine (Apidra)
What are the 3 short acting human insulins?
Human Regular (Humulin-R or Novolin-R)
What are the 2 long acting human insulins?
Insulin Detemir (Levemir)
Insulin Glargine (Lantus)
ADA’s Glycemic targets
Most patients: HbA1c
AACE/ACE’s glycemic targets
HbA1c
AACE/ACE’s diabetes algorithm
If A1c 7.6%-9% => Dual therapy (Metformin + GLP-1/DPP4/TZD/ SU/Glinide) for 2-3 months
Then, if A1c is not at goal => triple therapy for 2-3 months
Then, if A1c is STILL not at goal => insulin +/- other agents
What are four of the associated metabolic abnormalities in patients with DMII?
steatohepatitis
elevated triglycerides/low HDL
hyperuricemia
acanthosis nigricans
How many times higher is the risk for heart disease death and stroke in patients with DM compared to patients without DM?
2-4x higher
