Diabetische nefropathie: hoe verder?

VU medisch centrum
VU medisch centrum
Diabetische nefropathie
Diabetische nefropathie: hoe verder?
Prof dr. P.M. ter Wee
Department of Nephrology
Department of Nephrology
Epidemiologie
Epidemiologie
VU medisch centrum
RRT Diabetes mellitus type 1
Department of Nephrology
VU medisch centrum
RRT Diabetes mellitus type 2
Van Dijk P, et al. Kidney Int 2005;67:1489-9
Epidemiologie
Department of Nephrology
Epidemiologie
VU medisch centrum
Diabetes mellitus
Department of Nephrology
Van Dijk P, et al. Kidney Int 2005;67:1489-9
VU medisch centrum
Diabetes mellitus
Van Dijk P, et al. Kidney Int 2005;67:1489-9
Department of Nephrology
Van Dijk P, et al. Kidney Int 2005;67:1489-9
Epidemiologie
Epidemiologie: 2000-2030
VU medisch centrum
VU medisch centrum
De Hoorn studie (n=2484; 50-75 jaar; BL 1989-1990)
normal
9,2
10,4
80,5
6,7
3,7
intermediate
hyperglycemia
diabetes-new
diabetes-known
De Vegt et al. Diabetes Care 1998;10:1686-90
Department of Nephrology
Department of Nephrology
Potentiële nieuwe ontwikkelingen
VU medisch centrum
VU medisch centrum
Renine remmers
Waar te beginnen?
Uresin Y, et al. JRAAS 2007;8:190-8
Department of Nephrology
Department of Nephrology
Potentiële nieuwe ontwikkelingen
Potentiële nieuwe ontwikkelingen
VU medisch centrum
VEGF remmers
VU medisch centrum
Genetica en DN
Diabetische nefropathie komt vaker voor bij tweelingen,
in families in etnische groepen ⇒ genetische component
TGF-ß remmers?
p.m.: TZD’s ⇒ hartfalen
We have demonstrated multiple chromosomal regions
linked to eGFR in a multi-ethnic collection of families
ascertained by a proband with diabetic nephropathy.
Identification of genetic variants within these loci that
are responsible for the linkage signals could lead to
predictive tests or novel therapies for subsets of
patients at risk for diabetic nephropathy.
Schelling JR, et al. Diabetes 2008;57:235–243
Department of Nephrology
Sung SH, et al. JASN 2006; 17:3093-3104
Department of Nephrology
Vooralsnog de weg te gaan
Oorzaken DN: multifactorieel
VU medisch centrum
VU medisch centrum
Any diabetes-related complications per 1000 patient-years
Preventie
leefstijlaanpassing; kosteneffectief Herman WH, et al. Ann Intern Med 2002;346:393-403
vroege opsporing/bewustwording: niet effectief, cq lukt niet
Screening
RR
microalbuminurie
GFR
Behandeling
multifactorieel
Department of Nephrology
Department of Nephrology
Oorzaken DN: multifactorieel
Stratton I, et al. Diabetologia 2006;49:1761-9
Behandeling DN: HbA1c
VU medisch centrum
UKPDS 74:
patienten zonder (n=4031) en met albuminurie (n=5032)
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Eilandjes transplantatie
Niet-beïnvloedbare oorzaken
Indiaanse/Aziatische afkomst
microalbuminurie bij presentatie
creatininegehalte bij presentatie
geslacht
aanwezigheid retinopathie
Department of Nephrology
Beïnvloedbare oorzaken
systolische RR↑
roken
toegenomen ‘waist-hip’ ratio
LDL ↑
HbA1c ↑
Retnakaran R, et al. Diabetes 2006;55:1832–9
Behandeling DN: HbA1c
Department of Nephrology
Behandeling DN: HbA1c
VU medisch centrum
Pancreas-nier transplantatie
Department of Nephrology
Fiorina P, et al. JASN 2003;14:2150-8
VU medisch centrum
Pancreastransplantatie
Fiorina P, et al. Diabetes Care 2005; 28:1303-10
Department of Nephrology
Fioretto P, et al. N Eng J Med 1998;339:69-75
Behandeling DN: multifactorieel
VU medisch centrum
VU medisch centrum
Steno 2 study
Conventioneel behandelde groep
Intensieve therapie groep (3-maandelijkse controle)
30% afname dagelijkse vetinname; <10% verzadigd vet
lichamelijke inspanning, minimaal 30 min 3-5x per week
patiënten + partner: ‘stop roken’-programma
ACE-remmer (of AII-antagonist)
Vitamine-mineraal supplement
aspirine (150 mg)
Als cholesterol ↑ start statine
HbA1c <6,5%
Department of Nephrology
Department of Nephrology
Behandeling DN: multifactorieel
Behandeling DN: multifactorieel
VU medisch centrum
Steno 2 study
Department of Nephrology
VU medisch centrum
Steno 2 study
Gaede P, et al. N Eng J Med 2003;348:383-93
Behandeling DN: multifactorieel
Department of Nephrology
Behandeling DN: multifactorieel
VU medisch centrum
Steno 2 study
Department of Nephrology
Gaede P, et al. N Eng J Med 2003;348:383-93
VU medisch centrum
Steno 2 study
Gaede P, et al. N Eng J Med 2003;348:383-93
Department of Nephrology
Gaede P, et al. N Eng J Med 2003;348:383-93
Behandeling DN: multifactorieel
Behandeling DN: multifactorieel
VU medisch centrum
•20
•20
•18
•16
•17
•14
•14
•12
•12
•10
•CABG Surgery
•MI: non-fatal
•6
•3
•0
•Cardiovascular
•Death
•0
•7
•5
•PVD Surgery
•5
•Amputations
•5
•2
•fatal
•7 •7
•4
•Strokes: non-
•6
•Conventional
•intensive
•10
•8
•Percutaneous
•Coronary Rx
•Number of Events
VU medisch centrum
Steno 2 study; laat
Steno 2 study
Department of Nephrology
Gaede P, et al. N Eng J Med 2008;358:580-91
Department of Nephrology
Behandeling DN: multifactorieel
Behandeling DN: multifactorieel
VU medisch centrum
Steno 2 study; laat
Department of Nephrology
VU medisch centrum
Steno 2 study; laat
Gaede P, et al. N Eng J Med 2008;358:580-91
Behandeling DN: multifactorieel
Gaede P, et al. N Eng J Med 2008;358:580-91
Department of Nephrology
Behandeling DN: multifactorieel
VU medisch centrum
VU medisch centrum
Steno 2 study; laat
The Alphabet Strategy
•
•
•
•
•
•
•
•
Advice
Blood pressure
Cholesterol
Diabetes control
Eye examination
Feet examination
Guardian drugs
Heart risk score
Smoking , diet , exercise
< 140/80
TC ≤ 5, LDL : HDL ≤ 3
HbA1c ≤ 7%
Annual examination
Annual examination
Aspirin, ACEI, statins &c
UKPDS, Framingham
Patel V, Morrissey J. Br J Diabetes Vasc Dis 2002;2: 58-59
Department of Nephrology
Gaede P, et al. N Eng J Med 2008;358:580-91
Department of Nephrology
Behandeling DN: multifactorieel
Behandeling DN: multifactorieel
VU medisch centrum
Advice
How your eyes work
Your eye has a lens and an opening at the front,
which adjust to bring objects into focus on the
retina at the back of the eye.
preventing or reducing overweight will
help you control your diabetes
Exercise : Regular exercise will help to
maintain an optimum weight and will
benefit all members of the family
The retina is made up of delicate tissue that is
sensitive to light rather like the film in a camera.
At the centre of the retina is the macula, which is
a small area about the size of a pinhead. It is vital
because it enables you to see fine detail.
B lood P ressure
Smoking : It is widely accepted that smoking
• A person with diabetes can have eye disease and not even know it until
serious, irreversible vision loss has occurred
• The only way to diagnose early signs of diabetic eye disease is through a dilated
eye exam at least once a year
Feet
causes heart and lung disease. Most diabetic
complications are worsened by smoking
140 / 80
DIABETIC EYE
DISEASE
•During
a lifetime, your feet may walk the equivalent of four
Diabetic Eye Disease(Diabetic
times around the world!
retinopathy) is the commonest
Normal retina
Diabetic Retinopathy
cause of blindness•To
under
the age of
65 they continue their trip through life without
ensure
that
in the Western World
complaint, it pays to look after your feet!
37% of diabetes patients have
retinopathy at diagnosis of diabetes
1500 new cases of blindness could be People suffering from diabetes can often experience loss of sensation
prevented by yearly screening in UK in their feet. Even the smallest injury can lead to infection, which if
20 years after diagnosis 95% with Type
not treated promptly, may lead to serious complications.
Macula
Optic Disc Fatty Haemorrhage
1 diabetes have retinopathy
Deposits
20 years after diagnosis 60% of patients
with Type 2 diabetes have retinopathy
It issave
important
that you examine your feet regularly. You should
Laser treatment can
eye sight
also feel inside all shoes for any seams or stitching which could
getting worse in 90% of patients
Developing diabetes and heart disease with
increasing waist circumference
Very good control of blood pressure is required!
Finnish Diabetes Study
blood
This study was conducted toRaised
determine
the pressure can
effects of a programme of changes in lifestyle in
with ‘Pre’ diabetes
ofpatients
diabetes
increase all complications
C holesterol
rel ated de at h
FAT
Lo ss o f vi si on
Diabe tes
a ny dia be tes
What are Guardian Drugs?
BLOOD
-10 %
2 4%
3 2%
P=0 .0 0 4
3 4%
37 %
44%
P=0.0 19
56 %
D iabetes C ontrol
P=0 .0 0 4
P=0 .00 9
P=0 .01 3
How much fat does your blood
contain?
The optimal target for blood
cholesterol level is
47 %
P=0.0 0 4
-60 %
♦0
P=0.0 04
LESS THAN 5
Proportion without major
Heart problems (%)
1
2
3
4
5
6
15
- 14%
10
When was the last time you had your feet checked?
5
Also if: Indo - Asian, overweight, high
cholesterol, Heart Disease risk
greater than 15%, family history,
history of heart disease, smokers
40
0
-29%
Kidney Disease
Glucose Control Study
The UKPD study shows that good
glucose control can decrease the
risks of:
Pain or loss of the lower
legs due to impaired
blood flow
Heart attack by 16%
Cataract by 24%
Kidney problems by 33%
Peripheral Neuropathy
(nerve disease)
•
•
•
•
Risk of Diabetes Complications
7
3
0
6.5
7.0
Eyes
Annually
Annually
Any cardiovascular
problem
Heart Attack
Heart Disease
Stroke
Kidney
Eye disease
Feet
Annually
Annually
All
Most
Guardians : aspirin
ACEI / AIIA
-
All
Most
Events
UKPDS risk
>8
-
6 to 7
<6
-
Heart disease
7 to 8
-
-
> 16 0
1 40 to 15 0
130 -140
Blo od P res sure
H bA 1 c%
<13 0
Increasing
Are you in control of your diabetes?
What is your HbA1c%?
Department of Nephrology
5.0
Diabetes Control : HbA1c%
5
4
2
Enjoy the Posters!
4.5
The names of these drugs end in ‘PRIL’
9
8
6
140 / 80
Cholesterol
Do you know if you are taking any of
the guardian drugs?
10
1
If you think any area of your care needs to be addressed please
make a note and discuss this with your Diabetes Care Team.
Standard
ACE -inhibitors are drugs that have a special role in preventing diabetic complications.
The HOPE study showed that one ace inhibitor, ‘Ramipril’ reduced:
Metformin, Gliclazide, Glimepiride,
Pioglitazone , Rosiglitazone, Insulin and
many other drugs
Do you know what your level is?
Are you on target?
UK Prospective Diabetes
Standard
0
ACE INHIBITORS
7.0%
What drugs help to control diabetes?
Remember with
good care all
complications
can be reduced
or even
prevented!
FOOT PROBLEMS
15% of people with diabetes develop foot
ulcer; 5-15% of these need amputation
vessel diseases and kidney
problems
This value
Simvastatin
the amount of glucose
20 tells you
sticking to your blood
over the last 60 days
Pla cebo
0 how well your diabetes has been controlled
It reflects
High Blood Pressure
DIABETIC KIDNEY
DISEASE
20% of all new patients
needing renal dialysis
therapy have diabetes
Heart attack, angina, high blood
At 2 years ulceration was reduced to 2.4% compared with 3.5%
pressure, eye problems, blood
Amputation was reduced by 3 times
Risk
reduction
What is HbA1c%?
Number
of years
on simvastatin
The aim
is to have
a value
of less than
Heart Disease
HEART and BLOOD VESSELS
2 to 4 fold increased risk of
heart disease and stroke
75% have hypertension
trained podiatrist and foot education, it was found that
100 be helped by regular blood
This can
glucose80monitoring at home and keeping
an accurate written record. Bring it to clinic!
55%
60
30
Diabetes UK recommends taking
25
aspirin to prevent against heart
Liverpool Diabetes
Clinic:inFoot
Protection
Programme
problems
all diabetes
patients
(greate r than 30yrs) with any of the
20
When patients with diabetes and foot
deformities attended regular clinics with a
following:
4–7
This study showed that
long-term simvastatin
(cholesterol lowering drug)
therapy reduces chances
of dying and heart problems
in patients with diabetes
are given to protect you from further diabetes
complications
Foot ulcers come before 85% of amputations
in people with diabetes. Foot ulcers ASPIRIN
are the
commonest cause of amputation in the UK
glucose needs to be kept within
a controlled range
Alphabet
Strategy
130 / 80 (140 / 85)
Blood Pressure
Guardian Drugs
15% of patients with diabetes will develop
foot ulcers due to nerve damage and reduced
Guardian drugs
blood flow
0%
♦30
Too
much fat can cause you to be
-20 %
-30 %
♦20
overweight,
making it much more
-40 %
difficult
to control your diabetes♦10
-50 %
Any-70diabetes
Stroke
Hea rt heart problems
Blood
It%can also cause
problem
Failure
Remember your
target is 140/80
SCANDINAVIAN SIMVASTATIN
STUDY
Have you hit the SURVIVAL
bulls-eye?
Stroke
Eye
Disease
DIABETIC EYE DISEASE
Most common cause of
blindness in people of
working age
stro ke
provide important energy sources
♦40
Are you eating
healthy
foods?
Aggressive
blood
pressure
How often do
control
youreduces
exercise?
the risk of
complications in
Do youmost
smoke?
Diabetes
Do you know your target weight?
It’s as simple as that!
He artfail ur e
Blood Pressure Control Study
rub the foot and lead to problems.
SERUM
UK resulted
Prospective Diabetes
blood fats are necessary to♦50
Carrying out this programme
in lessStudy
diabetes bySome
58%
StenoSteno-2 intensive
cohort
Advice
important that you receive regular foot advice or treatment.
WhenIt iswas
the last time you had
Foot Problems
your eyes
checked?
♦60
Re tin o pathy pr og re ss io n
M icro va sc ula r dise ase
rela te d
e ndpoi nts
Lifestyle changes included
It is important that it is checked regularly
•Weight reduction greater than 5% (if needed)
•Fat intake less than 30% of calorie
intake
Tablets
maybe taken to control blood pressure
•Saturated fat less than 10% of calorie intake
This is the amount of fat in
•Fibre intake greater than 15grams/
1000need
calories
You may
to change what you eat and exercise more
•Exercise greater than 4 hours per week (brisk walking) blood
% Decrease in Events
Weight control : There is a greater risk of Target :
Diabetes Care 4 U!
StenoSteno-2 vs Alphabet Strategy : targets
Is Diabetes slowly stealing your vision?
Diet : Maintaining a healthy diet and
Welcome to Diabetes Care 4 U! Here you will find posters packed full
of information and innovative ideas to ensure you have great Diabetes
Care! Before you enter into the unique experience let us go over the
problems of diabetes.
VU medisch centrum
Eyes
Department of Nephrology
Behandeling DN: multifactorieel
Conclusie
VU medisch centrum
VU medisch centrum
400 nieuwe patië
patiënten type 2 DM; 5 jaar followfollow-up
Smoking ↓
Advice
Blood Pressure
Syst +diast 5 mmHg ↓
0,9 ↓
Cholesterol
Diabetes Control : HbA1c%
11% ↑
Feet
14% ↑
Guardians : aspirin
54% ↑
ACEI / AIIA
Department of Nephrology
Department of Nephrology
Multifactoriële en multidisciplinaire therapie
32% ↑
4% ↓
Lee JD et al. Curr Med Res Opin. 2004;20:765-72
VU medisch centrum
That’s it!
Vroege opsporing noodzakelijk
=
Eyes
Heart disease
Preventie essentieel
Department of Nephrology