10/15- Chronic Complications of Diabetes 1 & 2 Flashcards Preview

MS2 Endocrine > 10/15- Chronic Complications of Diabetes 1 & 2 > Flashcards

Flashcards in 10/15- Chronic Complications of Diabetes 1 & 2 Deck (63):

What are some serious complications of diabetes?

- Diabetic retinopathy: leading cause of blindness in working-age adults

- Diabetic nephropathy: leading cause of end-stage renal disease

- Stroke: 2-4x increase in CV mortality and stroke

- CV disease: 80% of diabetic pts die from CV events

- Diabetic neuropathy: leading cause of nontraumatic lower extremity ampuations


What causes diabetic retinopathy?

Cellular abnormalities resulting from hyperglycemia:

- Increased polyol accumulation, decreased myo-inositol

- Formation of AGEs

- Increased oxidant stress

- Increased protein kinase C – β activity


Describe the "Polyol pathway"

The reactions deplete NADPH, leading to decreased glutathione synthesis and increased oxygen free radicals 

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Describe the formation of AGEs?

- Increased glucose production causing glycosylation of hemoglobin (?)

- Forms reversible Schiff base at first, but over extended amount of time, may get irreversible product

- Used in HbA1c measurements


How common is eye disease in diabetics?

- Prevalent in ½ of all diabetic patients

- Incidence initially greater in older patients

- Incidence “flattens out” after 25y at ~ 80%


Describe the stages of eye disease in diabetics


- Microaneurysms

- "Dot-blot" hemorrhages

- Hard exudates


- Soft exudates


- Large hemorrhages


- Neovascularization -> pre-retinal/vitreous hemorrhage

- Vitreous fibrosis -> retinal detachment


Describe the pathophysiology of retinopathy

- Increased epithelial cells and decreased pericytes 

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What is seen here? 

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Normal retina


What is seen here? 

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Fairly advanced background retinopathy

- Micro-aneurysms: little red dots

- Micro-hemorrhages

- White spots are lipid deposits from old hemorrhages


What is seen here?

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Even more advanced background retinopathy

- Micro aneurysms

- Exudates WITH additional complication

- Proliferation of vessels with leaked blood

- Fairly acute hemorrhage resulting from blood vessel proliferation

- This is an emergency


What is seen here? 

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Neovascularization sitting right over the macula

- Rupture of this would lead to complete blindness

- Needs emergent laser therapy


What is seen here? 

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- Multiple hemorrhages have caused fibrosis

- Retina gets stuck to vitreous and vitreous pulls retina off the back of the eye


How can you treat diabetic retinopathy?

Pan-retinal laser photocoagulation

- Series of controlled burns

- Problem is that hypoxia in the center of the eye and drive of VEGF and vessel proliferation; laser ablation drives blood from periphery to center


What is seen here?

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Eye post-laser photocoagulation

- Laser burns in periphery

- Better appearance centrally


What is seen here?

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Rubeosis Iridis

- Abnormal blood vessels that may be seen in naked eye


What are the effects of glycemic control in diabetic retinopathy?

Intensive treatment reduced the treatment of:

- First appearance of any retinopathy by 30%

- Severe NPDR, proliferative retinopathy and laser Rx by 50%

- “Clinically meaningful retinopathy” by 30-80%


Is kidney disease more common in type I or type II diabetes

Type 1 > 2

- Very high morbidity and mortality


T/F: Distinct susceptibility genes play a role in kidney disease in diabetics


- Na/H pump overexpression

- Ethnic differences

- Seen in sibling-pair analysis


What is the pathogenesis of kidney disease in diabetes?

- Timeline

- Initial hyperfiltration

- Increase in glomerular pressure, GFR, and kidney size

- Glomerulosclerosis and proliferation of mesangium

- Onset of proteinuria, azotemia

- Increased creatinine and eventual end stage renal failure

Timeline from start to symptomatic kidney disease is ~ 15 yrs


What test may reflect initial changes of kidney disease in diabetes before they become symptomatic?


- Any amount of protein in the urine means that you've stared down the slippery slope of diabetic nephropathy


What are the end histological features of diabetic nephropathy?

- Thickening of basement membrane

- Mesangial proliferation

- Glomerulosclerosis

- Tubular atrophy

- Interstitial fibrosis and cellular infiltration


What is seen here?

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Left: normal glomerulus

Right: diabetic nephropathy


What is seen here? 

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Diabetic nephropathy with ESRD

- Glomerulosclerosis

- Vessels sclerotic

- Urinary space almost gone


What treatments may improve survival after treatment of ESRD in diabetes?

- Living-related transplant (best)

- Cadaver transplant (Although diabetes will end up destroying new kidneys as well)

- Hemodialysis


Describe albuminuria levels

- Normal

- Microalbuminuria

- (Macro)abluminuria

- Normal: under 30 mg/24 hr

- Microalbuminuria: 30-300 mg/24 hr

- (Macro)albuminuria: > 300 mg/24 hr


Macro-albuminuria is associated with what?

Increased risk for:

- Renal failiure

- CV disease


How does glycemic control affect nephropathy?

In type I pts, intensive treatment reduced development of:

- MIcroalbuminuria (by 40%)

- Macroalbuminuria (by 50%)

Treat HTN with ACEI...


What is the most common chronic complication of diabetes?

Affected nervous system


What nervous systems are affected in diabetic retinopathy?

Systems affected:

- Sensory

- Motor

- Cranial

- Autonomic


How are nervous system complications classified in diabetic neuropathy?


- Symmetric, distal polyneuropathy

- Mononeuropathy (simplex or multiple)

- Radiculopathy

- Autonomic neuropathy


Describe the pathophysiology of diabetic neuropathy?

- Distal, multiple neuropathies usually metabolic (polyol pathway)

- Proximal, mononeuropathies usually vascular


The DCC study focused on what pt cohort?

Type I diabetes


Fun fact: within 5 yrs of diagnosis, about half of the patients with type II diabetes had developed some kind of neuropathy



Classification of diabetic neuropathies: symmetric

- Distal, primarily sensory polyneuropathy

  • Mainly large fibers affected
  • Mixed*
  • Mainly small fibers affected*

- Autonomic neuropathy

- Chronically evolving proximal motor neuropathy* (recovery likely)

*Often painful


Classification of diabetic neuropathies: asymmetric

- Acute or subacute proximal motor neuropathy* (painful)

- Cranial mononeuropathy*

- Truncal neuropathy* (painful)

- Entrapment neuropathy in the limbs

*Recovery (partial or complete) is likely


What is seen here?

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Overactivity of extensors

- Sign of diabetic neuropathy (at least 3-4 yrs)

- At this point, typically have lost sensation as well


What test can be done as a (cheap) alternative to nerve conduction test?

Monofilament test

- Press into foot until it just bends


What is seen here?

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Distal/peripheral symmetric polyneuropathy in hands

- Interossei and lumbricals lost

- Sensation lost as well


What is seen here?

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Charcot's foot


What is seen here? 

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Splintered tarsal bones and splintered head of metatarsal; Charcot's foot

- Result of very severe symmetric polyneuropathy

- Due to loss of sensation and bone nutrition


What is seen here? 

- What is causing this? Onset?

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Mononeuropathy: wrist drop

- "Mononeuritis simplex"

- Due to radial neuropathy

- Large nerves damaged due to block of BV supplying that nerve

- Acute onset; not much you can do after it happens


What is seen here? 

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Diabetic amyotrophy (or myoatrophy); mononeuritis

- "Mononeuritis multiplex"

- Tremendous wasting of both hamstrings and quadriceps

- Also a large vessel problem (affecting both groups of muscles)

- This would be preceded by tremendous pain (infarction of the muscle)

- At big risk for falls


What are some diabetic autonomic neuropathy syndromes?

- Cardiovascular:

  • Orthostatic hypotension
  • Tachycardia
  • Sudden death

- Gastroparesis

  • Vomiting; typically food that was ingested a day before

- Erectile dysfunction (have to asked; very rarely volunteered)

  • ED is very closely related to CV risks

- Cystopathy

  • Ask about dribbling or prostatic sort of symptoms in men; sense of incomplete voiding

- Sudomotor disorders

  • Sweating

- Hypoglycemia unawareness


How common is ED in diabetes?

- Diabetes results in ED in 50%-75% of men

- In men with diabetes, the incidence of ED is:

  • 9% from age 20 to 29 years
  • 95% by age 70

- ED may be the presenting symptom of diabetes

- > 50% of men develop ED within 10 years of diagnosis, and it may precede the other complications of diabetes


What are the 4 phases to the arterial pulse and volume change with Valsalva maneuver?

First 3 are sympathetic responses and 4th is parasympathetic

Bedside test will tell you about phase 2 (S) and 4 (PS)

- Normal response in heart rate is sinus arrhythmia

  • Deep breathing causes wide variations in heart rate
  • Bradycardia upon resumption of breathing after Valsalva(?)- PS part of response?

- In diabetic autonomic neuropathy, pt already has baseline tachycardia

  • No change with Valsalva maneuver/deep breathing

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What are strategies to reduce microvascular complications?

Prevention (proven by intervention trials):

- Hyperglycemia


Treatments (proven by intervention trials):

- ACE inhibition for nephropathy

- Laser photcoagulation for retinopathy


What is diabetic dermopathy?

- Slightly depressed brownish lesions

- They are tiny infarcts in dermis

- May feel slightly painful or itchy

- Sign of long-standing and poorly controlled diabetes

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What is seen here? 

- What commonly accompanies it?

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Necrobiosis Lipoidica Diabeticorum

- Will see pretty advanced retinopathy with this

- Sign of terribly controlled diabetes with both micro and macrovascular complications


What are the macrovascular complications of diabetes?

Diabetes increases the risk of occlusive vascular disease several fold

Angina, exercise intolerance --> CAD

  • If autonomic neuropathy, “silent”
  • (50% of pts who come into ER with heart attack deny any chest pain, but have had progressive SOB)

- Claudication --> PVD

- TIAs, strokes --> CVA

- Renal artery sclerosis --> renal failure

  • First sign of diabetes clinically is micro-albuminemia (?)


How does diabetes affect Cardiovascular risk?

Diabetic has:

2-3x higher risk of CAD

- 4x higher risk of dying during acute MI

- 2x higher risk of post-MI death

- Persons with Impaired Fasting Glucose are also at increased risk of all these implications

Relative to other diabetic complications:

- 80% of all mortality

- Present in 50% of newly diagnosed diabetics


HbA1C is predictive of what in Type 2 Diabetes?

HbA1C predicts CHD in Type 2 Diabetes

- Other things may be more important: 


What factors are implicated in macrovascular disease (contributing/mechanistic factors)?

- Hyperglycemia

- Dyslipidemia

- Hypertension

- Insulin resistance

- Obesity/sedentary lifestyle

- Altered coagulation, platelet function, and fibrinolysis

- Nephropathy

- Cigarette smoking (seems to be multiplicative rather than just additive)


Describe the pathophysiology of macrovascular lesions in diabetics

- "AGE" of endothelial proteins


- Accelerated atherosclerosis

- Dyslipidemia


What are some strategies for reducing macrovascular complications?

Prevention proven by intervention trials

- Dyslipidemia

- Hypertension

- Antiplatelet therapies

Prevention suggested by epidemiologic analysis

- Disorders of thrombolysis

- Endothelial disorders


What is the most easily measured (but not only) aspect of pathophysiology of diabetes and atherosclerosis?


- Also, dysplipidemia diminishes the risk


What are 4 key features of diabetic dyslipidemia?

- Increased fraction of small, dense LDL-cholesterol (without increase in total quantity of LDL-C)

- Decreased HDL-cholesterol

- Hypertriglyceridemia

- Postprandial lipemia


What are the different types of dyslipidemia?

- Blood tests?

- Symptoms?

1. High chylomicrons

- High TGs

- Eruptive xanthomas

2. High cholesterol (homo/heterozygous)

- Normal TGs, but high cholesterol, high LDL

- Tendinous xanthomas (large lumps on large tendons)

3. High interdensity lipoproteins

- Palmar xanthoma (yellow streaks across palm)

4. High VLDL 

- Blood appears milky

- Eruptive xanthomas

- Often in 2' disease (diabetes, hyperthyroidism)

5. High chylomicrons and high VLDL

- Genetic or acquired

Diabetics get type 1, 4, or 5 dyslipidemia with eruptive xanthomas

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Describe normal lipoprotein metabolism

When fasting, insulin drops

- Hormone sensitive lipase converts TGs to free fatty acids and sent to liver where they are converted into VLDL

- Some converted into IDL and tehn LDL 

When you eat, insulin rises and inhibits HSL

- Preserves TGs within adipocytes

- Activates lipoprotein lipase (stores circulating TGs in adipose)

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Describe lipoprotein metabolism in diabetics

No insulin

- Can't restrain lipases

-> Excess fatty acids, more TG formation, more VLDL

- Insulin prevents/supresses transcription of cholesteryl ester trnasfer protein

- CETP normally takes transfers TGs from VLDL to HDL; without insulin, this is not suppressed and excess transfer actually makes HDL abnormal

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How should dyslipidemia be managed in pts with diabetes?

- ATP-III diet for Metabolic Syndrome

- Hyper-TG/low HDL-C

  • Niacin (may not reduce CV risk; controversial)
  • Fibrates

- LDL-C:

  • Statins

- Combinations: statins + fibrates (beware rhabdomyolysis)


Body type/obesity may also be a risk factor for macrovascular complications. How so?

- Apple-shaped (andrenoid?) (more weight carried above waist) is higher risk vs. pear-shaped (gynecoid?); marker of visceral obesity and dyslipidemia


What is the biggest predictive factor for risk of diabetes?

Visceral fat distribution

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How to manage AMI in Diabetes?

- Medical Management

  • β-blockers
  • ASA
  • ACE inhibitors

- Angioplasty vs. bypass (BARI)

  • Outcomes are much better with bypass than balloon angioplasty or stents (although elusion may get it close) for diabetics!
  • Rate of restenosis is really high in diabetics (atherosclerosis, high coagulability...)

- Glucose control (DIGAMI)

  • Continuous intravenous insulin infusion
  • Followed by intensive glucose control