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

1
Q

What are some serious complications of diabetes?

A
  • 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
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2
Q

What causes diabetic retinopathy?

A

Cellular abnormalities resulting from hyperglycemia:

  • Increased polyol accumulation, decreased myo-inositol
  • Formation of AGEs
  • Increased oxidant stress
  • Increased protein kinase C – β activity
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3
Q

Describe the “Polyol pathway”

A

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

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4
Q

Describe the formation of AGEs?

A
  • 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
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5
Q

How common is eye disease in diabetics?

A
  • Prevalent in ½ of all diabetic patients
  • Incidence initially greater in older patients
  • Incidence “flattens out” after 25y at ~ 80%
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6
Q

Describe the stages of eye disease in diabetics

A

Background:

  • Microaneurysms
  • “Dot-blot” hemorrhages
  • Hard exudates

Pre-proliferative

  • Soft exudates
  • IRMA
  • Large hemorrhages

Proliferative:

  • Neovascularization -> pre-retinal/vitreous hemorrhage
  • Vitreous fibrosis -> retinal detachment
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7
Q

Describe the pathophysiology of retinopathy

A
  • Increased epithelial cells and decreased pericytes
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8
Q

What is seen here?

A

Normal retina

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9
Q

What is seen here?

A

Fairly advanced background retinopathy

  • Micro-aneurysms: little red dots
  • Micro-hemorrhages
  • White spots are lipid deposits from old hemorrhages
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10
Q

What is seen here?

A

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
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11
Q

What is seen here?

A

Neovascularization sitting right over the macula

  • Rupture of this would lead to complete blindness
  • Needs emergent laser therapy
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12
Q

What is seen here?

A
  • Multiple hemorrhages have caused fibrosis
  • Retina gets stuck to vitreous and vitreous pulls retina off the back of the eye
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13
Q

How can you treat diabetic retinopathy?

A

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
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14
Q

What is seen here?

A

Eye post-laser photocoagulation

  • Laser burns in periphery
  • Better appearance centrally
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15
Q

What is seen here?

A

Rubeosis Iridis

  • Abnormal blood vessels that may be seen in naked eye
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16
Q

What are the effects of glycemic control in diabetic retinopathy?

A

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%
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17
Q

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

A

Type 1 > 2

  • Very high morbidity and mortality
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18
Q

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

A

True

  • Na/H pump overexpression
  • Ethnic differences
  • Seen in sibling-pair analysis
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19
Q

What is the pathogenesis of kidney disease in diabetes?

  • Timeline
A
  • 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

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20
Q

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

A

Micro-albuminemia

  • Any amount of protein in the urine means that you’ve stared down the slippery slope of diabetic nephropathy
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21
Q

What are the end histological features of diabetic nephropathy?

A
  • Thickening of basement membrane
  • Mesangial proliferation
  • Glomerulosclerosis
  • Tubular atrophy
  • Interstitial fibrosis and cellular infiltration
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22
Q

What is seen here?

A

Left: normal glomerulus

Right: diabetic nephropathy

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23
Q

What is seen here?

A

Diabetic nephropathy with ESRD

  • Glomerulosclerosis
  • Vessels sclerotic
  • Urinary space almost gone
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24
Q

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

A
  • Living-related transplant (best)
  • Cadaver transplant (Although diabetes will end up destroying new kidneys as well)
  • Hemodialysis
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25
Q

Describe albuminuria levels

  • Normal
  • Microalbuminuria
  • (Macro)abluminuria
A
  • Normal: under 30 mg/24 hr
  • Microalbuminuria: 30-300 mg/24 hr
  • (Macro)albuminuria: > 300 mg/24 hr
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26
Q

Macro-albuminuria is associated with what?

A

Increased risk for:

  • Renal failiure
  • CV disease
27
Q

How does glycemic control affect nephropathy?

A

In type I pts, intensive treatment reduced development of:

  • MIcroalbuminuria (by 40%)
  • Macroalbuminuria (by 50%)

Treat HTN with ACEI…

28
Q

What is the most common chronic complication of diabetes?

A

Affected nervous system

29
Q

What nervous systems are affected in diabetic retinopathy?

A

Systems affected:

  • Sensory
  • Motor
  • Cranial
  • Autonomic
30
Q

How are nervous system complications classified in diabetic neuropathy?

A

Classification:

  • Symmetric, distal polyneuropathy
  • Mononeuropathy (simplex or multiple)
  • Radiculopathy
  • Autonomic neuropathy
31
Q

Describe the pathophysiology of diabetic neuropathy?

A
  • Distal, multiple neuropathies usually metabolic (polyol pathway)
  • Proximal, mononeuropathies usually vascular
32
Q

The DCC study focused on what pt cohort?

A

Type I diabetes

33
Q

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

A

):

34
Q

Classification of diabetic neuropathies: symmetric

A
  • Distal, primarily sensory polyneuropathy
  • Mainly large fibers affected
  • Mixed*
  • Mainly small fibers affected*
  • Autonomic neuropathy
  • Chronically evolving proximal motor neuropathy* (recovery likely)
  • *Often painful*
35
Q

Classification of diabetic neuropathies: asymmetric

A
  • Acute or subacute proximal motor neuropathy* (painful)
  • Cranial mononeuropathy*
  • Truncal neuropathy* (painful)
  • Entrapment neuropathy in the limbs
  • *Recovery (partial or complete) is likely*
36
Q

What is seen here?

A

Overactivity of extensors

  • Sign of diabetic neuropathy (at least 3-4 yrs)
  • At this point, typically have lost sensation as well
37
Q

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

A

Monofilament test

  • Press into foot until it just bends
38
Q

What is seen here?

A

Distal/peripheral symmetric polyneuropathy in hands

  • Interossei and lumbricals lost
  • Sensation lost as well
39
Q

What is seen here?

A

Charcot’s foot

40
Q

What is seen here?

A

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
41
Q

What is seen here?

  • What is causing this? Onset?
A

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
42
Q

What is seen here?

A

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
43
Q

What are some diabetic autonomic neuropathy syndromes?

A
  • 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

44
Q

How common is ED in diabetes?

A
  • 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
45
Q

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

A

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
46
Q

What are strategies to reduce microvascular complications?

A

Prevention (proven by intervention trials):

  • Hyperglycemia
  • HTN

Treatments (proven by intervention trials):

  • ACE inhibition for nephropathy
  • Laser photcoagulation for retinopathy
47
Q

What is diabetic dermopathy?

A
  • Slightly depressed brownish lesions
  • They are tiny infarcts in dermis
  • May feel slightly painful or itchy
  • Sign of long-standing and poorly controlled diabetes
48
Q

What is seen here?

  • What commonly accompanies it?
A

Necrobiosis Lipoidica Diabeticorum

  • Will see pretty advanced retinopathy with this
  • Sign of terribly controlled diabetes with both micro and macrovascular complications
49
Q

What are the macrovascular complications of diabetes?

A

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 (?)
50
Q

How does diabetes affect Cardiovascular risk?

A

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
51
Q

HbA1C is predictive of what in Type 2 Diabetes?

A

HbA1C predicts CHD in Type 2 Diabetes

  • Other things may be more important:
52
Q

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

A
  • 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)
53
Q

Describe the pathophysiology of macrovascular lesions in diabetics

A
  • “AGE” of endothelial proteins
  • HTN
  • Accelerated atherosclerosis
  • Dyslipidemia
54
Q

What are some strategies for reducing macrovascular complications?

A

Prevention proven by intervention trials

  • Dyslipidemia
  • Hypertension
  • Antiplatelet therapies

Prevention suggested by epidemiologic analysis

  • Disorders of thrombolysis
  • Endothelial disorders
55
Q

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

A

Hyperlipidemia

  • Also, dysplipidemia diminishes the risk
56
Q

What are 4 key features of diabetic dyslipidemia?

A
  • Increased fraction of small, dense LDL-cholesterol (without increase in total quantity of LDL-C)
  • Decreased HDL-cholesterol
  • Hypertriglyceridemia
  • Postprandial lipemia
57
Q

What are the different types of dyslipidemia?

  • Blood tests?
  • Symptoms?
A

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

58
Q

Describe normal lipoprotein metabolism

A

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)
59
Q

Describe lipoprotein metabolism in diabetics

A

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
60
Q

How should dyslipidemia be managed in pts with diabetes?

A
  • 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)
61
Q

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

A
  • Apple-shaped (andrenoid?) (more weight carried above waist) is higher risk vs. pear-shaped (gynecoid?); marker of visceral obesity and dyslipidemia
62
Q

What is the biggest predictive factor for risk of diabetes?

A

Visceral fat distribution

63
Q

How to manage AMI in Diabetes?

A
  • 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