Microvascular Complications of DM

Question 1

4 molecular pathways implicated in pathogenesis of diabetic tissue damage?

Answer 1

Polyol pathway (involves oxidative stress).
Advanced glycosylation end-products (AGE) -> inflammation.
Protein Kinase C (PKC) activation.
Hexosamine pathway.

Question 2

What are the big 3 areas of microvascular complications of DM?

Answer 2

Retinopathy, nephropathy, and neuropathy.

Question 3

What has hyperglycemia got to do with retinopathy? (5 processes)

Answer 3

Causes altered blood flow, inflammation, edema, ischemia, and proliferation.

Question 4

Two major categories of diabetic retinopathy?

Answer 4

Non-proliferative diabetic retinopathy (NPDR)

Proliferative diabetic retinopathy (PDR)

Question 5

What’s the most common cause of vision loss of diabetes?

Answer 5

Macular edema.

Question 6

3 signs of mild edema?

Answer 6

Microaneurysms
Dot hemorrhages
Hard exudates (macrophages leaking lipids)

Question 7

3 signs of moderate/severe retinopathy?

Answer 7

Soft exudates (“cotton wool spots”)
Venous beading
Intraretinal microvascular abnormalities (messed up, dilated, tortuous vessels)

Question 8

What’s the main characteristic of proliferative diabetic retinopathy (PDR)? Why is that bad?

Answer 8

Neovasculariztion.
Bad because new vessels are fragile and prone to hemorrhage, fibrosis, and ischemia.
Can cause retinal detachment.

Question 9

2 main ways to prevent retinopathy in diabetes?

3 treatments with less evidence?

Answer 9

“Cornerstones”: Glycemic control, antihypertensives.

Less evidence: Lipid lowering, antiplatelets, carbonic anyhydrase inhibitors.

Question 10

Is glycemic control better for primary prevention or delaying progression of retinopathy?

Answer 10

Primary prevention, unsurprisingly.

Question 11

3 treatments for severe PDR?

Answer 11

Panretinal photocoagulation (PRP).
Medical Tx: intravitreal steroids, VEGF-inhibitors.
Vitrectomy (only for very severe cases).

Question 12

3 pathological changes in glomerular disease (of diabetes)?

Answer 12

Mesangial (i.e. stromal) expansion.
Basement membrane thickening.
Sclerosis.

Question 13

What’s the difference between microalbuminuria and proteinuria?

Answer 13

Proteinuria is more. ( > 300 mg/g Creatinine)

Microabuminuria is 30-300 mg/g Creatinine.

Question 14

5 stages in the natural history of diabetic nephropathy? At what point is this most likely still reversible?

Answer 14

Glomerular hypefiltration (w/ enlarged kidneys).
Microalbuminuria.
Macroalbuminuria.
Decreased GFR.
End stage kidney failure.
This is most likely still reversible at the microalbuminuria stage.

Question 15

4 ways to prevent nephropathy?

Answer 15

Glycemic control.
Blood pressure control.
Treat dyslipidemia <- note this helps nephropathy, less clear for retinopathy.
Monitor urine microalbumin:creatinine ratio.

Question 16

When should screening for nephropathy start in T1D vs. T2d?

Answer 16

T1D: annually starting 5 years after Dx.
T2D: right away.

Question 17

2 medical treatments for diabetic nephropathy?

2 behavioral changes?

Answer 17

ACE inhibitors.
Angiotensin II receptor blocker.
Restrict sodium and protein intake. Lose weight.

Question 18

Why do antihypertensives help nephropathy?

Answer 18

Efferent arteriole from glomerulus is dilated, reducing glomerular pressure.

Question 19

Where does diabetic neuropathy first present?

Answer 19

Usual in hands in feet.

Question 20

4 types of diabetic neuropathy?

Answer 20

Distal symmetric sensorimotor polyneuropathy (i.e. peripheral/diabetic neuropathy).
Autonomic neuropathy.
Polyradiculopathy.
Mononeuropathy.

Question 21

Symptoms of peripheral neuropathy?

What’s lost first in peripheral neuropathy?

Answer 21

Decreased sensation, paraesthesia, or hyperesthesia.
Vibration and proprioception are lost first?
Motor stuff is lost later.

Question 22

2 physical exam findings in polyneuropathy?

Answer 22

Sensory loss.

Loss of ankle reflexes.

Question 23

4 things on DDx of polyneuropathy? (other than diabetes-related)

Answer 23

Alcohol, B12 deficiency, Uremia (from kidney disease), hypothyroidism.

Question 24

Treatment of painful neuropathy?

Answer 24

Lots of things: Anticonvulsants, TCAs, SNRIs, opioids, topical stuff…

Question 25

4 types of autonomic neuropathy?

Answer 25

Cardiovascular
GI
GU
Peripheral (sudomotor)

Question 26

4 CV manifestations of autonomic neuropathy?

Answer 26

Resting tachycardia.
Exercise intolerance (HR won't increase).
Orthostatic hypotension.
Silent MI.
(can be fatal)

Question 27

Big picture of GI autonomic neuropathy? What 4 things can this lead to?

Answer 27

Loss of smooth muscle tone.
Lower esophageal sphincter relaxed -> GERD.
Gastroparesis.
Diabetic enteropathy. (Constipation / diarrhea / fecal incontience).
Gall bladder atony and enlargement (increased risk of stone formation).

Question 28

Treatment of gastroparesis secondary to diabetic autonomic neuropathy? (3 things)

Answer 28

Glycemic control
Diet modification: less fat, more fiber.
Prokinetic agents: Eg. erythromycin, metoclopramide (Reglan)

Question 29

How does delayed gastric empyting mess up glycemic control?

Answer 29

People take insulin with meals, but if food doesn’t get absorbed quickly, people will have a period of hypoglycemia followed by hyperglycemia.

Question 30

4 GU manifestations of autonomic neuropathy?

Answer 30

Urinary retention -> UTIs + overflow incontinence.
Erectile dysfunction.
Retrograde ejacuation (internal urethral sphincter not closing).
Female sexual dysfunction (pain, no lube).

Question 31

Skin changes secondary to peripheral autonomic neuropathy?

Answer 31

Less sweating -> dry, itchy skin.
Peripheral edema.
Biomechanical changes -> callus and ulceration.

Question 32

Can the neuropathy from diabetes be acute?

Answer 32

Yes. Can manifest as sudden weakness and pain in single nerve. (doesn’t look like stroke, because it’s more LMN than UMN)

Question 33

Presentation of acute-onset radculopathy aka diabetic amyotrophy?

Answer 33

Pain followed by weakness… often of L2-L4 -> legs, hips, buttocks.
Can be truncal and happen in a dermatomal pattern.

Question 34

Why are foot ulcers bad?

Answer 34

Amputations, sepsis, death.

Question 35

4 risk factors for diabetic foot ulcers?

Answer 35

Neuropathy (can't feel pain, skin changes)
Foot deformity -> pressure points
Peripheral vascular disease
Poor glycemic control
(the latter 2 impair wound healing)

Question 36

What is Charcot arthropathy?

Answer 36

In diabetes, loss of arch of foot. Can predispose to ulcers.