Diabetes Flashcards
Diagnostic criteria for DM
Fasting plasma glucose of 7.0 + on 2 separate occasions
Random glucose of 11.1+ w/ symptoms of hyperglycemia
2-hr glucose of 11.1+ on 75g OGTT
HbA1C of 6.5% +
(and/or)
What blood sugar = impaired glucose tolerance/prediabetes?
FPG of 6.1-6.9 mmol/L = impaired fasting glucose
A1C 6.0-6.4 = prediabetes
Family history in T1DM?
Not usually family Hx (vs type 2 usually has FmHx)
Recommended screening for T1DM & T2DM?
T1DM not recommended (educate parents about signs of hyperglycemia such as polydipsia/polyuria)
T2DM: every 3 yrs for adults >40 or high risk (33% chance in 10 years)
If very high risk (50% in 10 years), screen every 6-12 mo
A1C% targets?
<6.5 if low risk of hypoglycemia (e.g. meds, pt characteristics)
<7.0 for most adults w/ T1DM/T2DM
7.1-8.5 if hypoglycemia issues, limited life expectancy, frail/elderly/dementia
HbA1C averages sugars over how long?
3 months (lifespan of RBCs)
FPG and 2-hr postprandial PG targets
FPG: <7 mmol/L
2-hr PP PG: <10
Upon diagnosis of T2DM, what is the threshold for starting metformin in addition to just lifestyle mods?
A1C >1.5% above target
(if less, just try lifestyle mods for 3 months before starting metformin if not reached target by then)
**if symptomatic hyperglycemia/metabolic decompensation –> Insulin +/- metformin
How do biguanides work? Example? Benefits? Can you use in pregnancy?
Improve insulin sensitivity @ liver Metformin = 1st line drug!! Doesn't cause hypoglycemia, improves lipid profile, weight-loss CV benefit Useful in pregnancy
What are 2 classes of meds that cause insulin secretion via diff mechanisms?
1) Affect K+ channels on B cells (sulfonylureas, meglitinides) glucose-mediated insulin release (DPP IV inhibitors or GLP-1 agonists)
Secretagogues (Sulfonylureas & meglitinides): examples, pros/cons, contraindications
Sulf: glyburide, gliclazide, glimepiride
Meglitinides: repaglinide, nateglinide, mitiglinide
Pros: rapid onset of action, lower postprandial glucose
Cons: hypoglycemia, weight gain
Contraindications: renal/liver disease (?? but some sulfonylureas recommended in severe DKD)
Incretin-based therapies: examples, route of admin, pros/cons, contraindication
DPP-IV inhibitors (gliptins): oral; Sitagliptin, Saxagliptin, Linagliptin
GLP-1 agonists: injection;Liraglutide, Semaglutide (Ozempic), etc; weight loss!! (also used to treat obesity) + nausea; CV benefits
No hypoglycemia! (glucose-DEPENDENT insulin secretion; incretins are endogenous)
SGLT2 inhibitors: Examples Mechanism of action Pros Cons Contraindications
Canagliflozin, Dapagliflozin (Forxiga), Empagliflozin (Jardiance)
Inhibit glucose reuptake in PCT by blocking Na-glucose co-transporter
Pros: better CV/renal outcomes, weight loss, lower BP (diuretic)
Cons: polyuria/dehydration, GU infections, DKA (rare)
Contraindications: moderate renal insufficiency, insulin-dependent DM
Alpha-glucosidase inhibitors: Example Mechanism of Action Why is use limited? Contraindications?
Acarbose
Inhibits enzyme that breaks down complex carbs so not absorbed
GI side effects due to undigested sugar in bowels (–> gas/bloating/diarrhea)
Contraindications: renal/liver disease
Thiazolidinediones:
Examples
Mechanism of action
Why is use restricted?
Rosiglitazone, Pioglitazone
Improve insulin sensitivity
Concerns of CV events (retracted, but can mess with fats, cause edema/weight gain, reduce hematocrit
Contraindicated if liver disease or CHF
2 types and examples of bolus insulin
Rapid-acting (just before eating): Lispro, Aspart
Short-acting (30 min before eating): Regular, Toronto
2 types and examples of basal insulin
Intermediate (12-16 hrs w/ peak): NPH
Long-acting (~24 hrs, no peak): glargine, detemir
In what situations might insulin be used initially in T2DM
Severe weight loss
Renal/hepatic disease prevent pills
Acute illness
Severe hyperglycemia (FPG >13.9), glucose toxicity
In T2DM insulin is usually administered how?
1 dose of long-acting before bed (endogenous usually sufficient for meals)
When pt w/ diabetes had illness w/ vomiting/diarrhea, what meds should be held until able to eat/drink normally?
SANDMANS Sulfonylureas & other secretagogues ACE-inhibitors Diuretics, direct renin inhibitors Metformin Angiotensin receptor blockers NSAIDs SGLT2 inhibitors
If pt with diabetes becomes pregnant, what are 3 things you should stop and 3 things you should start?
Stop:
- non-insulin antihyperglycemic agents (except metformin and/or glyburide)
- *most experts believe that intensive insulin therapy is the only means of achieving the degree of glycemic control desirable throughout pregnancy in women with type 1 and type 2 diabetes.
- statins
- ACEi/ARB (stop pre-conception if possible)
Start:
- Folic acid 1mg/day (start 3 months before conception if possible)
- Insulin if target A1C (<6.5%) not achieved on metformin or glyburide (T2DM)
- other hypertensive agents safe for pregnancy (e.g. labetalol)
ABCDESSS of diabetes care
A1C <7 (or 6.5 to reduce CKS/retinopathy)
BP <130/80
Cholesterol: LDL-C <2mmol/L or 50% reduction
Drugs for CVD risk reduction (ACEi/ARB, stains, ASA, SGLT2i/GLP1ra, as indicated)
Exercise + healthy eating
Screening for complications (ECGs, feet, kidney, retinopathy)
Smoking cessation
Self-management, stress, barriers
Which CV protection meds are indicated for patients with…
CV disease (cardiac ischemia, peripheral arterial disease, cerebrovascular/carotid disease)?
if also not at glycemic target?
Statin +
ACEi/ARB +
ASA
If not at glycemic target –> + liraglutide (GLP-1ra), empagliglozin or canagliflozin (SGLT-2 inhibitors)
Which CV protection meds are indicated for patients with…
No CV disease but microvascular disease (retinopathy, kidney disease, neuropathy)
Stain +
ACEi/ARB
Which CV protection meds are indicated for patients with…
No CV disease or microvascular disease but age 55+ w/ CV RFs
Statin + ACEi/ARB
Which CV protection meds are indicated for patients with…
No CV disease or microvascular disease
Age 40+ or 30+ w/ diabetes 15+ years
Statin
Name 4 drug classes that lower PG immediately & 2 that lower PG over weeks
Secretagogues, GLP-1 receptor agonists/DPP-IV inhibitors, alpha-glucosidase inhibitors, SLGT2 inhibitors
Delay for biguanides (metformin), thiazolidinediones
Name 5 diabetes drugs that don’t directly cause hypoglycemia
Biguanides Thiazolidinediones SGLT2-inhibitors Incretin therapies (GLP-1ras/DPP-IVi) Alpha-glucosidase inhibitors
Hypoglycemia = blood glucose of what? Associated with what meds?
<4 mmol/L
Insulin, secretagogues (sulfonylurea)
What leads to recurrent hypoglycemia w/ unawareness?
Hypoglycemia-associated autonomic failure
Reduced adrenomeduallary epi responses –> defective glucose counterregulation
Reduces symp neural responses –> hypoglycemia unawareness
What are the symptoms of hypoglycemia (2 categories)
Adrenergic: tremor, sweating, anxiety, palpitations, nausea, tingling (can be lacking w/ autonomic neuropathy)
Neuroglycopenia: headache, confusion, behaviour changes, weakness, drowsiness/coma, seizure, vision changes
What type of sugar can be administered and is identical to D-glucose (biologically active form of glucose found in plasma)
Dextrose
D50w = Dextrose 50% in water
Treatment for hypoglycemia
15g carbs as single sugars (e.g. 1/2 glass juice)
If reduced LOC and can’t eat –> IV D50w push or IM/SC glucagon
What med can mask hypoglycemica symptoms?
Beta blockers (stop tremor, palpitations, etc; catecholamine-mediated Sx)
Name 3 microvascular & 3 macrovascular complications of diabetes
Micro: neuropathy, nephropathy, retinopathy
Macro: CAD, CVD (TIA, stroke), peripheral vascular disease (amputation!)
What is the most common form of diabetic neuropathy?
Distal symmetric sensorimotor polyneuropathy
- distal sensory loss & pain (50% asymptomatic); glove-and-stocking distribution
- numbness/tingling/burning in feet, spreads proximally
Loss of protective sensation & motor defects may develop
+PVD –> foot ulcers + amputation
Name 4 manifestations of autonomic neuropathy
CV system: HR issues, tachycardia, orthostatic hypotension, sudden death
GU: gastroparesis, bladder-emptying issues
SNS: hyperhidrosis/anhirdosis
Reduced counterreg hormones (catecholamines) –> failure to sense hypoglycemia (hypoglucemia-associated autonomic failure)
Name 3 reasons why infections common in uncontrolled diabetes
Sugars available for bact/fungi
Immune abnormalities
Diminished vascularization/poor wound healing
How often are eye exams recommended in DM patients?
T1DM: annually
T2DM: annually or biannually
___ and ___ are the best ways of preventing diabetic retinopathy
Once it develops, the best treatment is ___
Annual dilated fundoscopy
Glucose/BP control
Photocoagulation therapy for existing proliferative retinopathy (laser –> thermal burn of retinal tissue –> corrects ischemic hypoxia, minimizes neovascularization)
Also VEGF-inhibitors
Describe proliferative retinopathy
New friable BVs on retina –> bleeding, vision impairment, can lead to retinal hemorrhage/detachment –> blindness
2 types of diabetic retinopathy
Nonproliferative: retinal vascular microaneurysms, blot hemorrhages, cotton-wool spots
Proliferative: neovascularization response to retinal hypoxemia –> new vessel rupture easily –> hemorrhage, retinal detachment
Catch nonprolif early to PREVENT progression to proliferative
Describe screening and progression of renal failure in DM
Yearly screening for microalbuminuria w/ urine albumine:creatinine
Microalbuminuria (smaller quantity) progresses to proteinuria; before progression much easier to treat, progression strongly associated w/ end-stage renal failure
Name 3 prevention strategies for renal failure
1) BP control
2) ACEi/ARBs
3) Glycemic control
LDL in diabetes should be controlled how?
<2mmol/L (aggressive control), even lower if very high risk
Statin therapy
LDL particulars in DM are more atherogenic (glycated, susceptible to oxidation)
Target BP in DM
<130/80 (lower than Htn!)
What is MODY? Inheritance pattern?
Mature Onset Diabetes of the Young
Distinct from type 1 & type 2
Genetic defects in B cell function, autosomal dominant inheritance
What is LADA?
Latent Autoimmune Diabetes in Adults (often misdiagnosed as type 2!)
What is C-peptide and how is it useful?
Substance secreted w/ insulin
Useful because can distinguish from synthetic insulin
Tumor in pancreas (insulinoma) would increase C-peptide with insulin level
Define metabolic syndrome
3+ of…
1) BP >130/85 or on meds
2) FPG >5.6 or on meds (or 6)
3) TAGs >1.7 or on meds
4) HDL <1 in men, <1.3 in women
5) Large waist circumference
Why does excess insulin secretion in T2DM lead to beta cell destruction?
B-cell fatigue +
Amylin co-released w/ insulin –> deposits on B-cells
What is the most common cause of CKD?
Diabetic nephropathy
Name 2 mechanisms leading to complications of DM?
1) Non-enzymatic glycation of proteins/lipids –> proinflamm molecules, hyaline arteriosclerosis –> reduces perfusion –> CAD, PAD, CVD, retinopathy, nephropathy
2) Glucose –> sorbital in cells that lack enzyme to convert –> osmotic cell death (demyelination of Schwann cells, lens of eye, tubular cells)
The 6 “I”s of DKA
1) Reduced insulin supply (undiagnosed, not taking meds)
2) Infections
3) Inflammation
4) Intoxication (alcohol, cocaine, methamphetamines for ADHD)
5) Infarction (MI, stroke)
6) Iatrogenic (corticosteroids, surgery)
* *mostly increases in insulin demand or decreases in supply
What is the triad of characteristics for DKA/HHS? Pathophys?
Stress –> SNS stimulation –> E/NE –> glucagon
Gluconeogenesis, glycogenolysis, lipolysis
–> hyperglycemia, glucosuria, osmotic diuresis, hyperosmolar state
Triad = ketoacidosis + dehydration + hyperosmolarity
DKA has mainly 1+2
HHS has 2+3
What happens to potassium in DKA?
Acidosis –> H+ moves into cells, K+ into ECF
also insulin required for Na/K ATPase, so K influx reduced
Results = LOW total body K but normal/HIGH serum k!!
Arrhythmias –> palpitations, chest pain
What type of respiration is seen in DKA?
Kussmaul respiration due to acidosis
What type of acidosis is seen in DKA?
High anion gap metabolic acidosis
What does HHS stand for?
Hyperglycemic hyperosmolar syndrome
What is the issue with hyperosmolarity in HHS? How does it impact neurons/muscles?
Water moves out of cells into blood stream
Neurons: AMS –> seizures, coma
Muscles: weakness
Serum glucose in DKA & HHS
DKA: >13.9
HHS > 33.3
pH in DKA & HHS
DKA pH<7.3, can get VERY low
HHS >7.3
HCO3- in DKA & HHS
DKA: low
HHS: normal
Urine/serum ketons in DKA & HHS
DKA: high
HHS: negative
Anion gap in DKA & HHS
DKA: high (>12)
HHS: normal, or slightly increased due to lactic acid
Serum osmolality in DKA & HHS
DKA: variable
HHS: very high (>320 mOsm/kg)
What is interesting about the way we measure ketones?
We measure acetoacetate even though B-hydroxybutyrate synthesized 3x as much
May appear to INCREASE during treatment because B-hydroxy gets converted to acetoacetate first
DKA & HHS: which has worse prognosis and why?
HHS has much worse prognosis (15% mortality vs <1%) vs patients older, more likely life-threatening precipitating event, comorbitities
___ is a possible severe complication during DKA treatment esp in kids
How to avoid?
Cerebral edema
Avoid quick correction of serum glucose, overreplacement of free water, bicarb admin unless absolutely necessary
4 components of DKA treatment
1) Rehydration w/ 0.9% normal saline (may have to change to 0.45% half-normal or D5W if high Na or low glucose respectively)
2) Insulin
3) Potassium (insulin pushes K back into cells)
4) Bicarb only if pH really low
(also start w/ ABCs of course!)
Describe translational hyponatremia in hyperglycemia
Water moves into ECF
No change in total body water but lower [Na] in serum
Will return to normal once plasma glucose corrected
Need to correct for Na measurements in this state
Recommended physical activity per week
150 min moderate exertion
Why might a diabetic patient by put on pip-tazo for an infected ulcer?
Because of higher likelihood of pseudomonas infection
Meds for blood sugar in stage 4 and 5 DKD (no dialysis)
Stage 4 = GLP-1 (sulfonylureas possible)
Stage 5 = sulfonylureas (GLP-1 possible)
**need sulfonylureas with inactive metabolites and lower risk of hypoglycemia, because with CKD hypoglycemia is even more likely (reduced renal clearance of insulin)
In hemodialysis pts, ____ is preferred
In peritoneal dialysis pts, ___ is preferred (for glycemic control)
Hemo –> insulin
PD –> sulfonylureas (may also require Subq insulin)
____ should NOT be used in pts w/ advanced CKD
Metformin
SGLT2 inhibitor DKD paradox
Not effective for glycemic control in advanced DKD
BUT prescribed due to cardiorenal protective effects in pts w/ declining GFR
Why might ESKD patients not present “typically” w/ severe hyperglycemia?
Anuria (no glycosuria/volume depletion)
6 key things to monitor in DKD patients
Blood pressure Volume status eGFR A1C UACR Serum K
In pt w/ T2DM who needs insulin, what regime should you start with and why?
Basal rather than prandial
Because more convenient for patient, better adherence, less hypoglycemia
The possibility of _____ should be considered in diabetic patients with foot wounds associated with signs of infection in the deeper soft tissues and in patients with chronic ulcers, particularly those overlying bony prominences that do not heal after several weeks of wound care and off-loading
Exogenous osteomyelitis
Empiric Abx in pt with osteomyelitis (adult)
IV Vancomycin PLUS either antipseudomonal cephalosporins (ceftazidime, cefepime) OR antipseudomonal fluoroquinolones (ciprofloxacin, levofloxacin)
Diagnosis of osteomyelitis (definitive)
isolation of bacteria from a sterilely obtained bone biopsy sample with histologic evidence of inflammation and osteonecrosis
If bone biopsy isn’t possible, what clinical findings related to diabetic foot ulcer support diagnosis of osteomyelitis
●Grossly visible bone or ability to probe to bone
●Ulcer size larger than 2 cm2
●Ulcer duration longer than one to two weeks
●Erythrocyte sedimentation rate (ESR) >70 mm/h
Do x-ray, if it doesn’t show it do MRI
Amputation indicated if…
Critical limb ischemia (PAD) w/out option of revascularization
Severe infection w/ extensive soft tissue or bony destruction
Most commonly recommended Abx prophylaxis for vascular surgery/limb amputation
Cefazolin (1st gen IV cephalosporin)
=”Ancef”
What ankle-brachial index indicates arterial disease?
<1
0.5-0.9 = mild-mod, <0.5 = severe
There is a strong, interdependent association between diabetes and what other endocrine disorder?
Thyroid dysfunction (hyper & hypo)
