Institut for Idræt og Ernæring Appetitt og matinntak Hva bør vi spise og hvordan får vi det til? Arne Astrup Professor, overlæge, dr.med. Leder af Institut for Idræt og Ernæring, KU & Klinisk Ernæring, Herlev Universitets Hospital 19-09-2013 Dias 1
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Institut for Idræt og Ernæring The Atkin s type of lowcarb diets are extreme, and not consistent with a balanced food culture The elimination of important food groups leeds to poor adherence in the long-term and adverse effects due to carbohydrate deficiency = headache, muscle cramps, low physical performance 19-09-2013 Dias 4
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Institut for Idræt og Ernæring The GI concept as a weight loss strategy? 19-09-2013 Dias 6 New York Times Bestseller Released January 2005
Institut for Idræt og Ernæring 40% 100% Glucose load 19-09-2013 Dias 7 Time Stomach and small intestine, showing (A) slow absorption of energydilute nutrient in a fibre-rich primitive diet, and (B) rapid absorption of energy-dense nutrient from low-fibre, modern Western foods.
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Institut for Idræt og Ernæring RCT on Type 2 diabetes 19-09-2013 Dias 12
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Institut for Idræt og Ernæring Cochrane Review - MAIN RESULTS: We identified six eligible randomised controlled trials (total of 202 participants). Interventions ranged from five weeks to six months duration with up to six months follow-up after the intervention ceased. LGI decreased body mass (WMD -1.1 kg, 95% confidence interval (CI) -2.0 to -0.2, P < 0.05) (n = 163) LGI decreased total fat mass (WMD -1.1 kg, 95% CI -1.9 to -0.4, P < 0.05) (n =147) LGI decrease total cholesterol (WMD -0.22 mmol/l, 95% CI -0.43 to -0.02, P < 0.05) LGI decreased LDL-cholesterol (WMD -0.24 mmol/l, 95% CI -0.44 to -0.05, P < 0.05). No study reported adverse effects, mortality or quality of life data. 19-09-2013 Dias 14
Proposed Hierarchy of Satiety Need hypothesis-driven studies to determine differences Protein leucine LOW Glycemic Index Whole grain HIGH Glycemic Index Carbohydrate Sucrose/Fructose Fat
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Institut for Idræt og Ernæring Glucose and insulin responses 19-09-2013 Dias 17
4-h VAS Satiety (mm) Institut for Idræt og Ernæring Replacement of carbohydrate for protein increases satiety in a dosedependent manner 70 HP MHP NP 60 50 40 30 20 10 0 0 30 60 90 120 150 180 210 240 Time (minutes) NP vs HP: 16%, P<0.0001 MHP: 7%, P=0.001 HP vs MHP: 10%, P<0.0001 19-09-2013 Dias 18
GLP-1 (pm) Institut for Idræt og Ernæring 4-h dose-dependent effect on GLP-1 50 HP M HP NP 40 30 20 10 0-10 0 30 60 90 120 150 180 210 240-20 Time (minutes) NP vs. HP: 25%, P<0.0001 MHP: 9%, P=0.02 HP vs MHP: 14%, P=0.002 19-09-2013 Dias 19
PYY (pm) Institut for Idræt og Ernæring 4-h dose-dependent effect on PYY 40 HP M HP NP 35 30 25 20 15 10 5 0 0 30 60 90 120 150 180 210 240 Time (minutes) NP vs HP: 14%, P<0.0001 MHP: 7%, P=0.0002 HP vs MHP: 7%, P<0.0001 19-09-2013 Dias 20
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Contract no. FP6-2005-513946 The Diogenes project A pan-european programme targeting the obesity problem www.diogenes-eu.org
Weight loss on 8 week LCD www.diogenes-eu.org
Role of ad libitum diet composition in prevention of weight gain Glycemic Index Protein content www.diogenes-eu.org
Diet Composition (Targeted) Group Fat Protein Carbo- Hydrates 1 (LP, low GI) 2 (LP, high GI) 3 (HP, low GI) 4 (HP, high GI) 27 (25-30% ) 27 (25-30% ) 27 (25-30% ) 27 (25-30% ) 13 (10-15%) 13 (10-15%) 25 (23-28%) 25 (23-28%) www.diogenes-eu.org 60 (57-62%) 60 (57-62%) 48 (45-50%) 48 (45-50%) Glycemic Index Low High Low High 5 Control ~25 % ~ 15 % ~ 60 % Medium
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Patient flow II www.diogenes-eu.org
Glycemic Index in diet groups 68 66 64 62 60 58 56 54 52 50 * * * * * * ~8 units baseline 4 weeks 26 weeks LP/LGI LP/HGI HP/LGI HP/HGI control www.diogenes-eu.org * LGI diets significantly different from HGI and recommended diets (p<0.001)
Compliance to dietary protein intake as assessed by 24 hour urinary nitrogen excretion FOOD Diaries: All 8 centres: 5.4 E% difference Pre-LCD www.diogenes-eu.org ICO, Stockholm 11th-15th July 2010
Major end-point: Drop-out rate www.diogenes-eu.org
Completers at Week 26 19-09-2013 Larsen TM et al NEJM 2010
Weight loss after 8 weeks LCD and change in hscrp hscrp = -41 % www.diogenes-eu.org
Effects of diets on hscrp adjusted for weight change 0,1 HP/HGI 0,0 Change in hscrp (mg/l) -0,1-0,2-0,3-0,4-0,5-0,6 LP/LGI LP/HGI HP/LGI HP/HGI Control Control LP/HGI HP/LGI LP/LGI -0,7 0 5 10 15 20 25 weeks www.diogenes-eu.org Gögebakan et al. (Circulation 2011)
Changes in HOMA-IR www.diogenes-eu.org The effect on HOMA-IR was due to an increase in plasma insulin conc., and remained significant after adjustment for weight change
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www.diogenes-eu.org
Result in Children The HP groups had higher protein intake (20.7±0.7 versus 17.9±0.7 %, P=0.004) than the LP groups at mo 6. GI was reduced 3.5 points with LGI versus HGI (P<0.001). HP resulted in 2.6 cm [95% CI 0.6;4.8] (P=0.007) lower waist circumference than LP and a 0.25 mmol/l (P=0.003) lower LDL cholesterol, compared to LP. LGI vs. HGI reduced CRP (P=0.007). In the supermarket centers, where intervention foods were provided to the participants, protein compliance was higher, and effects more marked (P<0.001). Trap Damsgaard www.diogenes-eu.org et al. 2012
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Institut for Idræt og Ernæring Higher protein diets increase/preserve REE 19-09-2013 Dias 40
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Institut for Idræt og Ernæring Cheese intake lowers diabetes risk 19-09-2013 Dias 42
Institut for Idræt og Ernæring More protein and less carbs : Ratio > 0.5 = 1:2 19-09-2013 Dias 44
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Institut for Idræt og Ernæring Overskrift Forskningen ved Institut for Xxxxxxxx belyser basale xxxxx og xxxxxx processer, deres regulering og deres betydning for xxxxxxx funktion, interaktion og organisation i xx. Xxxxx yder undervisning inden for bl.a. xxxxxxxxxx, xxxxxx, basal xxxxxx inkl. xxx, xxxxxx, xxxxxxx samt xxxxxx. M 19-09-2013 Dias 46
Look AHEAD weight loss results at 4-years 4 meetings monthly 3 meetings monthly 1 meeting monthly
In September 2012, the NIH stopped the intervention arm, acting on the recommendation of the study s data and safety monitoring board. The independent advisory board, charged with monitoring the study data and safety of participants, found that the intensive lifestyle did no harm but did not decrease occurrence of cardiovascular events, the primary study goal. At the time, participants had been in the intervention for up to 11 years. Because there was little chance of finding a difference in cardiovascular events between the groups with further intervention, the board recommended stopping the intensive lifestyle intervention, but encouraged the study to continue following all Look AHEAD participants to identify longer-term effects of the intervention. Look AHEAD has shown other important health benefits of the lifestyle intervention, including: *Decreasing sleep apnea *Reducing the need for diabetes medications *Helping to maintain physical mobility *Improving quality of life. 48
Institut for Idræt og Ernæring Thank you for your attention 19-09-2013 Dias 49
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Greater initial weight loss is associated with greater long-term outcome Institut for Idræt og Ernæring 19-09-2013 Dias 51
Institut for Idræt og Ernæring Not one diet fits all personalised lifestyle management 19-09-2013 Dias 52
Institut for Idræt og Ernæring 1) The study population was more healthy that was originally anticipated (partly because the participants had to be able to complete a physical activity test, so they had to exclude the most diseased type-2 diabetics). This lead to a lower-than-expected number of primary outcome events, and thus lower power. 2) The intervention group clearly had problems retaining the initial weight loss and the (initially) higher fitness level. In contrast, the Control group had a surprisingly steady and even increasing - weight loss throughout the study. I still speculate whether the publication of 1 and 4 year weight loss results (prior to the study close down) could have motivated control participants (and their respective general practician) to pay more attention to weight loss and more exercise. 3) In general, the control group were given more medication, whereas the intervention group generally were able to use less medication (because of the benefits from the intervention). This probably also tended to minimize any effect of the intervention. 4) They emphasized caloric restriction more than healthy diet. If/when using meal replacement products (as they did), this have probably helped the intervention group to achieve an initial large weight loss, but on the other hand, this may have been a sub-optimal solution for long term results (compared to recommendation of optimal healthy diet ). I am not aware of any published dietary data from the intervention, and I am not sure if such data was obtained. 19-09-2013 Dias 53
The Look AHEAD lifestyle intervention: 5,145 overweight/obese men and women with type 2 diabetes Randomly assigned to: *An intensive lifestyle intervention (ILI) *A usual care group, referred to as Diabetes Support and Education (DSE) ILI treatment: Designed to induce >7% weight loss at year 1. Participants are encouraged to lose 10% (or more). Planned maximum follow-up of 11.5 years. Primary outcome: First occurrence of fatal or nonfatal myocardial infarction or stroke or other fatal cardiovascular event. 54
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Recommendations: Max 30% kcal from fat and max 10% from saturated fat. Calorie goal 1200 1500 kcal/day (<250 pounds) Calorie goal 1500 1800 kcal/day (>250 pounds) Initial phase: Two meal replacement products/day From week 20 year 4 One meal replacement product/day. The physical activity program: Unsupervised exercise Goal: 175 minutes of moderate intensity physical activity weekly. Encouraged to exercise 5 days per week. 56
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The Obesity Society: The trial's Data and Safety Monitoring Board (DSMB) reviewed the data. Since it was extremely unlikely that a difference would develop with additional follow-up, the NIH, acting on the DSMB's recommendations, determined that the study's primary question had been answered and that the intervention should be stopped and inform the study participants of the results. It is noteworthy that the overall rates of heart attacks and strokes among both groups of patients were much lower than had been anticipated. The science continues to support the idea that losing a modest amount of weight can have substantial health benefits for overweight and obese people, and the Look AHEAD trial has affirmed that for diabetics in particular (www.lookaheadtrial.org). At the 4-year follow-up, lifestyle intervention participants had an average weight loss of 6.2% of their start weight (vs. 0.9% among the diabetes support and education group). They also had greater improvements in diabetes control (and reduced diabetes medications), blood pressure, HDL cholesterol, triglycerides, and fitness and functional mobility. Reports from their earlier follow-ups found greater improvements in quality of life and in sleep apnea. Such benefits are very important for a healthier, more fulfilling life. http://www.prnewswire.com/news-releases/nih-stops-treatment-arm-in-the-lookahead-trial-interpretation-and-implications-175647651.html 58
Questions raised: 1)Was the Diabetes Support and Education intervention too effective as a comparator group? 2)Should the participants included have been at higher CVD risk at baseline in order for the intervention to be effective within the study period? 3)Is prevention of cardiovascular disease using behavioural intervention only not possible once the diabetes condition is established? 4)Is weight loss simply just (only) effective for the prevention/treatment for type-2 diabetes, but not for cardiovascular disease? 59
Institut for Idræt og Ernæring A randomized 12-month trial on Low protein versus high protein 19-09-2013 Dias 60 Skov AR, Toubro S, Bülow J, Krabbe K, Parving HH, Astrup A. Int J Obes 1999;23:1170-1177.
Institut for Idræt og Ernæring A randomized 12-month trial on Low protein versus high protein 19-09-2013 Dias 61 Skov AR, Toubro S, Bülow J, Krabbe K, Parving HH, Astrup A. Int J Obes 1999;23:1170-1177.
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Replacement of fat/carb for protein is associated with a decrease in energy intake Institut for Idræt og Ernæring 19-09-2013 Dias 64
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Institut for Idræt og Ernæring Cheese intake lowers diabetes risk 19-09-2013 Dias 66
Institut for Idræt og Ernæring Jakobsen et al. 2010 19-09-2013 Dias 67
Institut for Idræt og Ernæring Konklusions Weight loss and physical activity are the key elements in prevention of type 2 diabetes. Lomg-term weight control is not simply achieved by caloric restriction and low-fat More focus should be on protein:cho ratio, and the types of carbs (whole grain, GI) Food based advise should replace nutrient based: More dark chocolate, dairy, cheese, (eggs), lean protein sources, etc. Epigenetics, genetics, stress 19-09-2013 Dias 68