Diabetes Flashcards
Diagnostic Values for Dx of Diabetes/PreDM
FPG of 126 mg/dl or more PreDM 100-125
2 hour OGTT >200 mg/dl or more, pre-diabetes 140-199
Sx of DM with random glucose of >200 mg/dl
HbA1c >6.5% (pre-diabetes 5.7-6.4%)
Risk Factors for Type 2 DM
First Degree Relative with type 2 DM Overweight (BMI 25-29.9) or obesity BMI >30 African, Hispanic, or Native American Physical Inactivity History of Gestational DM or birth of a 9 lb or greater baby Hx of Prediabetes Hx of HTN Hx of TG >250mg/dl Hx of low HDL <35 Hx of PCOS Hx of CVD
Gestational DM- New Criteria 2011
Screen b/t 24-28 weeks gestation if no DM risk factors otherwise screen at first prenatal visit.
Use 75 gram 2 hour OGTT
Cut off points
Fasting 92mg/dl
1 hour 180 mg/dl
2 hour 153 mg/dl
two-step screening no longer recommended. Women with hx of gestational DM should be screened for DM 6-12 weeks post-partum.
When to screen for Type 2 DM?
All adults over 45 y/o, with risk factors could consider earlier.
Type 2 DM Pathophysiology
- Insulin deficiency
- Insulin resistance
- Increased hepatic glucose production
- Increased hepatic glucose production (b/c it is not responding to insulin signal)
- Increased gastric emptying rate
- Neuroendocrine dysfunction (decreased amylin secretion, impaired incretin effect.)
ADA & AACE Diabetes Treatment Goals
HbA1c less than 7%
Fasting 70-130mg/dl
2 hour pp , 180 mg;dl
AACE
hbA1c < 6.5%
Fasting less than 110mg/dl
pp less than 140mg/dl.
Elderly optional goal less than 8%.
Sulfonylureas
MOA: Binds to a sulfonylurea receptor on the B cell, ATP- dependent potassium channel, depolarizes the cell membrane and results in increase in intracellular calcium concentration causing insulin to be released.
HbA1c lowering of 1-2%
Effects on fasting and post-prandial
Generally avoid 1st gen.
Use
Glyburide (5-20mg/day)
Glipizide 5-20mg/day) (DOC for SU in Renal Insufficency)
Glimepiride1-8 mg/day
50% of the dose gets 80% of effect. Typically why we see the first two doses at 10mg/day (ie 5 mg BID) to avoid SE.
ADRS
Hypoglycemia
Weight gain
Less common, Rash photosensitivity, dyspepsia, nausea.
Contraindications Diabetic Ketoacidosis Type 1 DM Severe liver or kidney dz Hypoglycemic unawareness
Advantages:
Works quickly
High initial response rate
Inexpensive
Disadvantages:
Hypoglycemia
Weight Gain
Eventual treatment failure
Biguanide- Metformin
MOA: Primarily inhibits hepatic glucose production, secondarily some improvement of peripheral insulin resistance, may also decrease intestinal absorption of glucose
HbA1c lowering 1-2%, primarily acts on FPG
Dose 500mg /day increase by 500mg/day at weekly intervals. Max dose 2550mg/day (850 TID)
Most common dose 1 gram BID
ADRS
NVD
Uncommon, Macrocytic anemia (b12 deficiency), lactic acidosis
Contraindications:
Scr > 1.5 men, 1.4 women (debatable with current literature but still in PI) Others say CrCl less than 30-50 ml/mi.
SEVERE hepatic, pulmonary, or cardiac disease. Although some evidence improves outcomes in CHF, concern is lactic acidosis when it gets severe.
Should be withheld for 48 hours after contrast dye.
Advantages:
No hypoglycemia in monotherapy/weight neutral, high intitial response rate, inexpensive.
Disadvantages- patients eventually stop responding, GI side effects.
Meglitinides
Similar MOA to SU but stimulates meglitinide receptor. glucose dependent.
Efficacy 0.5%-1%
Reduces post prandial blood glucose
Mealtime, 3 times /day
Drugs:
Repaglinide (Prandin) 0.5-1 mg before meals up to 16 mg/day.
Nataglinide (Starlix): 60-120 mg before meals.
Weight gain and hypoglycemia are less than SU but the drugs also aren’t as effective as SU.
Contraindications: DKA, Type 1 DM, Hypoglycemia unawareness. Repaglinide and gemfibrozil can not be used d/t gemfibrozil increasing serum concentrations of repaglinide.
Alpha-Glucosidase Inhibitors
MOA: Inhibits the enzyme alpha-glucosidase, found along the brush border of the small intestine, which is reponsible for the breakdown of complex carbs into glucose.
HbA1c reduction 0.5-1%
Reduces post-prandial glucose
Mealtime 3/day dosing.
Dose Acarbose (Precose) 25 mg with first bite of meal, start once daily then increase to 2, then 3x daily. Usual dose 50-100mg with meals 3x/day.
Miglitol (Glyset) 25 mg with first bite of meal; start once daily then increase to 2, then 3 x day. Max dose 100mg TID.
ADRs
Flatulence, abdominal discomfort, diarrhea, not well tolerated, although Sx improve after 4-8 weeks of therapy. Rare LFT elevation
CI: IBD Intestinal obstruction Malabsorption CrCl less than 25 ml/min Cirrhosis
Advantages:
No hypoglycemia with mono therapy Weight netural
Disadvantages
Modest efficacy
Poorly tolerated GI SE
Need for slow titration.
TZD
MOA: PPR-Gama agonists, results in an increase in insulin dependent glucose disposal in skeletal muscle and adipocytes and a decrease in hepatic glucose production.
Efficacy:
0.8-1.5% HbA1c reduction
Mixed blood glucose lowering effect, can take 8-12 weeks before maximal efffect seen. Increases HDL, lowers TG (pioglitazone)
Pioglitazone (Actos) 15-45 mg/day
Avandia 1-8mg/day-RESTRICTED ACCESS PROGRAM
ADRS: Weight gain Fluid retention (more often with concomitant insulin, NSAID, glucocorticoid, or DHP-CCB use) CHF Exacerbation Atypical (hands/feet fractures) in women Rare hepatotoxicity Bladder Cancer potential
CI
Alanine aminotransferase > 2.5 x ULN
Class III and IV CHF
Advantages: No hypoglycemia in mono therapy Favorable metabolic effects Can use in renal insufficiency Potential B-cell sparing can induce ovulation in PCOS
Disadvantages:
Delayed onset of action
ADRS
LFT monitoring
DDP-IV Inhibitors
MOA: inhibits the enzyme dipeptidyl peptize 4 from breaking down endogenous glucagon-like peptide 1 (GLP-1) and glucose dependent insulinoptropic polypeptide (GIP) causing glucose-dependent increase in insulin secretion, and inhibition of glucagon secretion.
HbA1c reduction of 0.6-0.8%, primarily post-prandial glucose.
Dose: Sitagliptin (Jauvia ) 100 mg unless renal insufficient 50 mg/da for 30-50 ml/min CrCl or 25 mg/day for CrCL less than 30ml/min.
Saxagliptin (onglyza) 5 mg once daily, decrease dosage in renal insufficiency 2.5 mg day for CrCl less than 50ml/min.
Linagliptin (tradjentia) 5 mg daily no dosage adjustment required in renal or hepatic insufficiency.
ADRS
Rare Pancreatitis, skin reactions
CI
Hx of pancreatitis, DKA, Type 1 DM
Advantages
No hypoglycemia as mono therapy, weight neutral placebo-like adverse effect profile, potential b-cell sparing?
Bile Acid Sequestrant-Colesevelam
MOA: Farnesoid X Receptor (FXR) antagonist. Bile acids activate the FXR, which leads to increased expression of phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme necessary for hepatic gluconeogenesis. Colesevelam inhibits bile acid reabsorption, thus preventing FXR activation and up-regulation of PEPCK, leading to decreased hepatic glucose production.
HbA1c reduction 0.4% to 0.6%. Mixed blood glucose-lowering effect, LDL reduction of 15-18%.
Dose 625 mg , 3 tabls BID or 6 tabs every day with meals. Suspension 3.75 g/packet, 1 every day with largest meal.
ADRs:
Constipation/dyspepsia
Potential TG increase
CI:
Bowel obstruction
TG > 500mg/dl
Hx of >TG induced pancreatitis
Advantages: No hypoglycemia as monotherapy, LDL lowering
Disadvantages:
Low efficacy, high pill burden, may raise TG, absoprtion drug interaction concerns.
Nobody uses this for DM! :)
Bromocriptine (Cycloset)
MOA: Dopamine receptor agonists, glucose lowering MOA unknown.
HbA1c lowering 0.4%- 0.6%, modestly reduces post prandial blood glucose, even less effect on FBP
Dose 0.8 mg each morning with food, titrate up to 4.8mg (6 tabs each morning)
ADRs NV Asthenia Constipation Dizziness Somnolence
CI
Hypersensitivity to ergot derivative or dopamine
lactation
syncopal migraines
Unique MOA but low efficacy, hight ADR
Amylin analog (Symlin)
MOA: synthetic analog of human amylin, causes a glucose dependent inhibition of glucagon secretion, reduced rate of gastric emptying, increased satiety.
Only indicated for patients receiving mealtime insulin.
HbA1c lowering 0.5-0.7%
MUST DECREASE MEALTIME INSULIN DOSE BY 50% WHEN INITIATING!
Type 1 DM: 15 mcg sub q starting, can titrate up to 60 mcg.
Type 2 DM 60 mcg with meals increase to 120 mcg in 3-7 days
CI: Gastroparesis Hypoglycemic unawarenss HbA1c > 9% Patients unwilling to do SMBG
Advantages: Weight loss, post-prandial coverage
Disadvantages: 3 additional injections/day, may reduce oral drug absorption, GI ADRS.
