Randomized Controlled Trial to Improve Adiposity, Inflammation, and Insulin Resistance in Obese African-American and Latino Youth

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1 nture publishing group rticles Rndomized Controlled Tril to Improve Adiposity, Inflmmtion, nd Insulin Resistnce in Obese -Americn nd Ltino Youth Rebecc E. Hsson 1, Tnj C. Adm 1, Jimie N. Dvis 1, Louise A. Kelly 2, Emily E. Ventur 1, Courtney E. Byrd-Willims 3, Cludi M. Toledo-Corrl 1, Christin K. Roberts 4, Christinne J. Lne 1, Stnley P. Azen 1, Chih-Ping Chou 1, Donn Spruijt-Metz 1, Mrk J. Weigensberg 1,5, Kiros Berhne 1 nd Michel I. Gorn 1,5 The purpose of this study ws to exmine ethnic differences in the metbolic responses to 16-week intervention designed to improve insulin sensitivity (SI), diposity, nd inflmmtion in obese -Americn nd Ltino dolescents. A totl of 100 prticipnts ( : n = 48, Ltino: n = 52; ge: 15.4 ± 1.1 yers, BMI percentile: 97.3 ± 3.3) were rndomly ssigned to interventions: control (C; n = 30), nutrition (N; n = 39, 1 /week focused on decresing sugr nd incresing fiber intke), or nutrition + strength trining (N+ST; n = 31, 2 /week). The following were mesured t pre- nd postintervention: strength, dietry intke, body composition (dulenergy X-ry bsorptiometry/mgnetic resonnce imging) nd glucose/insulin indexes (orl glucose tolernce test (OGTT)/intrvenous glucose tolernce test (IVGTT)) nd inflmmtory mrkers. Overll, N compred to C nd N+ST reported significnt improvements in SI (+16.5% vs. 32.3% vs. 6.9% respectively, P < 0.01) nd disposition index (DI: +15.5% vs. 14.2% vs. 13.7% respectively, P < 0.01). N+ST compred to C nd N reported significnt reductions in heptic ft frction (HFF: 27.3% vs. 4.3% vs. 0% respectively, P < 0.01). Compred to N, N+ST reported reductions in plsminogen ctivtor inhibitor-1 (PAI-1) ( 38.3% vs. +1.0%, P < 0.01) nd resistin ( 18.7% vs %, P = 0.02). There were no intervention effects for ll other mesures of diposity or inflmmtion. Significnt intervention by ethnicity interctions were found for in the N group who reported increses in totl ft mss, 2-h glucose nd glucose incrementl res under the curve (IAUC) compred to (P s < 0.05). These interventions yielded differentil effects with N reporting fvorble improvements in SI nd DI nd N+ST reporting mrked reductions in HFF nd inflmmtion. Both ethnic groups hd significnt improvements in metbolic helth; however some improvements were not seen in. Obesity (2012) 20, doi: /oby Introduction Impired fsting glucose nd future risk of type 2 dibetes hve emerged s significnt helth issues in obese -Americn nd Ltino youth (1). The highest rtes of peditric type 2 dibetes re documented mong 15- to 19-yer-old ethnic minority dolescents (1). This ethnic disprity in dibetes risk my result from greter rtes of obesity, low-grde inflmmtion nd insulin resistnce in -Americn nd Ltino youth reltive to non-ltino whites (2,3). Intervention strtegies tht trget eting behvior nd physicl ctivity my be effective wys of reducing metbolic risk fctors for type 2 dibetes in minority youth. Our group recently completed 16-week intervention in obese -Americn nd Ltino dolescents tht ssessed the incrementl effects of the following three intervention groups on reducing diposity, low-grde inflmmtion, nd improving insulin sensitivity (SI): (i) control; (ii) once per week modified crbohydrte nutrition eduction progrm tht focused on decresing sugr intke nd incresing fiber intke; nd (iii) sme nutrition eduction progrm with twice per week strength trining (4). In the Ltino prticipnts, there were significnt improvements in the glycemic response to orl glucose, with significnt decreses in 1 Deprtment of Preventive Medicine, Keck School of Medicine, University of Southern Cliforni, Los Angeles, Cliforni, USA; 2 Deprtment of Exercise Science, Cliforni Luthern University, Thousnd Oks, Cliforni, USA; 3 Michel & Susn Dell Center for Helth Living, University of Texs School of Public Helth, Austin, Texs, USA; 4 Progrm on Genomics nd Nutrition, Deprtment of Epidemiology, University of Cliforni, Los Angeles, Cliforni, USA; 5 Deprtment of Peditrics, Keck School of Medicine, University of Southern Cliforni, Los Angeles, Cliforni, USA. Correspondence: Michel I. Gorn (gorn@usc.edu) Received 14 My 2010; ccepted 15 December 2010; published online 3 Februry doi: /oby obesity VOLUME 20 NUMBER 4 pril

2 orl glucose response by 18% nd 6% in the nutrition (N) nd nutrition with strength trining (N+ST) groups respectively, compred with 32% increse in the control group (C) (4). Bseline comprisons between the -Americn nd Ltino prticipnts showed distinct differences in obesityrelted metbolic risk fctors by ethnicity. Specificlly, hd higher volumes of subcutneous ft nd tended to hve lower volumes of viscerl ft nd heptic ft frction compred to Ltino dolescents (5). Dt from the intrvenous glucose tolernce test (IVGTT) demonstrted tht - Americn dolescents were more insulin resistnt compred to Ltino dolescents nd this difference ws independent of totl ft mss s well s viscerl ft mss (5). As result of this lower SI, -Americn dolescents hd compenstory higher cute insulin response to glucose (AIR), which further excerbted their inherently higher AIR responses to glucose (5). However, β-cell function (s reflected by greter disposition index (DI)) ws enhnced in compred to, resulting in greter glucose tolernce s mesured by n orl glucose tolernce test (OGTT). Given these ethnic differences previously reported in diposity nd insulin ction between -Americn nd Ltino dolescents (5), we were interested in ssessing whether these two ethnic groups would respond similrly to rndomized controlled tril intervention. Therefore, the purpose of this study ws to exmine ethnic differences in the metbolic responses to 16-week intervention designed to reduce diposity nd low-grde inflmmtion s well s improve SI in obese -Americn nd Ltino dolescents. It ws hypothesized tht chnges in crbohydrte qulity long with strength gins in the N+ST group would produce the lrgest improvements in diposity, low-grde inflmmtion nd SI compred to the C nd N groups. Becuse our -Americn prticipnts were more insulin resistnt with greter volumes of subcutneous ft compred to Ltino prticipnts t the strt of the intervention, we hypothesized tht would demonstrte greter improvement in metbolic helth (i.e., SI, diposity, nd inflmmtion) compred to their Ltino counterprts. Methods nd Procedures Prticipnt chrcteristics, description of intervention, nd generl procedures used in this study hve been previously reported (4,5), however the most relevnt informtion is described below. Prticipnts One hundred obese, but otherwise helthy -Americn (n = 48) nd Ltino (n = 52) boys nd girls volunteered to prticipte in this study. Prticipnts nd prents were provided with full description of the study nd ll prticipnts signed n informed ssent document while consent ws obtined from their prents. The University institutionl review bord pproved this study. Pretesting visit t the Generl Clinicl Reserch Center (GCRC) Outptient visit. Prticipnts rrived t the GCRC t 7:30 m fter n overnight fst to complete detiled medicl history nd physicl exm where Tnner stging (6,7) ws determined s well s weight nd height mesured to clculte BMI nd BMI percentiles (8). Totl ft mss nd totl len mss were mesured by dul energy X-ry bsorptiometry using Hologic QDR 4500W (Hologic, Bedford, MA). Abdominl ft (viscerl, subcutneous, nd heptic ft frction (HFF)) were ssessed by mgnetic resonnce imging using Generl Electric 1.5-Tesl mgnet (GE Helthcre, Wukesh, WI). Multiple-slice xil TR 400/16 view of the bdomen t the level of the umbilicus ws nlyzed for cross-sectionl re of dipose tissue. The stndrd body trnsmit nd receive coil ws used, long with rectngulr field-of-view of 420 mm (right/left) by 315 mm (nterior/posterior). The slice thickness ws 10 mm with no inter-slice gps. The ft-only dt set ws used in the subsequent quntifiction of subcutneous nd viscerl dipose tissue volume, while the ft frction dt set ws used to ssess percent heptic ft content. A commercilly vilble imge segmenttion nd quntifiction softwre (SliceOmtic, Tomovision, Mgog, Quebec) ws used. Subcutneous nd viscerl volumes were computed cross ll 19 imge slices in ech prticipnt. Heptic ft frction ws computed s the men ft frction in ll imging slices within which the liver ws present. Following the exm, 3-h OGTT ws conducted (4,5). In-ptient visit. Approximtely 7 14 dys following the outptient visit, prticipnts were dmitted to the GCRC in the evening hours nd served stndrdized dinner nd evening snck. After 12-h fst, prticipnts completed n IVGTT the following morning (4,5). Rndomiztion All eligible prticipnts were rndomized to one of three groups: (i) control group, (ii) once per week modified crbohydrte nutrition eduction progrm, nd (iii) sme nutrition eduction progrm with twice per week strength trining. Within ech ethnicity, rndomiztion ws blocked by sex to chieve blnce in rndomiztion between sexes. A detiled description of the interventions employed in the present study hve been previously reported (4,5). Dietry intke nd strength ssessment During the outptient visit both before nd fter the intervention, prticipnts were given 3-dy dietry records to complete t home. During the in-ptient visit, prticipnts were instructed to bring their completed dietry records to be reviewed nd clrified by reserch stff, who were trined nd supervised by registered dietitin. Nutrition dt were nlyzed using the Nutrition Dt System for Reserch (NDS-R ver 5.0_35). Using estblished procedures (9), upper- nd lower-body strength ssessments were completed before nd fter the intervention by onerepetition mximum in the bench press nd leg press, respectively. Post-testing procedures At the conclusion of the 16-week control/intervention period, prticipnts returned to the GCRC for follow-up testing. The procedures were identicl to those conducted t the pretest visits. Assys Assys for glucose nd insulin blood smples hve been previously reported (4,5). Inflmmtory mrkers mesured during the IVGTT including: interleukin-8, leptin, tumor necrosis fctor-α, monocyte chemotctic protein-1, heptocyte growth fctor, nerve growth fctor, diponectin, plsminogen ctivtor inhibitor (PAI)-1, nd resistin were ssyed in duplicte using specific humn insulin enzyme-linked immunosorbent ssy kit from Linco (St Chrles, MO). Outcome mesures Fsting nd 2-h OGTT glucose concentrtions were used to determine norml or impired glucose tolernce s defined by the Americn Dibetes Assocition (10). Three-hour glucose nd insulin incrementl res under the curve (IAUC) were clculted from the OGTT dt, in nmol/l/min. Plsm collected during the IVGTT ws nlyzed for glucose nd insulin, nd concentrtions were entered into the MINMOD Millenium 2003 computer progrm (Ver 6.02, Bergmn, University of Southern Cliforni, Los Angeles, CA) to determine SI, AIR, DI, nd glucose effectiveness. 812 VOLUME 20 NUMBER 4 pril

3 Sttisticl nlysis Across-group comprisons of bseline chrcteristics were conducted for evluble prticipnts using ANOVA to identify possible rndomiztion imblnce. Student s t-tests nd χ 2 tests were used to compre ethnic differences in continuous nd ctegoricl vribles t bseline. An nlysis of covrince (ANCOVA) ws used to compre ethnic differences in SI nd mrkers of inflmmtion t bseline, fter controlling for preplnned covrites. The min effects nd interctions of intervention groups nd ethnicity were ssessed using two-wy ANCOVA on the chnge score (post-pre), fter controlling for pretest vlues nd preplnned covrites. Covrites included Tnner stge, sex, totl ft mss, nd totl len mss. Chnge scores were evluted for normlity nd log trnsformtions were mde when needed. When significnt differences cross intervention group were identified, post hoc pirwise comprisons with Bonferroni djustments were conducted. Residul nlyses were performed for ll min outcome vribles to test for ssumption of normlity nd subsequent outliers greter thn two stndrd devitions (n = 2) were removed from the nlyses. For ll nlyses, α < Results Consort digrm for the -Americn nd Ltino prticipnts is presented in Figure 1. Of the 212 potentil prticipnts (ged yers) who were vilble for consenting, 126 qulified prticipnts were rndomized to one of the three groups. Of these 102 completed the intervention but becuse two Ltino prticipnts were identified s outliers (insulin Outlier N = 1 (1 LA) Control N = 59 Control N = 42 (19 AA/22 LA) Post-test N = 30 (15 AA/15 LA) Were not interested/ did not qulify N = 687 Not interested N = 44 Dropped before pretest N = 29 Did not qulify N = 13 Dropped before end of pretesting N = 2 Dropped out N = 11 (4 AA/6 LA) Invited to prticipte N = 899 Avilble for consenting N = 212 Prescreen & consented N = 168 Dropped out N = 2 (1 AA/1LA) Nutrition N = 50 OGTT visit N = 139 Qulified N = 126 Nutrition N = 42 (19 AA/ 22 LA) Post-test N = 39 (18 AA/21 LA) Nutrition + Strength Trining N = 59 Nutrition + strength trining N = 42 (20 AA/22 LA) Outlier N = 1 (1 LA) Post-test N = 31 (15 AA/16 LA) Dropped out N =11 (5 AA/ 5 LA) Figure 1 Consort digrm of prticipnt flow for -Americn (n = 48) nd Ltino (n = 52) prticipnts. OGTT, orl glucose tolernce test. prmeters were >2 s.d. bove the men), they were removed from the nlysis. Hence, the evluble cohort consisted of 100 prticipnts, (, n = 48;, n = 52). There were no sttisticlly significnt differences in bseline demogrphics, nthropometrics, or body composition mesures between the 24 prticipnts who dropped out of the progrm nd the 100 prticipnts who completed the progrm. Evluble prticipnts (n = 100) included 30 in the C group, 39 in the N group, nd 31 in the N+ST group. Prticipnt chrcteristics t bseline The overll men ge of prticipnts (n = 100) ws 15.4 ± 1.1 yers nd the men Tnner stge ws 4.5 ± 0.8 with 41% of the prticipnts mle (Tble 1). Similr to previous findings (5), -Americn prticipnts hd significntly greter volumes of subcutneous ft (P < 0.01) s well s lower volumes of viscerl ft (P = 0.07) nd HFF (P = 0.02) compred to Ltino prticipnts. Furthermore, hd significntly lower SI derived from the IVGTT (P < 0.01) nd mrkers of inflmmtion (P < 0.05; with the exception of dipo nectin) compred to their Ltino counterprts. When compring the intervention groups within ech group, there were no significnt differences in ny of the bseline chrcteristics (dt not shown). Chnges in strength nd dietry vribles For the combined ethnic groups, there ws significnt intervention group effect for bench press (P < 0.01; dt not shown). The N+ST group hd greter increse in upper body strength compred to the N group (29.7% vs. 2.9%, P < 0.01). There ws lso significnt intervention group effect for leg press (P < 0.01). The N+ST group incresed lower body strength by 24.1% compred to 9.4% nd 2.7% increse in the C nd N group, respectively. In ddition, there ws significnt intervention by ethnicity interction with -Americn prticipnts demonstrting smller increse in lower body strength compred to Ltino prticipnts (21.0% vs. 26.2%, P < 0.01, Tble 2). For the combined ethnic groups, there ws significnt intervention group effect for totl energy intke (P < 0.01; dt not shown). The N nd N+ST groups decresed their energy intke by 9.2% nd 13.7%, respectively, compred to 15.7% increse in the C group. There ws lso significnt intervention group effect for crbohydrte intke (P = 0.02). The N+ST group decresed crbohydrte intke by 13.0% compred to 6.7% decrese in the N group nd 17.2% increse in the C group. In ddition, there ws lso significnt intervention group effect for dded sugr intke (P = 0.04). The N nd N+ST groups decresed dded sugr intke by 26.0% nd 32.5% respectively, compred to 1.3% increse in the C group. Furthermore, there ws trend towrd decresed totl sugr intke in the N nd N+ST group (19.6% nd 15.9%, respectively) compred to n increse in the C group (4.6%, P = 0.09). There were no significnt intervention group effects for dietry protein, ft, or fiber intke. There were lso no significnt intervention by ethnicity interctions for chnges in dietry vribles. obesity VOLUME 20 NUMBER 4 pril

4 Tble 1 Prticipnt chrcteristics t bseline (n = 48) (n = 52) P vlue Tnner stge 4.6 ± ± Tnner stge, n (%) 1 1 (2.1) 0 (0.0) 2 0 (0.0) 1 (1.9) 3 5 (10.4) 4 (7.7) 4 15 (31.3) 6 (11.5) 5 31 (64.6) 37 (71.2) Gender, n femle (%) 34 (70.8) 27 (48.1) 0.03 Age (yers) 15.3 ± ± Weight (kg) ± ± BMI (kg/m 2 ) 36.0 ± ± BMI Z-score 2.2 ± ± BMI percentile 97.8 ± ± Ft-free mss (kg) 55.6 ± ± Ft mss (kg) 35.7 ± ± Subcutneous diposity (liters) 15.2 ± ± 4.0 <0.01 Viscerl diposity (liters) 1.3 ± ± Heptic ft frction (%) 4.1 ± ± 1.5 <0.01 Insulin sensitivity ( 10 4 min 1 /µu/ml) 1.2 ± ± IL-8 (pg/ml) 2.6 ± ± Leptin (ng/ml) 66.2 ± ± 3.8 <0.05 TNF-α (pg/ml) 6.4 ± ±1.1 <0.01 MCP-1 (pg/ml) ± ± 19.9 <0.01 HGF (pg/ml) ± ,388.4 ± NGF (µg/ml) 7.1 ± ± 1.5 <0.01 Adiponectin (µg/ml) 17.2 ± ± PAI-1 (µg/ml) 61.6 ± ± 9.8 <0.01 Resistin (µg/ml) 27.0 ± ± 3.8 <0.01 Dt re presented s men ± s.d. Boldfce vlues represent significnt difference by ethnicity (P < 0.05). HGF, heptocyte growth fctor, IL-8, interleukin-8; MCP-1, monocyte chemotctic protein; NGF, nerve growth fctor; PAI-1, plsminogen ctivtor inhibitor; TNF-α, tumor necrosis fctor-α. Chnges in nthropometry nd body composition For the combined ethnic groups, there ws significnt intervention group effect for HFF (P < 0.01, Figure 2). The N+ST group hd 27.3% decrese in HFF compred to 4.3% decrese in the C group nd no chnge in the N group. There were no significnt intervention group differences for BMI, BMI z-score, BMI percentile, or body weight, totl len mss, subcutneous nd viscerl ft. There ws however significnt intervention group by ethnicity interction for chnge in totl ft mss with in the N group demonstrting greter increse in totl ft mss compred to (+6.4% vs. 1.1%, P = 0.03, dt not shown). Chnges in glucose nd insulin indexes For the combined ethnic groups, there ws significnt intervention group effect for SI (P < 0.01, Figure 3). The N group incresed by 16.5% compred to the N+ST nd C group, which decresed by 6.9% nd 32.3%, respectively. Subsequently, there ws lso significnt intervention group effect for DI (P < 0.01). The N group incresed by 15.5% compred to the N+ST nd C groups, which decresed by 13.7% nd 14.2%, respectively (Figure 3). There were no significnt intervention group effects for fsting nd 2-h glucose nd insulin, glucose nd insulin IAUC mesured by the OGTT, or for AIR nd glucose effectiveness mesured by the IVGTT. There were significnt group by ethnicity interctions for 2-h glucose (P < 0.01) nd glucose IAUC (P = 0.02, Tble 3). In the N group, -Americn prticipnts hd significnt increses in 2-h glucose (7.1% vs. 14.5%, P < 0.01) nd glucose IAUC derived from the OGTT (14.5% vs. 20.4%, P = 0.02), compred to decreses in Ltino prticipnts. In the N+ST group, there ws trend for AIR to decrese in compred to (18.0% vs. 2.9%, respectively, P = 0.05). Chnges in mrkers of inflmmtion For the combined ethnic groups, there ws significnt intervention group effect for PAI-1 (P < 0.01, Figure 4). The N+ST group decresed by 38.3% compred to the N group, which incresed by 1.0%. There ws lso significnt intervention group effect for resistin (P = 0.02). The N+ST group decresed by 18.7% compred to the N group, which incresed by 11.3% (Figure 4). There were no other significnt intervention group effects for ny other mrkers of inflmmtion. There ws significnt intervention group by ethnicity interction for nerve growth fctor (P < 0.01, Tble 4). Specificlly, in the N+ST group hd significnt decrese in nerve growth fctor compred to n increse in ( 14.9% vs %). Discussion The primry purpose of this study ws to exmine ethnic differences in the metbolic responses to 16-week intervention designed to reduce diposity nd low-grde inflmmtion nd improve SI in obese -Americn nd Ltino dolescents. We hypothesized tht chnges in crbohydrte qulity long with strength gins in the N+ST group would produce the lrgest improvements in diposity, inflmmtion, nd insulin ction compred to the C nd N groups. Becuse our - Americn cohort ws more insulin resistnt with greter volumes of subcutneous ft (5), we lso hypothesized tht the -Americn dolescents would hve greter improvement in metbolic helth compred to Ltino dolescents. Our findings demonstrte tht this intervention hd differentil outcomes, with the N group demonstrting significnt improvements in SI nd β-cell function, while the N+ST group exhibited mrked reductions in HFF nd mrkers of inflmmtion. These improvements were reported in both - Americn nd Ltino dolescents, however ethnic differences 814 VOLUME 20 NUMBER 4 pril

5 Tble 2 Strength nd dietry outcomes: intervention group effects for evluble prticipnts (n = 100) Outcomes Strength Control (C) (N = 30) Nutrition eduction (N) (N = 39) (n = 18) (n = 21) Nutrition + strength trining (N+ST) (N = 31) (n = 16) Significnt effect b Bench press (lb) 9.6 (12.8) 11.7 (9.0) 5.9 (13.4) 0.5 (10.7) 28.3 (14.7)** 27.2 (14.4) ** I (< 0.01) Leg press (lb) 51.1 (107.6) 20.9 (299.1) 81.6 (70.3)* 36.4 (114.9)* 77.0 (80.2)*, ** (123.8)*, **, *** I (<0.01) I E (<0.01) Dietry Energy (kcl/d) 99.6 (710.5) (880.9) (605.9)* (459.5)* (760.6)* (587.0)* I (<0.01) Crbohydrte (g/d) 22.5 (81.8) 46.2 (130.6) 15.2 (106.6) 22.3 (94.7) 19.3 (103.8)* 38.3 (69.5)* I (0.02) Protein (g/d) 7.4 (33.9) 14.7 (31.6) 9.0 (40.1) 4.8 (20.3) 2.5 (33.7) 4.7 (22.1) Ft (g/d) 3.5 (35.4) 12.2 (35.6) 8.9 (27.8) 10.2 (20.5) 6.5 (37.5) 12.5 (27.5) Totl sugr (g/d) 9.3 (38.9) 11.4 (64.4) 31.6 (56.7) 10.1 (51.4) 18.4 (60.7) 13.3 (40.4) I (0.09) Added sugr (g/d) 9.7 (43.9) 4.3 (53.9) 19.3 (41.1)* 17.6 (51.5)* 26.6 (45.8)* 10.4 (40.9)* I (0.04) Fiber (g/1,000 kcl) 0.3 (7.0) 3.8 (7.5) 4.6 (14.4) 1.0 (9.5) 6.6 (10.1) 1.2 (9.9) Dt re undjusted chnge scores: men (s.d.). Smple sizes for dietry vribles re s follows: C (n = 28); N (n = 37); N+ST (n = 29). b P-vlues were clculted using two-wy ANCOVA. Covrites included: Tnner stge, sex, DEXA ft nd len tissue mss. Anlyses were bsed on log scores for the following vribles: bench press, leg press, crbohydrte, protein, ft, totl sugr, dded sugr, nd fiber. Men differences nd interctions cross intervention (I) nd ethnic (E) groups re significntly different from one nother using Bonferroni multiple comprisons (P < 0.05). *Denotes significntly different from C group t (P < 0.05). **Denotes significntly different from N group t (P < 0.05). ***Denotes significntly smller improvement in leg press in compred to t P < Chnge in heptic ft frction (%) C N N + ST Figure 2 Undjusted men ± s.e. chnge scores for heptic ft frction. C, control; N, nutrition eduction; N+ST, nutrition + strength trining. *Significntly different from C; Significntly different from N t P < were present in some of the metbolic responses to the interventions. Specificlly, in the nutrition intervention group, 2-h glucose concentrtions nd glucose IAUC during the OGTT s well s totl ft mss incresed in the -Americn cohort compred to generl improvements for these outcomes in the Ltino cohort. In the N+ST group however, experienced greter decreses in AIR, nerve growth fctor, nd PAI-1 compred to. To our knowledge this is one of the first studies to exmine ethnic differences in the metbolic responses to nutrition nd physicl ctivity intervention. Improvements in insulinemi nd glycemi in the N group Few intervention studies hve been conducted tht focus on reducing sugr nd incresing fiber intke however our findings re in greement with Ebbeling et l. (11) who reported tht low glycemic lod diet improved insulin resistnce compred to conventionl low-ft diet in 16 overweight dolescents (ged 13 21). In this study, reductions in dietry energy intke, nd more specificlly dded sugr intke resulted in significnt * Chnge in SI ( 10 4 min 1 /µu/ml) b Chnge in DI ( 10 4 min 1 ) 1.0 C N 0.5 * N + ST , Figure 3 Undjusted men ± s.e. chnge scores for () insulin sensitivity (SI) nd (b) disposition index (DI). C, control; N, nutrition eduction; N+ST, nutrition + strength trining. *Significntly different from C; Significntly different from N + ST t P < improvements in SI nd β-cell function. Specificlly, SI nd β-cell function improved by 16.5% nd 15.5%, respectively, in the N group. These glycemic improvements my be relted to the chnge in fiber-to-crbohydrte rtio noted in the N group only (12). Post hoc nlyses reported greter postintervention fiber-to-crbohydrte rtio in the N group compred to the C group (P = 0.05). This chnge ws not ssocited with improvements in 2-h glucose, glucose IAUC, AIR, DI, the improvement * obesity VOLUME 20 NUMBER 4 pril

6 Tble 3 Glucose nd insulin dynmics from orl glucose tolernce test (OGTT) nd frequently smpled intrvenous glucose tolernce test (FSIVGTT): intervention group effects for evluble prticipnts (n = 100) Outcomes Control (C) (N = 30) Nutrition eduction (N) (N = 39) (n = 18) (n = 21) Nutrition + strength trining (N+ST) (N = 31) (n = 16) Significnt effect b OGTT (3-h) Fsting glucose (mg/dl) 2.7 (3.6) 5.3 (6.6) 2.8 (5.9) 0.9 (7.6) 2.7 (4.8) 2.5 (4.8) 2 hglucose (mg/dl) 6.9 (22.3) 0.7 (20.0) 7.9 (13.6)*** 17.0 (26.1) 0.1 (22.7) 10.7 (23.6) I E (<0.01) Fsting insulin (µu/ml) 2.2 (6.3) 1.0 (13.7) 1.3 (7.5) 2.6 (7.1) 2.3 (6.9) 4.0 (8.6) 2-h Insulin (µu/ml) 1.2 (82.7) 35.1 (133.0) 21.8 (55.0) 80.9 (246.8) 34.9 (79.3) 34.1 (110.8) Glucose IAUC (nmol/min/l) 1.9 (36.1) 22.1 (41.5) 9.8 (31.5)*** 19.3 (35.8) 15.8 (29.0) 4.1 (37.9) I E (0.02) Insulin IAUC (nmol/min/l) 18.5 (148.6) 8.1 (156.5) 33.8 (184.4) 78.9 (127.2) 49.1 (100.4) 43.9 (137.3) HOMA 0.4 (1.7) 1.1 (1.8) 0.1 (1.4) 0.6 (1.9) 0.7 (1.5) 1.0 (1.9) FSIVGTT SI ( 10 4 min 1 /µu/ml) 0.4 (0.7) 0.4 (1.8) 0.1 (0.6)* 0.3 (1.3)* 0.0 (0.7) 0.2 (0.9) I (<0.01) AIR (µu/ml 10 min) (753.8) (1,433.5) (400.3) 29.4 (1,153.1) 96.8 (569.1) 40.4 (985.3) I E (0.05) DI ( 10 4 min 1 ) I (<0.01) (1,003.7) (1,344.3) (1,081.1)*, ** (1,090.5)*, ** (1,287.6) (1,271.9) SG (% per min) 0.0 (0.02) 0.0 (0.04) 0.0 (0.01) 0.0 (0.04) 0.0 (0.01) 0.0 (0.02) Dt re undjusted chnge scores: men (s.d.). b P-vlues were clculted using two-wy ANCOVA. Covrites included: Tnner stge, sex, DEXA ft nd len tissue mss. AIR included SI s covrite. While undjusted scores re reported here for ll vribles, nlyses were bsed on log scores for fsting insulin, 2-hr insulin, insulin IAUC, HOMA, SI, AIR, DI, nd SG. Mens differences nd interctions cross intervention (I) nd ethnic (E) groups re significntly different from one nother using Bonferroni multiple comprisons (P < 0.05). *Denotes significntly different from C group t (P < 0.05). **Denotes significntly different from N+ST group t (P < 0.05). ***Denotes significnt intervention by ethnicity interction t P < AIR, cute insulin response to glucose; DI, disposition index; HOMA, homeostsis model ssessment; IAUC, incrementl res under the curve; SG, glucose effectiveness; SI, insulin sensitivity. in SI ws no longer significnt when fiber-to-crbohydrte rtio ws included s covrite. Hence, the mintennce of fiber intke while reducing crbohydrte intke my hve medited the improvement in SI in the N group. Surprisingly, there were no significnt reductions in diposity in the N group however, it is possible tht the significnt reductions in totl cloric intke nd crbohydrte intke in this group were insufficient to reduce ft mss, prticulrly HFF. It is importnt to note tht the improvements in SI nd β-cell function previously published in the Ltino cohort did not rech sttisticl significnce (4). The differences in the results reported by Dvis et l. (4) nd this study re likely explined by lrger smple size employed (n = 54 vs. n = 100), which gve us more power to detect significnt difference in SI nd β-cell function. This lrger smple size however, ws not powered to detect sex differences. An even lrger smple size would hve llowed for better explortion of sex differences cross intervention nd ethnic groups. Reductions in diposity nd inflmmtion in the N+ST group In this study, strength trining pired with dietry chnges resulted in significnt reductions in HFF in both ethnic groups. Specificlly, HFF decresed by 27.3% in the N+ST group compred to 4.3% decrese in the C group nd no chnge in the N group. This reduction in HFF my be relted to reductions in inflmmtory mrkers reported in this intervention group (13). PAI-1 decresed 38.3% in the N+ST group compred to 1.0% increse in the N group nd resistin decresed by 18.7% compred to n 11.3% increse in the N group. Post hoc nlyses lso reveled reductions in monocyte chemotctic protein-1 when subcutneous nd viscerl ft were included s covrites (P = 0.01). A cuse nd effect mechnism cnnot be deduced from this study, nevertheless these findings suggest tht combintion therpy tht trgets both exercise nd eting behviors ttenute potentil increses in ft mss previously reported with strength trining lone (14) nd reduces HFF nd mrkers of inflmmtion in obese -Americn nd Ltino dolescents. Reductions in dded sugr intke long with reductions in HFF nd inflmmtion did not result in improved SI nd β-cell function in the N+ST group. One explntion for this null finding is the possibility of energy compenstion in response to the strength trining. Little is known bout the effects of energy compenstion in response to exercise in children, however reserch in dults hve demonstrted tht when individuls exercise they often compenste with incresed energy intke nd this compenstion is even more pronounced in femles. Thus, the prticipnts in the N+ST group my hve ltered their dietry intke or hbitul levels of physicl ctivity in response to the exercise throughout the progrm nd the diet records collected fter completion of the intervention might not reflect this cute compenstory intke. 816 VOLUME 20 NUMBER 4 pril

7 Ethnic disprity in dibetes risk This intervention ws successful t retining minority youth throughout the course of the study (-Americn prticipnt retention: 81.0% nd Ltino prticipnt retention: 81.8%). In ddition, dherence rtes were similr cross both intervention groups with ll evluble prticipnts ttending minimum of 12 of the 16-week nutrition clsses nd minimum of 28 of the 32 exercise clsses. As result, this rndomized controlled Chnge in PAI-1 (µg/ml) b Chnge in Resistin (µg/ml) C N N + ST Figure 4 Undjusted men ± s.e. chnge scores for () plsminogen ctivtor inhibitor-1 (PAI-1) nd (b) resistin. C, control; N, nutrition eduction; N+ST, nutrition + strength trining. denotes significntly differently from N t P < tril resulted in significnt improvements in select spects of metbolic helth in both -Americn nd Ltino dolescents t incresed risk for type 2 dibetes. This intervention ws however insufficient to eliminte the ethnic disprities in diposity, SI, nd inflmmtion reported t bseline. At postintervention, in the N group were still more insulin resistnt compred to (1.2 vs min 1 µu/ml, respectively) nd in the N+ST group still hd greter volumes of HFF compred to (6.3% vs. 3.6%, respectively). In ddition, in the N+ST group lso hd greter concentrtions of PAI-1 nd resistin compred to t the conclusion of the intervention (PAI- 1: 90.1 vs µg/ml, respectively; resistin: 36.7 vs µg/ml, respectively). In response to the nutrition intervention, tended to gin weight, ft mss in prticulr, reltive to the nd exhibited no improvement in glycemic control. Post hoc nlyses lso reveled tht in the N group lso hd significnt increse in 2-h insulin nd monocyte chemotctic protein-1 compred to, when subcutneous nd viscerl ft were used s covrites. Tken together these findings suggest tht metbolic responses to dietry interventions my vry by ethnicity nd further reserch is wrrnted to better identify pproprite intervention strtegies imed t reducing the disprity in diposity, inflmmtion, nd SI between -Americn nd Ltino dolescents. In summry, this 16-week rndomized controlled tril, designed specificlly for obese -Americn nd Ltino dolescents living in the greter Los Angeles re resulted in differing outcomes bsed on intervention group. The intervention focused on chnging the qulity of crbohydrte intke resulted in significnt improvements in SI (16.5%) nd β-cell function (15.5%). When the dietry intervention ws combined with strength trining, these improvements Tble 4 Mrkers of inflmmtion: intervention group effects for evluble prticipnts (n = 100) Outcomes Control (C) (N = 30) Nutrition eduction (N) (N = 39) (n = 18) (n = 21) Nutrition + strength trining (N+ST) (N = 31) (n = 16) IL-8 (pg/ml) 0.2 (0.9) 0.4 (1.5) 0.1 (0.5) 0.6 (3.4) 0.0 (0.8) 0.1 (1.3) Leptin (ng/ml) 7.6 (34.6) 6.6 (15.7) 0.3 (16.1) 1.7 (20.2) 1.3 (17.4) 4.4 (9.6) TNF-α (pg/ml) 0.3 (2.2) 0.7 (2.7) 0.4 (1.9) 1.1 (5.4) 0.2 (1.3) 0.1 (2.9) MCP-1 (pg/ml) 23.3 (59.7) 36.9 (38.9) 13.9 (60.4) 8.3 (78.8) 16.9 (26.7) 12.9 (59.7) HGF (pg/ml) (272.7) (640.0) 39.4 (378.3) 81.6 (741.0) 53.6 (343.7) (383.3) Significnt effect b NGF (µg/ml) 2.2 (2.9) 1.6 (5.9) 1.9 (3.1) 2.9 (19.2) 1.4 (4.8) 1.9 (4.1)** I E (<0.01) Adiponectin (µg/ml) 0.4 (5.2) 0.6 (6.5) 1.9 (4.3) 0.8 (7.8) 4.3 (8.6) 0.5 (7.8) PAI-1 (µg/ml) 1.6 (14.5) 7.3 (34.8) 2.3 (22.6) 7.9 (45.1) 18.8 (47.7)* 35.0 (85.7)*, ** I (<0.01) I E (0.06) Resistin (µg/ml) 0.8 (10.4) 7.0 (12.3) 0.8 (10.7) 8.1 (16.1) 7.5 (21.0)* 1.4 (19.1)* I (0.02) Dt re men (s.d.). b P-vlues were clculted using two-wy ANCOVA. Covrites included: Tnner stge, sex, DEXA ft nd len tissue mss. Anlyses were bsed on log scores for ll vribles. Mens differences nd interctions cross intervention (I) nd ethnic (E) groups re significntly different from one nother using Bonferroni multiple comprisons (P < 0.05). *Denotes significntly different from N group t (P < 0.05). **Denotes significnt intervention group by ethnicity interction t (P < 0.05). HGF, heptocyte growth fctor, IL-8, interleukin-8; MCP-1, monocyte chemotctic protein; NGF, nerve growth fctor; PAI-1, plsminogen ctivtor inhibitor; TNF-α, tumor necrosis fctor-α. obesity VOLUME 20 NUMBER 4 pril

8 were meliorted but mrked reductions were seen in other outcomes, including HFF (27.3%), PAI-1 (38.3%), nd resistin (18.7%). Despite the expected ethnic differences in bseline mesures of SI, diposity, nd mrkers of inflmmtion, similr improvements in metbolic outcomes were reported in both ethnic groups. However, not ll improvements were noted in the whose outcomes relted to glucose tolernce nd totl ft mss worsened. These results emphsize the importnce of promoting helthy eting nd physicl ctivity to trget underlying metbolic bnormlities tht increse risk for type 2 dibetes. Furthermore, these findings lso highlight the possibility tht response to dietry interventions my vry between -Americn nd Ltino dolescents. Acknowledgments This work ws supported by the USC Trnsdisciplinry Reserch on Energetics nd Cncer (U54 CA ), the Ntionl Institute of Child Helth nd Humn Development (RO1 HD/HL 33064), the Dr Robert C. nd Veronic Atkins Foundtion, the Ntionl Cncer Institute (T32 CA 09492). C.K.R. ws supported during this project by Ntionl Institute on Aging Trining Awrd (5 T32 AG ). We would like to thnk the SANO LA (Strength nd Nutrition Outcomes for Ltino Adolescents) nd STAND (Strength Trining nd Nutrition Development in Americn Youth) tem s well s the nursing stff t the GCRC. In ddition, we re grteful for our study prticipnts nd their fmilies for their involvement. Disclosure The uthors declred no conflict of interest The Obesity Society REFERENCES 1. Dbele D, Bell RA, D Agostino RB Jr et l.; Writing Group for the SEARCH for Dibetes in Youth Study Group. Incidence of dibetes in youth in the United Sttes. JAMA 2007;297: Crroll JF, Fuld KG, Chip AL et l. Impct of rce/ethnicity on the reltionship between viscerl ft nd inflmmtory biomrkers. Obesity (Silver Spring) 2009;17: Gorn MI, Bergmn RN, Cruz ML, Wtnbe R. Insulin resistnce nd ssocited compenstory responses in -Americn nd Hispnic children. Dibetes Cre 2002;25: Dvis JN, Kelly LA, Lne CJ et l. Rndomized control tril to improve diposity nd insulin resistnce in overweight Ltino dolescents. Obesity (Silver Spring) 2009;17: Hsson RE, Adm TA, Dvis JN et l. Ethnic differences in insulin ction in obese Americn nd Ltino dolescents. J Clin Endocrinol Metb 2010;95: Mrshll WA, Tnner JM. Vritions in pttern of pubertl chnges in girls. Arch Dis Child 1969;44: Mrshll WA, Tnner JM. Vritions in the pttern of pubertl chnges in boys. Arch Dis Child 1970;45: Mei Z, Grummer-Strwn LM, Pietrobelli A et l. Vlidity of body mss index compred with other body-composition screening indexes for the ssessment of body ftness in children nd dolescents. Am J Clin Nutr 2002;75: Figenbum AD, Milliken LA, Westcott WL. Mximl strength testing in helthy children. J Strength Cond Res 2003;17: Assocition AD. Stndrds of medicl cre in dibetes Dibetes Cre 2009;32:S13 S Ebbeling CB, Leidig MM, Sinclir KB, Hngen JP, Ludwig DS. A reducedglycemic lod diet in the tretment of dolescent obesity. Arch Peditr Adolesc Med 2003;157: Aleixndre A, Miguel M. Dietry fiber in the prevention nd tretment of metbolic syndrome: review. Crit Rev Food Sci Nutr 2008;48: Tsochtzis EA, Pptheodoridis GV, Archimndritis AJ. Adipokines in nonlcoholic stetoheptitis: from pthogenesis to implictions in dignosis nd therpy. Meditors Inflmm 2009;2009: Benson AC, Torode ME, Fitrone Singh MA. The effect of high-intensity progressive resistnce trining on diposity in children: rndomized controlled tril. Int J Obes (Lond) 2008;32: VOLUME 20 NUMBER 4 pril