Signe Toft Andersen MD PhD fellow Section of General Practice Department of Public Health Aarhus University Background Lowgrade inflammation is associated to obesity and type 2 diabetes ID: 463446
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THE MACROPHAGE ACTIVATION MARKER SOLUBLE CD163 IS ASSOCIATED TO DIABETIC NEUROPATHY
Signe Toft AndersenMD, PhD fellowSection of General PracticeDepartment of Public HealthAarhus UniversitySlide2
BackgroundLow-grade inflammation is associated to obesity and type 2 diabetes
Previous studies show an association between low-grade inflammation and diabetic neuropathy
1Low-grade inflammation in adipose tissue is characterised by a high number of activated macrophages
1
The MONICA/KORA Study Group Slide3
3Slide4
Background
The macrophage-derived biomarker soluble CD163 is secreted to the blood when the macrophages are activated
sCD163 is associated with obesity, insulin resistance and it predicts the development of type 2 diabetes in the general population
2-5
A trend towards higher sCD163 levels in both serum and cerebrospinal fluid was found in a pilot study of diabetic polyneuropathy in patients with type 2 diabetes
6
2
Axelsson J. Am
J
Kidney
Dis 2006 Dec;48(6):916-925
.
3
Sporrer D.
Eur
J Clin Invest 2009 Aug;39(8):671-679. 4Shakeri-Manesch S. Int J Obes (Lond) 2009 Nov;33(11):1257-1264. 5Moller HJ et al. Clin Chem 2011 Feb;57(2):291-297. 6M.Kallestrup et al. Diab.Med 2014 Aug;32,54-61.Slide5
Aim
To investigate whether
soluble CD163 is associated
with
the
presence
of
neuropathy among
individuals
with type 2 diabetesSlide6
Methods
Cross-sectional study on five year follow up on screen-detected type 2 diabetes patients from the ADDITION-DK trial7-8
Diabetic polyneuropathy (DPN) was assessed by vibration perception threshold, using CASE IV
Cardiac autonomic neuropathy (CAN) was assessed using three standard tests (lying/standing, deep breathing and
valsalva
manoeuvre), using VAGUS
TM
7
Sandbæk A et al; Diab Care 2014 Jul 37(7)
8
Herman WH et al; Diab Care 2015
Aug
, 38(8)Slide7
Five year follow up
biobank serum analysed for sCD163 by ELISA Logistic regression models with relevant adjustments.Slide8
Patient
characteristics
All,n701
Demographic factorsAge (years), median (IQR)
64.9 (64.4;65.4)
Women
,
n (%)271 (39)Diabetes duration (
years)5.9 (5.8;6.0)Clinical measurements
BMI (kg/m2),
mean
(95%CI)
30.7 (30.3;31.1)
Systolic
blood
pressure(mmHg), median (IQR)134 (132;135)Blood measurementsHbA1c (IFCC) (mmol/l), median(IQR)46 (42;51)HbA1c (DCCT) (%), median (IQR)6.4 (6.0;6.9)Ln sCD163, mean (95%CI)0.77 (0.74;0.80)Slide9
Results
Diabetic polyneuropathyAdjustment
DPN
OR (95% CI)
Age,
sex
1.72 (1.14;2.62)
Age, sex, BMI, HbA1c
1.64 (1.07;2.52)
Age, sex, BMI, HbA1c,
ACEi
, insulin,
metformin
,
statins
, aspirin,
systolic BP1.59 (1.02;2.48)9Odds ratios per doubling of sCD163Slide10
Results
Cardiac autonomic neuropathy
Adjustment
CAN
early
OR (95% CI)
CAN manifest
OR (95% CI)
Age, sex
1.28 (0.90;1.84)
2.41 (1.44;4.02)
Age, sex, BMI, HbA1c
1.15 (0.79;1.66)
2.06 (1.02;3.56)
Age, sex, BMI, HbA1c,
ACEi
, insulin, metformin, statins, aspirins, systolic BP1.14 (0.78;1.67)2.34 (1.32;4.16)10Odds ratios per doubling of sCD163Slide11
Discussion
Screen-detected diabetes
Large cohort
Clinically
usable
measurements
Cross-
sectional
study
Slide12
Conclusion
Soluble CD163 is associated
to diabetic neuropathy
.
This
indicates
,
that macrophage
–
related
low
grade inflammation,
may
play a role in the pathophysiology of diabetic neuropathy.Thanks to:Pia DeichgræberDaniel WitteTorsten LauritzenHenning Andersen,Annelli SandbækMorten CharlesSlide13Slide14
OR
CAN any(181/678)CAN early (134/632)CAN manifest (47/545)Crude1.54 (1.13;2.09)
1.29 (0.91;1.83)2.46 (1.49;4.07)
Age, sex1.53 (1.11;2.10)1.29 (0.90;1.84)2.41 (1.44;4.02)+ BMI1.43 (1.03;1.97)
1.17 (0.81;1.70)
2.35 (1.39;3.96)
+ HbA1c
1.33 (0.97;1.87)1.15 (0.79;1.66)2.06 (1.20;3.56)+ ACE inhib
1.34 (0.96;1.87)1.15 (0.79;1.66)2.04 (1.18;3.53)+ Insulin1.34 (0.96;1.87)
1.15 (0.79;1.70)
2.06 (1.20;3.61)
+
Metformin
1.34 (0.96;1.87)
1.14 (0.78;1.65)
2.04 (1.18;3.54)
+ Statin1.35 (0.97;1.89)1.13 (0.77;1.65)2.18 (1.25;3.83)+ Aspirin1.35 (0.97;1.89)1.13 (0.77;1.65)2.19 (1.25;3.85)+ Systolic BP1.37 (0.98;1.93)1.14 (0.78;1.67)2.34 (1.32;4.16)Slide15
Patient characteristics
CAN DPN
All,n701
371Demographic factorsAge (
years
), median (IQR)
64.9 (64.4;65.4)
63.6 (62.9;64.3)Women,
n (%)271 (39)134 (36)
Diabetes
duration
(
years
)
5.9 (5.8;6.0)
5.3
(5.2;5.5)Clinical measurementsBMI (kg/m2), mean (95%CI)30.7 (30.3;31.1)30.7 (30.2;31.1)Waist circumference (cm), mean (95%CI)104 (103;105)104 (103;105)Systolic blood pressure(mmHg), median (IQR)134 (132;135)135 (134;137)Diastolic blood pressure(mmHg), median (IQR)84 (83;85)85 (84;86)Blood measurementsHbA1c (IFCC) (mmol/l), median(25th, 75th percentile) 46 (42;51)45 (41;51)Cholesterol (total) (mmol/l)4.3 (4.2;4.3)4.4 (4.3;4.5)Micro albuminuria (20-200) (mg/l), n (%)175 (25)104 (28)Macro albuminuria (20-200) (mg/l), n (%)35 (5)26 (7)Ln sCD163, mean (95%CI)0.77 (0.74;0.80)
0.79
(0.74;0.83)
Self-reported
Smoking
daily
, n (%)
209 (30)
108 (29)Slide16
sCD163
sCD163 median (mg/L) (IQR)No DPN (n=283)2.12 (1.82;2.82)With DPN ( n=88)2.51 (1.80;5.07)
16
sCD163 median(mg/L) (IQR)No CAN (n=520)2.07 (1.89;2.58)
CAN
early
(n=134)2.18 (1.87;2.85)CAN manifest (n=47)2.50 (1.85;5.55)