Prädisposition – Phänotyp der Adipositas

Zusammenfassung

Adipositas stellt eines der fünf wesentlichen Gesundheitsrisiken moderner Gesellschaften dar und ist mit einer Prävalenz von ca. 20 % in der deutschen Normalbevölkerung eine sehr häufige Erkrankung. Adipositas erhöht das Risiko für Typ 2 Diabetes, Erkrankungen des Herz-Kreislaufsystems, des Stütz- und Bewegungsapparats, der Psyche und andere Organsysteme. Obwohl der Zusammenhang zwischen Adipositas Stoffwechsel- oder Herz-Kreislauf-Folgeerkrankungen epidemiologisch gut belegt ist, scheinen 10–20 % der Personen mit ausgeprägter Adipositas vor diesen Begleiterkrankungen geschützt zu sein. Diese Gruppe metabolisch gesunder Menschen mit Adipositas zeichnet sich gegenüber den Adipositas-Patienten mit hohem Risiko für Stoffwechsel- und Gefäßerkrankungen durch eine erhaltene Insulinsensitivität, geringere Leberverfettung, niedrigere viszerale Fettmasse und normale Fettgewebsfunktion aus. Personen mit metabolisch gesunder Adipositas können durch eine Gewichtsreduktion ihr Adipositas-assoziiertes Risiko nicht deutlich senken. Die bisher in der Klinik noch wenig etablierte Unterscheidung zwischen (metabolisch) gesunder und Hochrisiko-Adipositas ist für eine Stratifizierung der Adipositas-Behandlung wichtig, um Patienten zu identifizieren, die von einer frühzeitigen Lebensstil, pharmakologischen oder chirurgischen Intervention am meisten profitieren würden.

Abstract

Obesity belongs to the five most important health burdens in modern societies and reaches with ~20 % prevalence in Germany epidemic proportions. Obesity significantly increases the risk of developing metabolic (e. g. type 2 diabetes), cardiovascular, orthopaedic, psychologic and other disorders. Despite the well established epidemiologic relationship between obesity and these co-morbidities, there is a subgroup of metabolically healthy obese patients, which seems to be protected against metabolic and cardiovascular obesity related disorders. Compared to metabolically unhealthy or high risk obese patients, metabolically healthy obese individuals are characterized by preserved insulin sensitivity, lower liver fat content, lower visceral fat mass, as well as normal adipose tissue function. Noteworthy, metabolically healthy obese individuals do not significantly improve their obesity-associated risk for the development of type 2 diabetes and vascular diseases. Therefore, distinction between metabolically healthy from high-risk obese phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, pharmacological or bariatric surgery interventions. A stratified treatment approach considering these different obesity phenotypes should be introduced into clinical management of obese patients.

Schlüsselwörter

Adipositas - Typ-2-Diabetes - metabolisch gesunde Adipositas - Insulinresistenz - Fettgewebe - Fettverteilung

Keywords

obesity - type 2 diabetes - metabolically healthy obesity - fat distribution - insulin resistance - adipose tissue

• Literatur

• 1 Achenbach P, Bonifacio E, Koczwara K et al. Natural history of type 1 diabetes. Diabetes 2005; 4: 25-S31
• 2 Adams KF, Schatzkin A, Harris TB et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med 2006; 355: 763-778
• 3 Arsenault BJ, Cote M, Cartier A et al. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese post-menopausal women with elevated blood pressure. Atherosclerosis 2009; 207: 530-533
• 4 Bell LM, Byrne S, Thompson A et al. Increasing body mass index z-score is continuously associated with complications of overweight in children, even in the healthy range. J Clin Endocrinol Metab 2007; 92: 517-522
• 5 Blüher M. Are there still healthy obese patients?. Curr Opin Endocrinol Diabetes Obes 2012; 19: 341-346
• 6 Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab 2013; 27: 163-177
• 7 Bonora E, Kiechl S, Willeit J et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998; 47: 1643-1649
• 8 Bouchard C, Tremblay A, Depres JP et al. The response to long-term overfeeding in identical twins. N Engl J Med 1990; 322: 1477-1482
• 9 Calori G, Lattuada G, Piemonti L et al. Prevalence, metabolic features and prognosis of metabolically healthy obese Italian individuals: the Cremona Study. Diabetes Care 2011; 34: 210-215
• 10 Carlsson LM, Peltonen M, Ahlin S et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 2012; 367: 695-704
• 11 Dvorak RV, DeNino WF, Ades PA. Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women. Diabetes 1999; 48: 2210-2214
• 12 Ferrannini E, Natali A, Bell P et al. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166-1173
• 13 Hamer M, Stamatakis E. Metabolically Healthy Obesity and Risk of All-Cause and Cardiovascular Disease Mortality. J Clin Endocrinol Metab 2012; 97: 2482-2488
• 14 Kantartzis K, Machann J, Schick F et al. Effects of a lifestyle intervention in metabolically benign and malign obesity. Diabetologia 2011; 54: 864-868
• 15 Karelis AD, Messier V, Brochu M et al. Metabolically healthy but obese women: effect of an energy-restricted diet. Diabetologia 2008; 51: 1752-1754
• 16 Klöting N, Fasshauer M, Dietrich A et al. Insulin sensitive obesity. Am J Physiol Endocrinol Metab 2010; 299: E506-E515
• 17 Klöting N, Stumvoll M, Blüher M. The biology of visceral fat. Internist (Berl) 2007; 48: 126-133
• 18 Kuk JL, Ardern CI, Church TS et al. Edmonton Obesity Staging System: association with weight history and mortality risk. Appl Physiol Nutr Metab 2011; 36: 570-576
• 19 Lee DC, Sui X, Church TS et al. Associations of cardiorespiratory fitness and obesity with risks of impaired fasting glucose and type 2 diabetes in men. Diabetes Care 2009; 32: 257-262
• 20 McAuley PA, Blair SN. Obesity paradoxes. J Sports Sci 2011; 29: 773-782
• 21 Meigs JB, Wilson PW, Fox CS et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 2006; 91: 2906-2912
• 22 Mokdad AH, Ford ES, Bowman BA et al. Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA 2003; 289: 76-79
• 23 Muscelli E, Camastra S, Gastaldelli A et al. Influence of duration of obesity on the insulin resistance of obese non-diabetic patients. Int J Obes Relat Metab Disord 1998; 22: 262-267
• 24 Padwal RS, Pajewski NM, Allison DB et al. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ 2011; 183: E1059-E1066
• 25 Perusse L, Depres JP, Lemieux S et al. Familial aggregation of abdominal visceral fat: results from the Quebec family study. Metabolism 1996; 45: 378-382
• 26 Plomin R, Owen MJ, McGuffin P. The genetic basis of complex human behaviors. Science 1994; 264: 1733-1739
• 27 Raggi MC, Sharma AM, Jacob S. Edmonoton Obesity Staging Sysstem: Therapiedringlichkeit bei Adipositas abschätzen. Diabetologie, Stoffwechsel und Herz 2012; 21: 321-324
• 28 Reaven GM. Importance of identifying the overweight patient who will benefit the most by losing weight. Ann Intern Med 2003; 138: 420-423
• 29 Schulze MB, Hoffmann K, Boeing H et al. An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes. Diabetes Care 2007; 30: 510-515
• 30 Sharma AM, Kushner RF. A proposed clinical staging system for obesity. Int J Obes (Lond) 2009; 33: 289-295
• 31 Shin MJ, Hyun YJ, Kim OY et al. Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women. Int J Obes (Lond) 2006; 30: 1529-1534
• 32 Sims EAH. Are there persons who are obese, but metabolically healthy?. Metabolism 2001; 50: 1499-1504
• 33 Stefan N, Kantartzis K, Machann J et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609-1616
• 34 Thomas EL, Parkinson JR, Frost GS. The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat. Obesity (Silver Spring) 2012; 20: 76-87
• 35 Tuomilehto J, Lindström J, Eriksson JG et al. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343-1350
• 36 van Vliet-Ostaptchouk JV, Nuotio ML, Slagter SN et al. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe. BMC Endocr Disord 2014; 14: 9
• 37 Voulgari C, Tentolouris N, Dilaveris P. Increased heart failure risk in normal-weight people with metabolic syndrome compared with metabolically healthy obese individuals. J Am Coll Cardiol 2011; 58: 1343-1350
• 38 Wadden TA. Treatment of obesity by moderate and severe caloric restriction. Results of clinical research trials. Ann Intern Med 1993; 119: 688-693
• 39 Weinstein AR, Sesso HD, Lee IM et al. Relationship of physical activity vs body mass index with type 2 diabetes in women. JAMA 2004; 292: 1188-1194
• 40 Wildman RP, Muntner P, Reynolds K et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med 2008; 168: 1617-1624