Chronic complications of diabetes mellitus include macrovascular complications like atherosclerosis and coronary artery disease, as well as microvascular complications involving the eyes, kidneys, and nerves. Key microvascular complications include diabetic nephropathy, the leading cause of end-stage renal disease; retinopathy, the most common cause of blindness; and neuropathy resulting in numbness, pain, and increased risk of foot ulcers and infection. Management involves controlling risk factors like hypertension and hyperglycemia, as well as treatments tailored to each complication such as ACE inhibitors for nephropathy and laser therapy for retinopathy.

1. Chronic complication of
DM
By Lara Masri
4th year medical student

2. Types of chronic complications of DM
1) Macrovascular complications
2) Microvascular complications

3. Macrovascular complication
(Atherosclerosis)
Atherosclerosis : The formation of lipid, cholesterol, and/or calcium-laden
plaques within the tunica intima of the arterial wall, which can restrict blood flow
Narrowing of the arteries
Plaque may brust cause blood clot
Blocking the blood flow

4. Prevalence: more common in patients with type 2 diabetes.
Risk factors: The major determinants are metabolic risk factors, which include
obesity, dyslipidemia, and arterial hypertension.
Hyperglycemia may be less related to the development of macrovascular disease.
Manifestations
• Coronary heart disease
 RISK 2-4 times greater than non diabetics.
 Most common cause of death in diabetic patients.
 Silent myocardial infarctions are common.
• Cerebrovascular disease (Strokes)
• Peripheral artery disease (up to 60%)
• Monckeberg arteriosclerosis
• Gangrene

5. • Monckeberg arteriosclerosis
 A form of arteriosclerosis characterized by calcification of the
media and internal elastic lamina that do not cause arterial
stenosis.
 Associated with diabetes mellitus and/or progressive kidney
disease.
 Usually affects arteries in the extremities.
 PAD diagnostic tools are unreliable in patients with
Mönckeberg's arteriosclerosis.
 X-rays show long, pipestem arteries (calcifications)

6. The interventions
 Target LDL < 100 mgdl
 Target HTN < 13080

7. 1.Diabetic Nephropathy
2.Diabetic Retinopathy
3.Diabetic Neuropathy
4.Diabetic Foot

9. 1) Diabetic nephropathy
 Most important cause of End stage renal disease (ESRD).
Pathophysiology
o Seen in patients with diabetes for > 10 years
o Chronic hyperglycemia → glycation of the basement membrane (protein glycation)
→ increased permeability and thickening of the basement membrane and
stiffening of the efferent arteriole → hyperfiltration (increase in GFR) → increase in
intraglomerular pressure → progressive glomerular hypertrophy, increase in renal
size, and glomerular scarring (glomerulosclerosis) → worsening of filtration
capacity.
o Microalbuminuria is the earliest clinical sign of diabetic nephropathy
o If microalbuminuria is present, strict glycemic control is critical.
o Without effective treatment, the albuminuria gradually worsens—HTN usually
develops during the transition between microalbuminuria and progressive
proteinuria. Persistent HTN and proteinuria cause a decrease in glomerular
filtration rate (GFR), leading to renal insufficiency and eventually ESRD.

11.  Initiate ACE inhibitors or ARB immediately to
decrease the rate of progression of nephropathy.
 Microalbuminuria is the screening test!
It usually takes 1 to 5 years for microalbuminuria
to advance to full-blown proteinuria. However,
with proper treatment time can be prolonged.

12. Pathology: Three major histological changes can be seen on light microscopy.
1. Diffuse glomerular sclerosis
2. nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)
3. Glomerular basement membrane thickening
Clinical features
 Often asymptomatic  patients may complain of foamy urine
 Progressive diabetic kidney disease with signs of renal failure and risk of uremia (e.g.,
uremic polyneuropathy)
 Arterial hypertension
Urine analysis - proteinuria
 Initially moderately increased albuminuria (microalbuminuria) ,
 Eventually significantly increased albuminuria (macroproteinuria)  nephrotic
syndrome may develop.

13. 2) Diabetic retinopathy
• Prevalence is 75% after 20 years of DM
• The most common cause of visual impairment and blindness in patients aged 25–
74 years.
• Clinical features
– Asymptomatic until very late stages of disease
– Visual impairment
– Progression to blindness
• Ocular problems in diabetic patients include cataracts, retinopathy, and glaucoma.
• (Non-proliferative) Retinopathy
 Funduscopic examination shows hemorrhages, exudates, microaneurysms, and venous
dilatation.
 Usually asymptomatic unless retinal edema or ischemia involves the central macula.
 HTN and fluid retention exacerbate this condition.
• Proliferative Retinopathy
 Neovascularization and scarring formation.
 Two serious complications are vitreous hemorrhage and retinal detachment.
 Can lead to blindness. Laser photocoagulation is the treatment.

14. Overview of diabetic retinopathies
Nonproliferative retinopathy Proliferative retinopathy (PDR)
Mechanism
 Retinal vessel microangiopathy →
blood leaks → retinal
hemorrhages → retinal infiltration
with lipids and fluid → macular
edema
 Retinal vessel microangiopathy →
chronic retinal hypoxia →
abnormal proliferation of blood
vessels → traction on retina → retinal
detachment
Clinical
features
 Intraretinal microvascular abnorma
lities (IRMA)
o Microaneurysms;
o Caliber changes in venous
vessels;
o Intraretinal hemorrhage
o Hard exudates
o Retinal edema
o Cotton-wool spots
 Findings of nonproliferative
retinopathy are usually present.
 Preretinal neovascularization is the
hallmark
of PDR , fibrovascular proliferation , vi
treous hemorrhage, traction retinal
detachment , rubeosis iridis →
secondary glaucoma.
Visual loss
 Most commonly due to macular
edema
 Usually due to vitreous
hemorrhage, retinal detachment,
or neovascular glaucoma.

15. •Screening
• Type 1 DM: initial dilated and comprehensive eye examination within 5
years after the onset of diabetes and then annually.
• Type 2 DM: initial dilated and comprehensive eye examination at the
time of the diabetes diagnosis and then annually.
•Management
• General measurements
• Blood sugar control
• Blood pressure and serum lipid control to reduce the risk or slow the
progression of diabetic retinopathy
• Invasive treatment
• Laser photocoagulation

16. 3) Diabetic neuropathy
 Pathophysiology: Chronic hyperglycemia causes glycation of axon
proteins.
 Peripheral neuropathy (distal symmetric neuropathy)
 Typically begins in feet, later involves hands (longest nerves affected first).
Numbness and paresthesia are common.
 Loss of sensation leads to: ulcer with subsequent ischemia of pressure
point areas; Charcot joints.
 Painful diabetic neuropathy—hypersensitivity to light touch; severe
“burning” pain (dysesthesia) , especially at night, that can be difficult to
tolerate.

17. secondary to nerve infarction:
• Types
– Mononeuropathy
• Cranial mononeuropathy
• Peripheral mononeuropathy
• Mononeuropathy multiplex: asymmetric neuropathy,
affecting the multiple peripheral and cranial nerves
• Diabetic truncal neuropathy
– Diabetic lumbosacral plexopathy
• A form of lumbosacral plexus injury caused by diabetes
mellitus
• Microvasculitis causes damage to the plexus formed by
the spinal roots T12-S4, which results in a variety of
symptoms, including pain in the lower back and legs and
progressive weakness of the proximal legs.

18. Autonomic neuropathy
• Impotence in men (most common presentation)
• Decreased sweating , dry and further increase the risk for ulceration
• Neurogenic bladder—retention, incontinence
• Gastroparesis—chronic nausea and vomiting,
early satiety
• Constipation and diarrhea (alternating)
• Postural hypotension

19. Screening
• Tuning fork: decreased vibration sense
(https://www.youtube.com/watch?v=X3kW26L_7dA)
• Monofilament test: decreased pressure sense
• Pinprick (pain assessment) or temperature assessment: decreased sensation
(https://www.youtube.com/watch?v=yERSYlRpnh4)

20. 4) Diabetic foot
o A combination of artery disease (ischemia) & neuropathy.
o The patient does not feel pain.
o In addition, neuropathy may mask symptoms of Peripheral Vascular
Diseases (claudication/rest pain). Also, calcific medial arterial
disease is common.
o Increased susceptibility to infection due to impaired WBC function,
reduced blood supply, and Wound healing.
o Patients are at increased risk of: cellulitis, candidiasis, pneumonia,
osteomyelitis, and polymicrobial foot ulcers.

21. • Malum perforans
• hammer toe
• hallux valgus

22. Specific Treatment of Chronic Diabetic Complications
1. Macrovascular disease: reduction of risk factors (e.g., BP
reduction, lipid-lowering agents, smoking cessation, exercise), a daily
aspirin and strict glycemic control.
2. Nephropathy: ACE inhibitors
3. Retinopathy: laser photocoagulation.
4. Neuropathy: NSAIDs, tricyclic antidepressants, and gabapentin.
For gastroparesis, a promotility agent such as metoclopramide, in
addition to exercise and a low-fat diet.
5. Diabetic foot: Amputation is a last resort.