Diabetes complications Flashcards
Diabetic nephropathy stages
Treatment of nephropathy in DM
Statins, antihypertensive drugs, ACE inhibitors.
Good glycemia control
Pathogenesis of diabetes acute metabolic changes and mechanisms
1) Formation of AGEs. Advanced Glycation End products
- nonenzymatic glycation reactions between glucose derived products with amino acids both intracellularly and extracellularly.
- Bind to RAGE receptors on inflammatory cells, endothelial cells, vascular smooth msucle, pericytes, podocytes, astrocytes and microglia.
- Generates proinflammatory cytokine signaling, and growth factor release
- Generates ROS
- Increased procoagulative state of platelets and endothelial cells.
- Increased proliferation of vascular smooth muscle cells and ECM synthesis.
2) Increased activation of PKC
- Increased angiogenesis via downstream VEGF, neovascularization
- Increased permeability
- Increases TGF-beta and ECM deposition
- decreases fibrinolysis
3) Disturbed polyol pathway.
- increases sorbitol production (a polyol)
- Consumes NADPH and depletes reduced Glutathione
- Increased oxidative stress.
- Major cause of diabetic neuropathy
Diabetic microangiopathy
Diffuse thickening of basement membranes, especially in capillaries of the retina, renal glomeruli, renal medulla, skeletal muscle, and skin, also in renal tubules, peripheral nerves. Thickened layers of hyaline material, mostly Collagen IV.
Diabetic retinopathy and other ocular lesions of diabetes.
Nonproliferative retinopathy:
- microangiopathy of the retinal capillaries
- intraretinal hemorrhages
- exudates
- microaneurysms
- venous dilations
- edema
Proliferative retinopathy:
- Excessive neovascularization
- vitreous hemorrhages, possible retinal detachment in the organizing/retracting phase of the hemorrhage.
- Fibroblast proliferation and fibrosis.
Catarct formation
Glaucoma
Diabetic neuropathy
most frequent pattern of involvement is that of a peripheral, symmetric neuropathy of the lower extremities affecting both motor and sensory function, especially sensory.
Other forms include autonomic neuropathy, which produces disturbances
in bowel and bladder function and sometimes sexual dysfunciton.
mononeuropathies, foot or wrist partial paralysis, or isolated cranial nerve palsy.
Resulting from the AGEs, PKC, polyol pathway increase, ischemia.
Screening for diabetic retinopathy
Screening once a year if there is no retinopathy and good metabolic control
every 6 months if there is mild DR
every 3-6 months if it is poorly controlled and there is no DR
Signs of diabetic retinopathy
dilated pupil
cataract
glaucoma
Visus, pressure, fundus!
• Laser photocoagulation!! (FLAG, OCT)
Classifications of diabetic neuropathies.
• Diffuse neuropathy
- somatic np.: sensorimotor
- autonomic np.: cardiovascular, gastrointestinal, genitourinary, pupil
• Focal syndromes
- focal np.: mononeuritis, entrapment syndr.
- multifocal np.: proximal neuropathies
• Subclinical neuropathy
- abnormal electrodiagnostic tests
- abnormal quantitative sensory tests
- abnormal autonomic function tests
Quantitative sensory tests
Quantitative sensory tests
• Tuning fork (vibration perception)
• Monofilament (touch sensation, predict foot
ulceration)
• Pain and thermal sensation
• Tendon reflexes (Achilles)
• Neurometer, nerve transmission, measures nerve conductace in large myleinated, small myelinated, and small unmyelinated fibers.
Tests to measure autonomic neuropathy
Parasympathic function, heart rate
- Variability:
- Valsalva’s maneuver
- Deep breathing
- Supine vs. standing
Sympathic function
- blood pressure
- Orthostatic hypotension
Autonomic neuropathy increases the five-year mortality with 3 times!
Hypertension control goals and treatments in diabetes
• Medication to reduce < 140/<90 Hgmm
- 130-139/80-89 Hgmm lifestyle for 3 months
- RR ³ 140/90 Hgmm drug therapy
- Ace inhibitors, Ang receptor blockers
Statins always except in pregnancy
low dose aspririn antiplatelet therapy.
What are the rare life threatening infections of diabetes
• Mucormycosis (rhinocerebralis)
• Malign otitis externa (Ps. aeruginosa)
• Psoas abscessus (St. aureus)
• Emphysematosus cholecystitis (E. coli, Cl.
Perfringens)
• Emphysematosus urocystitis, pyelonephritis
(E. coli, K. pneumoniae)
• Fasciitis necrotisans (polymicrobe)
