Endo 1-7 Diabetes Complications

Front 1

Micro or macro is the major killer?

Back 1

macro

Front 2

Macrovascular disease complications

Back 2

heart disease, stroke, heart failure, lower extremity amputations.

Front 3

microvasc complications

Back 3

retinopathy, nephropathy, neuropathy (which can lead to loss of limb)

but mainlt retinopathy and nephropathy

Front 4

Why do premature cataracts form?

Back 4

sugar-protein reactions leading to opacity.

Front 5

most common cause of blindness in the US?

Back 5

diabetic retinopathy

Front 6

why do you see white exudates on the retina?

Back 6

endothelial cell and pericytes are damaged-->BM thickens-->greater permeability to proteins easily leak.

Front 7

Proliferative diabetic retinopathy

Back 7

In response to retinal ischemia (due to microaneurysms), VEGF is released to form abnormal fragile vessels that easily rupture and bleed and eventually cause blindness.

Front 8

Macular edema

Back 8

This must be treated promptly. It is when flow through larger vessels originally increases.

Front 9

if vision is blurry...

Back 9

it can be a good sign of the body responding to lower blood glucose and their eyes will be better in a week.

Front 10

VEGF associated with...

Back 10

proliferative diabetic retinopathy

Front 11

Changes in glomerulus with diabetes

Back 11

Mesangial cells (structural) are damaged.

Deposition of basement membrane to make it more permeable.

Everything expands and thickens and you occlude the capillaries and gradually lose glomeruli.

Front 12

Progression of diabetic nephropathy

Back 12

There is a latent period where it can be IDed.

There can be hyperfiltration because of greater flow to the kidney. This can lead to proteinuria (microalbuminuria is first).

Front 13

Dysfunc of vascular autoregulation in diabetic nephropathy

Back 13

Hyperglycemia leads to more glomerular filtration rate and glomerular capp pressure.

This leads to glomerular sclerosis and nephron loss which exacerbates the filtration rate and capp pressure. (which leads to more sclerosis...)

Front 14

Role of AII in diabetic nephropathy

Back 14

Constricts efferent renal arteriole to increase the intra-arterial pressure. (the afferent is already dilated)

Also stimulates TGF-beta and this leads to glomerular sclerosis and proteinuria.

Front 15

microalbuminuria

Back 15

This is the earliest indicator of nephropathy

>30 mg/24 hours

can't be picked up with a dipstick

Front 16

macroalbuminuria

Back 16

>300mg/24 hours

can be picked up with dipstick

Front 17

is diabetic nephropathy familial?

Back 17

yes

Front 18

what is the most serious problem for people with diabetes?

Back 18

CV disease

can even get this with impaired glucose tolerance (macrovasc, not micro).

Front 19

Who has more cv risk? someone with prev mi or someone with diabetes?

Back 19

someone with diabetes

Front 20

do diabetic women have the same risk as men for cv events?

Back 20

yes

Front 21

Test for peripheral vascular disease

Back 21

it is present if pressure at ankle is much lower than at arm.

Front 22

Pathogen of macrovascular complications of diabetes

Back 22

Endothelial cell has dysfunction and dropout due to increased constitutive glucose uptake
in contrast with muscle, fat, cardiac cells which can regulate how much gluc comes in.

Front 23

Diabetes does the follow to endothelium...

Back 23

constriction
growth promotion
pro-thrombotic

Front 24

Non-enzymatic glucation

Back 24

idea behind a1c

glucose fuses to amine group of a protein and form an Amadori product which then forms an advanced glycation end product (AGE)

Front 25

Where do advanced glycation end products deposit?

Back 25

arterial wall

Front 26

Compounds that lead to formation of AGEs

Back 26

glucose, methylglyoxal (inc in diabetics), 3-deoxyglycosone, glyoxal

Front 27

Point of measuring AGEs

Back 27

they are markers for complications.

Front 28

what does hyperglycemia do with radicals?

Back 28

increases ROS (peroxides, superoxide free radicals, hydroxyl radicals)

Front 29

Aldose reductase and polyol pathway

Back 29

If pts are glycemic, more substrate for aldose reductase and thus more sorbitol levels.

Sorbitol increases intracell osmolality and decreases the activity of Na/K pump. This leads to less levels of antioxidant GSH (glutathione).

This leads to toxic effect on microcirculation.

Front 30

Brownlee unifying hypothesis

Back 30

With lots of glucose, mitochondria keep working to produce more superoxide (a ROS)

this reduces activity of glyceraldehyde phosphate dehydrogenase and activates the 4 pathways of tissue damage--
AGE pathway
PKC pathway-inc prod of growth factors
polyol pathway
hexosamine pathway - more PAI-1 and TGF-beta.

Front 31

Role of fructoselysine

Back 31

May be protective (causes deglycation)

Front 32

methylglyoxal prod is _____ in pts with diabetic nephropathy

Back 32

increased

Front 33

GAPDH (glyceraldehyde phosphate dehydrogenase) activity is ____ in nephropathy

Back 33

decreased

Front 34

people putting on weight where have higher risk of athero and insulin resistance?

Back 34

Central obesity.

Front 35

insulin resistance leads to all the following bad things...

Back 35

complex dyslipidemia (inc TG, LDL, small dense LDL, and dec HDL)

type 2 diab
HTN
visceral obesity
systemic infalmm
hyperinsulinemia
disordered fibrinolysis
endothelial dysfunc
atheroscler

Front 36

Distal symm neuropathy

Back 36

Loss of pain/temp sensation

commonly interpreted as poor circulation.

worse px

Front 37

diabetic neuropathy can cause...

Back 37

lower extremity amputation

pain and disability

GI sx, erectile and CV dysfunction.

Front 38

Types of neuropathy you can get

Back 38

Autonomic

Diffuse (proximal motor or distal symmetric)

Focal
Mononeuritis
Entrapment syndromes

Front 39

Pathogen of diabetic neuropathy

Back 39

Prolonged hyperglycemia slows nerve conduction because hypoxia leads to the polyol pathway (poisons Na/K pump)

Inhibiting the pump leads to sodium retention, edema, myelin swelling...

Front 40

General note

Back 40

the notes in syllabus are very very good.

Front 41

Tx

Back 41

Good glycemic control is key
Body remembers your initial behavior, so early intervention is key.

Goal - 6.5-7% A1C to prevent microvascular disease

ACEinh

Control lipids

Front 42

Tx of proliferative retinopathy

Back 42

Photocoagulation therapy (laser)

Front 43

What did one study find in type 1 vs. type 2 diabetic tx?

Back 43

Type 1 - good glycemic control prevented atherosclerosis and reduced cv events

Type 2 - Slight reduction of CV events but more deaths (the pts with intensive control had more hypoglycemia and gained more weight...)

basically..."Whether achieving glycemic targets below 7% will be beneficial to the vast majority of patients with type 2 diabetes and a low risk of cardiovascular disease remains another unanswered question."

Front 44

Imp factors to treat to rpevent atherosclerosis

Back 44

dyslipidemia
HTN
hypercoag
oxidative stress
inflamm
central obesity
smoking

Front 45

Better px - background or proliferative retinopathy

Back 45

Background retinopathy