diabetes prevention: benefits and challenges...diabetes prevention does benefit but can be improved...
Post on 24-May-2020
7 Views
Preview:
TRANSCRIPT
Duality of interest declaration
• Consulted for:
Amgen, AstraZeneca,
Boehringer Ingelheim,
Eli Lilly, NAPP, Novo
Nordisk, Pfizer, Sanofi
• Grant: Boehringer
Ingelheim Sunnie H-index 21
Cardiometabolic space
Family history T2DM
Top line
• The scale of the problem
• Its nearly all about obesity…..weight, weight, weight
• What are the risks / benefits – long term
• English programme
• We need to do more to help people to manage weight
• For some, we need to fund more bariatric surgery – Scottish rates VERY low – cf Norway, Sweden etc….
Year of follow-up
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.00 10 20 30 40
Cum
ula
tive m
ort
ality
fr
om
CVD
(%
)
BMI Percentile
85th–94th
75th–84th
50th–74th
25th–49th
5th–24th<5th
≥95th
BMI during adolescence and CV mortality
BMI, body mass index; CV, cardiovascular; CVD, cardiovascular disease.Twig G et al. N Engl J Med 2016;374(25):2430–40.
No. at risk
Participants at risk 1,712,018 1,042,018 540,636 160,145
Cumulative person-yr 17,201,301 30,718,320 38,472,521 41,926,636
Cumulative CV deaths 185 609 1,577 2,676
CHD risks up with BMI, W, WHR but largely due to BP, lipids, DM
*Intermediate risk factors were systolic blood pressure, history of diabetes, and total and HDL cholesterol.The Emerging Risk Factors Collaboration. Lancet 2011; 377:1085–95.
BMI Waist WHR
HR
(9
5%
CI)
Some evidence
Obesity α
HF / CM
> CHD
16
8
4
2
Alcohol/drug-induced CM
15 20 25 30 35 40
Dilated CM
CM, cardiomyopathy. Robertson J et al. Circulation 2019; 140:117–125
Higher BMI adolescence vs midlife CM risks
Diabetes/obesity accelerate atherogenic pathways and cause haemodynamic stress
Adapted from Sattar N, & McGuire D. Circulation 2018;138(1):7-9
Obesity
Traditional
focus
Recent
Insights
Lipids
Glucose
BP
Thrombotic
tendency
Insulin
Renal SGLT2
Glomerular
hyperfiltration
TGF
other mechanisms?
Na+ & glucose
retention
Intravascular
volume increase
Accelerated
Atherogenesis MI, CVA, PAD
Heart
Failure
Kidney
disease
Volume Status/
Hemodynamic
& Glomerular
stress
Genes predict 1 kg/m2 increase in BMI causes 14 cardiovascular outcomes from UK Biobank
(Nature’s randomized trial)
Larsson et al (2019) European Heart Journal
Pre-diabetes – 80% higher CVD risk but explained by usual risk factors
Diabetes Care, In press
15.0
-30.
3
30.4
-32.
0
32.1
-33.
1
33.2
-34.
0
34.1
-34.
9
35.0
-35.
8
35.9
-36.
7
36.8
-37.
9
38.0
-39.
5
39.6
-47.
9
Unk
nownD
M
Kno
wnD
M
1
2
3
4
Unadjusted
Adjusted
HbA1c (mmol/mol) category
HR
of
CV
D (
QR
ISK
)
Pre-diabetes
- 3 years older
- 3 units higher BMI (9-10kg
heavier)
- 6 mmHg higher SBP
- Higher TC/HDL-c
- More were smokers
Excess calories(increased intake or
reduced energy expenditure)
FAT
‘Spill over’pancreatic
beta cell
muscle
Subcutaneous stores
overwhelmed
(genes / FHx,
ethnicity, ageing)Hepatic lipid accumulation
Perivascular fat
Endothelial dysfunction
Insulin resistance
Hyperglycaemia
Sattar and Gill
(2014) BMC Medicine
Summary so far, and high diabetes risk
• Higher weight
– Higher SBP
– Abnormal lipids (TG/HDLc)
– Increased risk renal dysfunction
– Increased fluid gain
– More inflammation/prothrombotic tendencies
– Higher diabetes risk *10 fold more greater than CVD
• At risk for Diabetes:
– HbA1c 42-48 mmol/mol or 6.0 to 6.5% of FBG 5.5 to 6.9 mmol/l
– Risk score first – 30 seconds
– How to lessen – lifestyle
Gilles C et al. BMJ
2007
Hazard ratio
0.0 0.5 1.0 1.5 2.0
Hazard Ratio
(95% CI)
Study Favours
Intervention
Favours
Control
DietDa Qing, 1997 0.64 (0.41, 0.99)
Jarrett, 1979 0.85 (0.40, 1.81)
Wein, 1999 0.63 (0.35, 1.14)
Pooled effect 0.67 (0.49, 0.92)
ExerciseDa Qing, 1997 0.53 (0.34, 0.82)
Pooled effect 0.53 (0.34, 0.82)
Diet and ExerciseDa Qing, 1997 0.61 (0.39, 0.95)
DPP, 2002 0.42 (0.34, 0.52)
DPS, 2003 0.40 (0.26, 0.61)
Kosaka, 2005 0.29 (0.09, 0.94)
Liao, 2002 0.52 (0.05, 5.69)
Pooled effect 0.44 (0.37, 0.52)
Overall Pooled Effect 0.50 (0.42, 0.59)
2b. Da Qing RCT of DM prevention – 30 years follow-upLifestyle fast for DM, slow for CVD outcomes
Gong Q et al. Lancet Diabetes Endocrinol 2019;7(6):P452-461
Small sustainable changes reap
immediate QoL, DM prevention
benefits And CVD benefits later
Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With T2DM and Obesity
Ali Aminian. JAMA. 2019;322(13):1271-1282. doi:10.1001/jama.2019.14231
MACE-3
• Intervention effectiveness for high diabetes risk
– HbA1c 6.0–6.4% or fasting glucose 5.5–6.9 mmol/L
• 53% attended of referred, 19% completed intervention
– ½ of those who attended one session, completed it
• ITT 2.3kg weight loss (completers 3.3kg), 1.26 mmol/mol change HbA1c
(c=2.04mmol/mol)
• More evaluation needed BUT Reductions in weight and HbA1c compare
favorably with those reported in recent meta-analyses of pragmatic studies
Process in England
• ID: NHS Vascular health check or retrospective GP records or
routine practice.
• Ingeus UK / Living Well Taking Control / ICS Health & Wellbeing /
Reed Momenta
• Provider’s initial assessment, core & maintenance sessions, min
13 F2F group-based sessions 9 months,16 h contact time.
• Known framework for behaviour change.
Valabhji et al. Diabetes Care 2019
Can learn much from English experience
• Worth to screen over 80 year olds? Perhaps not…
– Sattar / NHS England discussions
• Younger, more deprived people harder to reach
• Uptake <1/2, success in those who uptake <1/2
– But for those succeed, less diabetes?
– Yes, but may delay about 1-3 years on average – some more
• Need sustained weight loss for better success, sustained benefit
What about weight loss in general: we can and must do better
• We can do better than present
• Few HCP discuss weight
• Few chance to give best advice
• Conversations could be better
• Encourage to try and be sympathetic
1st
change2nd
change 3rd
change
Retrain your taste buds gradually – goal setting
Wardlaw et al – small exposure repeated daily in children
Sugar removal from Tea / Coffee
Diabetes prevention does benefit but can be improved
• Minor weight loss to lessen Diabetes risk happens quickly and yelds CVD
over 30 years – 2-3kg weight loss in at risk….
– Find those at risk – yes – but miss some
– English programme – lots of effort needed
• Ongoing programs mostly small, except England – finding their way
• Helping more people lose weight sustainably must be goal
– A menu of options proven to work
• Scotland MUST allow more bariatric surgery – cost effective
top related