Vascular

problems in
diabetes
Why does diabetes cause
vascular problems?
• “the pathophysiology of diabetes is clearly linked to
hyperglycemia”
• High glucose damages blood vessels
• No one knows exactly why – some theories
• High glucose levels reduce the levels of nitric oxide in
blood vessels
• powerful vasodilator
• Long term – leads to narrowing of blood vessels
• O-GlcNAc
• glucose-derived molecule
• Phosphorylation role in NO release
• O-GlcNAc – competes with phosphorylation
What vascular problems does
diabetes cause?
Microvascular Macrovascular

Retinopathy Ischaemic Heart Disease

Nephropathy Stroke

Neuropathy Peripheral vascular disease

Microvascular
• nephropathy, neuropathy, retinopathy
• “A strong relationship exists between
glycaemic control and the incidence and
progression of microvascular complications”
• For every 1% reduction in glycated
haemoglobin concentration there is a 35%
reduction in microvascular disease (T2DM;
estimated)
• Hypertension and smoking also play a role
Nephropathy
• Starts as incipient nephropathy/
microalbuminuria, in which the urine
contains trace quantities of protein
• Not detectable by urinalysis
• ACE inhibitors – renoprotective
• Proteinuria as a marker of widespread
vascular damage
• Increased risk of subsequent end stage
renal disease and macrovascular
complications - CHD
Diabetic Nephropathy Risk
Factors (full list)
• Poor blood sugar control
• High blood pressure
• Smoking
• Relatives have had kidney disease or high
blood pressure
• Diabetes began in teens
• Male
• Indo-Asian or Afro-Carribean background
Neuropathy
• commonest form is a diffuse progressive
polyneuropathy affecting mainly the feet
• It is sensory, often asymptomatic, and
affects 40-50% of all patients with diabetes
• Lead to foot ulcers, although aetiology is
mixed with vascular origins
• Foot care advice
Diabetic Foot Ulcer
Diabetic foot ulcer
Diabetic foot ulcer
Retinopathy
• commonest cause of blindness in people
aged 30-69 years
• a combination of microvascular leakage
and microvascular occlusion
• neovascularisation in type 1 diabetes
• maculopathy in type 2 diabetes
• 20% of T2DM patients have some form on
diagnosis
• After 15 years almost all patients with
T1DM & 2/3 with T2DM have background
retinopathy.
Maculopathy – types
• exudative maculopathy (when hard
exudates appear in the region of the
macula)
• ischaemic maculopathy (characterised by)
a predominance of capillary occlusion
which results in clusters of haemorrhages)
• oedematous maculopathy (extensive
leakage gives rise to macular oedema)
• Depends on the relative contribution of
leakage or capillary occlusion
Exudative Maculopathy
Ischaemic maculopathy
Oedematous maculopathy
Macrovascular
• Atherosclerotic disease accounts for most of the
excess mortality in patients with diabetes.
• Relationship with glucose concentrations is less
powerful than for microvascular disease
• smoking, blood pressure, proteinuria, and
cholesterol concentration are more important risk
factors
• Blood pressure control is very important in
patients with DM!
Coronary heart disease
• Statins have been shown to have a beneficial effect
• Raised risk for diabetics due to aggregation of
earlier factors – high BP, vascular damage, etc
• Prevalence of fatal and non-fatal coronary heart
disease events 2-20 x higher than for non-diabetics
of similar age
• Protective effect of female sex is lost
• Higher incidence of diffuse, multivessel disease
• Plaque rupture leading to unstable angina and
myocardial infarction is more
Myocardial Infarction
• In-hospital and 6 month mortality double that
in non-diabetics
• Complications (eg, arrhythmias, heart failure,
death) more common
• Reperfusion rates after thrombolysis are
similar to those of non-diabetics, but
reocclusion and reinfarction rates are higher
• Mortality reduced by insulin glucose infusion
immediately after myocardial infarction
Stroke
• 85% of acute strokes are atherothrombotic
• Diabetics more at risk of these types of
stroke
• “Patients with diabetes are probably more
prone to irreversible rather than reversible
ischaemic brain damage, and small
lacunar infarcts are common”
• Stroke patients with diabetes have a
higher death rate and a poorer
neurological outcome with more severe
disability
Peripheral vascular disease
• Atheromatous disease in the legs affects
more distal vessels
• This results in multiple diffuse lesions that
are less straightforward to bypass or dilate
by angioplasty.
• Medial calcification of vessels is common
• ABPI is therefore less reliable as a
screening test in patients with diabetes
and intermittent claudication.
Erectile dysfunction
• Multifactorial – autonomic neuropathy,
vascular insufficiency and psychological
factors
• 50% of men aged 50+ (compared with 15-
20% in normal population)
• Probably underreported
• Can cause social and psychological
problems
• Sildenafil - 50-70% success rate
Surveillance and management
• Screening for diabetes
Up to 50% of T2DM patients have vascular
complications on diagnosis
• Eye screening
Mobile retinal photography
• Cardiovascular risk prediction
“Channelling of treatment”
Surveillance and management II
• Annual complications assessment
Should be offered to all diabetics
• Areas of debate in surveillance of diabetes
complications
Difference between T2 and T1 management
and detection - microalbuminuria
• Team approach to integrated diabetic care
“A systematic, integrated, and collaborative
approach must be developed at a regional
level”
Predictors of cardiovascular
mortality
Type 1 diabetes Type 2 diabetes

Overt nephropathy Presence of CHD

Hypertension Overt proteinuria

Smoking Glycated haemoglobin

Microalbuminuria Hypertension

Age
Clinical features of "high risk"
diabetic foot
• Impaired sensation (monofilament)
• Past or current ulcer
• Maceration
• Fungal or gryphotic (thickened or horny)
toenails
• Biomechanical problems (corns or callus)
• Fissures
• Clawed toes
Fungal toe - progression
Risk of morbidity associated with
all types of diabetes mellitus
Complication Relative Risk

Blindness 20

End stage renal disease 25

Amputation 40

Myocardial infarction 2-5

Stroke 2-3