Lecture on weight loss vs. diabetes at the 2014 Steno Diabetes Symposium in Copenhagen Denmark by Professor Mike Trenell twitter: @miketrenell

1. Professor Mike Trenell Newcastle University, UK www.MoveLab.org
@miketrenell

2. UKPDS Head to Head Therapy Comparison
Overweight patient cohort
Body mass index 31.4 kg/m2
0%
6%
7%
8%
9%
10%
0 2 4 6 8 10
Years from randomisation
HbA1c
Conventional
Chlorpropamide
Glibenclamide
Insulin
Metformin
UKPDS 34. Lancet 1998; 352: 837-853

3. Progressive Decline in Beta Cell Function
UKPDS 16. Diabetes 1995; 44: 1249-58
20
40
60
80
100
Conventional Sulphonylurea Metformin
Non overweight Overweight
Beta cell loss ~4% per year
HOMA%B
0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Years from randomisation

5. The challenge
Adapted from: Barabási AL.
N Engl J Med. 2007 26;357(4):404-7.
Everyday life?
Metabolic
Deregulation?
Cellular defects?
Muscular
dystrophy
Type 2
diabetes
NAFLD
Dementia
CVD

7. Are people with Type 2 diabetes physically active?
0
10
20
30
40
50
60
70
Type 2 diabetes
All
WITHOUT heart disease Risk Factors
WITH Heart disease risk factors
No diabetes
All 0 diabetes risk factor
1 diabetes risk factor 2 diabetes risk factor
%PhysicallyActive
Morrato EH, et al. Diabetes Care 30: 203-209, 2007.
Heart disease risk factors were history of cardiovascular disease, diagnosis of hypertension and/or
diagnosis of hyperlipidaemia: Type 2 diabetes risk factors were; age over 45yrs, non-Caucasian
ethnicity, BMI >25 kg/m2, diagnosis of hypertension, and history of cardiovascular disease.

8. ?
Type?
Walking (general PA)
High Intensity Intermittent
Aerobic (Cycling / Running)
Resistance (Weights)

9. ?
How much?
Walking (general PA)
High Intensity Intermittent
Aerobic (Cycling / Running)
Resistance (Weights)
30 – 40min/day (extra)
30mins 3/4 x week
45mins 3/4 x week
?

10. Yates, Lancet. 2013
Trenell, Diab Care. 2008
Sigal RJ, JAMA. 2010

11. Clothes
washing
Dish
washing
Stairs
Walk to
work
Lavine, JA. Am J Physiol Endocrinol Metab 2004
Sales of domestic machines and energy intake
vs. obesity rates for the US population
Energy costs of combined daily
tasks in healthy subjects (n = 122).
Why is physical activity important?
% of US population with obesity
Sales/year
20000
15000
10000
5000
10 15 20 25 30
0
-40
-80
-120
Dishwasher
Washing Machine
Cars
EnergyIntakeKcal.day
500
1000
1500
2000
2500
Food intake

12. ChangeinHealthCostover2years(£)
Di Loreto C, et al. Diabetes Care 28: 1295-1302, 2005.
Extra Walking Time (mins / per day)
10 20 40 60 80 100

13. Pro-inflammatory
TNF
Anti-inflammatoryIL-6
TNF-R
IL1-ra
IL-10
Activity and immune function

14. Anti-inflammatoryIL-6
TNF-R
IL1-ra
IL-10
Activity and immune function

15. Yates, Lancet. 2013
Trenell, Diab Care. 2008
Sigal RJ, JAMA. 2010

16. Is your chair giving you a heart attack?
Morris JN, et al. Lancet 265:1053–1057, 1953
Weller I, Epidemiology 9:632– 635, 1998
Manini TM, JAMA 296:171–179, 2006

17. 24h of no-activity also signals mitochondria
Genesup-regulated
Fold change
Genesdown-regulated

18. Dunstan, et al. (2007). Diabetes Care 30(3): 516-522.
8.0
7.5
7.0
6.5
6.0
5.5
<1 1 to <2 >4
P for trend = 0.03 (men) and 0.001 (women)
2 to- <3 3 to <4
2hglucose(mmol.l)
Time watching TV (h.day)

19. Yates, Lancet. 2013
Trenell, Diab Care. 2008
Trenell MI. CEPP. 2007
Sigal RJ, JAMA. 2010

20. vs.

21. CardiorespiratoryFitness
(maxMETs)
Men
Women
5
10
15
8030
CardiorespiratoryFitness
(%peak)
60
80
100
40 50 60 70 9020
Jackson, et al. Arch Intern Med 169, 1781–1787 (2009)

22. Jackson, et al. Arch Intern Med 169, 1781–1787 (2009)
Women
Cardiofitness
(maxMETs)
BMI 20; PAI 3
BMI 20; PAI 0
5
10
15
8030 40 50 60 70 9020
Men
Cardiofitness
(maxMETs)
5
10
15
BMI 30; PAI 3
BMI 30; PAI 0
Age years

23. 0.25
0.5
0.75
1
Quintiles of maximal exercise capacity
1 2 3 4 5
Relativeriskofdeath
Adjusted for age, sex, exam year, smoking status,
ECG response, baseline health conditions
As red but also % body fat
<8.7
>18.4
8.7–11.2
11.3–13.6
13.7–18.3
Sui X, et al. JAMA 298: 2507-2516 (2007)
Cardiovascular fitness and mortality: over 60yrs
2603 adults aged 60 years or older

24. Loosing weight works
Lim et al. Diabetologia 2011

25. Liver fat change in NAFLD & T2D
-3
-2.5
-2
-1.5
-1
-0.5
0
0.5
1
1.5
2
ChangeinHepac
TriglycerideContent(%)
Control
Exercise
DIET
Hallsworth et al. GUT 2011
Thoma et al. J Hepatol 2012
Lin et al. Diabetologia 2011

26. Franz J Am Diet Assoc. 2007;107:1755-1767.
Loosing weight works

27. Christakis & Fowler NEJM 2007

28. Your health decisions Are being made over here
Christakis N Engl J Med 2007; Avery Diab Care 2013

30. Franco M et al. BMJ 2013;346:bmj.f1515

31. Franco M et al. BMJ 2013;346:bmj.f1515

32. An emotional
reaction
Ability to act
A rational
understanding HEARTSHEADS
HANDS
Avery Diab Care 2013; Dombrowski BMJ 2014

33. 0
10
20
30
40
50
60
70
Type 2 diabetes
All
WITHOUT heart disease Risk Factors
WITH Heart disease risk factors
No diabetes
All 0 diabetes risk factor
1 diabetes risk factor 2 diabetes risk factor
%PhysicallyActive
Morrato EH, et al. Diabetes Care 30: 203-209, 2007.
Heart disease risk factors were history of cardiovascular disease, diagnosis of hypertension and/or
diagnosis of hyperlipidaemia: Type 2 diabetes risk factors were; age over 45yrs, non-Caucasian
ethnicity, BMI >25 kg/m2, diagnosis of hypertension, and history of cardiovascular disease.

34. Are healthcare professionals advising people with Type 2 diabetes to exercise more?
0
10
20
30
40
50
60
70
80
90
100
Type 2 diabetes
All
WITHOUT heart disease Risk Factors
WITH Heart disease risk factors
0
10
20
30
40
50
60
70
80
90
100
No diabetes
All 0 diabetes risk factor
1 diabetes risk factor 2 diabetes risk factor
3 diabetes risk factor 4 diabetes risk factor
%Toldabouttheimportanceofexercise
Morrato EH, et al. Diabetes Care 29: 543-548, 2006.
Heart disease risk factors were history of cardiovascular disease, diagnosis of hypertension and/or
diagnosis of hyperlipidaemia: Type 2 diabetes risk factors were; age over 45yrs, non-Caucasian
ethnicity, BMI >25 kg/m2, diagnosis of hypertension, and history of cardiovascular disease.

35. Your health decisions Are being made over here
Christakis N Engl J Med 2007; Avery Diab Care 2013

38. C-design – working with care teams and patients
Focus groups and interviews

40. UKPDS Head to Head Therapy Comparison
Overweight patient cohort
Body mass index 31.4 kg/m2
0%
6%
7%
8%
9%
10%
0 2 4 6 8 10
Years from randomisation
HbA1c
Conventional
Chlorpropamide
Glibenclamide
Insulin
Metformin
UKPDS 34. Lancet 1998; 352: 837-853

41. Seasonal Therapy (Push not Pull)

42. Professor Mike Trenell Newcastle University, UK www.MoveLab.org
vs.