10/15- Chronic Complications of Diabetes 1 & 2 Flashcards
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
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
Background:
- Microaneurysms
- “Dot-blot” hemorrhages
- Hard exudates
Pre-proliferative
- Soft exudates
- IRMA
- Large hemorrhages
Proliferative:
- Neovascularization -> pre-retinal/vitreous hemorrhage
- Vitreous fibrosis -> retinal detachment
Describe the pathophysiology of retinopathy
- Increased epithelial cells and decreased pericytes
What is seen here?
Normal retina
What is seen here?
Fairly advanced background retinopathy
- Micro-aneurysms: little red dots
- Micro-hemorrhages
- White spots are lipid deposits from old hemorrhages
What is seen here?
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?
Neovascularization sitting right over the macula
- Rupture of this would lead to complete blindness
- Needs emergent laser therapy
What is seen here?
- 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?
Eye post-laser photocoagulation
- Laser burns in periphery
- Better appearance centrally
What is seen here?
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
True
- 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?
Micro-albuminemia
- 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?
Left: normal glomerulus
Right: diabetic nephropathy
What is seen here?
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