Complications of Diabetes

Question 1

What are the 3 major types of complications with T2D?

Answer 1

1. Macrovascular complications → large blood vessels, heart, CVD (not linked to glucose)
2. Microvascular complications (eyes, kidneys, etc.) → linked to glucose
3. neuropathies → linked to glucose

Question 2

What forms with persistant hyperglycemia

Answer 2

AGEs → Advanced glycated end products
1. Glucose is sticky so in tiny capilleries the proteins can collide with glucose and bind through covalent reactions

Question 3

What is the problem with AGEs?

Answer 3

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

Question 4

What major circulating proteins are most exposed to hyperglycemia and glycation?

Answer 4

• albumin
• collagen
• fibrinogen
• immunoglobulin

Question 5

problems with glycation of albumin

Answer 5

• decreased delivery of LCFA
• platelat activated & aggregation
• generation of free radicals
• decrease intracellular glucose uptake

Question 6

problems with glycation of collagen

Answer 6

• development of fibrosis in diabetes
• athersclerosis developlment
• skin aging

Question 7

problems with glycation of immunoglobulin

Answer 7

• autoimmune disease
• inflammation
• immunosuppression

Question 8

problems with glycation of fibrinogen

Answer 8

• impaired fibrinolysis
• formation of less thrombogenic fibrin network
• vascular dysfunctioning (restricted with changes in elasticity)

Question 9

diabetic eye diseases

Answer 9

10% of diabetic patients will suffer from severe eye diseases, including
* Diabetic retinopathy (80%)
* Glaucoma
* Cataracts

Question 10

What is the leading cause of blindness in the world?

Answer 10

Diabetic retinopathy
* Prevalence increases with the duration of the disease with more than 80% after 20 years

Question 11

What causes diabetic retinopathy?

Answer 11

DR is caused by hemorrahages, venous bleeding, fibrous proliferation, etc.
* damage to small vessels

Question 12

What is diabetic retinopathy?

Answer 12

damage to blood vessels in the eye which burst, affecting structure neurons, vessels and macula densa

Question 13

glaucoma

Answer 13

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

Question 14

Cataracts

Answer 14

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

Question 15

Diabetic nephropathy

Answer 15

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

Question 16

physiological changes of kidney with Diabetic nephropathy

Answer 16

• granular surface
• decreased function
• smaller size
• high urine protein

Question 17

stages of albuminuria with Diabetic nephropathy

Answer 17

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

Question 18

Diabetic neuropathies

Answer 18

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, …)

Question 19

Problem with peripheral neuropathies

Answer 19

lose sensitivity in these areas and can get hurt without realizing it and wound can get infected
* proper footwear is important to prevent exposure

Question 20

The diabetic foot

Answer 20

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

Question 21

Gastrointestinal problems in diabetes

Answer 21

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

Question 22

Sexual problems in T2D

Answer 22

• The prevalence of erectile dysfunction in T2D is 35-50%
• Women are more likely to report dissatisfaction

Question 23

What effect does diabetes have on infections?

Answer 23

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

Question 24

Symptoms of diabetes

Answer 24

• 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