Transcript Diabetes Complications - University of Pretoria

Diabetes Complications
DG van Zyl
The Ticking Clock
Different Diabetes Complications
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Macro vascular
Micro vascular
Neuropathy
Infections
Mechanisms
Genetic susceptibility
*Repeated acute changes
in cellular metabolism
Hyperglycemia
Tissue damage
**Cumulative long term
changes in stable
macromolecules
Independent accelerating factors
Macro vascular Complications
Macro-vascular Complications
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Ischemic heart disease
Cerebrovascular disease
Peripheral vascular disease
Diabetic patients have a 2 to 6 times higher risk for
development of these complications than the
general population
Macro-vascular Complications
The major cardiovascular risk factors in the
non-diabetic population (smoking,
hypertension and hyperlipidemia) also
operate in diabetes, but the risks are
enhanced in the presence of diabetes.
Overall life expectancy in diabetic patients is
7 to 10 years shorter than non-diabetic
people.
Macro-vascular Disease
Once clinical macro-vascular disease
develops in diabetic patients they have a
poorer prognosis for survival than
normoglycemic patients with
macrovascular disease
The protective effect females have for the
development of vascular disease are lost
in diabetic females
CAD Morbidity and Mortality in
Type 2 DM
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Framingham Data: 20
year follow-up:Age
45-74:
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2-3 fold increase in
clinically evident
atherosclerotic
disease in diabetics
women
diabetics=male
diabetics in terms of
CAD mortality
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Multiple Risk Factor
Intervention Trial
(MRFIT)
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5000 men with type 2
DM
Followed for 12 years
Men with type 2 DM
had absolute risk of
CAD-related death 3
times higher than nondiabetic cohort
Risk Factor Clustering in Diabetes
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Type 2 Diabetes at Diagnosis:
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50% have hypertension
30% have dyslipidemia
UKPDS:
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Prospective study
Newly detected type 2 DM:
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335 with CAD, 8 year follow-up
Associated with elevated LDL-C, low levels of HDL-C,
systolic hypertension
Cardiovascular Death Rates:
MRFIT data
Stamler J., et al Diabetes Care: 16: 434-444
Risk of MI in Diabetes
Haffner, SM et al NEJM: 339: 229-234
Plasma Glucose as Independent
Risk Factor
Andersson, DK et al. Diabetes Care 18: 1534-1543
Glycemic Control to Reduce CAD
DCCT trial:
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1441 patients, type 1 diabetes
Randomized to intensive
glycemic control vs.
conventional therapy
Monitored prospectively for 6.5
years
Results:
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Less retinopathy by 50%
Macrovascular complications:
41% reduction (not statistically
significant)
-small number of events in
young patient cohort
UKPDS:
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3867 patients with
newly diagnosed type 2
DM
Intensive vs.
Conventional therapy
10 year follow-up
Microvascular
endpoints improved
Trend only towards
reduced incidence of MI
( p=0.052)
Effect of Hypertension
Mortality vs systolic blood pressure
Ten Year Mortality (per 1000)
70
60
50
40
Non-diabetic
Diabetic
30
20
10
0
110 120 130 140 150 160
Systolic Blood pressure
(mmHg)
Why worry about Hypertension in
Diabetic patients
Treating hypertension can reduce the risk of:
Death
Microvascular disease
Stroke
Heart failure
UKPDS BMJ 1998;317:703 - 713
32%
37%
44%
56%
Hypertension in Type 1 and 2
Diabetes
Type 1
Develop after several
years of DM
Ultimately affects ~30%
of patients
Type 2
Mostly present at
diagnosis
Affects at least 60% of
patients
Pathophysiology of hypertension
Type 1 DM
Type 2 DM
Secondary to
nephropathy
Hyperinsulinemia
Secondary to insulin
resistance
Activation of the
sympathetic nervous
system
Activation of the
RAAS
Goals of Treatment of Hypertension
Lower target for diabetic patients than nondiabetic patients:
130/85 vs. 140/90
UKPDS 38. BMJ 1998;317:703-713
HOT. Lancet 1998;351:1755-1762
Effect of Cholesterol
Ten Year Mortality (per
1000)
Serum cholesterol vs Mortality
70
60
50
40
30
20
10
0
Non-diabetic
Diabetic
4
5
6
s-Cholesterol (mmol/L)
7
Dyslipidaemia in DM
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Most common abnormality is  s HDL and
 s Triglyserides
A low HDL is the most constant predictor
of CV disease in DM
Target lipid values: LDL <2.6 mmol/l, HDL
>1.15 mmol/l, TG < 2.5 mmol/l
Micro vascular Complications
Eye Complications
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Cataracts
Non enzymatic glycation of lens protein and
subsequent cross linking
Sorbitol accumulation could also lead to osmotic
swelling of the lens but evidence of involvement
in cataract formation is less strong
Eye Complications
Retinopathy (stages)
Background
Pre-proliferative
Proliferative
Advanced diabetic eye disease
Maculopathy
Glaucoma
Diabetic Retinopathy (DR)
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DR is the leading cause of blindness in the
working population of the Western world
The prevalence increase with the duration
of the disease (few within 5 years, 80 –
100% will have some form of DR after 20
years)
Maculopathy is most common in type 2
patients and can cause severe visual loss
Background Retinopathy
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Micro aneurisms
Scattered exudates
Hemorrhages(flame
shaped, Dot and Blot)
Cotton wool spots
(<5)
Venous dilatations
Background retinopathy
Background retinopathy
Pre-Proliferative Retinopathy
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Rapid increase in
amount of micro
aneurisms
Multiple hemorrhages
Cotton wool spots
(>5)
Venous beading,
looping and
duplication
Proliferative retinopathy
Proliferative Retinopathy
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New vessels (on disc,
elsewhere)
Fibrous proliferation
(on disc, elsewhere)
Hemorrhages
(preretinal, vitreous)
Panretinal photo-coagulation
Proliferative retinopathy
Vitreous Bleeding
Rubeosis Iridis
Advanced Diabetic Eye Disease
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Retinal detachment
with or without retinal
tears
Rubeosis iridis
Neovascular
glaucoma
Maculopathy
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Macular edema (focal
or diffuse)
Ischaemic
maculopathy
Maculopathy
Diabetic Nephropathy (DN)
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Diabetes has become the most common
cause of end stage renal failure in the US
and Europe
About 20 – 30% of patients with diabetes
develop evidence of nephropathy
The prevalence of DN is higher in Black
Americans than in Whites (Figures for
South Africa is not available)
Stages of Diabetic Nephropathy
Stages of DN
Stage I
 glomerular filtration and kidney
hypertrophy
Stage II
u-albumin excretion < 30mg/24h
Stage III
Microalbuminuria (30 – 300 mg/24h)
Stages of DN (cont)
Stage IV
Overt nephropathy (> 300mg/24h, positive
u dipstick)
Stage V
ESRD characterized by  blood urea and
creatinine levels, hyperkalaemia and fluid
overload
Diabetic Neuropathy
Sensorimotor neuropathy (acute/chronic)
Autonomic neuropathy
Mononeuropathy
Spontaneous
Entrapment
External pressure palsies
Proximal motor neuropathy
Sensorimotor Neuropathy
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Patients may be asymptomatic / complain
of numbness, paresthesias, allodynia or
pain
Feet are mostly affected, hands are
seldom affected
In Diabetic patients sensory neuropathy
usually predominates
Complications of Sensorimotor
neuropathy
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Ulceration (painless)
Neuropathic edema
Charcot arthropathy
Callosities
Autonomic Neuropathy
Symptomatic
Postural hypotension
Gastroparesis
Diabetic diarrhea
Neuropathic bladder
Erectile dysfunction
Neuropathic edema
Charcot arthropathy
Gustatatory sweating
Subclinical abnormalities
Abnormal pupillary reflexes
Esophageal dysfunction
Abnormal cardiovascular
reflexes
Blunted counter-regulatory
responses to
hypoglycemia
Increased peripheral blood
flow
Mononeuropathies
Cranial nerve palsies
(most common are n.
IV,VI,VII)
Truncal neuropathy
(rare)
Entrapment Neuropathies
Carpal tunnel syndrome (median nerve)
 Ulnar compression syndrome
 Meralgia paresthetica (lat cut nerve to the
thigh)
 Lat Popliteal nerve compression (drop
foot)
All the above are more common in diabetic
patients
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Proximal Motor Neuropathy
Amyotrophy – most common proximal
neuropathy, affects the Quadriceps
muscles with weakness and atrophy
(synonym: Diabetic Femoral radiculoneuropathy)
Diabetic Amyotrophy
Thoracoabdominal Radiculopathy
Sudomotor Dysautonomia
Summary
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Diabetic neuropathy is a common
complication, and result in significant
morbidity
Diabetic neuropathy present in numerous
ways
Hyperglycemia is the cause of diabetic
neuropathy
Summary (cont)
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Diabetic neuropathy have bad
consequences
Diabetic neuropathy can be prevented in
only one way
Once diabetic neuropathy is present it can
only be managed symptomatically
Early diagnosis and aggressive
management can prevent progression
Infections
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The association between diabetes and
increased susceptibility to infection in general is
not supported by strong evidence
However, many specific infections are more
common in diabetic patients and some occur
almost exclusively in them
Other infections occur with increased severity
and are associated with an increased risk of
complications
Infections (cont)
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Several aspects of immunity are altered in
patients with diabetes
There is evidence that improving glycemic
control patients improves immune function
Specific Infections
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Community acquired
pneumonia
Acute bacterial
cystitis
Acute pyelonephritis
Emphysematous
pyelonephritis
Perinephric abscess
Fungal cystitis
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Necrotizing fasciitis
Invasive otitis externa
Rhinocerebral
mucormycosis
Emphysematous
cholecystitis
Rhino-Cerebral Mucormycosis
Screening and Management
Strategy for Diabetes
Complications
Screening for Macrovascular
Complications
1. Examine pulses and for cardiovascular
disease
2. Lipogram
3. ECG
4. Blood pressure
1-3 annually
4 every visit (quarterly)
Screening for Eye disease
Annually
Visual acuity (corrected with pinhole or
lenses)
Careful eye examination (noting the clarity
of the lens and any retinal changes
(Ophthalmoscopy through dilated pupils)
Screening for Eye disease
When to refer?
Severe non-proliferative/proliferative retinopathy
Macular edema or exudates in close proximity to
the macula
Cataract
Unexplained reduction in visual acuity
Screening for Nephropathy
Annually
Do one of the following:
u Albumin:Creatinine ratio (spot sample)
24h u Albumin excretion rate
Early morning Albumin concentration
(spot sample)
Dipstick for Microalbuminuria
If positive the test must be repeated twice in the ensuing 3 months. Microalbuminuria
with incipient nephropathy is diagnosed if 2 or more of the tests are within the
microalbumin range
Microalbuminuria
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Increased risk for overt nephropathy
Increased cardiovascular mortality
Increased risk of Retinopathy
Increased all-cause mortality
Thus
Microalbuminuria is an indication for screening
for possible vascular disease and aggressive
intervention to reduce all cardiovascular risk
factors
Screening Tests for
Microalbuminuria
Category
24h u
collection
(mg/24h)
Timed
collection
(mg/min)
Spot
collection
(mg/mg
creat)
Normal
 30
 20
 30
Microalbumi
nuria
30 - 299
20 - 199
30 - 299
Albuminuria
Overt
 300
 200
 300
Who to Screen For
Microalbuminuria
Type 1 Diabetes
Type 2 Diabetes
Begin with puberty
Start screening at
the Diagnosis of
After 5 years
diabetes
duration of disease
Should be done
Should be done
annually there after
annually there after
Management of Nephropathy
Improvement of glycemic control
 Treatment of hypertension
 Treatment with angiotensin converting
enzyme inhibitors
 Restriction of dietary intake of protein
Once persistent elevation in u-Albumin is
found refer to a Internist or Nephrologist
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Screening for Neuropathy
128 Hz tuning fork for
testing of vibration
perception
 10g Semmers
monofilament
The main reason is to
identify patients at risk
for development of
diabetic foot
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Using of the Monofilament
Management of Neuropathy
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Burning pain – TADs / Capsaicin
Lancinating pain – Anticonvulsants / TAD /
Capsaicin
Painful cramps – Quinidine sulphate
Restless legs - Clonazepam
Do’s and Don'ts of foot care
Patient should
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check feet daily
Wash feet daily
Keep toenails short
Protect feet
Always wear shoes
Look inside shoes before
putting them on
Always wear socks
Break in new shoes gradually
Conclusion
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This is just an outline of the major diabetic
complications, and doesn't aim to be
comprehensive
All complications are preventable with
good glycaemic control
The progression of most complications
can be halted if detected early and
appropriate therapy instituted