Diabetes Flashcards
Pathophysiology – T1D
Autoimmune reaction that destroys the beta-cells
- Immune mediated (T cell) 95% of cases
- Idiopathic 5% of cases
Relative or absolute reduction in insulin
- Decreased insulin –> Abnormal glucose homeostasis
- Takes months to years to see symptoms from beta cell dysfunction
risk fx for T1DM
- FHx
- Genetics (HLA genes)
- Monozygotic twins
- Environmental influences
dx of T1DM
Capillary refil & one of the following :
- Fasting plasma glucose (FPG) ≥ 126 mg/dL
- Sx + random blood glu >200 mg/dL
- 2-hour OGTT plasma glu >200 mg/dL
- HgbA1c >6.5%
ALL NEW DM 1 DRAW:
T1D antibodies: Anti-pancreatic antibodies (insulin, GAD, IA2)
- At least 2 abs usually present to tell if it is an immune attack
Thyroid Antibodies:
- TSH not helpful initially due to loss of metabolic control, draw again in 6 mo after new onset DM 1
Celiac:
- Anti-endomysial antibodies
- tissue transglutaminase antibodies
new dx of T1DM should immediatekly go to ED due to risk of
DKA
tx of T1DM
Insulin – keeps glucose levels down
Glucagon (hypoglycemia) - emergent
complciations of T1DM
DKA
Diabetic retinopathy (non-proliferative–> proliferative)
Symmetrical sensory polyneuropathy (“stocking-glove”)
Nephropathy (albuminuria)
Pregnancy complications (ex. macrosomia)
CV – tachycardia
define DKA
Hyperglycemia –> INC ketones from muscle/fat breakdown
si/sx of DKA
Can look just like flu or gastroenteritis!
- Vomiting
- Tachypnea
- Abd pain
- SOB
- AMS 2° to metabolic derangement
Dx of DKA
BS >250
Metabolic acidosis (pH <7.3 or bicarb <18)
Moderate ketosis
Tx of DKA
IV fluids
Insulin – of of choice for BS contreol
Potassium – CHECK, if low then repleat BEFORE you give insulin – insulin depletes K
- If normal insulin + K
- If high just give insulin
Bicarb – if acidotic w/ pH of <6.9
define Hypoglycemia
BS <70
si/sx of hypoglycemia
- Shakiness/ Dizziness / Anxious
- Teeth chattering
- Fatigue
- Diaphoresis
tx of hypoglycemia
Glucagon
Fast acting carbs (ex. juice/soda, soft candy, sugar cubes, honey)
2 physiologic causes of hyperglycemia in the morning: check 2 AM blood sugars
Tx??
Dawn phenomenon : Surge of hormones daily around 4-5am
- Treatment – increase overnight basal
Somogyi effect : patient low in the early morning à hormones are released and overshoot the correction
- 2 AM BS is 60 (low)
- Treatment – snack before bed or reduce overnight basal
list types of insulin
ultra rapid acitng
rapid acting
intermediate acting
long acting
inhaled
ultra rapid acitng (2-4 hrs)- lispro, aspart, glulisine
rapid acting (3-6 hrs)- humulin/novalinR
intermediate acting - humulin/novalinN
long acting (12-24 hrs) - glargine/detemir
inhaled (10-16 hrs)- exubera
name the types of Diabetic Retinopathy
Non-proliferative: Initial manifestation
- _Dilation of small vessel_s; vascular closure –> ischemia –> ↑ permeability
Progressive Diabetic Retinopathy: Proliferative
- Abnormal vascular proliferation (neovascularization)
- Late stage
“cotton wool” spots
dx?
Diabetic Retinopathy - Non-proliferative
tx of diabetic retinopahty
proliferative
nonprolif
Non-proliferative:
- Prophylactic laser photocoagulation - Fenofibrate
proliferative: VEGF inhibitors
si/sx of Peripheral neuropathy
Sensory loss ascends
By mid-calf, it begins in hands - “stocking-glove” pattern
vibratory sensation loss
altered proprioception
impaired pain, light touch, and temperature
↓ reflexes
leading cause of (CKD), & (ESRD) requiring dialysis
Nephropathy
T1D and nephropathy:
Dx?
up to 30% will have increased albuminuria after 15 year duration of T1D
- Less than half of these will progress to nephropathy
dx:
- Albuminuria
- Sometimes hematuria
T1DM in pregnancy causes ???
Macrosomia (large baby)
- Increased glucose crosses the placenta; injected Insulin does NOT
- Fetus makes more insulin in response to high glucose (acts as growth factor for baby)
define T2DM & pathophys
Heterogeneous group of disorders which include some or all the following:
- Insulin resistance
- Impaired insulin secretion
- ↑ glucose production
=== Resultant hyperglycemia
is the most important environmental factor causing insulin resistance
Obesity (BMI >25)
pathophys of T2DM
- Dysregulation or deficiency in the release of insulin by beta cells
- Inadequate or defective insulin receptors
- Productive of inactive insulin or insulin that is destroyed
=== Results in inability to transport glucose into fat and muscle cells, thereby starving body cells and the breakdown of fat and protein is increased
si/sx of T2DM
- Polyuria
- Polydipsia – inc thirst
- Polyphagia – inc hunger
- Fatigue/weakness
- Electrolyte disturbances
- Chronic skin infection
- Acanthosis nigricans
- Loss of DTRs in ankles
use Oral Glucose Tolerance Test (OGTT) to dx prediabetes vs diabetes
Dx Pre-diabetes (impaired glucose tolerance IGT)
BG is 140-199 mg/dL after 2hrs
Dx Diabetes – BG is >200 mg/dL
dx critria for pre-diabtes
Fasting plasma glucose (FPG) 100-125 mg/dL
HgbA1c 5.7 – 6.4
2-hour OGTT plasma glu 140-199 mg/dL
dx criteria for diabetes
Fasting plasma glucose (FPG) ≥ 126 mg/dL
Sx + random blood glu >200 mg/dL
HgbA1c >6.5%
2-hour OGTT plasma glu >200 mg/dL
T2DM pharmacologic therapuy should be initiated when ..?
A1C >7.5 start at time of dx – early start of pharm therapy is assocw/ improved glycemic control over time and ↓ long-term complications
Screening for DM 2
All individuals ≥45yrs - if normal every 3 years
Earlier (<30 yr) in some pts
- BMI≥ 25 or central obesity / Habitually sedentary
- 1 st degree relative with DM
- High-risk ethnic population
- delivered a baby >9lbs
- HTN (>140/90)
- HDL < 35mg/dL or triglycerides >250 mg/dL
- Hx prediabetes or CV dz
Routine Health Maintenance T2DM
Monitor Hgb A1C every 3 mo
urine microalbumin yearly as predictor of kidney disease
Podiatry & Ophthal referral
Self-monitoring of glucose levels with glucometer (check fingersticks) (1-4 times per day)
Long Term Complications T2DM
non-vascular
microvascular
macrovascular
Non-vascular
- Gastroparesis
- Sexual dysfunction
- Glaucoma
- Cataracts
- Skin Δ
- Infections
Microvascular
- Retinopathy – leading cause of blindness in US
- Neuropathy
- Nephropathy
Macrovascular
- CAD / MI/ stroke
- PVD
- Cerebrovascular disease
- Nonhealing ulcers
target A1c T2DM
Target A1C - set higher for the elderly, pts with multiple comorbidities
•Goal - A1C value ≤7.0%
defien Hyperglycemic Hyperosmolar State (HHS)
complication of T2DM
Hyperglycemic condition resulting in hypovolemia & electrolyte abnormalities
Precipitating Factors of HHS
Major illness: MI, CVA, Sepsis, pancreatitis
Drugs that affect carb metabolism:
- Glucocorticoids
- thiazides
- ‘atypical’ antipsychotic agents
Compliance issues
dx HHS
Hyperglycemia (>1000 mg/dL)
Hyperosmolality
Pre-renal azotemia (volume depletion)
↓ potassium, Mg and phosphate
In contrast to DKA –> acidosis and ketonemia are absent or mild
tx HHS
IV insulin infusion
IV fluid
Electrolyte monitoring and repletion (potassium, magnesium, phosphate)
inital theray for T2DM
Metformin – 1st line in most guidelines for most patients
Add a second agent if/when goal A1C <7% is not achieved within 3 mo of initial therapy
- Oral agent (sulfonylureas), insulin
- Switch to insulin (A1C >8.5)
If goal A1C is not met while on 2 oral agents
- add insulin (alternatively add GLP-1 receptor agonist)
T2DM *Alternative 1st line therapy (also added to Metformin when necessarily)
Sulfonylurea
Sulfonylurea safest in CKD
Glipizide
•metabolized by liver to inactive metabolites, excreted by kidney
which T2DM medications have CVD benefit?
(GLP1) R agonists - “glutide”
- Liraglutide (Victoza)
- Semaglutide
(SGLT-2) - “liflozin”
- Empagliflozin
- Canagliflozin
T2 DM med most likely to cause hypoglycemia
Sulfonylurea
Glyburide
Glipizide *safest in CKD
Glimepiride
side effects of metformin
Can cause lactic acidosis (rare)
- Impairs lactate uptake by liver (avoid in liver failure)
- In renal failure patients, ↓ in metformin excretion, lactate excretion
list DPP-4 inhibitors
“gliptin”
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
list GLP1 R agonists
“glutide” ELS
Exenatide (Byetta) -
Liraglutide (Victoza) - CVD benefit
Semaglutide - CVD benefit
list SGLT-2 inhibitors
Empagliflozin ** CV benefit!
Canagliflozin *CV benefit!
T2DM medication that
Black Box Warning: medullary thyroid ca. in mice
CI: personal or family hx thyroid cancer
(GLP1) R agonists
Exenatide (Byetta)
Liraglutide (Victoza) - CV benefit
Semaglutide - CV benefit
tx of Diabetic nephropathy
Glycemic control & Strict blood pressure control
Administration of ACE-I or ARB
Avoid some glucose-lowering medications in advanced renal insufficiency (sulfonylureas and metformin)
Reduce daily protein intake
Nephrology consult
- Referral for transplant with GFR approaches 20ml/min
Diabetic Neuropathy most common type
Most commonly Distal Symmetric Polyneuropathy (DSPN)
tx of Diabetic Neuropathy
Duloxetine (Cymbalta)
Pregabalin (Lyrica)
decribe a normal erection
- Increased arterial flow
- Relaxation of smooth musculature in both corpora cavernosa
- Increased venous resistance
- Muscle contraction increases rigidity of penis w/ increase in intra-cavernous mmhg > systolic BP
define ED
Consistent inability to attain or maintain sufficiently rigid penis for sexual performance
>50% 40-70 yo
types of ED
Vascular -
- Arterial (obstruction)
- Venous (leak)
Neurogenic
- Multiple sclerosis
- Parkinson’s disease
- CVA, Spinal injury/Tumor
Hormonal -
- Hypogonadism
- Hyperprolactinemia
- HPA dysfunction
- Hypothyroid
Drug induced (25%) – A
- Antihypertensives
- Antidepressants
- Opioids
Psychogenic - Typically younger
Local penis factors
- Peyronie’s Disease (5-10% >50yo)
- Surgery, XRT, Pelvic trauma
describe link b/w ED and CAD
ED may be early sign of CAD or just precedes it development
- ED and CAD develop from endothelial dysfunction (same pathophysiology)
- Endothelial dysfunction results from decrease in Nitric Oxide thus impaired arterial vasodilation
- Share many RF’s
- ED w/o obvious cause should be screened for CVD (esp before initiating pharmacologic therapy for sexual dysfunction)
dx ED
Testosterone – Serum prolactin (if testosterone is low), LH
NPT testing (nocturnal penile tumescence testing)
Home testing kit : Rigi-Scan monitor
While sleeping detects number, tumescence, rigidity
- _Normal NP_T = psychogenic or hormonal
- Impaired NPT = vascular or neurogenic
Duplex Doppler Imaging or Angiography
- Deep penile artery angio identifies obstruction
- Doppler identifies venous leak
NPT testing (nocturnal penile tumescence testing)
- Normal NPT = indicates…??
- Impaired NPT = indicates…??
Normal NPT = psychogenic or hormonal
Impaired NPT = vascular or neurogenic
Duplex Doppler Imaging or Angiography
- Deep penile artery angio identifies ____
- Doppler identifies _____ ____
Duplex Doppler Imaging or Angiography
- Deep penile _artery angio identifie_s obstruction
- Doppler identifies venous leak
what is the SHIM - 5 used to help dx??
mild
mild-mod
moderate
severe
ED - assess severity of sx
mild - 17-21
mild-mod - 12-16
moderate - 8-11
severe 1-7
define Peyronie’s Disease
- Penile deformity or curvature of varying degree (fibrotic disorder)
- Etiology is from subtle trauma to penis and subsequent scarring
tx for Low libido
SSRI
5-alpha-red- inhib (finasteride)
testosterone + PDE5 inhib (sildenifil)
tx ability to sustain erection
pharmacologic - first line
vacuum assisted devices
penile self injecables
penile prothetics
first line tx of ED
list options
CI
PD-5 Inhibitors
-
Sildenafil (Viagra) - 1 hr before sexual encounter and lasts 4 hrs ,
- Diabetic, radical prostatectomy, parkinson’s
- Vardenafil (Levitra) - 1hr/4hr but available in ODT for faster absorption
-
Tadalafil (Cialis) - Can take low dose daily esp for pt’s with “complete” ED,
- Can also improve LUTS d/t BPH
- Avanafil (Stendra) - rapid onset of action 15-30 min
Absolute CI use w nitrates = hypotension
Relative CI use w alpha-adrenergic antagonists = hypotension
second line tx of ED
Vacuum Assisted Devices –
- Devices applied for max 20-30min
- Most often used by couples in stable relationships
Penile Injection: Injection or intraurethral placement of Prostaglandin-E1 directly into the corpus cavernosa and acts as smooth muscle vasodilator
- Method of injection w/ insulin needle directly into corporeal body
- Intraurethral placement & massage for 1 min to ensure = distrib into corpora cavernosa
- Erection w/in minutes
3rd line tx of ED
Penile prostheses - 3rd line when pharmacological and vacuum devices failed
- Peyronie’s disease pts at time of reconstruction candidates for placement of prosthesis at time of surgery
Penile revascularization- Low success rates unless strict criteria young, nonsmoking, otherwise healthy w/ recent focal arterial occlusion (50-65% success)
define Priapism
Prolonged >4-6 hours erection unresolved by ejaculation = urologic emergency
untreated leads to ischemia and then corporal fibrosis and necrosis of penis
tx priapism
Intracavernosal phenylephrine (Neo-Synephrine) injection
Aspiration of the corpora cavernosa dark blood followed by saline irrigation and, if necessary, injection of an alpha-adrenergic agonist
- A diluted solution of phenylephrine may be used for irrigation
Surgical intervention
define BPH
Cellular proliferation of the prostate at the central transition zone = histologic dx (most common benign tumor in men)
si/sx BPH
Storage/Irritative symptoms
Obstructive symptoms
Storage/Irritative symptoms
- Urgency / Frequency
- Nocturia
- Incontinence
Obstructive symptoms
- Hesitancy
- ↓ force or caliber of stream
- Splitting or spraying of the stream
- Dribbling post-void
- Straining to urinate
- Unable to or incomplete emptying of bladder
Dx BPH
Serum PSA (preferably 50-69yo)
- Men w/ prostate CA can have normal PSA and men w/ high PSA can have prostatic dz other than CA
Upper tract imaging = U/S or CT
- If Cr is high, UTI, hematuria, hx of calculi, CKD
Transrectal U/S can detect mass as well as total prostate volume (monitor for consideration of medical therapy vs surgical therapy w/ BPH)
BPH tx options
Watchful waiting/Behavioral modifications - IPSS <8 (mild
Pharmacologic treatment - IPSS <20 w/o
- Refractory retention
- BPH induced
- Kidney disease
- Bladder calculi
- Recurrent or persistent gross hematuria
Minimally invasive therapy
Conventional surgical therapy
BPH pts what must we always do before starting tx
Must refer for urologic evaluation prior to tx
what is the AUA?
Mild
Mod
Severe
assesses severity of sx of BPH
before staring therapy this must be calciulated - single most important tool in evaluation
Mild - 0-7
Mod - 8-19
Severe - 20-35
optional BPH testing
Maximal urinary flow rate (urodynamic profile)
- Flow rate >15ml/sec excludes clinically important BOO
Post-void residual volume -
- Normal = <12ml
- Bladder scanner (U/S)
Urine cytology
- Mostly irritative sx’s & RF’s for bladder malignancy (ie smoking, industrial exposure)
Cystoscopy –Not routine recommendation
- Assist in planning for surgical management of BPH
- Useful for detecting bladder malignancy, urethral stricture, calculi
BPH is not considered RF for prostate CA…?
as primarily central transition zone
versus prostate CA is peripheral part of prostate
tx of BPH
first line
second line
ED and BPH
sx’s assoc w/ overactive bladder
first line- Alpha 1a blocker
- Terazosin, Doxazosin, Tamulosin, Alfuzosin, Silodosin
second line- 5-alpha-reductase inhibitors
- More effective in men with larger prostates (>40ml by TRUS)
- Finasteride, Dutasteride
ED and BPH - PDE-5 Inhibitors
sx’s assoc w/ overactive bladder - Anticholinergic agents
- No elevated post-void residuals
- Oxybutynin, Tolterodine, Darifenacin, Solifenacin, Fesoterodine, Trospium
BPH tx when to initate Combo Therapy
- Severe symptoms of BPH IPSS>20
- Poor response to monotherapy
- Prostate >40ml
what is BPH combo therapy
Alpha- blocker AND 5-alpha reductase inhibitor - Both are superior to either agent alone in men w/ large prostate
Combination therapy over long term improved sx’s and reduced risks of clinical progression, acute urinary retention, and prostate surgery significantly versus monotherapy (MTOPS trial w/ doxazosin and finasteride)
BPH surgical options
Minimally invasive
- Laser - TRUS guidance w/ TULIP
- Microwave hyperthermia or electrovaporization - Transurethral catheter or rectoscope
- Radiofrequencies -TUNA (transurethral needle ablation)
Conventional Surgical Options
- TURP (transurethral resection prostatectomy
- TUIP (transurethral incision of prostate)
- small prostate severe sx
- Open simple prostatectomy - Operation of choice if coinciding bladder pathology (diverticulum or calculi
BPH pharm therapy should be initated when…?
mild to moderate IPSS <20 w/o
- Refractory retention
- BPH induced
- Kidney disease
- Bladder calculi
- Recurrent or persistent gross hematuria
list Alpha 1a blockers
Terazosin
Doxazosin
Tamulosin
Alfuzosin
Silodosin
list 5-alpha-reductase inhibitors
more effective in??
More effective in men with larger prostates (>40ml by TRUS)
- Finasteride
- Dutasteride
PDE-5 Inhibitors for BPH
Consider use if both ED and BPH <20 IPSS -
Tadalafil (Cialis)
list Anticholinergic agents used in BPH
indication?
examples?
Predominantly irritative sx’s assoc w/ overactive bladder
No elevated post-void residuals
- Oxybutynin
- Tolterodine
- Darifenacin
- Solifenacin
- Fesoterodine
- Trospium
