Exercise, type 2 diabetes and
weight reduction
Hans A. Keizer, M.D., Ph.D.
Dept. Human Physiology and Sportsmedicine,
Free University of Brussels, Brussels, Belgium
Emeritus Associate Professor Dept. Movement Sciences, Maastricht
University, Maastricht, The Netherlands
Adviesbureau voor Bewegen en Gezondheid
NORMAAL
GLUCOSE
Obesitas/type2
Spier
Insuline resistentie
In obesitas &
Type 2 Diabetes
BLOED
GLUCOSE
gezond
GLUCOSE
Spier
Tijd
GLUCOSE OPNAME
OP INDIVIDUEEL SPIERNIVEAU
INSULINE
RESISTENTIE
gezond
GLUCOSE
OPNAME
Obesitas/type 2
INSULINE
Fysieke inspanning?
Wat gebeurt er
bij inspanning?
Spiercontractie
kan ook de
de glucose opname
van de spier verhogen
VERGELIJK GLUCOSE OPNAME
t.g.v.
INSULINE en SPIER CONTRACTIE
O2
Glucose
Insuline
O2
Glucose
Contractie
Let op verschillen
Normale
respons
Insuline
resistentie
gezond
2 SYSTEMEN!
GLUCOSE
OPNAME
gezond
GLUCOSE
OPNAME
Obees/type 2
INSULINE
Obees/type 2
CONTRACTIE
Hoe kan het hydrofiele glucosemolecuul de hydrofobe
celwand passeren?
insuline
GLUCOSE
Insuline
receptor
contractie
signals
signalen
GLUT4
SPIER CEL
TWEE
SYSTEMEN!
TWEE MECHANISMEN BEVORDEREN GLUCOSE OPNAME
Dit is een feit!
INSULINE
CONTRACTIE
Werken ONafhankelijk om
glucose opname
van de spier
te verhogen!
Substrate use during aerobic exercise has
changed, as well (Borghouts/Keizer, 2002)
% total energy expenditure
1 hour exercise (40% VO2max)
100%
TG derived FA oxidation
90%
80%
70%
Plasma FA oxidation
60%
50%
40%
Glycogen oxidation
30%
20%
10%
Glucose Rd
0%
Type-2 diabetes
Control
FA overflow changes insulin stimulated glucose uptake
insuline
GLUCOSE
FAs
Insuline
receptor
FAs
TG
signalen
ceramides
GLUT4
SPIER CEL
CO2
FAs
FAs
Is inspanning gunstig voor de insuline werking?
Na inspanning
Insuline sensitiviteit is verhoogd
Na inspanning
GLUCOSE
OPNAME
Rust
INSULINE
Positieve effect kan
24-48 u aanhouden
Wat zijn de voordelen van regelmatige inspanning
(training)?
Hierdoor toename
van insuline
gestimuleerde
GLUT4 translocatie
naar cel membraan
Toename eiwit expressie
Toename ‘signaling’
eiwit concentraties
Toename GLUT4 concentratie
Inactiviteit heeft
omgekeerde
effecten!!
PROPHYLACTIC EFFECTS OF EXERCISE
Reduction in the incidence of type 2 diabetes with lifestyle intervention or
metformin
New England J Medicine 346:393-403, 2002
3234 non-diabetics (BMI = 34)
With elevated plasma glucose
control
Diabetes
After 4 years
11/100
Person years
metformin
7.8/100
Person years
Lifestyle
Exercise 150 min/week
7% weight loss (~4 kg)
4.8/100
Person years
-31%
-58%
Prevent 1 case
of diabetes
per 3 years
13 people
need to take
Metformin
7 people
need to be in
Lifestyle
Physical exercise
affects our whole
body, given it
complies with
certain
physiological laws
However, training for type 2
diabetes is only effective if.......

Enough muscles are involved

Exercise intensity and duration
surpasses a certain level

Training frequency is enough
Such adaptive responses are
only achieved when:

Training occurs according to the
overload principle, i.e. when intensity,
duration and frequency of the
workouts is high enough.

Training is specific and planned.

(Subjects adhere to the training).
Effect of training volume
Effect of training volume on performance
Carroll, Thaden, Wright. Exp Biol Med 230: 180, 2005
Obese and lean
rabbits, trained
and control
Training: 5
days/week, 12
weeks, treadmill.
Work output (per
kg muscle)
similar in obese
and lean
No differences in
training
adaptation
among groups
Effect of training volume and intensity on
insulin sensitivity in pre-diabetes patients
Houmard, Tanner, Slentz et al. JAP 96: 101, 2004
154 overweight or obese
subjects were assigned to:
1.
Low volume-moderate
intensity (40-55% VO2
peak=walking 12
miles/wk)
2.
Low volume-high
intensity (65-80% VO2
peak, 12 miles/wk jogging
3.
High volume-high
intensity (65-80% VO2
peak, 20 miles/wk jogging
Caloric expenditure was for
group 1 and 2: 1200 kcal/wk,
group 3± 2100 kcal/wk.
No change in
body weight!!
Effect of training frequency
Effect of a 2 month combined endurance and strength training program with
different training frequencies in type 2 diabetic patients n=20/group
Keizer et al. In preparation
Glucose (mmol/l)
0,1 U insulin/kg BW
> 2 x /week before
> 2 x /week after
< 2 x /week before
< 2 x /week after
*
Significantly
different (p < 0.05)
from before
Time (min)
Almost completely similar results were obtained when subjects exercised continously at 40% VO2peak (60 min/session, 3 x/week, or
an interval training 92 min 80% VO2peak alternated with 2 min 40% VO2peak. No improvement with 40% VO2peak!
Is aerobic training really the
most efficient?
Meeste glycogeen en GLUT4 zit in de snelle (type 2b) spiervezels
(Borghouts et al., 2000; Hesselink et al., 2001)
A
B
Changes in HbA1C, VO2max and strength
after 4-6 months of strength- or aerobic
training in T2D
Soort
training
HbA1C VO2max
(%)
(%)
Kracht
(%)
N=
Aeroob
-9.3
7.8
-
20
Kracht
-2.1
-
74
23
7.0
50
20
0
25
Aeroob
+kracht
-14.6
Control
e
0
0
Dunstan, 2002; Dittmann, 2003, Tokmakidis, 2004)
What about long term (2 year) training with reliable
training frequencies and moderate-high intensities?
(Borghouts/Keizer et al., submitted)






14 Type 2 diabetes patients, mean age 57y, mean BMI 27,2.
Training consisted of bicycling (interval) and adjusted to
individual exercise capacity. Once a week a resistance training
was done.
In the first 6 months, training volume was gradually increased
from 20 min/ session to about 60 min/session.
50% of training time was between 75 and 85 VO2 peak.
Mean training time at the end of the first year was 161±39
min/week. Caloric expenditure 3260 kcal (13649 kJ).
The second year training volume was decreased. Mean training
time 104 ± 37 min/week, caloric expenditure 980 kcal (4103kJ).
Exercise intensity was maintained or even somewhat higher.
Biphasic changes in insulin stimulated whole body
glucose uptake and HbA1C after 1, respectively 2
year training (Borghouts/Keizer et al., submitted)
**
11.0
10.0
10.0
9.0
9.0
8.0
8.0
7.0
7.0
6.0
n=14
6.0
HbA1C (%)
WBGU (mg.kg-1.min-1)
11.0
WBGU
HbA1C
5.0
5.0
Before
After 1 y After 2 y
But at the end of the second
year...






Body weight was unchanged, but body
fat content was still 3% lower, but
increased with 3,5% in the control
group!
VO2peak was still increased.
Blood lipid profile was still improved
Blood pressure was decreased by 12
and 6 mmHg (systolic/diastolic, resp.)
Medication was reduced by 26%
86% OF THE SUBJECTS ADHERED TO
THE ACTIVE LIFESTYLE
In both endurance- and strength
training 70-75% VO2max, or 70-75%
1RM is most effective, but...
even if total power output is
similar! Why?
Contrasting results are found in the literature
with moderate-high exercise intensities

Jogging 30-40 min/day, 4 x wk improves
cardiovascular fitness and glucose metabolism
significantly (Oshida et al. JAP 66: 2206, 1989; Mayer-Davis et al., JAMA
328: 669, 1998).

But...moderate-high intensity exercise (60-85% VO2
peak) may impair glucose metabolism (Kang et al., Diabetes
Care 19: 341, 1996; Seals et al., JAMA 252: 645, 1984), although other
investigators found significant improvements both in
glucose metabolism as in lipoprotein profile (Alam et al., J
Clin Endocrinol Metab 89: 688, 2004).

Authors employing strength exercise reported the
best results with moderate-high intensities (Ishii et al.,
Diabetes Care 21: 1353, 1998; Dunstan et al., Diabetes Care 25: 1729,
2002).
Why these differences??



Continuous exercise of moderate-high
intensity is extremely stressing
(increases cortisol levels during the day).
Interval training with the same or higher
intensity is much better sustainable. One
can achieve higher training loads (energy
expenditure) in a shorter time.
Much more variation can be achieved
with interval training. Training monotony
is significantly less.
What does it mean if HbA1C
decreases from 9.0 to 8.1%?




-25% microvascular complications
-21% retinopathy after 12 y
-33% protein in urine (=marker
kidney function) after 12y
-46% chance on myocard infarction
providing an improvement of 15%
VO2max
According tp UKPDS study
Target exercise intervention
•Reduce postprandial hyperglycemia because it is a direct
and independent risk factor for the development of CVD
(DCCT, UKPDS study)
•Reduce hyperglycemic spikes because they are more
relevant to the onset of CVD than elevated fasting glucose
concentrations
(Ceriello, 2004, 2005; Heine 2004)
Standard parameters for the assessment of glycemic control
do not provide sufficient information on post-prandial
glycemic spikes
T2D patients
Controls
Praet et al., 2006
Hyperglycaemic Periods Pre vs Post Exercise
70
% time >10.0 mmol/l
60
50
*
40
30
20
10
0
%high 0-24
Mean
SD
t-test
%high 24-48
%high 0-24
%high 24-48
31.7
19.2
19.8
15.4
p= 0.026
Target exercise intervention
•Improve lipoprotein profile Increase fat burning capacity of
the muscles
•Improve muscle strength in order to increase glucose uptake
and prepare the subject on intensity driven exercise
Changes in body weight or fat mass by
exercise? Which type of training is effective?



Low-intensity exercise is equally effective to reduce
fat-cell size (tigh, intra-abdominal) than high intensity,
given energy expenditure is similar (You et al., 2006).
If energy expenditure is not different, low intensity
(45% VO2peak) exercise decreases body-mass,
whereas high-intensity (72% VO2peak) exercise does
not. However, decrease in fat mass is similar
(Mougias et al., 2006). A decrease in body mass is
an unfavorable effect, because it means decrease in
muscle mass.
Unlike low-intensity, high intensity exercise increases
post-exercise energy expenditure (basal
metabolism)(Broeder et al., 1991; Gill et al., 2002).
Mensen kunnen drie veranderings-fasen
doorlopen. Deze categoriën moeten gedifferentiëerd
benaderd worden.
Ongemotiveerd
Waarom moet je
veranderen?
Gemotiveerd
Hoe kun je aan verandering werken?
Reeds begonnen
te veranderen
Aanbrengen faciliteiten.
Brug, Erasmus Univ.
More measures to increase compliance





Buddies
What do they like or dislike
Good and enthousiastic instructions
Feed back
Be honest
In conclusion

Beneficial effects of training on glucose and fat
metabolism can only be anticipated when training
frequency ≥ 3 x per week (± 170 min/week) and
energy expenditure ≥ 1200 kcal/week.

Both low- and high intensity exercise are able to
reduce fat cell size and fat mass. Moderate-high
intensity exercise is more efficient, but may mask
favorable effects on body composition

Strength training has proven to be very effective to
improve glucose metabolism. Besides it is THE
training modality to begin with in the untrained
elderly.
In conclusion, continued

Adherence to training decreases with too
high intensity training, especially with
continuous exercise bouts.

Use interval training, which is more efficient,
pleasant and less boring for the patient.
Interval training is very effective in improving
cardiovascular health, including glucose and
fat metabolism.
Tot slot: Hebben de voordelen van lifestyle interventies
enige impact gemaakt, zowel in profylactische als
therapeutische zin?
ADA/EASD symposia
fabrikanten
“lifestyle”
problemen
Hebben nagelaten
zich te identificeren
Pharmaceutische
Industrie
>99%
“lifestyle”
Industrie
Niet
aanwezig!
Goede lifestyle
voorschriften en faciliteiten
niet bekend bij
artsen/patienten
NOODZAAK
voor een nationale
aanpak hiervan