Document

Diabetes
Mellitus
Hart,
Nieren &
Hypertensie
Microalbuminurie bij Diabetes
Definitions of Microalbuminuria
and Macroalbuminuria
Parameter Normal
Microalbuminuria
Macroalbuminuria
Urine AER
(g/min)
< 20
20 - 200
>200
Urine AER
(mg/24h)
< 30
30 - 300
>300
Urine
albumin/
Cr# ratio
(mg/mmol)
<3
3 - 30
>30
AER=Albumin excretion rate
CR# =creatinine
Behandeling van Diabetes moet dus
in hoge mate zijn gericht op
preventie van cardiovasculaire ziekte
...
Treatment Targets for Diabetic
Renal Disease With Hypertension
Meta Analysis: Lower Systolic BP
Results in Slower Rates of Decline in
GFR in Diabetics and Non-Diabetics
SBP (mmHg)
130
134
138
142
146
150
154
170
180
GFR (mL/min/year)
0
-2
r = 0.69; P < .05
-4
-6
-8
Untreated
HTN
-10
-12
-14
Parving HH, et al. Br Med J. 1989.
Moschio G, et al. N Engl J Med. 1996.
Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996.
Klahr S, et al. N Eng J Med. 1994.
Bakris GL. Hypertension. 1997.
Hebert L, et al. Kidney Int. 1994.
The GISEN Group. Lancet. 1997.
Lebovitz H, et al. Kidney Int. 1994.
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.
Behandeling Microalbuminurie bij DM
~ 2e-doel RR: 120-130/<80 mmHg
• ACEi met diureticum
(eg. Captopril/HCT of Lisinopril/HCT)
• 2e middel op indicatie (eg. BB bij angina pectoris)
• 2-3e middel: Spironolacton,
(z.n. + kaliumbeperkt dieet of HCT/chloortalidon of sorbisterit)
• 3-4e middel: Allopurinol
Consultatie van of verwijzing naar de
tweede lijn is aangewezen bij
• twijfel over de diagnose,
• problemen bij de glycemische instelling,
• problemen bij behandeling van risicofactoren,
• het onvoldoende onder controle krijgen van de gevolgen
van complicaties
• zwangerschap(swens).
LTA DM-II, 2012
From Dr J Vora
DM-II
• Losartan verhoogt de incidentie van microalbuminurie
• RR-verlaging < 120 mmHg systolisch induceert meer sterfte
• Vitamine-D vermindert microalbuminurie
• Intensieve behandeling hyperglycemie in de initiële fase van DM-I/II
reduceert nefropathie en CVR
• Mortaliteit stijgt bij HbA1c > 85 en < 42 mmol/mol
• Intermitterende episodes van acute nierinsufficientie verslechteren de
lange termijn prognose
Allopurinol initiation and all-cause
mortality in the general population
Results Of 5927 allopurinol initiators and 5927
matched comparators, 654 and 718, respectively,
died during the follow-up (mean=2.9 years).
The baseline characteristics were well balanced in
the two groups, including the prevalence of gout in
each group (84%). Allopurinol initiation was
associated with a lower risk of all-cause mortality
(matched HR 0.89 (95% CI 0.80 to 0.99)). When
we limited the analysis to those with gout, the
corresponding HR was 0.81 (95% CI 0.70 to 0.92).
http://dx.doi.org/10.1136 annrheumdis-2014-205269
Urinezuur is een cardiovasculaire
risicofactor
Allopurinol bij DM
• Vermindert insuline resistentie
• Verlaagt CRP
• Vertraagt Atherosclerose
• Vermindert Microalbuminurie
• Vermindert Chronische nierschade
• Vermindert Linkerventrikelhypertrofie
• Vermindert Oxidatieve stress
Allopurinol risico’s
• Acute allergische reactie 4,7 promille
JAMA Intern Med. 2015;175(9):1550.
• Gerelateerde mortaliteit 0,4 promille
• Heupfractuur Odds Ratio (OR) 1,07
• Lager risico op Hartinfarct: OR 0,73
OR 0,52, dosis en duur afhankelijk
• Atriumfibrilleren:
OR 0,73
Archives of Osteoporosis
annrheumdis-2012-202972
heartjnl-2014-306670
annrheumdis-2012
2015, 10:36
Metformine
Metformine risico’s
• Bij eGFR<15:
Mortaliteit OR 1,35
• Lactaat acidose 1,6 vs 1,3/100jaar (n.s.)
• Bij eGFR > 30 ml/min/1,73m2:
nuttig en veilig
• Bij eGFR 15- 30 ml/min/1,73m2: waarschijnlijk
nuttig en veilig.
Effectiveness and safety of metformin in 51675 patients with type 2
diabetes and different levels of renal function: a cohort study from the
Swedish National Diabetes Register.
BMJ Open. 2012 Jul 13;2(4).
Verschillen tussen ACE-remmers
CV Mortality in General Population
(GP) & Dialysis Patients, By Race
Annual % Mortality (Log Scale)
100.000
10.000
1.000
0.100
GP Black
GP White
Dialysis Black
Dialysis White
0.010
0.001
25-34
35-44
45-54
55-64
Age (years)
Sarnak MJ, Levey AS. Semin Dial. 1999;12:69-76.
65-74
75-84
85+
Tot slot,
praktisch: . . .
Mijn behandelingsstrategie bij:
diabetes + chronische nierziekte
(≥ microalbuminurie) ± hypertensie
• ≥3x1uur bewegen/week; roken -; gewicht ; voeding.
• Bloeddruk ≤125/75 mmHg
• Start met een ACE-remmer, liefst een combinatiepil met
een lage dosis diureticum !
• +/-Zoutarm dieet (<6 g NaCl/d)
• Doseren totdat proteinuria ≤ 0,5 g/dag is
• Behandel dislipidemie (LDL <2,5 mmol/L, Trigl ≤ 2,0)
• HbA1C < 60 mm/m
P C Chang, RZZ
UKPDS: Relationship Between BP Control
And Diabetes-Related Deaths
Hazard ratio
5
1
p<0.0001
17% decrease per 10 mmHg decrement in BP
0.5
110
120
130
140
150
Mean systolic blood pressure (mmHg)
Adler AI, et al. BMJ. 2000;321:412-419.
Reprinted by permission, BMJ Publishing Group.
160
170
Risk of Ischemic Heart Disease
Related to SBP and Microalbuminuria
N=2,085; 10 year follow-up
Relative Risk
6
5
Normoalbuminuria
Microalbuminuria
4
3
2
1
0
SBP <140
Borch-Johnsen K, et al.
Arterioscler Thromb Vasc Biol. 1999;19(8):1992-1997.
SBP 140-160
SBP>160
Relative Importance of CV Risk
Factors in Diabetes
12
10.0
10
8
6.5
6
3.2
4
2.3
2
0
Microalbuminuria
Smoking
Diastolic BP
Cholesterol
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.
Diabetes and Chronic Renal Disease
as CV Risk
Behandeling van Diabetes moet dus
in hoge mate zijn gericht op
preventie van cardiovasculaire ziekte
...
Cardiovasculaire
Preventie
in
Diabetes
Vascular Protection:
Glycaemic Control
Glycaemic Control for Vascular Protection:
after all Patients are on ACE Inhibitor,
ASA and Lipid Control (statin)
Hazard ratio
5
Fatal and Non - Fatal Myocardial Infarction
14% decrease per 1% decrement in HbA1c
p<0.0001
CDA 2003 Glycaemic
Targets
A1c  7% for most
patients
1
0.5
0 5
A1c  6% when safely
achievable
6
7
8
9
10
11
Updated mean HbA1c
UKPDS 35. BMJ 2000; 321: 405-12.
Vascular Protection:
Diabetes and Control of
Hypertension
Treatment Targets for Diabetic
Renal Disease With Hypertension
CV Mortality Risk Doubles with
Each 20/10 mm Hg BP Increment*
8
7
6
CV
mortality
risk
5
4
3
2
1
0
115/75
135/85
155/95
SBP/DBP (mm Hg)
*Individuals aged 40-69 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
Lewington S, et al. Lancet. 2002; 60:1903-1913.
JNC VII. JAMA. 2003.
175/105
Goal BP Recommendations for
Patients with DM or Renal Disease
Systolic
Organization
Year
BP
American Diabetes Association 2001
<130
Diastolic
BP
<80
2000
<130
<80
Canadian Hypertension Society 1999
<130
<80
1999
<140
<80
1999
<130
<85
1997
<130
<85
125
75
National Kidney Foundation
British Hypertension Society
WHO & International
Society of Hypertension
Joint National Committee
(JNC VI)
Renal Disease & Proteinuria >1g
(JNC VI)
From Dr J Vora
Management of Chronic
Renal Disease: Initial Diet Therapy
• For patients with modest renal insufficiency, reduce
intake of high biological quality protein* intake of 1
gm/kg body weight/day
• For patients with marked renal insufficiency, reduce
dietary protein intake to 0.8 gm/kg body weight/day
• Restrict dietary sodium intake to 4-6 gm/day
• Avoid foods rich in potassium
*high biological quality proteins are those rich in essential amino acids
Impact of Blood Pressure Reduction
on Mortality in Diabetes
Trial
Conventional Intensive
Risk
care
care
reduction
P-value
UKPDS
154/87
144/82
32%
0.019
HOT
144/85
140/81
66%
0.016
Mortality endpoints are:
UK Prospective Diabetes Study (UKPDS) – “diabetes related deaths”
Hypertension Optimal Treatment (HOT) Study – “cardiovascular deaths” in diabetics
Turner RC, et al. BMJ. 1998;317:703-713.
Hansson L, et al. Lancet. 1998;351:1755–1762.
Diabetes and Hypertension
3.0%
No DM
DM
2.0%
Annual
Mortality
1.0%
0.0%
<120
120139
140159
160179
180199
>200
Systolic BP
Stamler J, et al, Diabetes Care, 1993;16(2):434-444.
Treatment Targets for Diabetic
Renal Disease With Hypertension