Diabetes Prevention: Benefits and Challenges

Naveed Sattar

Professor of Metabolic Medicine

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….

Diabetes up, CVD death down

CHD death

rates

Diabetes

Obesity

Last three decades

Does weightaffect cardiovascular

risk?

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

Obesity and T2DM

• BMI 35 vs 21

– HR for T2DM 50-80 times

• For CVD HR 2-3 higher

• For HF HR 3-10

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

Weight watchers beats GP practice (Jebb et al Lancet 2011 RCT, 722 patients)

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

Valabhji et al. Diabetes Care 2019

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