Complications of Diabetes Flashcards
What are the 3 major types of complications with T2D?
- Macrovascular complications → large blood vessels, heart, CVD (not linked to glucose)
- Microvascular complications (eyes, kidneys, etc.) → linked to glucose
- neuropathies → linked to glucose
What forms with persistant hyperglycemia
AGEs → Advanced glycated end products
1. Glucose is sticky so in tiny capilleries the proteins can collide with glucose and bind through covalent reactions
What is the problem with AGEs?
AGEs can cross link and bind as ligand to RAGE receptor which is a signal transduction receptor that propagates cellular dysfunction in several inflammatory disorders, in tumors and in diabetes.
* A bunch of signalling pathways lead to nuclear transcription factors which orchestrates inflammation and cytokine production
* RAGE is expressed at low levels in normal tissues, but becomes upregulated at sites where its ligands accumulate
What major circulating proteins are most exposed to hyperglycemia and glycation?
- albumin
- collagen
- fibrinogen
- immunoglobulin
problems with glycation of albumin
- decreased delivery of LCFA
- platelat activated & aggregation
- generation of free radicals
- decrease intracellular glucose uptake
problems with glycation of collagen
- development of fibrosis in diabetes
- athersclerosis developlment
- skin aging
problems with glycation of immunoglobulin
- autoimmune disease
- inflammation
- immunosuppression
problems with glycation of fibrinogen
- impaired fibrinolysis
- formation of less thrombogenic fibrin network
- vascular dysfunctioning (restricted with changes in elasticity)
diabetic eye diseases
10% of diabetic patients will suffer from severe eye diseases, including
* Diabetic retinopathy (80%)
* Glaucoma
* Cataracts
What is the leading cause of blindness in the world?
Diabetic retinopathy
* Prevalence increases with the duration of the disease with more than 80% after 20 years
What causes diabetic retinopathy?
DR is caused by hemorrahages, venous bleeding, fibrous proliferation, etc.
* damage to small vessels
What is diabetic retinopathy?
damage to blood vessels in the eye which burst, affecting structure neurons, vessels and macula densa
glaucoma
Damage to the optic nerve associated with increased pressure inside the eye
* Can cause blindness
* Symptoms include: seeing halos around lights, vision loss, reduced field of vision, redness and pain in the eye
* Treated with drops (alleviate pain) or surgery
Cataracts
Caused by non enzymatic glycation of proteins in the lens and osmotic swelling of the lens
* lens should focus light rays on macula densa but cannot contract properly with cataracts so causes blurry vision
Diabetic nephropathy
Progressive kidney disease caused by damage to the capillaries of the kidney’s glomeruli which involves increased intraglomerular pressure, shearing forces, glucotoxicity, glycation of proteins
* Changes result in disruption of the membrane, which normally act as a filter
* Large molecules (proteins) ultimately leak into the urine
physiological changes of kidney with Diabetic nephropathy
- granular surface
- decreased function
- smaller size
- high urine protein
stages of albuminuria with Diabetic nephropathy
Management involves optimal control of blood glucose and blood pressure.
* In healthy individuals, urinary albuminuria is less than 30 mg/day
* Microalbuminuria occurs at 30-300 mg/day
* Macroalbuminuria is defined as urinary albumin secretion > 300 mg/day
Diabetic neuropathies
Neuronal disorders linked to diabetic microvascular injuries (damages to small blood vessels which supply nerves)
* Peripheral (extremities) neuropathies (fingers, toes)
* Proximal (limbs) neuropathies (thighs, hips, legs)
* Focal neuropathies (head, abdomen)
* Autonomic (involuntary) neuropathies (heart, lungs, GI tract, …)
Problem with peripheral neuropathies
lose sensitivity in these areas and can get hurt without realizing it and wound can get infected
* proper footwear is important to prevent exposure
The diabetic foot
Loss of sensation in toes (and foot) and walk in a different manner. Develop different pressure points from a normal subject increasing risk for injury
* Important to have good footwear to support foot and prevent injury and reduce pressure points
Gastrointestinal problems in diabetes
Gastroenteropathies are frequent in diabetes with changes to capilleries and neurons regulating transit and urination
* Influenced by neuropathy, changes in gastric emptying, dehydration, etc.
* Incontinence = sensation deficit
Sexual problems in T2D
- The prevalence of erectile dysfunction in T2D is 35-50%
- Women are more likely to report dissatisfaction
What effect does diabetes have on infections?
Diabetes increases the risk of infections modifies the course of many infections (ex: delayed
healing) Some potential causes:
* Disturbances of the immune system (organs or cells)
* Some microorganisms benefit from hyperglycemic environments (feed on glucose)
* Vascular diseases, neuropathies
leads to: Necrosis, gangrene (blood flow cut off), etc. which require amputation
Look back at problems with glycation of circulating proteins
Symptoms of diabetes
- always tired
- frequent urination
- always hungry
- sexual problems
- sudden weight loss
- wounds that wont heal
- vaginal infections
- numb or tingling hands or feet
- always thirsty
- blurry vision
