Patho PCT I - Final

Dr. Blake (intro to diabetes) + Dr. McGee (insulin) + Dr. Clements (obesity) + Dr. McGee (complications)

meds that predispose pt to DM (5)

acronym: GHAST

• glucocorticoids

• (some) HIV meds

• atypical anti psychotics

• (potentially) statins (increase blood glucose)

• thiazide diuretics

diagnosis of diabetes (A1c, FBG, OGTT, random BG)

• A1c >/= 6.5%

• FBG >/= 126

• OGTT >/= 200 mg/dl

• random BG >/= 200 mg/dl

stats for pre-diabetic that indicate STARTING metformin

• FBG >/= 110 mg/dl

• A1c >/= 6% (normal </= 5.6%)

• increasing A1c despite lifestyle changes

• BMI >/= 35

what is the A1c rule?

8/180

• starting at 8% and 180 mg/dl, every 1% increase/decrease corresponds to a 30 point mg/dl changes in BG in the respective direction

ADA glucose goals

• A1c <7% (pt variability- can trigger hypo/hyper in some pts for ex)

• FBG 80-130 mg/dl

• 2 hr post prandial <180 mg/dl

• CGM: TIR > 70%

  • time below range < 4%

what is an AGP

• ambulatory glucose profile report, is a type of rtCGM (real time CGM)

• measures and stores glucose levels continuously

what is UACR range in healthy pt

• should be < 3 mg/mmol (aka 30 mg/g)

  • 3-300 indicates kidney disease

some things that increase risk of hypoglycemia

• drinking alcohol (but mixers will decrease risk of it)

• use of sulfonylureas

• kidney disease (impaired clearing of insulin)

• cognitive impairment

stages of hypoglycemia

• stage 1- glucose < 70 mg/dl

• stage 2- glucose < 54 mg/dl

• stage 3- characterized by severe event (altered mental status, seizure, coma, etc)

hypoglycemia symptoms

• tachycardia

• sweating (BB can mask some symptoms)

• irritability

• HA

• shaking, dizziness

• confusion

hyperglycemia symptoms

• trouble seeing (retinopathy)

• slow wound healing

• dry skin

• three Ps

• peripheral neuropathy

how to treat unresponsive hypoglycemic pt

cannot do the treat and eat part of check, treat, check, eat so

• give glucagon or glucose gel OR

• IV dextrose (if you have IV access)

medical nutrition therapy

• limit sodium to < 2300 mg/day

• fresh or frozen non-starchy veggies preferred over canned

• 45-60 g of carbs/meal

• 15 g of carbs/serving or snack

• complex carbs high in fiber can subtract from the carbs

  • goal is 30g fiber/day

• lose 3-7% of baseline wt (can aim for 10%)

• limit alcohol

• artifical sweeteners are safe and ok in DM diets

lipid control

• statin therapy ± ezetimibe (or PCSK9 inhibitor)

• bempedoic acid if statin intolerant

CKD treatment

• first: maximally tolerated ACEi/ARB

• then SGLT2 or GLP-1

• if needed, start another med, this med being whichever of the two above that you did not initiate

SGLT1

• mainly affects the gut

• inhibits glucose/galactose normal reabsorption causing large intestine elimination

• causes diarrhea and dehydration

• has second function- acts in the PCT in kidneys to facilitate glucose reabsorption (10%)

SGLT2

• mainly affect the kidneys, predom expressed in PCT at brush border cells

• facilitate glucose absorption (80-90%)

• increases glucosuria and decreases gluotoxicity

Donislecel (CellTrans Lantidra)

• for brittle T1DM (rare and hard to control form associated with more symptoms, unpredictable hypoglycemic attacks)

• is a transfusion of purified, allogenic pancreatic islets from deceased donor

• they supplement endogenous insulin and glucagon production to improve glucose control, (delays or prevents need for insulin!!)

• 1000 ml bag with about 10 ml of packed islet tissue in 400 ml bag

• can get up to 3 transfusions, each must be at least 1 year apart

Teplizumab-MZWV

• biosimilar MAB that delays progression of DM stage 2 to stage 3 (by 2 years)

• form: IV bag, infuse over 14 days

• premedicate (since its a -mab): APAP, anti histamine, anti emetic

• causes vaccines to be less effective so hold them for certain duration after

• common side effects: N/V/D, HA, fatigue

• ADE: hematological toxicity

• also did a trial on ind who were relatives to those w T1DM and therefore at higher risk. trial showed that teplizumab delayed the progression to onset of T1DM by 2 years

stages of DM

• stage 1 + 2- no overt symptoms

• stage 3: presence of >/= 2 autoantibodies to insulin producing cells AND impaired glycemic response to a glucose load, otherwise normal A1c

insulin formation

• pre pro insulin gets its protein cleaved off via proteases

• result is pro insulin (insulin + C peptide)

• insulin is aka as peptides A and B (C peptide connects the 2)

• C peptide is cleaved off and result is insulin

insulin origins

• was initially made via animal sources (but this caused immune reactions)

  • now produce insulin via recombinant DNA technology, using e.coli or S. cerevisiae

regular vs native human insulin

regular insulin has an identical structure to native human insulin (so hypersensitivity reaction is less likely)

insulin MOA

• in liver, promotes making glycogen + fatty acids

• in skeletal muscle, promotes making glycogen + protein

• in adipose, make/store TAGs and inhibit hydrolysis of TAGs (may be more liekly to have high TAG level, address diabetes then manage lipids)

• also increases permeability ot K, Mg, PO4

• *********ACTIVATES Na/K pump CAUSING INTRACELLULAR SHIFT OF K (poses hypokalemic risk); normal Na/K ATPase pump movement is 3 Na out + 2 K in

adverse effects of insulin

• peripheral edema (causes volume changes due to K shifts)

  • can be concerning for HF pt (like TZDs)

• eyrthemia at inj site, hypokalemia

• hypertrophy/lipoatrophy if inj site is not rotated

med induced diabetes

• glucocorticoids (#1 offender)

• anti-psychotics (cause wt gain therefore BG increases)

• niacin (affects glu tolerance)

• phenytoin (affects glu tolerance)

dawn phenomenon

• natural rise in glucose in the morning

somogyi phenomenon

• rebound effect

• so typ caused by high insulin doses the evening/night before

• hypo in early morning hours

• hyper in morning hours

• mistakenly treated as hyper so insulin dose is increased (makes the situation worse)

• need to ask pt to check their BG in early morning hrs when it occurs to confirm

• best tx: decrease evening/bedtime insulin dose or have bedtime snack

rapid acting insulins

• Merilog (aspart biosimilar)

• Afrezza (inhaled/oral)

  • come in cartridges of 4, 8, or 12u

  • rapid insulin but wont meet all your needs

  • option if pt doesnt want injectables

• lispro, aspart, glulisine

long acting insulin

• degludec, glargine, detemir

insulin production in healthy ind

• naturally produce about 20u in one day

insulin pumps

• closed loop pumps automatically dose and hold insulin based on CGM readings

• Tslimx2- hardware or actual insulin pump

• Omnipod 5- simplified, tubeless, automated insulin pump integrated w dexcom g6

  • “starter pump” or good for geriatric pt

• Cequr Simplicity- 3 day “patch” for bolus doses

  • not a pen or pump, but has a canula (thin flexible tube for fluids, meds, samples, etc)

  • lower end of desired product

• MiniMed Medtronic- for T1DM, automated basal delivery

  • assessed q5min, advantages- can hold 300u, replace q7days

• Ilet Bionic Pancreas

  • does everything for you, like an artificial pancreas

A1c

• more accurate representation at end of 3 months

BMI

• reasonable measurement for initial screening

• how to calculate: (in kg/m²)

  • get kg

  • get m² by getting height in cm, divide by 100, then square

  • divide kg by m²

• healthy: 18.5-24.9

• overwt: >35-39

• obesity: >40

preclinical vs clinical obesity

• preclinical: metabolically healthy people living w obesity

• clinical: has obesity related/precipitated symptoms

  • adiposity, lipotoxicity, pro-inflammatory state

meds that can cause wt gain

• atypical anti psychotics

• tricyclic antidepressants

• glucocorticoids

• sulfonyureas

• insulin

• TZDs

receptors physiology

• stimulate alpha 1- suppress appetite

• stimulate alpha 2- increase food intake

• stimulate 5-HT 2c- suppress appetite

• stimulate 5T1 1a- increase food intake

neuropeptides (3)

• orexin: increase food intake

• melanocyte concentrating hormone (MCH): regulates feeding behavior

• leptin: satiety hormone

GI hormones (2)

• ghrelin: increases food intake

• GLP/peptide YY: suppresses appetite

pancreatic hormones:

• amylin + insulin

  • promote satiety

effects of certain meds on wt:

• amitriptyline + olanzapine (biogenic amines) = wt gain

• tirzepatide (GI hormone) = wt loss

• topiramate (limbic system) = wt loss

• pramlintide (pancreatic hormone) = wt loss

types of adipose tissue

• brown adipose: good

  • related to energy expenditure + insulin sensitivity

• white adipose: bad

  • related to energy storage + inflammation

reduction of body wt goal

• goal: loss of 5-10% from baseline

• overwt: lose 0.5lb/week in first 6 months

• obese: lose 1-2lb/week in first 6 months

• increased wt loss = increased benefits (up to 15%)

lifestyle therapy for obesity

• yes exercise, diet, etc

  • reduce cals by 500-1000 per day to lose 1-2 lb/week

  • set caloric goal:

    • women: 1200-1500/day

    • men: 1500-1800/day

• good sleep (if circadian rhythm is off, pt is more likely to eat more + of the “wrong” foods)

when would you start PCT for wt loss?

• BMI >30

• BMI >/= 27 and wt related comorbidity (HTN, dyslipidemia, diabetes, CAD, obstructive sleep apnea0

other wt loss methods (not medications)

• medical devices

  • implanted gastric balloons

  • vagus nerve stimulator

  • gastric aspiration therapy

  • oral hydrogel

• metabolic surgery

  • gastrectomy

  • roux-en-Y gastric bypass

unique assessments in DM

• dilated eye exam

• comprehensive foot exam

• dental exam

• BMD (bone mineral density) screening

ASA

• 81mg for secondary prevention after CV event

• primary prevention in diabetes if established risk, low bleed risk, and no CI

• not recommended in <50yo w/o risk or >70yo w/o risk

clopidogrel

• if intolerant to ASA

• 75mg QD

• DAPT for up to 1 yr post ACS event or stent placement

bleed risks

• >75yo

• PUD

• renal disease, liver disease

• anemia

• smoking, alcohol

HTN + drug initiation?

• >180/110 = start PCT now

• <140/90 in gestational DM and HTN and frail pt

• ACE/ARB preferred if UACR > 300 or eGFR < 60 (+ should be titrated to maximally tolerated dose)

• CCB and thiazides also ok

statin initiation?

• pt 20-39 = consider if ASCVD risk factors

• pt 40-75 = recommended

• 75 yrs = consider mod intensity

• CI in pregnancy

• high intensity > 50% reduction in LDL

  • atorva 40mg, 80mg

  • rosuva 20mg, 40mg

• mod intensity > 30% reduction in LDL

lipid goals in DM

• TG < 150 mg/dl

• HDL > 40 in men

• HDL > 50 in women

lipid management algorithm:

• statin, zetia, icosapent ethyl

• statin intolerant:

  • evolucumab (Repatha)- PCSK9 inhibitor binds to low density lipoprotein

• bempedoic acid (Nexletol)

  • inhibits synthesis of LDL in liver

• Praluent

• inclisiran

  • siRNA/PCSK9 inhibitor