This is a lecture I gave to primary care clinicians in Sept 2011 looking at physical activity, exercise and the management of Type 2 diabetes.

1. Physical Activity and Type 2 diabetes:
Worth spending energy on?
Dr Mike Trenell
NIHR Senior Research Fellow & Director; MoveLab
MRC Centre for Brain Ageing and Vitality
NIHR Biomedical Research Centre for Ageing and Age Related Disease
E: michael.trenell@ncl.ac.uk w: www.MoveLab.org

2. In Out

3. Real world metabolism
The role of physical activity
and exercise in health.
Physical activity, exercise and
glucose control.
A defect in physical fitness

6. Change in muscle glycogen concentration after a mixed meal
20
Glycogen
10
mmol /l
0
-10
-120 0 120 240 360 480
Minut es
Taylor et al. 1993 1993
Taylor et al. AJP

8. Changes in muscle glycogen
120
Control
100 Diabetic
80
60
40
0 2 4 6 8
Time (hours)
Carey et al 2002 (2003). Am J Physiol Endocrinol Metab 284(4): E688-94.
Carey, P. E., et al.

9. Serum Insulin
150
Diabetic
Control
Insulin (mU/l)
100
50
0
0 2 4 6 8
Time (hours)
Carey, P. E., et al. (2003). Am J Physiol Endocrinol Metab 284(4): E688-94.

10. Blood glucose
15 Diabetic
Control
Blood Glucose
(mmol/l)
10
5
0
0 2 4 6 8
Time
(hours)
Carey, P. E., et al. (2003). Am J Physiol Endocrinol Metab 284(4): E688-94.

11. Intramyocellular
Lipid Droplets
Mitochondria
Contractile
Myofibrils

12. Fat
Fat
Glycogen Fat
Fat Mitochondria Fat
Glycogen
Glycogen Fat
Fat
Fat Fat

13. The story so far -
• Meal carbohydrate is stored in muscle
• Muscle glycogen stores are dynamic
• Failure of glycogen storage in type 2
diabetes
• Lipid accumulation impedes insulin
action

14. Real world metabolism
The role of physical activity
and exercise in health.
Physical activity, exercise and
glucose control.
A defect in physical fitness

15. In Out

16. Adult Obesity in the US and UK
Prevalence from Annual Health Surveys
2006
2005
2004
2003
2002
2001
2000
1998
1999
1997
1996
1995
1993
1992
1991
1990
1989
1988
1987
1986
1985
1994
No data <10% 10-14% 15–19% 20-24% 25–29% ≥30%
Obesity: BMI>30
Source: CDC Behavioral Risk Factor Surveillance System, Health Survey for England
Slide produced by Doncaster PCT PHIU

17. Why is physical activity important?
Food intake Washing Machine
Cars Dishwasher
2500 0 Clothes
washing
Energy Intake Kcal.day
20000
Dish
2000 washing
-40
Sales / year
15000 Stairs
1500
10000 -80
Walk to
1000 work
5000
500 -120
0 10 15 20 25 30
% of US population with obesity Figure 2:
Energy costs of combined daily tasks in healthy subjects
Figure 1: (n = 122). Subjects completed the indicated tasks with
Sales of domestic machines and energy intake and without the aid of equipment or machines while
vs. obesity rates for the US population energy expenditure was measured
Lavine, JA. Am J Physiol Endocrinol Metab 286: E675-E685, 2004

18. Morris JN, et al. Lancet 265:1053–1057, 1953
Weller I, Epidemiology 9:632– 635, 1998
Manini TM, JAMA 296:171–179, 2006

19. 2h glucose (mmol.l) 8.0 P for trend = 0.03 (men) and 0.001 (women)
7.5
7.0
6.5
6.0
5.5
<1 1 to <2 2 to- <3 3 to <4 >4
Time watching TV (h.day)
Dunstan, et al. (2007). Diabetes Care 30(3): 516-522.

20. Are people with Type 2 diabetes physically active?
70
60
% Physically Active
50
40
30
20
10
0
Type 2 diabetes No diabetes
All
WITHOUT heart disease Risk Factors All 0 diabetes risk factor 1 diabetes risk factor
WITH Heart disease risk factors 2 diabetes risk factor 3 diabetes risk factor 4 diabetes risk factor
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.
Morrato EH, et al. Diabetes Care 30: 203-209, 2007.

21. The next chapter of the story:
• Daily movement is related to weight gain
• Physical inactivity is related to increased risk
of CAD / mortality
• Physical inactivity is related to glucose
control
• People with Type 2 diabetes are less active
than people without diabetes

22. Real world metabolism
The role of physical activity
and exercise in health.
Physical activity, exercise and
glucose control.
A defect in physical fitness

23. 0.6% reduction
in HbA1c
(long term glucose control)

24. What does this mean in real terms?
45min walking
2 per day
Weight (kg)
FPG (mmol.l)
1 HbA1c (%)
Pre-Post Delta
0
10 20 45 80 120 150
-1
-2
-3
-4
Physical Activity Delta (minutes walking)
Di Loreto C, et al. Diabetes Care 2005. Trenell et al. Diabetes Care 2008

25. The benefits extend beyond just glucose control.....
Drug costs
1000
Other healthcare costs
Pre-Post Delta ($)
Combined costs
500
0
10 20 45 80 120 150
-500
-1000
-1500 Physical Activity Delta (minutes walking)
Di Loreto C, et al. Diabetes Care 28: 1295-1302, 2005.

26. Are people with Type 2 diabetes physically active?
70
60
% Physically Active
50
40
30
20
10
0
Type 2 diabetes No diabetes
All
WITHOUT heart disease Risk Factors All 0 diabetes risk factor 1 diabetes risk factor
WITH Heart disease risk factors 2 diabetes risk factor 3 diabetes risk factor 4 diabetes risk factor
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.
Morrato EH, et al. Diabetes Care 30: 203-209, 2007.

27. Are healthcare professionals advising people with Type 2 diabetes to exercise more?
100 100
% Told about the importance of exercise
90 90
80 80
70 70
60 60
50 50
40 40
30 30
20 20
10 10
0 0
Type 2 diabetes No diabetes
All
WITHOUT heart disease Risk Factors
All 0 diabetes risk factor 1 diabetes risk factor
WITH Heart disease risk factors 2 diabetes risk factor 3 diabetes risk factor 4 diabetes risk factor
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.
Morrato EH, et al. Diabetes Care 29: 543-548, 2006.

28. Real world metabolism
The role of physical activity
and exercise in health.
Physical activity, exercise and
glucose control.
A defect in physical fitness

29. Fat
Fat
Glycogen Fat
Fat Mitochondria Fat
Glycogen
Glycogen Fat
Fat
Fat Fat

30. 10
8
M (mg.min.kgFFM)
6
4
2
0
Lean Obese T2D Trained
Goodpaster, et al. JCEM 2001;86:5755-5761

31. 4
* * 60
SDH staining (optical density units)
3 ** 45
Intramuscular lipid (% lipid)
2 30
1 15
Lean Obese T2D Trained Lean Obese T2D Trained
IMCL content in lean and obese subjects, obese
subjects with type 2 DM, and exercise-trained subjects. SDH staining activities in lean and obese
*, P < 0.05 vs. obese and lean groups; **, P < 0.05 vs. subjects, obese subjects with type 2 DM, and exercise-
lean group only. Results are mean ± SE trained subjects. *, P < 0.05 vs. obese and type 2 DM
groups. Results are mean ± SE.
Goodpaster, et al. JCEM 2001;86:5755-5761

32. Apabhai, Gorman, Turnbull & Trenell PLoS ONE in press 2011

33. Apabhai, Gorman, Turnbull & Trenell PLoS ONE in press 2011

35. Apabhai, Turnbull & Trenell Unpublished data 2008

36. The final chapter of the story:
• People with Type 2 diabetes have low oxidative
capacity (but normal function)
• People with Type 2 diabetes have a low ability to
burn fat
• Physical inactivity has a powerful effect on muscle
• Reversing the effects of physical inactivity has the
potential to be the most powerful therapeutic
strategy

37. Summary
4
* * 60
SDH staining (optical density units)
3 ** 45
Intramuscular lipid (% lipid)
2 30
1 15
Lean Obese T2D Trained Lean Obese T2D Trained
IMCL content in lean and obese subjects, obese
subjects with type 2 DM, and exercise-trained subjects. SDH staining activities in lean and obese subjects,
*, P < 0.05 vs. obese and lean groups; **, P < 0.05 vs. obese subjects with type 2 DM, and exercise-trained
lean group only. Results are mean ± SE subjects. *, P < 0.05 vs. obese and type 2 DM groups.
Results are mean ± SE.
Mike Trenell
MoveLab, Newcastle University.
E: michael.trenell@ncl.ac.uk W: www.MoveLab.org