ENDOKRINOLOGISKE ASPEKTER VED SYKELIG OVERVEKT

Transkript

1 ENDOKRINOLOGISKE ASPEKTER VED SYKELIG OVERVEKT Namsos 18. september 2014 Overlege/Professor Bård Kulseng Regionalt senter for behandling av sykelig overvekt St. Olavs Hospital og NTNU

2 ENDOKRINOLOGISKE ASPEKTER VED SYKELIG OVERVEKT Hormonsykdommer som kan føre til fedme Fedme som årsak til hormonelle endringer Noen hormonelle endringer etter fedmekirurgi

3 Vi spiser for mye og er for lite aktiv Hvorfor er det slik?

4 Hormonsykdommer som kan føre til fedme Hypotyreose Cushing's syndrom Veksthormon mangel Testosteron mangel Insulinom Hypotalamisk skade Genetiske syndromer -Fedme

5 Increased food energy supply is more than sufficient to explain the epidemic of obesity

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8 Sukkerforbruk I Norge

9 Daglig tilsatt sukkerforbruk i Norge

10 High Fructose Corn Syrop is % Fructose Sucerose is 50 % Fructose

11 Fructose is not glucose Fructose does not suppress ghrelin (hunger hormone) Acute fructose do not stimulate insulin Hepatic fructose metabolism is different Chronic fructose exposure promotes the Metabolic Syndrome

12 Metabolism of fructose

13 Hvorfor har fysisk trening betydning for fedmeutvikling? Fordi det brenner kalorier Ikke så mye Fordi det forbedrer skjelettmuskulatur insulinfølsomhet Fordi det reduses stress, og kortisol utgivelsen Fordi det gjør at Kreps syklus går raskere, og reduserer fruktose effekter, bedrer insulinfølsomhet i lever

14 Obesity is a natural reaction to the food environment we live in Obesity is controlled by the hedonic and homeostatic systems Hedonic hunger is a physiological response to food, involving the brain s reward centres. The result is that we eat not according to energy needs, but purely for pleasure Feelings of hunger; is released in the presence of high-fat, high-sugar foods even when the body does not need calories The job of the homeostatic system is to defend those stored calories and a progressively higher body weight

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16 Zheng H, and Berthoud H Physiology 2008;23:75-83

17 Figure 1 A simplified model of the leptin signalling pathway Lines with arrowheads show stimulatory action. Lines with perpendicular endblocks show inhibitory action. AgRP=agouti-related protein. BDNF=brain-derived neurotrophic factor. CART=cocaine-amphet... The Lancet Volume 375, Issue

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19 OR Leptin Resistance Modified from Nature 395, (22 October 1998)

20 Leptin acts as part of a feedback loop to maintain constant stores of fat Nature 395, (22 October 1998)

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22 The Maintenance of Energy Balance Is Compromised after Weight Loss Figure 1 Changes among metabolic tissues, hormones and brain reward systems in maintaining an energy balance in a weight-reduced state. CCK, cholecystokinin; CR, cognitive restraint; GLP-1, glucagon-like peptide-1; NE, norepinephrine; PAEE, physi... Canadian Journal of Diabetes Volume 37, Issue

23 Inter-individual differences in response to exercise FFM: 0.89±2.12kg FFM: 0.47±1.51kg, P<0.05 hunger and EI hunger and EI Participants ex for 12 weeks, 5 times /week (all ex sessions were supervised). Each session was individually designed to expend 500kcal at approximatly 70% max HR. King et al, 2008 (IJO)

24 From: Weight Change and Health Outcomes at 3 Years After Bariatric Surgery Among Individuals With Severe Obesity Percent Weight Change TrajectoriesGrowth mixture models were used to estimate weight change trajectories for each participant and to classify participants with similar modeled trajectories into groups. Lines indicate modeled group trajectories; data markers, observed median values; bars, observed interquartile ranges. JAMA. 2013;310(22): doi: /jama

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26 After an overnight (10 12 hours) fast, patients ingested a semiliquid meal (26% protein, 28% fat, and 45% carbohydrate; 350 kcal in total). measurement of plasma glucose, insulin, C-peptide, glucagon, amylin, des-acyl ghrelin, pancreatic polypeptide (PP), PYY, and glucagon-like peptide-1 (GLP-1).

27 Nannipieri.M, J Clin Endocrinol metab 2013

28 Nannipieri.M, J Clin Endocrinol metab 2013

29 Nannipieri.M, J Clin Endocrinol metab 2013

30 RYGB SLG Nannipieri.M, J Clin Endocrinol metab 2013

31 On the OGTT, both fasting and 2-hour plasma glucose concentrations were markedly reduced with both kinds of surgery. By defining partial remission as HbA 1c <6.5%, fasting glucose <7.0 mmol/l, and 2-hour glucose <11.1 mmol/l with no antidiabetic treatment, diabetes remission was seen in 20 of the 35 patients at 1 year postsurgery (13 RYGB and 7 SLG); this left 15 patients in whom diabetes was still improved but not in partial remission even at 1 year. Age, initial BMI, and the kind of surgery did not distinguish remitters from nonremitters. Duration of diabetes (6 ± 4 vs 12 ± 5 years, P <.0001), baseline HbA 1c (7.5 ± 1.4 vs 9.2 ± 2.4%, P <.01), mean plasma glucose levels (P =.001), and β-cell glucose sensitivity (P =.002) were all worse in nonremitters than in remitters.

32 Hormonal response to a mixed-meal challenge after reversal of gastric bypass for hypoglycemia. Konklusjon: Det hjelper ikke mot hypoglykemier i dette eksemplet. Lee C.J, J Clin Endocrinol Metab. 2013

33 Gut Miceobiota

34 Konklusjon Fedme fører til sykdom og tidlig død Kvaliteten på maten vi spiser er viktig for helsen. Proteiner, fett og karbohydrater er bra for helsen. Det handler om kvalitet og kvantitet. Vi trenger å endre kostholdet til lavere glukose indeks, økt fiber og redusert fruktose og sukker En kalori er ikke en kalori, men de biokjemiske prosessene som mat fører til Overspising og latskap kan være et resultat av nevroendokrin responser til maten vi spiser

35 The homeostatic pathway of energy balance Lustig RH (2006) Childhood obesity: behavioral aberration or biochemical drive? reinterpreting the first law of thermodynamics Nat Clin Pract Endocrino Metabol 2: doi: /ncpendmet0220