Metabolikus szindróma gyermekkorban Molnár Dénes Pécsi Tudományegyetem Klinikai Központ Gyermekklinika - IDEFICS konzorcium nevében- A gyermekorvosi alapellátás XVII. tudományos konferenciája 2015. május 14 17., Siófok Funded by the EC, FP 6, Contract No. 016181 (FOOD)
Metabolikus szindróma Rövid történelmi áttekintés Definíció, prevalencia, problemák IDEFICS eredmények Quo vadis metabolikus szindróma? 2
Történelmi háttér 1923 The combination of hypertension, hyperglycemia and hyperuricemia, Kylin Ztrbl Inn Med 44: 105 1966 Trysyndrome metabolique Camus Rev Rhumat 33: 10 1968 Wealthy syndrome Mehnert & Kuhlmann Deutsch Med J 19: 567 1980 Das Metabolische Syndrome - Hanefeld &Leonhardt Deutsch Ges Wes 36: 545 3
Történelmi háttér 1988 Reaven - Syndrome X alap az inzulin rezisztenia - Diabetes 37: 1595 Későbbi elnevezések: GHO syndr. (gl. intol., hypert. & obesity) Deadly quartet Metabolic cardiovascular syndrome 4
Jelenlegi terminológia Metabolikus szindróma 5
Gyermekkori elhízás következményei Ebbeling CB et al. Lancet 2002; 360: 473-482
MS leggyakrabban használt komponensei Elhízás Hipertónia Dyslipidaemia (emelkedett triglycerid és/vagy alacsony HDLkoleszterin szint) Inzulin rezisztencia hiperinzulinémia glukóz intolarencia és/vagy 2-es tíypusú diabetes Hansen BC. Ann N Y Acad Sci 1999; 892: 1-24
MS különböző definíciói Criteria Lee et al J Pediatr 152:177-84, 2008 Age 8-19 (participated in various metabolic studies) efinition VII. Definition (Weiss) (Cook) (Ford) (Cruz) Waist cc - >=90 th percentile for age, sex BMI RR Glucose fasting HDL-chol Z score >= 2 age and sex specific >=95 th percentile for age, sex and height Impaired glucose tolerance <=5 th percentile for age, sex and race >=90 th percentile for age, sex >=90 th percentile for age, sex, race - - >=85 th percentile for age >=90 th percentile for age, sex and height >= 6.1 mmol/l or impaired glucose tolerance >=90 th percentile for age, sex and height >=6.1mmol/l or impaired glucose tolerance >90 th percentile for age, sex and height Impaired glucose tolerance <=40 mg/dl <=40 mg/dl <=10 th percentile for age, sex LDL-chol - - - - Triglyceride 8 >=95 th percentile for age, sex and race >=110 mg/dl >=110 mg/dl >=90 th percentile for age and sex Prevalence 18.7 21 25.1 13.4
Vizsgált elhízott gyermekek antropometriai jellemzői Polish (n = 90) Greek (n = 145) Italian (n = 274) French (n = 283) Hungarian (n = 449) Whole group (n = 1241) Boys/Girls 39/51 74/71 135/139 91/192 221/228 560/681 Age (years) 12.9 (3.3) 11.3 (2.5) 12.1 (1.6) 14.5 (1.6) 12.9 (2.7) 12.9 (2.5) Weight (kg) 78.7 (24.5) 70.4 (20.9) 63.9 (13.9) 102.4 (19.9) 80.5 (21.7) 80.53 (24.1) Height (cm) 158.4 (16.0) 151.3 (14.6) 153.6 (9.4) 164.5 (8.4) 159.4 (13.5) 158.2 (12.8) BMI (kg/m 2 ) 30.8 (4.9) 30.1 (4.9) 26.8 (3.6) 37.7 (5.9) 31.1 (4.8) 31.5 (6.1) Data 9 are expressed as mean (SD). Bokor S..Molnar D Int J Pediatr Obes 3(Suppl 2): 3, 2008
Vizsgált MS definíciók Waist circumference (cm) Ferranti et al WHO NCEP IDF 3 of 5 criteria Impaired glucose regulation* + 2 of criteria 3 of 5 criteria high waist circumference: > 90th percentile for age and gender (20) High waist circumference + 2 of 4 criteria Glucose (mmol/l) 6.1 5.6 Insulin (μu/ml) - Top quartile of insulin among nondiabetic subjects Triglyceride (mmol/l) 1.1 1.7 HDL-cholesterol (mmol/l) Blood pressure (mmhg) < 1.3, < 1.2 older than 15 years < 0.9 in < 1.0 in - - 1.03 in 1.29 in < 1.03 in < 1.29 in systolic and/or diastolic BP > 95th percentile for age gender and height (19) NCEP: National Cholesterol Education Program, WHO: World Health Organisation, IDF: International Diabetes Federation. 10 *Impaired glucose regulation: glucose intolerance, IFG or diabetes mellitus and/or insulin resistance
MS prevalencia (%) 40% 35% 30% 25% 20% 15% 10% 5% 0% Ferranti et al. WHO NCEP IDF MS definition: Ferranti et al., National Cholesterol Education Program (NCEP) : 3 or more of the criteria s; WHO, International Diabetes Federation (IDF) 11 Bokor S..Molnar D Int J Pediatr Obes 3(Suppl 2): 3, 2008
MS prevalencia a 4 definíció szerint 30% MS or not?? 15% 5% 8% 17% 55% Without MS according to 4 definitions MS according to 1 definition MS according to 2 definitions MS according to 3 definitions MS according to 4 definitions Bokor S..Molnar D Int J Pediatr Obes 3(Suppl 2): 3, 2008 12
További kérdések MS diagnózisának stabilitása Goodman et al. (Circulation 115: 2316-22, 2007) szerint A páciensek fele kategóriát vált a követés során a negatívok pozitívvá válnak és fordítva 13
IDF új definíciót alakított ki gyermekek számára The Lancet 369: 2059-61, 2007 Age 6 to <10 years Obesity >=90th percentile as assessed by waist cc Metabolic syndrome cannot be diagnosed Age 10- <16 years Abdominal obesity >=90th percentile (or adult cutoff if lower) as assessed by waist cc + 2 or more of the following: Triglyceride >= 1.7 mmol/l HDL-C < 1.03 mmol/l SBP >= 130 mm Hg or DBP >= 85 mm Hg Glucose >= 5.6 mmol/l (oral glucose tolerance test recommended) or known type 2 diabetes mellitus Age > 16 years Use existing IDF criteria for adults 14
Miért nem sikerül konszenzusra jutni a a MS meghatározását illetően? Konszenzus hiányának okai: A gyermekkori fejlődéssel járó fiziológiai változások hiányos ismerete (gyermek- és pubertáskor testösszetétel, laboratóriumi paraméterek) Nem és életkor specifikus referencia értékek hiánya derékkörfogat, HDL-kol., triglycerid, insulin, HOMA, stb. A MS meghatározásának nehézségei felhívják a figyelmet, hogy a MS mint koncepció igen érdekes, de mint diagnosztikus eszköz, óvatosan kezelendő. 15
Metabolikus szindróma meghatározása gyermekkorban Background: The diagnostic criteria of the metabolic syndrome (MS) have been applied in studies of obese adults to estimate the metabolic risk-associated with obesity, even though no general consensus exists concerning its definition and clinical value. We reviewed the current literature on the MS, focusing on those studies that used the MS diagnostic criteria to analyze children, and we observed extreme heterogeneity for the sets of variables and cutoff values chosen. Objectives: To discuss concerns regarding the use of the existing definition of the MS (as defined in adults) in children and adolescents, analyzing the scientific evidence needed to detect a clustering of cardiovascular risk-factors. Finally, we propose a new methodological approach for estimating metabolic risk-factor clustering in children and adolescents. Results: Major concerns were the lack of information on the background derived from a child's family and personal history; the lack of consensus on insulin levels, lipid parameters, markers of inflammation or steato-hepatitis; the lack of an additive relevant effect of the MS definition to obesity per se. We propose the adoption of 10 evidence-based items from which to quantify metabolic risk-factor clustering, collected in a multilevel Metabolic Individual Risk-factor And CLustering Estimation (MIRACLE) approach, and thus avoiding the use of the current MS term in children. Conclusion: A gyermekgyógyászoknak új megközelítést kell alkalmazniuk a MS meghatározásához. Felnőttekben alkalmazott meghatározások nem adaptálhatóak gyermekkorra. A MS egyes komponensei akkor vehetők figyelembe, ha a megfelelő referencia értékek rendelkezésre Pediatricians should consider a novel and specific approach to assessing children/adolescents and should not simply derive or adapt definitions from adults. Evaluation of insulin and lipid levels should be included only when specific references for the relation of age, gender, pubertal status and ethnic origin to health risk become állnak available. This és new azok approach could egészségügyi be useful for improving the overall quality of patient evaluation and for optimizing the use of the limited resources available facing to the obesity epidemic. kockázatai tisztázottak. Brambilla P et al. Int J Obes 2007; 31: 591-600
IDEFICS: Identification and prevention of Dietaryand lifestyle-induced health EFfects In Children and infants 17
IDEFICS: 31 partner 11 országból Belgium Cyprus Estonia Hungary Germany Italy Spain Sweden Ghent Strovolos Tallin Pécs Bremen Avellino Zaragoza Gothenburg 18
IDEFICS tanulmány struktúrája Intervention T0 survey: 2007/08 sch yr 16 228 children T1 survey: 2009/10 sch yr 13 795 children T2 survey: 2010 autumn 10 268 children 19
IDEFICS kohorsz 16228, 2-9 éves gyermeket vizsgáltak az alap-felmérésben További 2517, 2-10.9 éves gyermek kerult bevonásra a második felmérés során Így a végleges csoport legnagyobb létszáma 18169 gyermek volt Az alábbiakban ismertetett analízisek elemszáma varábilis volt, tekintettel arra, hogy a szülők és a gyermekek szabadon választhattak, mely vizsgálati modulban vesznek részt 20
IDEFICS eredmények A MS egyes komponenseire vonatkozó európai standardok kerültek kialakításra 21
Chittaranjan S Yajnik, and John S Yudkin: The Y-Y paradox The two authors share a near identical body-mass index (BMI), but as dual X-ray absorptiometry imagery shows that is where the similarity ends. The first author (figure, right) has substantially more body fat than the second author (figure, left). Lifestyle may be relevant: the second author runs marathons whereas the first author's main exercise is running to beat the closing doors of the elevator in the hospital every morning. The contribution of genes to such adiposity is yet to be determined, although the possible relevance of intrauterine under-nutrition is supported by the first author's low birthweight. The image is a useful reminder of the limitations of BMI as a measure of adiposity across populations. 22
Brit vs. IDEFICS/Europai percentilisek 2. 205 9.2 59. 51. 54. 329 52.0 54.9 59.2 51.3 53.9 59.5 9.5 HD McCarthy1*, KV Jarrett1 and HF Crawley: The development of waist circumference percentiles in British children aged 5.0 ± 16.9 y. European Journal of Clinical Nutrition (2001) 55, 902 907 23
US vs. IDEFICS percentilisek (fiúk; 50 percentilis, életkor 5,7,10 év) 52.8 vs. 52.0 56.4 vs. 54.9 Cook, Auinger, Huang,: Growth Curves for Cardio-Metabolic Risk Factors in Children and Adolescents. J Pediatr. 2009 September ; 155(3): S6.e15 S6.e26. doi:10.1016/j.jpeds.2009.04.051. 63.3 vs. 59.2 24
Waist circumference (cm) Waist circumference (cm) Különböző refrencia standardok a derékkörfogatra (90 percentilis értékek) 110 100 Girls 110 100 Boys 90 80 70 60 US UK Spain Canada Adults 90 80 70 60 US UK Spain Canada Adults 50 50 40 2 4 6 8 10 12 14 16 18 40 2 4 6 8 10 12 14 16 18 Age (years) Age (years) Luis A. Moreno Aznar lmoreno@unizar.es GENUD Research Brambilla Group P et al. Int Universidad J Obes 2007; de 31: Zaragoza 591-600
Csípő körfogat percentilis görbéi normál súlyú európai fiúkban és lányokban 26
Csípő-magasság hányados girls boys Age Age 27 Int J Obes (2014) 38, S15 S25; doi:10.1038/ijo.2014.131
28 Plazma inzulin
HOMA-IR index Reference limit for adults: < 2* 29 * Keskin et al.: Pediatrics. 2005 Apr;115(4)..
Plazma glukóz Reference limit for adults: 5.6 mmol/l (100 mg/dl)* 30 * Alberti et al.: Lancet. 2005 Sep 24-30;366(9491):1059-62.
HDL-koleszterin - lányok 0,68 mmol/l Percentile: 5 th 10 th 25 th 50 th 75 th 90 th 95 th 2-2.5y 22.3 26.4 33.2 40.7 48.5 56.4 61.4 2.5-3y 23.4 27.5 34.6 42.2 50.3 58.3 63.6 3-3.5y 24.4 28.7 35.9 43.8 52.0 60.3 65.6 3.5-4y 25.5 29.9 37.2 45.3 53.7 62.2 67.6 4-4.5y 26.5 31.0 38.5 46.7 55.3 64.0 69.6 4.5-5y 27.5 32.1 39.7 48.1 56.8 65.6 71.3 5-5.5y 28.4 33.0 40.8 49.3 58.2 67.1 72.8 5.5-6y 29.3 34.1 42.0 50.6 59.6 68.6 74.4 6-6.5y 30.2 35.0 43.0 51.7 60.8 70.0 75.8 6.5-7y 31.1 35.9 44.0 52.8 62.0 71.2 77.1 7-7.5y 31.8 36.7 44.8 53.7 62.9 72.1 78.1 7.5-8y 32.4 37.3 45.5 54.3 63.5 72.8 78.7 8-8.5y 32.9 37.7 45.9 54.7 63.9 73.1 79.0 8.5-9y 33.1 38.0 46.1 54.8 63.9 73.0 78.9 9-9.5y 33.3 38.1 46.1 54.7 63.7 72.7 78.5 9.5-10y 33.5 38.2 46.1 54.6 63.5 72.4 78.1 10-10.5y 33.6 38.3 46.0 54.4 63.2 71.9 77.6 10.5-10.9y 33.6 38.3 45.9 54.2 62.8 71.4 76.9 International Journal of Obesity (201438, S67 S75; doi:10.1038/ijo.2014.137 31 0,99 mmol/l
HDL-koleszterin fiúk 0,74 mmol/l Percentile: 5 th 10 th 25 th 50 th 75 th 90 th 95 th 2-2.5y 24.4 28.7 35.7 43.5 51.5 59.5 64.7 2.5-3y 25.4 29.7 37.0 44.8 53.0 61.2 66.5 3-3.5y 26.3 30.8 38.1 46.2 54.5 62.9 68.2 3.5-4y 27.3 31.8 39.3 47.5 56.0 64.4 69.8 4-4.5y 28.2 32.8 40.5 48.8 57.4 66.0 71.5 4.5-5y 29.2 33.8 41.6 50.0 58.8 67.5 73.1 5-5.5y 30.1 34.8 42.7 51.2 60.1 68.9 74.6 5.5-6y 31.0 35.8 43.8 52.5 61.4 70.4 76.1 6-6.5y 31.9 36.8 44.9 53.6 62.7 71.7 77.5 6.5-7y 32.7 37.6 45.8 54.6 63.7 72.8 78.6 7-7.5y 33.4 38.3 46.4 55.3 64.4 73.5 79.3 7.5-8y 33.9 38.8 46.9 55.7 64.8 73.9 79.7 8-8.5y 34.2 39.1 47.2 55.9 65.0 74.0 79.7 8.5-9y 34.5 39.3 47.3 56.0 65.0 73.9 79.6 9-9.5y 34.7 39.5 47.5 56.1 65.0 73.8 79.4 9.5-10y 35.0 39.8 47.7 56.2 65.1 73.8 79.4 10-10.5y 35.4 40.2 48.0 56.5 65.2 73.9 79.5 10.5-10.9y 35.8 40.6 48.4 56.8 65.5 74.2 79.7 32 1,05 mmol/l
A vizsgált gyermekkori MS definíciók Definition Cook et al. Viner et al. IDF* Excess adiposity WC 90 th percentile BMI 95 th percentile WC 90 th percentile Blood pressure Blood lipids Blood glucose/ insulin SBP or DBP 90 th percentile SBP 95 th percentile SBP 130 mmhg or DBP 85 mmhg Triacylglycerols 110 mg/dl or HDL cholesterol 40 mg/dl Triacylglycerols 150 mg/dl or HDL cholesterol <35 mg/dl or High total cholesterol 95 th percentile Triacylglycerols 150 mg/dl or HDL cholesterol 40 mg/dl Impaired fasting glucose 110 mg/dl Hyperinsulinemia 15 mu/l or Impaired fasting glucose 110 mg/dl Impaired fasting glucose 110 mg/dl Cook S et al.. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988 1994. Arch Pediatr Adolesc Med 2003; 157: 821-827. Viner RM et al.. Prevalence of the insulin resistance syndrome in obesity. Arch Dis Child 2005; 90: 10-14. Zimmet P et al.; IDF Consensus Group: The metabolic syndrome in children and adolescents an IDF consensus report. Pediatr Diabetes 2007; 8: 299-306. *IDF=International Diabetes Federation
Az egyes komponensek fontosága (súlya) a különböző definíciók szerint 30% 25% Cook et al. 32 20% 15% Girls Boys 10% 5% 0% WC BP Lipids Glucose MetS Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Az egyes komponensek fontosága (súlya) a különböző definíciók szerint 30% 25% Viner et al. 33 20% 15% Girls Boys 10% 5% 0% BMI BP Lipids Glucose MetS Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Az egyes komponensek fontosága (súlya) a különböző definíciók szerint 30% 25% IDF 34 20% 15% Girls Boys 10% 5% 0% WC BP Lipids Glucose MetS Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
IDEFICS által javasolt új meghatározás Definition Cook et al. Viner et al. IDF* Excess adiposity WC 90 th percentile BMI 95 th percentile WC 90 th percentile IDEFICSmonitoring percentile WC 90 th level IDEFICSaction level WC 95 th percentile Blood pressure Blood lipids Blood glucose/ insulin SBP or DBP 90 th percentile SBP 95 th percentile SBP 130 mmhg or DBP 85 mmhg SBP 90 th percentile or DBP 90 th percentile SBP 95 th percentile or DBP 95 th percentile Triacylglycerols 110 mg/dl or HDL cholesterol 40 mg/dl Triacylglycerols 150 mg/dl or HDL cholesterol <35 mg/dl or High total cholesterol 95 th percentile Triacylglycerols 150 mg/dl or HDL cholesterol 40 mg/dl Triacylglycerols 90 th percentile or HDL cholesterol 10 th percentile Triacylglycerols 95 th percentile or HDL cholesterol 5 th percentile Impaired fasting glucose 110 mg/dl Hyperinsulinemia 15 mu/l or Impaired fasting glucose 110 mg/dl Impaired fasting glucose 110 mg/dl HOMA-insulin resistance 90 th percentile or Fasting glucose 90 th percentile HOMA-insulin resistance 95 th percentile or Fasting glucose 95 th percentile *IDF=International Diabetes Federation
Az egyes komponensek fontosága (súlya) az IDEFICS meghatározás szerint 30% IDEFICS-monitoring level 25% 20% 15% Girls Boys 10% 5% 0% WC BP Lipids Glucose MetS Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Az egyes komponensek fontosága (súlya) az IDEFICS meghatározás szerint 30% 25% IDEFICS-action level 20% 15% Girls Boys 10% 5% 0% WC BP Lipids Glucose MetS Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Male MS gyakorisága az IDEFICS populációban IDEFICS action IDEFICS monitoring level level No MetS MetS No MetS MetS N % N % N % N % Normal/thin 4882 98,4 77 1,6 4948 99,8 11 0,2 Overweight 654 86,4 103 13,6 729 96,3 28 3,7 Obese 325 70,3 137 29,7 408 88,3 54 11,7 Total 5861 94,9 317 5,1 6085 98,5 93 1,5 Female Normal/thin 4687 98,6 67 1,4 4744 99,8 10 0,2 Overweight 768 85,5 130 14,5 851 94,8 47 5,2 Obese 326 66,7 163 33,3 417 85,3 72 14,7 Total 5781 94,1 360 5,9 6012 97,9 129 2,1 All Normal/thin 9569 98,5 144 1,5 9692 99,8 21 0,2 Overweight 1422 85,9 233 14,1 1580 95,5 75 4,5 Obese 651 68,5 300 31,5 825 86,8 126 13,2 Total 40 11 642 94,5 677 5,5 12 097 98,2 222 1,8
MS gyakorisága normál/sovány, túlsúlyos és elhízott gyermekekben 100% 80% 60% 40% 20% Obese Overweight Normal/ thin 0% MetS monitoring - MetS monitoring + MetS action - MetS action + 41 Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Folyamatos MS pontrendszer Continuous MetS score calculated according to Eisenmann as the sum of component z-scores: Adiposity: WC (waist circumference (cm)) Blood pressure: mean of SBP and DBP (systolic / diastolic blood pressure (mm Hg)) Blood lipids: mean of TRG and negative HDL (triglycerides / HDL cholesterol (mg/dl)) Insulin resistance: HOMA (homeostasis model assessment) MetS score = z WC + z SBP + z DBP 2 + z TRG z HDL 2 + z HOMA 42 Eisenmann JC. Cardiovasc Diabetol 2008; 7: 17 Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Négy példa a MS pontrendszerre Measured values Standardised residuals (z-scores) Subject Sex Age WC SBP DBP TRG HDL HOMA z WC z SBP z DBP z TRG z HDL z HOMA MetS score 1 M 6.5 59.5 109.0 67.5 48 38 0.65 1.66 0.85 0.72 0.29-1.22-0.15 3.05 2 F 5.8 60.4 92.0 52.5 50 52 1.59 2.20-0.96-1.77 0.17 0.10 1.39 2.26 3 F 5.2 53.0 94.0 58.0 45 61 1.00 0.58-0.51-0.81-0.73 0.88 0.68-0.07 4 M 5.5 57.5 99.0 66.0 78 45 0.99 1.64-0.13 0.59 1.15-0.54 0.71 3.43 43 Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
MS pontszám kor-specifikus referencia görbéi lányokban és fiúkban 44 Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Konklúzió Nemre és életkorra specifikus standardokat dolgoztunk ki a kardiometabolikus rizikófaktorokra 11 évnél fiatalabb gyermekek részére Új MS definícót javasoltunk, mely segítheti a klinikai döntést Megjegyzés: A javasolt határértékek statisztikai alapúak és nincsenek kapcsolatban a későbbi betegségek, szövődmények (infarktus, hipertónia, stb.) rizikójával. Folyamatos MS pontrendszer is kidolgozásra került mely elősegítheti a rizikóbecslést és a követéses vizsgálatok értékelését. A bemutatott eredmények az Int J Obes 2014, Suppl2-ben megjelent publikációkon alapulnak
Quo vadis METS? A tradicionális markerek mellett új komponenseket is be kell vonni a MS definíciójába? Oxidatív stressz indikátorok Alacsony szintű, krónikus gyulladás indikátorai Adipokinek Cytokinek Microalbuminuria? 46
Az IDEFICS Konzorcium 47 47
Previous achievements 48
BMI (kg/m2) International Obesity Task Force (IOTF) body mass index cut-offs for overweight and obesity in youth BMI (kg/m2) 32 Girls 32 Boys 30 30 28 28 26 24 22 25 30 26 24 22 25 30 20 20 18 18 16 0 2 4 6 8 10 12 14 16 18 20 16 0 2 4 6 8 10 12 14 16 18 20 Age (years) Age (years) Luis A. Moreno Aznar lmoreno@unizar.es GENUD Research (Cole Group TJ et al. BMJ Universidad 2000; 320: de 1240-1243) Zaragoza
Table 1. Names given to the clustering of metabolic syndrome disorders Terms Hypertension-hyperglycaemia-hyperuricaemia Kylin, 1923 syndrome (Hypertoni-Hyperglycemi-Hyperurikemi syndrom) Metabolic trisyndrome (trisyndrome Camus, 1966 metabolique) Plurimetabolic syndrome Avogaro and Crepaldi, 1967 Syndrome of affluence (wohlstandssyndrom) Mehnert and Kuhlmann, 1968 Metabolic syndrome (metabolische syndrom) Hanefeld and Leonhardt, 1981 Syndrome X Reaven, 1988 Deadly quartet Kaplan, 1989 Insulin resistance syndrome DeFronzo and Ferrannini, 199; Haffner, 1992 50
Lipoprotein metabolism Lusis AJ et al. Circulation 2004; 110: 1868-1873
Natural history of type 2 diabetes Obesity Diet Sedentary lifestyle Genetics Perinatal factors Insulin sensitive Insulin resistance Compensatory hyperinsulinaemia NORMOGLYCEMIA b-cell decompensation Relative insulin deficiency POSTPRANDIAL HYPERGLYCEMIA IMPAIRED FASTING GLUCOSE b-cell failure DIABETES MELLITUS Vascular complications Ludwig & Ebbeling. JAMA 2001; 286: 1427-1430
Insulin resistance Homeostatic model assessment (HOMA): the product of the fasting plasma insulin level (mu/ml) and the fasting plasma glucose level (mmol/l), divided by 22.5. Lower insulin-resistance values indicate a higher insulin sensitivity, whereas higher values indicate a lower insulin sensitivity.
Metabolic syndrome in children Cardiovascular risk factors tend to cluster Webber LS et al. Prev Med 1979; 8: 407-418 Chu NF et al. Am J Clin Nutr 1998; 67: 1141-1146. 8.9 % of obese children have the metabolic syndrome Csábi G et al. Eur J Pediatr 2000; 159: 91-94. Factor analysis of metabolic syndrome components show 2-4 factors Chen W et al. Am J Epidemiol 1999; 150: 667-674 Moreno LA et al. Horm Metab Res 2002; 34: 394-399
Definition of MS. Criteria Golley Int J Obes 30:853-60, 2006 Age Definition 55 (EGIR) hyperinsulinem ia + 2 or more Waist cc Male: 94, Female:80 (NCEP) >=3 Male: 94, Female:80 6-9 (overweight, obese) (WHO) hyperinsuline mia + 2 or more (WHO) hyperinsuline mia + 2 or more (EGIR) hyperinsulin emia + 2 or more (NCEP) >=3 - - >=91 th pc >=91 th pc BMI - - >=85 th pc >=85 th pc - - RR SBP: >140 SBP: >130 >= 95 th pc for height Glucose fasting 6.1 mmol/l 6.1 mmol/l 6.1-7.9 mmol/l >= 95 th pc for height 6.1-7.9 mmol/l >= 95 th pc for height 6.1-7.9 mmol/l Total chol - - - - - - >= 95 th pc for height 6.1-7.9 mmol/l HDL-chol 1 mmol/l 1 mmol/l 1.2 mmol/l 0.8 mmol/l 0.8 mmol/l 0.8 mmol/l LDL-chol - - - - - - Triglyceride 2 mmol/l 1.7 mmol/l M: 0.9, F: 1 mmol/l 1.8 mmol/l 1.8 mmol/l 1.8 mmol/l Prevalence 4 0 59 39 39 3
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Increasing stiffness Number of MetS risk variables and elasticity of common carotid artery Bogalusa Study Ep = Peterson's elastic modulus YEM = relative wall thickness-adjusted Young's elastic modulus Urbina EM et al. Atherosclerosis 2004; 176: 157-164
Prevalence of MetS in normal weight/ thin, overweight and obese children 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% MetS monitoring - MetS monitoring + 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Normal/ thin Overweight Obese MetS action - MetS action + Normal/ thin Overweight Obese MetS monitoring level = 5.5% MetS action level = 1.8% 58 Ahrens W & Moreno LA et al. Int J Obes 2014; 38: S4-S14
Correlation between waist circumference and visceral fat assessed by magnetic resonance imaging VAT (cm2) 160 140 120 Y = 1.1*X - 52.9 R2 = 0.64, p < 0.0001 RMSE = 14 cm2 (33%) 100 80 60 40 20 0 0 40 80 120 160 WC (cm) Luis A. Moreno Aznar lmoreno@unizar.es GENUD Research Group Universidad de Zaragoza Brambilla P, Bedogni G, Moreno LA et al. Int J Obes 2006; 30: 23-30