ICL 5.2: Chronic Complications of DM Flashcards
what i the common pathogenic means for the microvascular and macrovascular complications associated with chronic DM?
hyperglycemia and insulin resistance lead to endothelial dysfunction which leads to:
1. vascular inflammation
- inpmaired vascular funciton
- pro-thrombotic state
alteration in vascular homeostasis due to endothelial and smooth muscle dysfunction are the main features of diabetic vasculopathy
the vascular changes lead to atherosclerosis, inflammation and arteriosclerosis
what is the pathogenesis of microvascular and macrovascular complications associated with chronic DM at the cellular level?
endothelial cells dont need insulin to take up glucose so they take it up all the time
once inside the endothelial cells lots of ATP is produced and also ROS…with an increase in ROS there’s advanced glycated products, production of protein kinase C
protein kinase A increases VEGF which leads to cell growth and angiogenesis – there’s also increased endothelin production which leads to platelet activation – there’s also an increase in NFKB which is an inflammatory transcription factor and increases vascular permiability
increased vascular permeability allow for LDL and monocytes to enter the tissue and they become macrophages – combined with the macrophages they become foam cells!!
foam cells release inflammatory cytokines and growth factors creating smooth muscle proliferation and plaques form!
what are the microvascular complications of DM?
- nephropathy
- neuropathy
- retinopathy
what are the macrovascular complications of DM?
- CVD
- cerebrovascular disease
- peripheral vascular disease
what are the risk factors for microvascular DM complications?
- glycemic control
- duration of disease
- hypertension
- dyslipidemia
- smoking
- genetic factors
who does diabetic retinopathy effect?
one of the most important causes of visual loss worldwide
principal cause of impaired vision in pts 25-74 y/o
vast majority have no symptoms until very late stages
how do you classify diabetic retinopathy?
- non proliferative retinopathy
2. proliferative retinopathy
what is the clinical presentation of non-proliferative retinopathy?
- cotton wool spots = nerve fiber layer infarcts; usually near optic disk
- hard exudates = leakage from precapillary arterioles; deep yellow color with sharp margins
- intraretinal hemorrhages
- microvascular abnormalities like micro aneurysms, occluded vessels, dilated or tortuous vessels
- visual loss is primarily through development of macular edema!!
what are the clinical features of proliferative retinopathy?
this is marked by neovascularization arising from disc and/or retinal vessels
retinal and vitreous hemorrhage results from the neovascularization
eventually fibrosis ensues and the fibrosis can be a point of traction that leads to retinal detachment!
vision loss may occur acutely in bleeding from the abnormal vessels into the vitreous blocks the light path to the retina; blood is often reabsorbed and vision clears spontaneously –> more permanent loss of vision may occur through retinal detachment, ischemia of the macula, or combination of these factors
when does macular edema occur during diabetic retinopathy?
it can occur at any stage
ti’s defined as thickening and edema involving the macula
what are the clinical features of diabetic retinopathy?
most people have no symptoms until very late stages!!! and at that point it might be too late for effective treatment
vision loss can be due to macular edema, vitreous hemorrhage or retinal detachment
how do you screen for diabetic retinopathy?
start 5 years after diagnosis in type I or once they’re 10 years or older; yearly followup if they have retinopathy and every 2 years if they don’t
type II DM send to ophthalmologist immediately after diagnosis and it’s the same thing; yearly followup if they have retinopathy and every 2 years if they don’t
if they’re pregnant and have diabetes, couple on development of retinopathy during pregnancy
how do you manage diabetic retinopathy?
- good glcemi control
- good bP control
both reduce incidence and progression of retinopathy with type I and II DM
- pan-retinal laser photo-coagulation therapy –> indicated to reduce the risk of vision loss in patients with some cases of severe non proliferative diabetic retinopathy or in high risk proliferative diabetic retinopathy
how do you manage non proliferative diabetic retinopathy?
- glucemia control
- intravitreal anti-vascular endothelial growth factor (VEGF) or laser treatment (focal photocoagulation) are initial treatment options
- laser panretinal photocoagulation
how do you manage proliferative diabetic retinopathy?
- glycemic control
2. pan retinal photocoagulation or anti-VEGF agents
what happens to the kidney structure in diabetes?
- thickening and sclerosis of the basement membrane in the glomerulus
- expansion and proliferation of the mesangium between the capillaries
- effacement of podocytes
what histological finding is pathoneumonic of diabetic nephropathy?
Kimmelstiel Wilson nodules
what is the clinical presentation of diabetic nephropathy?
usually asymptomatic which is why screening is so important
they may present with new/onset worsening HTN, edema or reduced insulin requirement if the kidney isn’t clearing it
how do you screen for diabetic nephropahty?
- assess urinary albumin; asses albumin:creatinine ratio which should be less than 30
- check GFR
do this for type I DM 5 years after diagnosis
do it at the time of diagnosis for type II DM
do it for everybody who has comorbid HTN
what parameter is best for early detection of diabetic nephropathy?
urinary albumin:creatinine ration
should be under 30
microalbuminuria is the first sign of diabetic nephropathy and indicates progression of glomerular damage that leads to loss of albumin in the urine and even nephritic syndrome
what other complication is associated with diabetic nephropathy?
the extent of albuminuria in patients with diabetic nephropathy also correlates with the risk of future cardiovascular events
what are the types of neuropathy associated with diabetes? how do they present?
- peripheral
presents as increased or decrease in pain, painless injury and decreased reflexes
- autonomic
presents as resting tachycardia, ED, urinary frequency
hat parts of your body are effected by large fiber neuropathy?
lower legs/feet and hands
what parts of your body are effected by small fiber neuropathy?
half way down the calves and the feet
how do you screen for diabetic neuropathy?
screen type I 5 years after diagnsosi
screen type II at time of diagnosis
emphasize important of good foot care
how do you assess for diabetic neuropathy?
- careful history
- assessment of either temperature or pinprick sensation (small-fiber function) and vibration sensation using a 128-Hz tuning fork (large-fiber function)
- all patients should have annual 10-g monofilament testing to identify feet at risk for ulceration and amputation
how do you manage diabetic neuropathy?
- optimize glucose control to prevent or delay the development of neuropathy in patients
- assess and treat patients to reduce pain related to diabetic peripheral neuropathy and symptoms of autonomic neuropathy and to improve quality of life.
- pregabalin, duloxetine, gabapentin are recommended as initial pharmacologic treatments for neuropathic pain in diabetes
A 43-year-old woman comes to the physician because of a 3-month history of a painless ulcer on the sole of her right foot. There is no history of trauma. She has been dressing the ulcer once daily at home with gauze. She has a 15-year history of poorly-controlled type 1 diabetes mellitus and hypertension. Current medications include insulin and lisinopril. Vital signs are within normal limits. Examination shows a 2x2-cm ulcer on the plantar aspect of the base of the great toe with whitish, loose tissue on the floor of the ulcer and a calloused margin. A blunt metal probe reaches the deep plantar surface. Sensation to vibration and light touch is decreased over both feet. Pedal pulses are intact. An x-ray of the right foot shows no abnormalities. Which of the following sets of changes is the most appropriate initial step in management?
A. Total casting of right foot
B. Amputation of the right forefoot
C. Increase frequency of dressing change
D. Intravenous antibiotic therapy
E. Sharp surgical debridement of the ulcer
F. Surgical revascularization of the right foot
E. Sharp surgical debridement of the ulcer
what is a diabetic ulcer?
diabetic ulcer with slough (dead, whitish, stringy tissue at the ulcer base) and a calloused margin, both of which inhibit healing.
the dead tissue is also a good medium for bacterial proliferation and predisposes to bacterial infection of the ulcer
sharp surgical debridement of the slough and the calloused margins of this patient’s ulcer using a scalpel blade or scissors will promote healing and decrease the risk of bacterial infection
what is the most common cause of autonomic neuropathy in diabetics?
gastroparesis
this is a syndrome of objectively delayed gastric emptying of solids in the absence of a mechanical obstruction and cardinal symptoms of nausea, vomiting, early satiety, belching, bloating,and/orupper abdominal pain
present with epigastric distention or tenderness but not guardian or rigidity
diabetesis the most frequently recognized systemic disease associated with gastroparesis
what causes macrovascular complications in DM?
- hyperglycemia
- excess free FA
- insulin resistance
these cause increased oxidative stress, protein kinase activation, and activation of the receptor for advanced glycation end products, factors that act on the endothelium that lead to inflammation, increased vascular permeability and plaque formation
how do you monitor and manage macrovascular complications in DM?
- maintain good glycemic control
- control HTN
- statin therapy
- weight control
- exercise
what is the recommendation for statin therapy in diabetic patients?
- if they’re under 40 years old and their ASCVD risk is not over 20% then you don’t give them statins but if they are then you give them a statin
if their LDL doesn’t get below 70 despite maximum statin dose, then add another LDL therapy like ezetimibe or PCSK9 inhibitor
- if they’re over 40 years old and they dont have CVD and have risk under 20% then start them on moderate statins but if they do have CVD or elevated risk then give a high intensity statin like atorvastatin/rosuvastatin
high intensity statins lower LDL by 50% while moderate intensity statins reduce it by 30-50%
which skin complications can be assoacitd with dm?
- bacterial infections
- fungal infections
- itching
4 diabetic dermopathy
- necrobiosis lipoidica diabeticorum
- diabetic blister
- eruptive xanthomatosis
- digital sclerosis
- disseminated granuloma annulare
- acanthuses nigerians
what is diabetic dermopathy?
changes in the small blood vessels
looks like light brown, scaly patches
the disorder most often occurs on the front of both legs
the patches do not hurt, open up, or itch
dermopathy is harmless and does not require treatment
