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
