CHRONIC COMPLICATIONS OF

DIABETES MELLITUS
 Microvascular
complications:
• Diabetic retinopathy
• Diabetic nephropathy
• Diabetic neuropathy
 Macrovascular
complications
Systemic atheroscerosis
 Mixted: diabetic foot
 Pathogeny of chronic complications
in diabetes mellitus
Main factors:
• Genetic factors
• Duration of diabetes
• Metabolic control
Pathogenic mechanisms:
• Glycosilation of proteins
• Poliol pathway activation
• Increased production of oxidative stress
• Haemorrheological disturbancies
 CONTRIBUTIONS OF FASTING AND POST-
PRANDIAL GLYCEMIA IN INCREASING HbA1c
Uncontrolled Diabetes HbA1c 8%
Basal hyperglycaemia
300 contributes ~2%
Post-prandial
Plasma glucose (mg/dL)

hyperglycaemia
contributes HbA1c ~1%
200 Post-prandial
hyperglycaemia
Fasting
hyperglycaemia
100

Normal
HbA1c ~5%
0   
6 B 12 L 18 D 24 6
Time of day (h)
B=breakfast; L=lunch; D=dinner.
Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.
 Classification of diabetic
retinopathy
Non-proliferative DR:microaneurisms, “hard”
exudates,microhaemorrhagies
- Oftalmologic control in 1 year
Diabetic maculopathy:macular oedema or ischaemical
disorders
-ophtalmologic control in 3-4 months

Preproliferative DR:”soft” exudates,haemorrhagies

Ophtalmologic cntrol in 2-3 months
Proliferative retinopathy:capillary new vessels
Ophtalmologic control in 2-3 months.
Advanced eye disease:detached retina, rubeosis
iridis,neovascular glaucoma
 SCREENING OF DIABETIC
RETINOPATHY
TYPE OF FIRST EYE USUAL
DIABETES FUNDOSCOPY EXAMINATION
TYPE 1 3-5YEARS EVERY YEAR
AFTER
DIAGNOSIS
TYPE 2 AT FIRST EVERY YEAR
DIAGNOSIS
PREGNANCY Preconception
al and during
pregnancy
 Tratament
• Fotocoagulare cu laser: previne pierderea
vederii(hemoragii, retinopatie
neproliferativa severa)
• Injectii intravitreene cu anti-VEGF(anti-
vascular endotelial growth
factor):ranibizumab (retinopatie
proliferativa, edem macular)
DIABETIC NEPHROPATHY
The evolution of glomerular filtrate and urinary
albumin excretion
DN STADIALISATION
 STAGE I –RENAL HYPERFILTRATION AND
HYPERTROPHY
• AT FIRST DIAGNOSIS OF DIABETES
• reversible
  20-50 % of GFR (>150 ml/min/1,73 m2)
• After decreasing glycemia: 50% - GFR is normalising
50% - hiperfiltration

microalbuminuria
• Intermitent microalbuminuria:increasing the glomeruli
and kidneys
• Normal blood pressure
 STAGE II –SILENT, NORMOALBUMINURIC
STAGE

• In first five years of diabetes

• Renal biopsy:thickening of basal membrane and
mesangium
• GFR is increased ( 20-50 %)
• UAER is normal
• normal BP
 STAGE III – EARLY NEPHROPATHY

• After 6-15years of diabetes

• The progression is stopped by a good metabolic
control
• Persistent microalbuminuria (30-300 mg/24 h) –
• GFR is increased, but is decreasing with 3-5
ml/min/year
• Normal or little increased blood pressure ( with 3
mm Hg/year)
• Much more histological abnormalities +glomerular
obstructions
 STAGE IV –CLINIC DIABETIC
NEPHROPATHY
• After 15-25 years of diabetes
• Clinic proteinuria (albuminuria > 300 mg/24 ore)
• GF  progressivelly( 8-12 ml/min/year)
• 3 substages: - early(GF > 130 ml/min)
- intermmediary (GF < 100 ml/min)
- advanced (GF < 70 ml/min)
• BP ( with 5 mm Hg/year)
• Morphopatology:progressive glomerular sclerosis
distruction of renal mass
•Good glycemic and BP control is delaying the
progression of renal disease.
•
 STAGE V –CHRONIC RENAL FAILURE

• After 25-30 years of diabetes

• Proteinuria
• Urinary ureea<10g/24h
• GF < 10 ml/min
• BP
• Morphopatology: severe glomerular occlusions and lesion
 V. SCREENING FOR MICROALBUMINURIA

Every year :
• At puberty or 5 years of type 1 diabetes
• At first diagnosis of type 2 diabetes
Optimal treatment of arterial hypertension in
diabetic patient
Intensive glycemic Intensive treatment Optimising lifestyle
control to decrease
cadiovascular
risk

• HbA1c <7% • Dyslipidemia: Statines • Diet

• Glucose (mg/dL): • Hypertension : ≥2 classes • Physical exercise
Preprandial 90–130
of drugs • Smoking cessation
Postprandial <180
• Microalbuminuria: • Weight control
ACE or ARB
• Aspirin

• CHD: ACE, -blockers

• CVD/risc: ACE

ADA. Diabetes Care. 2005;28(suppl 1):S1-79.

 DIABETIC
MACROANGIOPATHY
 Main mechanisms of atherogenesis in
diabetes

 Disturbancies in concentration,composition and

lipoproteins
 Glycosilation end-products in plasma and arterial wall
 Oxidisation and glycosilatin of LDL
 Procoagulant status
 Insulinresistance and hyperinsulinism
 Muscle cell proliferation and “foam’cells in vascular
wall
 Main artery injuries

• Losing progressivelly
the elasticity of vessels
• Vascular remodelation
• intraluminal plaques
 Risk factors for atherosclerosis

• Smoking • Age
• Dislipidemia • Sex
• Arterial hypertension
• Genetic factors
• Diabetes mellitus,
insulin-resistance
• pro-trombotic status
• Lipoprotein(a)
 PATHOGENY of
ATHEROSCLEROSIS
ENDOTHELIAL DISFUNCTION

Production of cellular adhesion molecules

LyT attack on endothelium

LyT migration through arterial wall in subendothelial space

Macrofags are taking the oxidizated LDL

“FOAM” CELL
 Cardiac disturbancies in diabetes
Genetic factor Abdominal
Hyperglycemia
obesity
Age,sex
Arterial
Macroangiopathy hypertension
Family history Autonomic cadiac neuropathy dyslipidemia

Endothelial
dysfunction insulinresistence
Microangiopathy
Diabetic cardiomiopathy
Protein
Oxidative glycosilation
stress Procoagulant
status
 Peripheral artery disease
(PAD)
• Peripheral artery disease (PAD) is a
narrowing of the peripheral arteries to the
legs, stomach, arms, and head - most
commonly in the arteries of the legs
 PAD
• The most common symptoms of PAD
involving the lower extremities are
cramping, pain or tiredness in the leg or hip
muscles while walking or climbing stairs. 
• Typically, this pain goes away with rest and
returns when patient walk again.
 PAD
• Risk factors
• Factors that increase your risk of developing peripheral artery
disease include:
• Smoking
• Diabetes
• Obesity (a body mass index over 30)
• High blood pressure
• High cholesterol
• Increasing age, especially after reaching 50 years of age
• A family history of peripheral artery disease, heart disease or
stroke
• High levels of homocysteine, a protein component that helps
build and maintain tissue
 PAD
Complications

•Critical limb ischemia. This condition

begins as open sores that don't heal, an
injury, or an infection of your feet or legs.
Critical limb ischemia occurs when such
injuries or infections progress and can cause
tissue death (gangrene), sometimes
requiring amputation of the affected limb.
 PAD: diagnosis
Physical exam.
-weak or absent pulse below a narrowed area of your
artery, whooshing sounds (bruits) over your arteries
-Ankle-brachial index (ABI). evaluate blood pressure
and flow.
•Ultrasound. Special ultrasound imaging techniques,
such as Doppler ultrasound, Angiography. 
•Blood tests. A sample of your blood can be used to
measure your cholesterol and triglycerides and to check
for diabetes.
 PAD: treatment
• Cholesterol-lowering medications.
• High blood pressure medications. 
• Medications to prevent blood clots. daily
aspirin therapy/ clopidogrel (Plavix).
• Symptom-relief medications. The drug
cilostazol (Pletal) / pentoxifylline
• Angioplasty and surgery