Adipositas und chronische Inflammation bei phlebologischen und lymphologischen Erkrankungen

Zusammenfassung

Die Prävalenz der Adipositas ist in den letzten 15 Jahren weiter stark angestiegen. Dabei fällt besonders die deutliche Zunahme der morbiden Adipositas auf, die wiederum bei den Älteren besonders ausgeprägt ist. Da mit dem Alter auch venöse Thromboembolien, chronisch venöse Insuffizienz und sekundäre Lymphödeme zunehmen, steigt die Zahl der Patienten mit venösen oder lymphatischen Erkrankungen, die gleichzeitig schwer adipös und häufig multimorbide sind, überproportional an. Die Adipositas, vor allem die viszerale, verschlechtert alle Ödemerkrankungen, erhöht das Risiko für thromboembolische Erkrankungen und postthrombotisches Syndrom und kann alleinige Ursache sein für die Adipositas-assoziierte funktionelle Veneninsuffizienz ohne Nachweis von Obstruktion oder Reflux. Das Adipositasassoziierte Lymphödem stellt inzwischen den größten Anteil unter den sekundären Lymphödemen. Mehr als 50 Prozent der Lipödempatientinnen sind adipös, die bei ihnen im Verlauf zu beobachtenden sekundären Lymphödeme in der Regel Folge der Adipositas, nicht des Lipödems. Die Symptomatik wird bei allen Krankheitsbildern durch Gewichtsreduktion gebessert. Neben mechanischen Faktoren wie der Erhöhung des intraabdominalen und intertriginösen Drucks, der wiederum zu einer venösen Drucksteigerung in den Beingefäßen führt, sind es vor allem die durch die Zunahme des viszeralen Fettgewebes verursachten metabolischen, chronisch inflammatorischen und prothrombotischen Prozesse, die für diese Zusammenhänge verantwortlich sind, erkennbar an niedrigen Spiegeln von Adiponektin und hohen von Leptin, Insulin, intaktem Proinsulin, PAI-1 sowie proinflammatorischen Zytokinen (Il-6, Il-8, TNF-α). Therapeutische Maßnahmen müssen also in erster Linie auf die Reduktion der viszeralen Adipositas und damit der Hyperinsulinämie bzw. der Insulinresistenz sowie auf die Bekämpfung der chronischen Entzündung abzielen.

Schlüsselwörter

Adipositas-assoziierte funktionelle Veneninsuffizienz - Adipositas-assoziiertes Lymphödem - viszerale Adipositas - chronische Inflammation - Insulinresistenz

• Literatur

• 1 So dick war Deutschland noch nie. Ergebnisse des 13. DGE-Ernährungsberichts zur Übergewichtsentwicklung. Presseinformation: Presse, DGE aktuell. Februar 2017
• 2 Benigni JP, Cazaubon M, Tourneroche A, AchhammerI Mathieu M. Is obesity an aggravating factor in chronic venous disease? Results of a French epidemiological study in male patients. Int Angiol 2006; 25: 297-303.
• 3 Stunkard AJ, Sørensen TI, Hanis C. et al. An adoption study of human obesity. N Engl J Med 1986; Jan 23; 314 (04) 193-8.
• 4 Stunkard AJ, Harris JR, Pedersen NL. et al. The body mass index of twins who have been reared apart. N Engl J Med 1990; May 24; 322 (21) 1483-7.
• 5 Schienkiewitz Mensink GBM, Ronny Kuhnert, Lange C. Übergewicht und Adipositas bei Erwachsenen in Deutschland. Journal of Health Monitoring. 2017 02. (2) DOI 10.17886/RKI-GBE-2017-025 Robert Koch-Institut, Berlin.:
• 6 Cameron JD, Cyr MJ, Doucet E. Increased meal frequency does not promote greater weight loss in subjects who were prescribed an 8-week equienergetic energy-restricted diet. Br J Nutr 2010; Apr; 103 (08) 1098-1101.
• 7 Rosmond R, Dallmann MF, Björntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998; 83 (06) 1853-1859.
• 8 Watanabe M, Kikuchi H, Tanaka K. et al. Association of Short Sleep Duration with Weight Gain and Obesity at 1-Year Follow-Up: A Large-Scale Prospective Study. Sleep 2010; 33 (02) 161-7 DOI.org/10.1093/sleep/33.2.161.
• 9 Hasler G, Buysse J, Klaghofer R. et al. The Association Between Short Sleep Duration and Obesity in Young Adults: a 13-Year Prospective Study. Sleep 2004; Jun, 27 (04) 661-666.
• 10 Cappucchio FP, Taggart FM, Kandala NB. et al. Meta-Analysis of Short Sleep Duration and Obesity in Children and Adults. Sleep 2008; 31 (05) 319-326.
• 11 Faerber G. Der übergewichtige Patient mit CVI oder Lymphödem: Risikofaktor oder Ursache?. Vasomed 2014; 26: 10-11 Bonner Venentage 2014.
• 12 Göstl K, Obermayer A, Hirschl M. Pathogenesis of chronic venous insufficiency by obesity. Current data and hypotheses. Phlebologie 2009; 38: 108-113.
• 13 Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003; 89: 493-498.
• 14 Ageno W, Piantanida E, Dentali F. et al. Body mass index is associated with the development of the postthrombotic syndrome. Thromb Haemost 2003; 89: 305-309.
• 15 Chiesa R, Marone EM, Limonie C. et al. Chronic venous disorders: correlation between visible signs, symptoms, and presence of functional disease. J Vasc Surg 2007; 46: 322-330.
• 16 Padberg Jr F, Cerveira JJ, Lal BK. et al. Does severe venous insufficiency have a different etiology in the morbidly obese? Is it venous?. J Vasc Surg 2003; 37: 79-85.
• 17 Vlajinac HD, Marinkovic JM, Maksimovic MZ. et al. Body Mass Index and Primary Chronic Venous Disease - A Cross-sectional Study. European Journal of Vascular and Endovascular Surgery 2013; 45 (03) 293-298.
• 18 Danielsson G, Eklof B, Grandinetti A, Kistner RL. The influence of obesity on chronic venous disease. Vasc Endovascular Surg 2002; 36: 271-276.
• 19 Obermayer A, Göstl K, Walli G, Benesch T. Chronic venous leg ulcers benefit from surgery: long-term results from 173 legs. J Vasc Surg 2006; 44: 572-579.
• 20 Bjellerup M. Determining venous incompetence: a report from a specialised leg ulcer clinic. J Wound Care 2006; 15: 429-436.
• 21 Sugerman HJ, Sugerman EL, Wolfe L. et al. Risks and benefits of gastric bypass in morbidly obese patients with severevenous stasis disease. Ann Surg 2001; 234: 41-46.
• 22 Benigni JP. Wirksamkeit von Gewichtsabnahme auf die Entwicklung chronisch venöser Insuffizienz nach operativer Magenverkleinerung bei übergewichtigen Patienten. 15. Bonner Venentage vom 27./28. Februar 2008. Vasomed 2009; 01: 26-27.
• 23 Garzon K, Obermayer A, Hirscher M. Das adipositasassoziierte Dependency-Sndrom. Vasomed 2010; 22 (05) 218.
• 24 Doerler M, Altmeyer P, Stücker M. Ulcus cruris venosum auf dem Boden eines Adipositas-assoziierten Dependency-Syndroms. Phlebologie 2013; 42: 205-208.
• 25 Reich-Schupke S. Die besondere Rolle der Adipositas in der Lymphologie. Vasomed 2014; 05: 230-236.
• 26 Flaggl F, Döller W, Jäger G. et al. Prävalenz komorbider psychischer Störungen bei Lymphödempatienten in der medizinischen Rehabilitation. Praxis Klinische Verhaltensmedizin und Rehabilitation 2006; 07 (01) 75-82.
• 27 Greene AK, Grant FD, Slavin SA. Lower-extremity lemphedema and elevated body-mass index. N Engl J Med 2012; 366: 2136-2137.
• 28 Shaw C, Mortimer P, Judd PA. A randomized controlled trial of weight reduction as a treatment for breast cancerrelated lymphedema. Cancer 2007; 110: 1868-1874.
• 29 Reich-Schupke S. Compression therapy in obese patients Phlebologie. 2015; 44: 71-76.
• 30 Schmeller W, Hüppe M, Meier-Vollrath I. Langzeitveränderungen nach Liposuktion bei Lipödem. LymphForsch 14 (02) 2010; L: 17-28.
• 31 Rapprich S, Loehnert M, Hagedorn M. Therapy of lipoedema syndrome by liposuction under tumescent local anaesthesia. Ann Dermatol Venereol 2002; 129: 1S711.
• 32 Herpertz U. Die häufigsten Beinödeme. Differenzierung zwischen Phlebödem, Lymphödem und Lipödem. Phebologie 2001; 30: 48-52.
• 33 Schmeller W, Meier-Vollrath I. Lipödem - Aktuelles zu einem weitgehend unbekannten Krankheitsbild. Akt Dermatol 2007; 33: 1-10.
• 34 Willenberg T, Schumacher A, Amann-Vesti B. Impact of obesity on venous hemodynamics of the lower limbs. J Vasc Surg. 2010 52. 664-8 doi.org/10.1016/j.jvs.2010.04.023
• 35 Darvall KA, Sam RC, Silverman SH. et al. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33: 223-233.
• 36 Ageno W. et al. Association between the metabolic syndrome, its individual components, and unprovoked venous thromboembolism. Arterioscler Thromb Vasc Biol 2014; 34: 2478-2485.
• 37 Juhan-Vague I, Vague P, Alessi MC. et al. Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1..
• 38 Juhan-Vague I, Roul C, Alessi MC. et al. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients - relationship with plasma insulin. Thromb Haemost 1989; 61: 370-373.
• 39 Karaman S, Hollmén M, Robciuc MR. et al. Blockade of VEGF-C and VEGF-D modulates adipose tissue inflammation and improves metabolic parameters under high-fat diet. Molecular Metabolism 2015; 04 (02) 93-105.
• 40 Karaman S, Hollmén M, Yoon S-Y. et al. Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in mice. Scientific Reports 2016; 06: 31566.
• 41 Harford K, Reynolds C, McGillicuddy F, Roche H. Fats, inflammation and insulin resistance: Insights to the role of macrophage and T-cell accumulation in adipose tissue. Proceedings of the Nutrition Society 2011; 70 (04) 408-417.
• 42 Gomez-Ambrosi J, Catalan V, Rodriguez A, Ramirez B, Silva C, Gil MJ. Involvement of serum vascular endothelial growth factor family members in the development of obesity in mice and humans. Journal of Nutritional Biochemistry 2010; 21: 774-780.
• 43 Silha J, Krsek M, Sucharda P, Murphy L. Angiogenic factors are elevated in overweight and obese individuals. International Journal of Obesity 2005; 29: 1308-1314.
• 44 Elias I, Franckhauser S, Ferré T, Vilà L, Tafuro S, Muñoz S, Roca C, Ramos D, Pujol A, Riu E. et al. Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes 2012; 61: 1801-1813.
• 45 Escobedo N, Oliver G. The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity. Cell Metabolism 2017; 26 (04) 598-609.
• 46 Ogata Fusa. et al. Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4+ T Cells Drives the Pathogenesis of Lymphedema Journal of Investigative Dermatology. 2016; 136: 706-714.
• 47 Ly CL, Kataru RP, Mehrara BJ. Inflammatory Manifestations of Lymphedema. Jackson C, ed. International Journal of Molecular Sciences 2017; 18 (01) 171.
• 48 S1-Leitlinie Lipödem - AWMF: www.awmf.org/leitlinien/detail/ll/037-012
• 49 Marshall M, Schwahn-Schreiber C. Das Lipödem - ein wenig beachtetes Krankheitsbild. Vasomed 2008; 20: 59-65.
• 50 Faerber G. Ernährungstherapie bei Lipödem und Adpositas - Ergebnisse eines leitliniengerechten Therapiekonzepts. Vasomed 2017; 29: 122-123.
• 51 Faerber G. Antiinflammatorische Ernährung, was ist das und was bringt sie uns beim Lipödem?. Vasomed 2017; 29: 2-3 Vortrag, 59. Jahrestagung der Deutschen Gesellschaft für Phlebologie, Stuttgart, 20.-23. September 2017.
• 52 Cohen PG. Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. Med Hypotheses 2001; 56: 702-708.
• 53 Ivandić A, Prpić-Krizevac I, Sucić M. et al. Hyperinsulinemia and sex hormones in healthy premenopausal women: Relative contribution of obesity, obesity type, and duration of obesity. Metabolism - Clinical and Experimental 1998; 47: 13-19.
• 54 Nestler JE, LINDA P, Powers LP, Matt DW. et al. A Direct Effect of Hyperinsulinemia on Serum Sex Hormone-Binding Globulin Levels in Obese Women with the Polycystic Ovary Syndrome, The Journal of Clinical Endocrinology & Metabolism. 1991 72. 83-9 https://doi.org/10.1210/jcem-72-1-83
• 55 Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, Kramer K, Mikus CR, Myers V, Nauta M, Rodarte RQ, Sparks L, Thompson A, Earnest CP. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010; 304: 2253-2262.
• 56 Feinman RD, Pogozelski WK, Astrup A. et al. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition. 2015 31. 1-13 DOI: https://doi.org/10.1016/j.nut.2014.06.011
• 57 Mizushima N, Noda T, Yoshimori T. et al. (1998). A protein conjugation system essential for autophagy. Nature 1998; 395: 395-398.
• 58 Harvie M, Wright C, Pegington M. et al. The effect of intermittent energy and carbohydrate restriction vs. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. British Journal of Nutrition 2013; 110: 1534-1547 doi:10.1017/S0007114513000792.
• 59 Klempel MC. et al. Intermittent fasting combined with calorie restriction is effective for weight lossand cardio-protection in obese women. Nutr J 2012; 11: 98 Doi:10.1186/1475-2891-11-98.
• 60 Lim EL, Hollingsworth KG. et al. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54: 2506-2514.
• 61 Steven S, Taylor R. Restoring hyperglycaemia by very low calorie diet in long and short duration type 2 diabetes. Diabet Med 2015; 32 (09) 1149-1155.
• 62 Marsk R, Jonas E, Rasmussen F. et al. Nationwide cohort study 0f post-gastric bypass hypoglycaemia including 5 040 patients undergoing surgery for obesity in 1986-2006 in Sweden. Diabetologica 2010; 53: 2307-2311.
• 63 Tindle HA, Omalu B, Courcoulas A. et al. Risk of suicide after long-term follow-up from bariatric surgry. Am J Med 2010; 123: 1036-1042.
• 64 Conason A, Teixeira J, Hsu CH. et al. Substance use following bariatric weight loss surgery. Arch Surg. 2012: 1-6.
• 65 Ditschuneit HH, Flechtner-Mors M, Johnson TD, Adler G. Metabolic and weight-loss effects of a long-term dietary intervention in obese patients. Am J Clin Nutr. 1999 69. 02 198-204 http://www.ncbi.nlm.nih.gov/pubmed/9989680
• 66 Yancy WS, Olsen MK, Guyton JR. et al. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial. Ann Intern Med 2004; 140: 769-777 doi: 10.7326/0003-4819-140-10-200405180-00006.
• 67 Westman EC, Feinman RD, Mavropoulos JC. et al. Low-carbohydrate nutrition and metabolism. The American journal of clinical nutrition 2007; 86 (02) 276-284.
• 68 Noakes T. Low-carbohydrate and high-fat intake can manage obesity and associated conditions: Occasional survey. South African Medical Journal 2013; 103 (11) 826-830 doi:10.7196/SAMJ.7302.
• 69 Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain research reviews 2009; 59 (02) 293-315.
• 70 Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in pharmacology. 2012: 3.
• 71 Youm YH, Nguyen KY, Grant RW. The ketone metabolite β-hydroxybutyrate blocks NLRP3 in-flammasome-mediated inflammatory disease. Nature Medicine 2015; 21: 263-269 doi:10.1038/nm.3804.
• 72 Sofi F, Buccioni A, Cesari F. et al. Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study. Nutr Metab Cardiovasc Dis 2010; 20: 117-124 doi:10.1016/ j.numecd.2009.03.004.
• 73 Markova M, Pivovarova O, Hornemann S. et al. Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes. Gastroenterology 2017; 152 (03) 571-585 doi: 10.1053/j.gastro.2016.10.007.
• 74 Westerterp-Plantega MS, Lemmens S, Westerterp KR. Dietary protein - its role in satiety, energetics, weight loss and health. British Journal of Nutrition. Volume 108, Issue S2: 105-112 https://doi.org/10.1017/S0007114512002589
• 75 Paoli A, Bosco G, Camporesis EM. et al. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol. 2015 06. 1-7 https://doi.org/10.3389/fpsyg.2015.00027
• 76 Sumithran P, Prendergast LA, Delbridge E. et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr 2013; 67: 759-764.
• 77 Johnstone AM, Horgan GW, Murison SD. et al. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr 2008; 87: 44-55.
• 78 Smeets PA. et al. Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories. Am J Nutr 2005; 82 (05) 1001-1006.
• 79 Just T, Pau HW, Engel U. et al. Cephalic phase insulin release in healthy humans after taste stimulation?. Appetite 2008; 51: 622-627.
• 80 Pepino MY. et al. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care 2013; 36 (09) 2530-2535.
• 81 Abou-Donia M, El-Masry E, Abdel-Rahman A. et al. Splenda alters gut microflora and increases intestinal Pglycoprotein and cytochrome P-450 in male rats. Journal of Toxicology and Environmental Health 2008; 71: 1415-1421.
• 82 Suez J, Korem T, Zeevi D, Zilberman-Schapira G. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014; 514: 181-186.
• 83 Wölnerhanssen B, Cajacob L, Keller N. et al. Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects. Am J Physiol Endocrinol Metab 2016; 310: E1053-E1061 doi:10.1152/ajpendo.00037.2016.
• 84 Turnbaugh PG. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444: 1027-1031.
• 85 Dibaise JK. et al. Gut Microbiota and Its Possible Relationship With Obesity. Mayo Clinic Proceedings 2008; 83: 460-469.
• 86 Duncan SH. et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Applied and Environmental Microbiology 2007; 73: 1073-1078.