strategies targeting cv outcomes in diabetes: what have we … · 2016-06-16 · strategies...
TRANSCRIPT
Strategies targeting CV outcomes
in diabetes:
What have we learned so far?
Naveed Sattar, MDUniversity of Glasgow,
United Kingdom
Asian Cardio Diabetes ForumApril 23 – 24, 2016 – Kuala Lumpur, Malaysia
Tackle lipids, BP and glycaemia to prevent CVD
Lifestyle?
Aspirin?
Other points of
relevance
Young onset diabetes
Ethnic variations
Men versus women
Glucose-
lowering
BP
lowering
Statins
CVD* ↓* ↓↓↓ ↓↓↓
Affordability + +/++ +++
Simplicity + ++ +++
Renal
disease
↓/↓↓* ↓↓↓ (ACE/ARB)
↓
Retinopathy ↓↓↓ ↓↓↓ → (fibrates?)
Lowering LDL-c and BP are not difficult (Ferguson & Sattar DOM 2013)
LIFESTYLE to prevent CVD in diabetes
LOOK AHEAD TRIAL
Archives of Internal Medicine. 170(17):1566-1575, September 27, 2010.
LookAhead
NEJM
2013
Intervention control
Context / understanding
Weight loss can quickly lower glycaemia
– Minimal /negligible LDL-c change
Look Ahead folk had low classical risk factors
– Smoking low to begin with
– BP excellent – minor change
In general, CVD event ↓ hard via modest HbA1c
change
– Cf: recent DPP4 trials / Origin
Tackle lipids, BP and glycaemia to prevent CVD
Lifestyle?
Aspirin?
Other points of
relevance
Young onset diabetes
Ethnic variations
Men versus women
Percent with
vascular event
Odds ratio & 95% CI
ANTIPLATELET
better
CONTROL
betterCategory of patient
Previous MI 13.5 17.0
Acute MI 10.4 14.2
Previous stroke or TIA 17.8 21.4
Coronary Artery disease 6.2 8.9
High risk of embolism 13.5 16.8
Diabetes mellitus 15.7 16.7
ALL TRIALS 10.7 13.2
0.4 0.6 0.8 1.0 1.2 1.4
Antithrombotic Trialists’ Collaboration, 2002
Effects of antiplatelet therapy on vascular events
Allocated
antiplatelet
Allocated
control
% Odds
reduction
(SE)
25 (4)
30 (4)
22 (4)
37 (5)
26 (7)
7 (8)
13.2
ATTC, BMJ 2002;324:71-86
15.7 16.7
Events Avoided or Caused per 1000 Individuals
Treated with Aspirin for 5 Years
Avoided Caused
10 year risk CHD Ischaemic Haemorrhagic Majorof CHD event event stroke stroke bleed
<10% 5 0 1 5
10-20% 15 0 1 5
Secondary 25-50 25-50 1 5
http://www.ctsu.ox.ac.uk/ascend/
Armitage J (personal communication)
Aspirin: a secondary prevention drug?
4 ongoing trials in intermediate risk
ASCEND / ACCEPT-D
Case by Case: discuss with patient
DM + CVD: Yes
DM + proteinuria: YES/no
DM – no end organ damage: yes/NO
Tackle lipids, BP and glycaemia to prevent CVD
Lifestyle?
Aspirin?
Other points of
relevance
Young onset diabetes
Ethnic variations
Men versus women
Excess calories(increased intake or
reduced energy expenditure)
FAT
‘Spill over’pancreatic
beta cell
muscle
Subcutaneous stores
overwhelmed
(genes, ethnicity, ageing)
Hepatic lipid accumulation
Perivascular fat
Endothelial dysfunction
Insulin resistance
Hyperglycaemia
Sattar and Gill
BMC Medicine
2014
Diagnosis
~ 5-15
years
CHD equivalent
CH
D R
ISK
Age
Diabetes and CVD risk: durationDiagnosis and age of onset matter
Sattar (2013) Diabetologia (several studies support concept)
Tancredi M et al (2015) N Engl J Med
Higher lifetime risks in younger diabetes
Constantino et al (2013) Diabetes Care ePub
Tackle lipids, BP and glycaemia to prevent CVD
Lifestyle?
Aspirin?
Other points of
relevance
Young onset diabetes
Ethnic variations
Men versus women
Ntuk et al
(2014)
Diabetes
Care
Altered fat distribution: simplest evidence (WHR)
0.980.94Waist/hip ratio
25.725.9BMI (kg/m2)
SAn=1420
Europeann=1515
McKeigue Lancet 1991
South
Asian
(N≤87a)
European
(N≤99a)p-value % diff
Waist (cm) 97.3 95.6 0.31
Waist-to-hip ratio 0.98 0.95) 0.009 3%
Lean mass (kg) 57.2 63.3 <0.001
Fat mass (kg) 24.4 21.8 0.058
Percentage body fat 29.2 24.8 <0.001
Ghouri et al. Diabetologia (2013)
More fat and less muscle in SA’s
Yes built differently
We carry more fuel (higher fat levels)
AND smaller engines (lower muscle mass)
Closer to point for ectopic fat spill over?
– Into abdomen?
– Liver?
– Muscle?
Sattar and Gill (2014) BMC Medicine
Excess calories(increased intake or
reduced energy expenditure)
Central FAT
‘Spill over’
WHR
pancreatic
beta cell ??
SABRE?
Muscle
Forouhi et al
Subcutaneous stores
overwhelmed
(genes, ethnicity, ageing)
Hepatic lipid
Accumulation /?
Perivascular fat
Endothelial dysfunction
Insulin
resistance
Diabetes
Diabetes in Asians
Less uptake uptake of Insulin
Higher HbA1c despite being on insulin
More retinopathy– SAs younger, shorter DM
duration, higher HbA1c (Raymond et al,
Diabetes Care, 2009)
More renal disease - greater prevalence,
more rapid progression (Chandie Shaw et al,
Diabetes Care, 2006)
But less PVD and neuropathy
South Asians: more microvascular disease > CVD
Evidence shows more rapid rise in glycaemia over time
– Faster to nephropathy /microvascular complications
– CVD rates higher in South Asians but less in Chinese
– Need more data / evidence of less fatal events
Give statins & BP medications as in whites
More aggressive with
– Early lifestyle changes (very hard)
– Glycaemia therapies – trials to see which work best?
Tackle lipids, BP and glycaemia to prevent CVD
Lifestyle?
Aspirin?
Other points of
relevance
Young onset diabetes
Ethnic variations
Men versus women
0,0645
0,2427
0,1664
0,0923
0,069
0,0342
0,1609
0,1344
0,0631
0,0384
0%
5%
10%
15%
20%
25%
30%
White South Asian Black Chinese Overall
Ag
e-s
tan
dard
ized
dia
bete
s p
rev
ale
nce
Age standardised prevalence for males and females across ethnic groups
Men Women
More diabetes in men versus women across many ethnicities
More men have diabetes: why?Women's CVD risk rises more when DM: why?
Logue et al (2012) Diabetologia
Age at diagnosis of diabetes (years)
Avera
ge B
MI
(kg / m
^2)
30
35
40
30 40 50 60 70 80 90
Men Women
Summary
Lifestyle lessens glycaemia &improve QOL
– Diet first, then activity
Aspirin increasingly secondary prevention
Younger T2DM patients at higher CVD and mortality
risks: more aggressive management
South Asians: statins and blood pressure but more
aggressive glycaemia management
Women have to put on more weight to get diabetes than
men and so higher CVD risks once diabetes