Diabetes 2 Part 1

wasabi's version from 2015-10-14 19:01

Section 1

Question Answer
pathophysiology of type 2 diabetesinsulin resistance-cells fail to use insulin properly (muscle and adipose), increased hepatic glucose production, combined with absolute insulin deficiency (beta cells burn out) -loss of early phase insulin release
adults screening for diabetes=screen at 45 years old. if normal repeat every 3 years.
adults screen at any age if=BMI over or equal to 25 and have more than one or equal to one additional risk factors
children screening for diabetes=overweight (BMI > 85% for age and sex or weight > 120% of ideal for height) plus any 2 risk factors. age ten or onset of puberty every 2 years
screening risk factorsphysically inactive, 1st degree relative with DM, member of high risk ethnicity, delivered baby more than 9 pounds or GDM, HTN, HDL less than 35 or TG more than 250, women PCOS, A1C more than 5.7, obesity, history CVD
diabetes diagnosis fasting=more than or equal to 126 on two seperate occasions (seperated by two weeks)
diagnosis diabetes casual plasma glucose=over or equal to 200 and symptoms of hyerglycemia (polydipsia, polyuria, weight loss)
A1C diabetes diagnosis=over or equal to 6.5% confirmed with repeat test (clincial lab test not POC)
pre diabetes A1C=5.7-6.4%
2hr plasma glucose diagnosis diabetesover or equal 200 during OGTT
prediabetes fasting=100-125
prediabetes 2 hour glucose=140-199
what should you do for people with prediabetes?target 7% body weight loss, 150 mins per week mod exercise, resistance training 2x per week. limit sugar bev fiber 14grams per 1000kcal
prediabetes retest A1c?annually
if prediabetes when consider using metformin?high risk. people. BMI over 35, age below 60, HX GDM (dont need all for metformin consideration). lifestyle prevention better than metformin!
goals for glucose control before meals70-130
goals for glucose 2 hour post mealunder 180
goal for A1Cunder 7 (6.5% for some....long life expectancy, if acheived without hypoglcyemia, short duration diabetes)
less stingent a1c of 8 for?long duration uncontrolled diabetes, history severe hypo, limited life expectancy, advanced micro.macro complications or comorbidities
as patients approach goal A1C, the need to manage what increases?PPG increases (post pradial). plays more of a role in A1C

Section 2

Question Answer
therapy at time of diagnosismetformin + lifestyle
newly diagnosed with symptoms or marked elevated BG or A1Cinsulin therapy plus or minus additional agents. A1C above 9%=dual therapy
if non insulin therapy at max dose does not achieve A1C target over 3 months addsecond oral, GLP-1 agonist, insulin
each new class of noninsulin agents added to initials treatment lowers A1C about 1%
usual first target isfasting glucose
newly diagnosed pt dont put on sulfonylura beceausemay burn out beta cells. usually have some fxn newly diagnosed so want to preserve

Section 3

Question Answer
metformin primary MOAlowers gluconeogenesis (decreases hepatic output)
secondary MOA of metforminincrease insulin sensitivity and decrease intestinal absorption of glucose
place in therapy of metformin?first line (esp obesity and hyperlipi), mono therapy or in combo
what does metformin do to weight and glucose/lipids?weight neutal or negative (2-5kg weight loss), decrease TG,LDL, increase HDL, decreases fasting blood glucose
pregnancy cat of metformin?cat B
metformin dosing initial500 mg once or twice daily with meals
metformin titratingslowly weekly (500 mg per week). slower if adverse effects.
max effective dose metformin2000 mg daily
extended release formulations dosing metforminover 1000 daily. may decrease gi side effects by 50%.
metformin CI renal=impaired. women scr over 1.4 and men over 1.5 (FDA suggests no use if GFR under 60 ml/min)
CI metformin=renal, history acidosis, decrease perfusion (HF), radio contrast dye....d/c metformin fo4 48 hrs restart after scr normalizes
adverse effects metformin=diarrhea, bloating, nausea, worst first few weeks take with food, metalic taste, decrreased absorption of vit B12
lactic acidosis with metformin=rare, but severe side effect (0.03 per 1000). dialyses needed to correct acidosis and remove excess metformin
monitoring metformin=FBG, A1C every 3 months then 6 at target, renal function every 6 months, vitamin b12 levels,
avoid using metformin in heavy alcohol users!
monitor crcl every 3 months with metformin use ifcrcl approaching 60

Section 4

Question Answer
first generation sulfonylureas barely used becauseincreased hypoglycemia, disulfuram like reaction, hyponatremia/SIADH
sulfonylurea MOAstimulate insulin secretion from pancreatic beta cells, bind ATP dep k channels on cell mebranes beta cells
place in therapy of sulfonylureasmono or combo, relatively rapid glucose lowering effect, work best with non obese patients and younger DM pts, DM under 5 years duration, fasting blood glucose under 200
do not use sulfonylureas if patient oninsulin or over 40 units per day. d/c when patient starts bolus insulin or sooner
dosing=start low increase no more than weekly. start 1/8 to 1/4 max dose titrate weeks to months. take with meals
max effective dose sulfonylureas=50% of max stated soe in package insert
renal dosing glyburidedo not use if crcl under 50
renal dosing glipizidedo not use if crcl under 10
renal dosing glimepridecrcl under 20 start with 1 mg daily
CI sulfonylureastype 1 diabetes, pregnancy/lactation, severe renal impairment, severe hepatic impairment
adverse effects sulfonylureashypoglycemia (take 30 mins before meal), more freq elderly, weight gain 2-5kg, rash, gi upset, cv issues?
what if start insulin and on sulfonylurea?decrease dose if start basal or GLP-1. stop if start bolus insulin
monitoring for sulfonylureaFBG, A1C every 3 unless controlled then 6, renal function periodically

Section 5

Question Answer
meglitinides MOAstimulate insulin release from beta cells. glucose dependent. when glucose elevated after meals
how is megltiinides different from sulfonylurea?only stimulates insulin when glucose elevated!. affects post prandial. short acting
meglitinide place in therapyonly used in combo (provides no basal insulin release).
preg cat for meglitinidescat c
dosingtake 30 mins before meal. do not take if skip meal
CI meglitinidestype one diabetes, diabetic ketoacidosis, coadmin gemfibrozil
adverse effects metaglinideshypoglycemia (not as bad as sulfonylurea), GI, weight gain
monitoring meglitinidesFBG, A1C
drug interactions repalginideCYP 3a4 substrate
drug interactions nateglinideCYP 3a4 substrate and 2c9. highly protein bound-monitor other protein bound drugs like phenytoin, furosemide, metformin

Section 6

Question Answer
thiazolidinediones MOAactivating PPARY. primary: increase insulin sensitivity. increase density glut 4 on insulin dependent cells
thiazolidinediones secondary MOAdecrease hepatic glucose output
place in therapy of thiazolidenedionesmono or combo with almost anything, used in patients with metabolic syndrome and or nonalcoholic fatty liver disease
rosiglitazone not used due tocv mortality
takes how long for response thiazolidenediones?2 months for response
CI thiazelinedionestype one diabetes, diabetic keto, hepatic impairment (lft >2x normal limit), genreally dont use at all if HF.
cautions of using thiazelenidionesedema, current insulin use (increase edema, severe uncontrolled htn, gemfibrozil increase conc
black box warning thiazCHF increased incidience and fracture increased risk
adverse effects of thiazweight gain 4kg over time, fluid retention, fracture risk, lipid effects. hepatotoxicty, bladder cancer history of it check for blood in urine.
monitoring thiazFBG, A1c, liver function enzymes every 3-6 months first year then yearly pts with liver disease

Section 7

Question Answer
DPP4 inhibitors MOAinhibits enzymes inactivate GLP1 (pts DM makes less). increases glucose dependent insulin secretion from pancreas and decreased glucagon secretion
DPP4 inhibitors place in therapymono or combo with metformin, sulf, or thiaz. weight neutral.
DPP4 pregnancycat B
dosing renal sitagliptincrcl 30-50
dosing renal saxagliptincrcl under or equal 50
dosing renal linagliptinno adjustment needed
DPP4 inhibitors CI/warningspts on scretagogues may need to decrease secretagogue dose to prevent hyp. HF
dosing renal alogliptincrcl under 60
adverse effects DPP4hypoglycemia when used with sulfonyl/secretagogee, upper resp infection, pancreatitis (inconclusive)
affects what glucose?fasting and prandial
monitoring DPP4 inhibsFBG, A1C, renal function at least annually, signs and symptoms HF and pancreatitis
disadvantageshigh drug cost andlacking clnical data
preserve beta cell function?yes may help

Section 8

Question Answer
GLP1 agonists MOAimproves glucose dep insulin secretion, suppressed glucagon, slows rate gastric emptying, increases satiety
place in therapy GLP1monotherapy or combo therapy, weight loss, 1st line addition to metformin or monotherapy!
preg cat GLP1cat c
renal dosing byetta and bydureoncrcl under 30 dont use.
liraglutide renaldon't use in renal impairment.
albigultide renal dosingno renal adjustment needed
which one meal dependent?byetta!
CI/warnings GLP1may need to decrease secretagogue dose! pancreatitis, family history thyroid carcinoma, gastroparesis
adverse effects GLP1nausea, vomiting, (smaller meals, less fatty meals), hypoglycemia use with sulf/secret, may reduce rate and extent absorption orally admin drugs
monitoring GLP1FBG,PPG, A1C, renal function at least annually, side effects pancreatitis

Section 9

Question Answer
alpha glucosidase inhibs MOAinhibits digestion polysaccharrides in small intestine
place in therapymono or combo. decrease post prandial. wieght loss neutral or lose little
dosing=take with first bite of meal
CI =pregnancy, scr over 2, cirhossis, inflam bowel disease= UC, chrones, ok IBS
adverse effects=explosive gas!!!! improves with time. elevation liver enzymes
monitoring=glucose fasting and post, hypogly symptoms, A1c, liver enzymes

Section 10

Question Answer
dopamine agonists MOAincrease dopamine levels and inhibit excessive sympth tone within CNS. improve metabolism. decrease post prandial and fasting.
CIavoid with psychotic disoders, avoid with triptans
adverse effectsnausea, constipation, dizziness, asthenia
monitoringBG, A1C, BP. metabolized by CYP 3a4

Section 11

Question Answer
sodium glucose transporters 2 inhibitors MOAblock reabsoprtion glucose proximal tutuble of kidney, excreted in urine. improves styplic bp, increase endogenous glucose prod
weight lossneutral or loss
renal canaglifozin45-60 reduce
renal dapaglifozindont use crcl under 60
adverse effectsincreased genital and urinary infection rates. potential hypotension, hyperkalemia