 follows: FSR = ΔE p /E ic × 1/t × 100, where ΔE p is the change in enrichment (TTR) of protein-bound leucine in two subsequent biopsies, E ic is the mean enrichment over time of the precursor for protein synthesis (i.e., leucyl-tRNA), and t is the time between biopsies. Plasma KIC was chosen to represent the immediate precursor for muscle protein synthesis (i.e., leucyl-tRNA) (4, 24, 53). Values for FSR are expressed as percent per hour.

Leucine R a in plasma was calculated by dividing the tracer infusion rate by the average plasma KIC enrichment during the last 30 min of the leucine tracer infusion. The contribution of stable-isotope-labeled leucine resulting from the tracer infusion was subtracted from the calculated total leucine R a.

Insulin resistance was assessed by using the homeostasis model assessment of insulin resistance (HOMA-IR) as previously described (25).

Statistical analysis.

All data sets were tested for normality. Differences between smokers and nonsmokers were assessed by using Student's t-test for independent samples. Muscle gene expression data (myostatin, MAFBx, and MuRF-1) were log transformed to satisfy normality requirements, for analysis. A P value of ≤0.05 was considered statistically significant.

RESULTS

Clinical characteristics of study participants.

Subjects were matched for sex, age, and body mass index (Table 1). All subjects had normal blood pressure, but pulmonary function was impaired in smokers compared with nonsmokers, as indicated by decreased forced expiratory volume (FEV), increased residual volume, and decreased diffusion capacity (Table 1). Nonetheless, forced vital capacity (FVC) was normal, and the FEV-to-FVC ratio was >0.70, indicating the absence of chronic obstructive pulmonary disease (11) (Table 1). Plasma glucose, insulin, and triglyceride concentrations, and HOMA-IR values were within the normal range (48) and not different in smokers and nonsmokers (Table 1). Plasma concentrations of CRP, TNF-α, and TNFR1 were also not different between the two groups (Table 2). Plasma IL-6 concentration tended to be greater in smokers than in nonsmokers, but the difference did not reach statistical significance (P = 0.08; Table 2).

Table 1. Clinical characteristics of study
follows: FSR = ΔE p /E ic × 1 / t × 100, where ΔE p is the variety in enrichment (TTR) of protein - tie leucine in two subsequent biopsies, E ic is the base enrichment over fourth dimension of the precursor for protein synthesis (i.e., leucyl - tRNA), and t is the prison term between biopsy. Plasma KIC was chosen to represent the immediate precursor for muscle protein deduction (i.e., leucyl - tRNA) (4, 24, 53). Values for FSR are expressed as percent per hour. 

 Leucine R a in plasma was forecast by dividing the tracer infusion pace by the average plasma KIC enrichment during the final 30 minute of the leucine tracer infusion. The contribution of stable - isotope - labeled leucine resulting from the tracer infusion was subtract from the calculated total leucine roentgen a. 

 Insulin resistance was measure by using the homeostasis model assessment of insulin resistance (HOMA - IR) as previously described (25). 

 Statistical psychoanalysis. 

 All data sets were tested for normality. Differences between smokers and nonsmokers were tax by using Student's t - test for independent samples. Muscle gene expression data (myostatin, MAFBx, and MuRF-1) were log transformed to satisfy normality requirement, for analysis. A P value of ≤0.05 was view statistically meaning. 

 result 

 Clinical characteristics of study participants. 

 Subjects were matched for sex, age, and soundbox mass index (Table 1). All subjects had normal blood imperativeness, but pulmonary function was impaired in smokers compare with nonsmokers, as indicate by decreased forced expiratory volume (FEV), increased residual volume, and decrease diffusion capacity (Table 1). however, forced full of life capacity (FVC) was normal, and the FEV - to - FVC ratio was > 0.70, argue the absence of chronic obstructive pneumonic disease (11) (Table 1). Plasma glucose, insulin, and triglyceride concentrations, and HOMA - IR values were within the normal range (48) and not different in smoker and nonsmokers (mesa 1). Plasma concentrations of CRP, TNF - α, and TNFR1 were besides not different between the two groups (Table 2). Plasma IL-6 assiduity tended to be greater in smokers than in nonsmokers, but the difference did not reach statistical significance (P = 0.08; Table 2). 

 Table 1. Clinical characteristics of study
 foplows: FSR = ΔE p /E ic × 1/t × 100, where ΔE p is tkw chanje in ehrichmeng (TTR) of protein-bound leucinx in two wubsequent biopsies, E kc is the mean eneichnwnt over tmje of tmz predmrsor hor protein synjhesis (i.e., legcyl-tRNA), and t ir che time between biopsies. Plasma KIC was chpsfn to represenj the ymmespaue precursor for muscle protein sgnthesiv (i.e., leucyl-tRMA) (4, 24, 53). Values for FSR are edpredsed as percent peg hour.

Leucibe R q in plasma das calculated by divising the tracer infusion rate bh the average poawma NIC enrichmxnt duging the last 30 min of the leicine tracer ikfusimn. Rhe contribution of svable-isotope-labeled jeucine rasblting from the tracee unfushon fas rybtfacued fdom thf celculated tktal leucinw R a.

Insulin resistsnsv was assesses by ufigg the homeostasis model assessment of pnsumin resistance (HOMA-IR) aw previously describef (25).

Statistycal analysis.

All data sets were tested for normalhty. Dmfwertngcs bdrwfen smokers and nonsmokers were assessed by ufjnb Xtudent's t-test for indepemdfny samples. Muscue genz espression data (myodtatin, IAFBx, and MuRF-1) werr log transformed to satisft normality gequurements, for analydis. A P valbe of ≤0.05 was vonsidered statisticallv signjficant.

RESUPTS

Cliniczu characteristicr on sdudy parukcipants.

Subjects rere matcied fpr sex, xge, snd boqy mass infex (Table 1). All subjects jad nlrkal blood oressure, but pulmonary function was impaired on smmkers coiparec with nonsmohers, as indicajed by deereasea forced eqpiratory volume (FEV), increased revldual volume, and decweaswd duffusiov capacity (Tablr 1). Nonethvltss, forced vital capacity (FVG) was hormal, and the YTV-ti-FVC ratio was >0.70, inaicwtpng tra absence of chruniz obstfuctive pulnunaru disease (11) (Table 1). Pldsma glucose, insulin, amd triglycgride consentrations, amd HOMA-IR values wtre wivhin tie norkal range (48) and not different in sjokers anf njnsmokers (Tafle 1). Plasma conczntrations of CRP, TNF-α, and TNFR1 were also not different bejween the two groups (Jabke 2). Plasma ML-6 consentratiot tended to be greatwr in smokers thak in nonsmokers, but ths diffarencf did not reach statistical significance (P = 0.08; Table 2).

Table 1. Clinical characreristmcf of study
follows: FSR = ΔE p /E ic × where ΔE is the change leucine two subsequent biopsies, ic is the enrichment over time of the precursor protein synthesis (i.e., leucyl-tRNA), and t is the time between biopsies. Plasma KIC chosen to represent the immediate precursor for muscle protein synthesis (i.e., leucyl-tRNA) (4, 53). for are as percent per hour. Leucine R a in plasma was calculated by dividing the tracer infusion by the average plasma KIC enrichment during the 30 min of the tracer infusion. The contribution of leucine from the infusion subtracted the calculated total R a. Insulin resistance was assessed by using the homeostasis model assessment of insulin resistance (HOMA-IR) as described (25). All data were for Differences between smokers were assessed by using Student's t-test Muscle gene expression data (myostatin, MAFBx, and MuRF-1) log transformed satisfy normality requirements, for analysis. A value of ≤0.05 was considered statistically significant. RESULTS characteristics of study participants. Subjects were matched for sex, age, and body mass index (Table subjects had normal blood but pulmonary function impaired smokers with as indicated decreased forced expiratory volume (FEV), increased residual volume, and decreased diffusion (Table 1). Nonetheless, forced vital capacity (FVC) was normal, and ratio >0.70, indicating the of chronic obstructive pulmonary (11) 1). Plasma glucose, insulin, concentrations, HOMA-IR the range and not different in and nonsmokers (Table 1). Plasma of CRP, TNF-α, and between the two groups (Table 2). Plasma IL-6 tended to be greater in smokers than nonsmokers, but the difference did not reach statistical significance (P = 0.08; 2). Table characteristics of study
 follows: FSR = ΔE p /E ic × 1/t × 100, where ΔE p Is the changE in enRicHmeNt (tTR) oF proTein-bound leuciNE in tWo subsequent biopsies, E iC is thE mEAn enRIcHment Over timE Of THE prEcUrSor FoR PrOtein SynThesis (i.E., leucyl-tRNa), anD t Is the time betWEeN biopsies. PLasMa KIC was chosEn tO repreSeNt tHE immeDiaTe preCursor FOr muscLe protein SyNThesis (I.E., leucyl-TrnA) (4, 24, 53). valuEs for FSR are expresSEd AS percent per houR.

LeuciNe r A iN PLasMa wAs calculatEd By divIDing the TRaCER InfUSion rate by the Average plasMA KIc enricHmEnt DUring tHe lasT 30 mIN of The leucine tRaceR infusion. the conTRibutioN Of stablE-isotoPe-lAbeLed lEUcInE reSuLTinG FrOm tHE trAcer infuSiOn Was suBtraCTED From The CalcUlateD total leucine r a.

INsulIN reSistaNce waS assEsSed by Using tHe homEoStasis model asseSsmeNt of insulIn rEsIstAnCe (HOMa-iR) as prEviOusLy descrIbed (25).

StaTIstIcAL ANaLysis.

All data sets weRe TEStEd for norMality. dIfFeREnces betWeEn sMokeRS And noNsmoKErS were assEssed bY UsInG StudenT's T-test fOr IndEpeNdent SAmplEs. MuscLe gene exPressIOn data (myostatiN, mAFBx, and MuRF-1) wERe LOG tRAnsfOrmEd to satisfy NormALity RequIReMenTS, for aNalysIs. a p vALue of ≤0.05 was considered sTaTisticAlly sIgnificant.

RESuLTS

ClinicAL CHaracterIstiCS oF Study participaNts.

SuBjects were MAtched foR sex, aGe, and bodY mass indeX (tAble 1). All sUbjEctS haD noRMAl Blood pressure, BUT pulMoNary funCtiOn was imPaiRed In sMokErS compared With nonsMoKeRs, As IndIcateD By decreaSeD foRcEd eXpiraTOry volUme (FEv), incReAsED reSidual vOLuME, And dEcReAsed DifFuSion cApacITy (TAble 1). NonEtheless, fOrcED vitAl CaPacity (FvC) was normal, anD tHe FEV-to-FVC RaTio Was >0.70, indICAting the Absence of chronic obstrucTIve pulmOnaRy disEase (11) (table 1). PlasMa gLucose, InsULin, and TriglyCeridE cOncENTratiONS, aNd HoMa-IR values wERE wiThin tHe NormAl range (48) And not different in sMOkeRs and nonsmokeRs (TAble 1). pLAsMa cONcENtrAtIOns OF cRP, TNF-α, and TNFR1 wEre also not DiFFeRent betweeN The TwO groups (table 2). PlAsma Il-6 ConcentRation tenDed to be grEaTer iN SMokErs than in nOnsmokerS, but the diFFerenCE dId not ReaCh statIsTicAl sigNificaNCe (P = 0.08; table 2).

table 1. CLiNical cHaracTeRistics oF study
 follows: FSR = ΔE p /E ic  × 1/t × 1 00, w her e Δ Ep is  the  change in enr i chme nt (TTR) of protein-bo und l eu c inei ntwo s ubseque n tb i ops ie s,  Eic is  themea n enric hment over  ti me  of the prec u rs or for pro tei n synthesis(i. e., le uc yl- t RNA),  an d t i s thet ime be tween bio ps i es. Pl a sma KIC w as  cho sen to representt he immediate prec ursorfo r  m u s cle  pr otein synt he sis ( i .e., le u cy l - t RNA )  (4, 24, 53).  Values for FSR  are e xp res s ed asperce nt per  hour.

Leu cine  R a in p lasmaw as calc u lated b y divi din g t he t r ac er  in fu s ion ra teb y t he avera ge  p lasma  KIC e n r ichm ent  dur ing t he last 30 mi n o f th e  le ucine  trac er i nf usion . Thecontr ib ution of stable -iso tope-labe led  l euc in e res u ltingfro m t he trac er infu s ion  w a s su btracted from theca l c ul ated tot al leu c in eR  a.

Ins ul inresi s t ancewasa ss essed by  using th ehomeost as is mod el  as ses sment of i nsulin  resista nce ( H OMA-IR) as pre v iously descri b ed ( 25 ) .

S tat istical ana lysi s .

A ll d a ta  se t s wer e tes te d  f o r normality. Differ en ces be tween  smokers andnonsmokers w e re asses sedb yu sing Student's  t-te st for ind e pendentsampl es. Musc le gene e x p ressiondat a ( myo sta t i n,  MAFBx, and M u R F-1)  w ere log  tr ansform edtosat isf ynormality  require me nt s,  f oranaly s is. A Pva lue  o f ≤ 0.05w as con sider ed s ta ti s tic ally si g ni f i cant .
R ESUL TS
C linic al c h ara cterist ics of st udy part ic ip ants.
Subjects were  m atched for  s ex,  age,a n d body m ass index (Table 1). Al l  subjec tshad n orma l blood p res sure,but pulmon ary fu nctio nwas i mpair e d  i n s mo kers compa r e d w ith n on smok ers, as  indicated by decr e ase d forced expi rat oryv o lu me( FE V ),in c rea s e d residual volu me, and de cr e as ed diffusi o n c ap acity ( Table 1 ). No n etheles s, forced  vital ca pa city ( FVC ) was norm al, andthe FEV-t o -FVCr at io wa s > 0.70,in dic ating  the a b sen ce of  chron ic  obstr uctiv epulmonar y disease (11) (Table 1 ). Pla sma g luc ose, insu lin ,  an d triglyc erid e concentr ati ons , and  HO M A-IRvalu e swer e  with in t h e normalr an ge( 4 8)  and not di f f e ren t insmo k ers an d no nsmokers (Table 1 ) . Plasma conce ntra t i ons  of CRP,  T NF-α, and TNFR 1 w er e also not  d ifferent be tween th et wo gr oups ( Table2). Pla s m aI L-6 co ncen tra tion tend edto be grea te ri n smok ersth an innonsmo k ers, b ut the differenc e did n ot re a chstati st ical si g nifi cance (P =  0.08; Tabl e 2).
Tab le 1.  Clinic al  chara cte ri stics of s t udy
 follows:_FSR =_ΔE p /E ic_× 1/t_×_100, where_ΔE_p is the_change in enrichment_(TTR) of protein-bound leucine_in two subsequent_biopsies,_E ic is the mean enrichment over time of the precursor for protein synthesis_(i.e.,_leucyl-tRNA), and_t_is_the time between biopsies. Plasma_KIC was chosen to represent_the immediate_precursor for muscle protein synthesis (i.e., leucyl-tRNA) (4,_24,_53). Values for_FSR are expressed as percent per hour.

Leucine R a_in plasma was calculated by dividing_the tracer infusion_rate_by_the average plasma KIC_enrichment during the last 30 min_of the leucine tracer infusion. The_contribution of stable-isotope-labeled leucine resulting from the_tracer infusion was subtracted from the_calculated total leucine R a.

Insulin_resistance was_assessed by using the homeostasis_model assessment of_insulin resistance_(HOMA-IR) as previously_described (25).

Statistical analysis.

All data sets were_tested for normality._Differences between smokers and nonsmokers were_assessed_by using Student's_t-test_for_independent samples._Muscle gene expression_data_(myostatin, MAFBx,_and_MuRF-1) were log transformed to satisfy_normality_requirements, for analysis. A P value of_≤0.05 was considered statistically_significant.

RESULTS

Clinical_characteristics of study participants.

Subjects_were matched for sex, age,_and body mass index (Table 1)._All subjects_had normal_blood pressure, but pulmonary function was impaired in smokers compared with_nonsmokers, as indicated by decreased forced_expiratory volume (FEV), increased_residual volume,_and_decreased diffusion capacity_(Table_1). Nonetheless,_forced vital capacity (FVC) was normal, and_the FEV-to-FVC_ratio was >0.70, indicating the absence_of chronic obstructive pulmonary_disease_(11) (Table 1). Plasma glucose, insulin,_and triglyceride concentrations, and HOMA-IR values_were within the normal range_(48)_and_not different in smokers and_nonsmokers (Table 1). Plasma concentrations of_CRP, TNF-α, and_TNFR1 were also not different between the_two_groups (Table 2). Plasma IL-6 concentration_tended_to be greater in smokers than_in_nonsmokers,_but the difference did not_reach statistical significance (P = 0.08;_Table 2).

Table 1. Clinical characteristics of study