Metabolic syndrome as a risk factor for high-ocular tension

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1 Interntionl Journl of Oesity (2010) 1 9 & 2010 Mcmilln Pulishers Limited All rights reserved /10 $ ORIGINAL ARTICLE Metolic syndrome s risk fctor for high-oculr K Imi 1, M Hmguchi 2, K Mori 1, N Tked 3, M Fukui 4, T Kto 5, Y Kwhito 2, S Kinoshit 1 nd T Kojim 5 1 Deprtment of Ophthlmology, Grdute School of Medicl Science, Kyoto Prefecturl University of Medicine, Kyoto, Jpn; 2 Deprtment of Inflmmtion nd Immunology, Grdute School of Medicl Science, Kyoto Prefecturl University of Medicine, Kyoto, Jpn; 3 Deprtment of Endocrinology nd Metolism, Murkmi Memoril Hospitl, Ashi University, Gifu, Jpn; 4 Deprtment of Endocrinology nd Metolism, Grdute School of Medicl Science, Kyoto Prefecturl University of Medicine, Kyoto, Jpn nd 5 DeprtmentofGstroenterology,MurkmiMemorilHospitl, AshiUniversity,Gifu,Jpn Ojective: To investigte the reltionship etween the metolic syndrome nd introculr pressure (IOP). Methods: An oservtionl study ws conducted in medicl helth checkup progrm t generl hospitl. This study involved pprently helthy Jpnese men nd women, yers of ge, with men IOP of 14.8 (3.0) mm Hg. IOP ws exmined y noncontct tonometer. High-oculr ws defined s IOP 421 mm Hg without optic-disc normlities or history of receiving ny nti-glucom therpy. Modified criteri of the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III (ratpiii), the new Interntionl Dietes Federtion definition, nd the Jpn Society for The Study of Oesity definition were used to chrcterize the metolic syndrome. Air temperture ws ssessed from the Gifu Meteorologicl Oservtory, Gifu, Jpn. Results: In the mle nd femle sujects, men IOP nd the prevlence of high-oculr ecme high in direct correltion with the incresed numer of metolic syndrome components. To nlyze y logistic regression, the metolic syndrome defined y ratpiii ws positively nd mximum temperture ws negtively correlted with high-oculr in mles (djusted odds rtio: 2.0 [95% confidence intervl, CI, ] nd 0.63 [95% CI, ], respectively) nd in femles (djusted odds rtio: 7.09 [95% CI, ] nd 0.67 [95% CI, ], respectively). Three of five metolic syndrome components (fsting plsm glucose, lood pressure, nd triglycerides) were relted to high-oculr. Conclusion: The metolic syndrome is risk fctor for high-oculr. Interntionl Journl of Oesity dvnce online puliction, 16 Ferury 2010; doi: /ijo Keywords: introculr pressure; oculr hypertention; metolic syndrome; fsting plsm glucose; lood pressure; triglycerides Introduction The metolic syndrome is collection of risk fctors tht increse person s chnce of developing hert disese, stroke, nd dietes. The originl description of the metolic syndrome y Reven consisted of fctors including oesity, insulin resistnce, hyper, impired glucose tolernce or dietes, hyperinsulinemi, nd dyslipidemi Correspondence: Dr M Hmguchi, Deprtment of Inflmmtion nd Immunology, Grdute School of Medicl Science, Kyoto Prefecturl University of Medicine, 465 Kjii-cho, Kwrmchi-Hirokoji, Kmigyo-ku, Kyoto , Jpn. E-mil seele@mox.kyoto-inet.or.jp Received 28 July 2009; revised 14 Decemer 2009; ccepted 4 Jnury 2010 chrcterized y elevted triglyceride, nd low high-density lipoprotein (HDL) concentrtions. 1 It ffects gret numer of people worldwide, nd the prevlence of this syndrome increses with ge. Some studies estimte the current prevlence in the United Sttes to e up to 25% of the popultion, 2 nd mong ntive Jpnese to e 41% (rnge: 19 60%) in men nd 51% (rnge: 31 89%) in women. 3 As our understnding of the ction of insulin evolves to comprehensively include the recent insulin-relted discoveries, 4 it ecomes esier to see tht insulin resistnce is the sis of most, if not ll, of the fetures of the metolic syndrome. The originl conceptuliztion of the metolic syndrome ws on the sis of resistnce to the metolic ctions of insulin. 5 Oculr hyper (OH) is one of the mjor risk fctors of primry open ngle glucom. 6,7 OH is the stte in which

2 2 introculr pressure (IOP) is 421 mm Hg, the nterior chmer ngle is open, nd oth optic-disc normlity nd visul-field defect re not detectle. Menwhile, glucom is type of optic neuropthy, nd glucom ptients suffer from decrese in the qulity of vision, which cuses progressive visul-field defect. An erlier study hs shown tht the men IOP vlue tends to increse linerly ccording to the numer of risk fctors for the metolic syndrome. 8 However, the reltionship etween the metolic syndrome nd OH is unknown. We designed cross-sectionl study in helthy Jpnese popultion to exmine the possiility of n ssocition etween high-oculr, which represents OH in this study, nd the metolic syndrome. Mterils nd methods Metolic syndrome nd high-oculr K Imi et l Study design We performed cross-sectionl study involving prticipnts of medicl helth checkup progrm, including dominl ultrsonogrphy nd IOP mesurement. The study ws pproved y the ethics committee of Murkmi Memoril Hospitl, Gifu, Jpn. The progrm ws conducted in the Medicl Helth Checkup Center t Murkmi Memoril Hospitl. The purpose of the medicl helth checkup progrm is to promote pulic helth through erly detection of chronic diseses nd the evlution of their underlying risk fctors. Known s humn dock, medicl services of this kind re very populr in Jpn. Dt collection The helth checkup progrms tht were used for the collection of dt in this study included the following tests: eye exmintions, urinlysis, lood-cell counts, lood chemistry, electrocrdiogrphy, chest rdiogrphy, rium exmintion of the upper gstrointestinl trct, nd dominl ultrsonogrphy. Trined technicins, heptologists, nd rdiologists conducted the dominl ultrsonogrphy, nd heptologists or rdiologists dignosed the ultrsonogrphic findings in the Jpnese humn dock. Ophthlmologic specilists performed the eye exmintions. High-oculr ws defined s right-eye IOP of 421 mm Hg without optic-disc normlities or history of receiving ny ntiglucom therpy. The medicl history nd lifestyle fctors of ll prticipnts, including physicl ctivity nd hits pertining to smoking nd lcohol consumption, were surveyed y use of self-dministered questionnire. When the prticipnts hd difficulty completing the questionnire, trined nurses provided ssistnce. We undertook lood nd urine exmintions with MODULAR ANALYTICS (Hitchi High-Technologies Corp., Ltd, Tokyo, Jpn). Body mss index ws clculted s ody weight in kilogrms divided y the squre of the prticipnt s height in meters. The eye exmintions consisted of visul cuity, IOP mesurement etween 9- nd 10-o clock AM y noncontct tonometry (TOPCON CT-90A; TOPCON Corp., Tokyo, Jpn) nd fundus photogrphy (TOPCON TRC-NW200; TOPCON Corp.) with no mydrisis. Three successive IOP mesurements per eye were verged nd the vlues of right-eye IOP were dopted. Wether prmeters were otined from the Gifu Meteorologicl Oservtory, Gifu, Jpn. Study popultion All of the sujects prticipting in such helth checkup progrms t Murkmi Memoril Hospitl etween Jnury 2004 nd Decemer 2008 were invited to join this study. This study ws pproved y the ethics committee of Murkmi Memoril Hospitl. Prticipnts who reported erlier ophthlmic nti-glucom therpy or surgery, or the use of steroid drugs were excluded from this study. In ddition, prticipnts who reported the use of ny drugs, which could influence the metolic syndrome such s nti-dietic drugs, nti-hypertensive drugs, nti-dyslipidemic drugs, nti-got drugs, nd/or nti-oesity drugs, were lso excluded from the min nlysis, ut were used in sugroup nlysis. In the min nlysis, we ssessed the direct effects of the metolic syndrome nd its components on IOP. In the sugroup nlysis, we ssessed whether the prticipnts who hd well-controlled norml metolic profiles ecuse of mediction hd decresed risk of highoculr. In this study, ll prticipnts who reported the use of ny drugs were ctegorized s the mediction group. Those prticipnts discontinued their use of the mediction on the dy when they received the helth check up. Metolic syndrome There re severl differing criteri for the metolic syndrome worldwide In this study, we used the following three definitions for metolic syndrome: (1) the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III (ratpiii) definition, 13 (2) the new Interntionl Dietes Federtion (IDF) definition 11 (the IDF consensus worldwide definition of the metolic syndrome [rticle online]: ville from IDF_Met_def_finl.pdf/), nd (3) the Jpn Society for The Study of Oesity definition. 14 According to the ratpiii definition, 9 sujects who hd three or more of the following criteri were identified s hving the metolic syndrome: (1) triglycerides X1.69 mmol l 1 (X150 mg per 100 ml), (2) HDL cholesterol o1.03 mmol l 1 (o40 mg per 100 ml) for men nd o1.29 mmol l 1 (o50 mg per 100 ml) for women, (3) lood pressure X130/85 mm Hg, (4) fsting glucose X5.56 mmol l 1 (X100 mg per 100 ml) 13 insted of X6.11 mmol l 1 (X110 mg per 100 ml), or (5) dominl oesityfmodified wist circumference cutoffs (X90 cm for men nd X80 cm for women) were used 13,15 insted of the wist circumference cutoffs (X102 cm for men nd X88 cm for women) proposed in the existing definition. Interntionl Journl of Oesity

3 According to the new IDF definition, Jpnese people were defined s hving the metolic syndrome if the sujects hd dominl oesity (wist circumference cutoffs X90 cm for men nd X80 cm for women) plus two or more of the following risk fctors: (1) elevted triglyceride level X1.69 mmol l 1 (X150 mg per 100 ml) or on tretment, (2) low HDL cholesterol o1.03 mmol l 1 (o40 mg per 100 ml) for men nd o1.29 mmol l 1 (o50 mg per 100 ml) for women or on tretment, (3) high lood pressure X130/ 85 mm Hg, or (4) high fsting glucose X5.56 mmol l 1 (X100 mg per 100 ml). The Jpn Society for The Study of Oesity, s well s study conducted y Mtuzw, nother Jpnese resercher, recommended the following four normlities to define the metolic syndrome in Jpn: (1) dominl oesity (dominl circumference X85 cm for men nd X90 cm for women); (2) elevted serum triglyceride level (X150 mg per 100 ml) nd/or decresed (o40 mg per 100 ml); (3) elevted lood pressure (systolic lood pressure X130 mm Hg nd/or distolic lood pressure X85 mm Hg); nd (4) n elevted fsting glucose level (X110 mg per 100 ml). Of the four normlities listed ove, sujects with (1) plus two or more of (2) through (4) were considered to hve the metolic syndrome. 14 Smple size As the prevlence of high-oculr in persons with the metolic syndrome ws unknown, forml smple size estimte ws not mde priority in this study. Sttisticl methods The R version (ville from ws used for sttisticl nlyses. Dt ws expressed s men (s.d.). Two groups of sujects were compred y using the unpired t-test nd the w 2 test, nd P-vlue of o0.05 ws ccepted s significnt level. The difference of continuous vrile etween two groups mong multiple groups ws nlyzed y one-wy nlysis of vrince followed y the Tukey s Honestly Significntly Different test. We nlyzed the ssocition of the numer of components of the metolic syndrome with IOP y using liner regression model. Logistic regression ws used to nlyze ssocitions etween the incidence of high-oculr nd the metolic syndrome while controlling for other prmeters such s ge, durtion of sunshine, nd mximum temperture. The djusted odds rtio nd 95% confidence intervls (CIs) were clculted. Results Between Jnury 2004 nd Decemer 2008, we invited prticipnts in the helth checkup progrm to enroll in the study. Of those, totl of Jpnese prticipnts Metolic syndrome nd high-oculr K Imi et l ( men nd 6805 women) were enrolled fter giving informed consent to e included in the study. We excluded 841 prticipnts (527 men nd 314 women) who reported erlier ophthlmic nti-glucom therpy or surgery, or usge of steroid drugs. Moreover, 2085 prticipnts (1566 men nd 519 women) who reported the use of ny drugs, which could influence the metolic syndrome such s ntidietic drugs, nti-hypertensive drugs, nti-dyslipidemic drugs, nti-got drugs, nd/or nti-oesity drugs, were used for sugroup nlysis (mediction group). As result, this study ultimtely consisted of pprently helthy prticipnts (8031 men nd 5972 women). The men ge ws 46.0 yers (s.d.: 9.2) (rnge: yers) for men nd 44.1 yers (s.d.: 9.1) (rnge: yers) for women, respectively. The men ody mss index ws 23.2 kg m 2 (s.d.: 3.0) (rnge: kg m 2 ) in men nd 21.1 kg m 2 (s.d.: 3.0) (rnge: kg m 2 ) in women, respectively. The men dominl circumference ws 81.4 cm (s.d.: 8.0) (rnge: cm) in men nd 71.4 cm (s.d.: 8.3) (rnge: cm) in women, respectively. Among the mediction group, the men ge, ody mss index, nd dominl circumference were significntly higher thn those mong the min group of nlyzed sujects group (Tle 1). High-oculr ws detected in 2.4% of the pprently helthy mles (95% CI, %) (n ¼ 190 of 8031 sujects) nd in 1.1% of the pprently helthy femles (95% CI, %) (n ¼ 65 of 5972 sujects). The prevlence of high-oculr ws higher in the mles thn in the femles (Po0.001). The metolic syndrome defined y ratpiii ws detected in 15.3% of the pprently helthy mles (95% CI, %) (n ¼ 1226 of 8031 sujects) nd in 5.1% of the pprently helthy femles (95% CI, %) (n ¼ 306 of 5972 sujects) (Tle 1). High-oculr ws detected in 2.1% of the mles without the metolic syndrome defined y ratpiii (95% CI, %) (n ¼ 140 of 6805 sujects) nd in 0.9% of the femles without it (95% CI, %) (n ¼ 51 of 5666 sujects). High-oculr ws detected in 4.1% of the pprently helthy mles with the metolic syndrome defined y ratpiii (95% CI, %) (n ¼ 50 of 1226 sujects) nd in 4.6% of the pprently helthy femles with it (95% CI, %) (n ¼ 14 of 306 sujects). The prevlence of high-oculr ws higher in mles nd in femles with the metolic syndrome thn in those without it (Po0.001). The metolic syndrome defined y IDF ws detected in 8.2% of the pprently helthy mles (95% CI, %) (n ¼ 655 of 8031 sujects) nd in 4.3% of the pprently helthy femles (95% CI, %) (n ¼ 256 of 5972 sujects) (Tle 1). As the definitions of metolic syndrome used in this study require informtion out drug mediction, we compred the IOP etween metolic syndrome prticipnts who were free from mediction nd those who were receiving mediction. By using three definitions of the metolic syndrome, we seprted 9597 mles nd 6491 femles into four groups ccording to the sence or presence of 3 Interntionl Journl of Oesity

4 4 Tle 1 Metolic syndrome nd high-oculr K Imi et l The difference of sic chrcteristics etween study popultion who were free from mediction nd the sugroup who were receiving mediction Men Women Apprently helthy group Mediction group P Apprently helthy group Mediction group P N Age 46.0± ±8.4 o ± ±7.3 o0.001 BMI 23.2± ±3.2 o ±3 23.6±3.7 o0.001 Adominl circumference (cm) 81.4± ±8.4 o ± ±9.7 o0.001 Systolic lood pressure (mm Hg) 119.6± ±16.5 o ± ±18.6 o0.001 Distolic lood pressure (mm Hg) 75.8± ±10.2 o ± ±11 o0.001 Fsting glucose level (mg per 100 ml) 98.7± ±30.4 o ± ±28.8 o0.001 Triglyceride level (mg per 100 ml) 110.8± ±100.8 o ± ±56.3 o0.001 (mg per 100 ml) 48.3± ±12.2 o ± ±14.6 o0.001 Introculr pressure (mm Hg) 15.0± ±3.2 o ± ±3 o0.001 ratpiii-defined MS 15.3% (1226) 50.0% (783) o % (306) 50.1% (260) o0.001 IDF-defined MS 8.2% (655) 23.1% (33) o % (256) 34.3% (178) o0.001 JASSO-defined MS 9.4% (757) 33.5% (524) o % (35) 7.1% (37) o0.001 High-oculr 2.4% (190) 3.8% (60) % (65) 2.1% (11) o0.001 Arevitions: BMI, ody mss index; HDL, high-density lipoprotein; IDF, the new Interntionl Dietes Federtion definition; JASSO, the Jpn Society for the Study of Oesity; MS, the metolic syndrome; ratpiii, the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III definition. Tle 2 The rte of high-oculr nd the verged introculr pressure in ech MS criteri Men Women Totl numer High-oculr Introculr pressure (mm Hg) P Totl numer High-oculr Introculr pressure (mm Hg) P ratpiii-defined MS Prticipnts free from MS nd mediction % (140) 14.8±3 Prticipnts who met the criteri of MS, ut received no mediction % (50) 15.9±3.1 Prticipnts who received mediction, ut did not stisfy the criteri of MS % (22) 15.2±3.2 Prticipnts who met the criteri of MS nd received mediction % (38) 15.7±3.3,c,,c % (51) 14.4± % (14) 15.8± % (4) 14.5± % (7) 15.7±3,c IDF-defined MS Prticipnts free from MS nd mediction % (171) 14.9±3 Prticipnts who met the criteri of MS, ut received no mediction % (19) 15.9±3.1 Prticipnts who received mediction, ut did not stisfy the criteri of MS % (46) 15.3±3.2 Prticipnts who met the criteri of MS nd received mediction % (14) 15.9±3.3,c,,c % (53) 14.4± % (12) 15.7± % (8) 14.7± % (3) 15.8±14.4,c JASSO-defined MS Prticipnts free from MS nd mediction % (161) 14.8±3 Prticipnts who met the criteri of MS, ut received no mediction % (29) 16.1±3 Prticipnts who received mediction, ut did not stisfy the criteri of MS % (34) 15.2±3.2 Prticipnts who met the criteri of MS nd received mediction 524 5% (26) 16±3.2,c,,c % (61) 14.5± % (4) 16.8± % (10) 15± % (1) 16.6±2.5,,c Arevitions: IDF, the new Interntionl Dietes Federtion definition; JASSO, the Jpn Society for the Study of Oesity; MS, the metolic syndrome; ratpiii, the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III definition. Indictes Po0.05 when compred with prticipnts who were free from MS nd mediction. Indictes Po0.05 when compred with prticipnts who met the criteri of MS, ut received no mediction. c Indictes Po0.05 when compred with prticipnts who received mediction, ut did not stisfy the criteri of MS. metolic syndrome nd mediction. When prticipnts stisfied the criteri for metolic syndrome, the prevlence of high-oculr ws up to % of the pprently helthy mles, nd up to %, the pprently helthy femles (Tle 2). On the other hnd, when prticipnts did not stisfy the criteri for metolic syndrome, the prevlence of high-oculr ws down to % of the pprently helthy mles, nd down to % of the pprently helthy femles. High-oculr ws detected in % of the mles nd in % of the femles who were dignosed s metolic syndrome nd received mediction. The men IOP ws t the sme level, with nd without mediction, when prticipnts stisfied the criteri of metolic syndrome. The men IOP ws higher in prticipnts who were dignosed s metolic syndrome thn in those who were not dignosed s metolic syndrome, despite the use of mediction. When prticipnts received mediction, ut were not metolic Interntionl Journl of Oesity

5 Tle 3 Metolic syndrome nd high-oculr K Imi et l The effect of mediction for the rte of high-oculr nd the verged introculr pressure 5 Men Women Totl numer High-oculr Introculr pressure (mm Hg) P Totl numer High-oculr Introculr pressure (mm Hg) P Elevted fsting glucose level Prticipnts under criterion nd free from mediction % (105) 14.7± % (47) 14.4±2.8 Prticipnts over criterion nd free from mediction % (126) 15.4± % (26) 15.4±3.1 Prticipnts under criterion nd controlled y mediction 16 0% (0) 16.9± % (1) 16.7±5.5 Prticipnts over criterion despite of mediction % (19) 15.8± % (2) 16.6±2.5 Elevted lood pressure Prticipnts under criterion nd free from mediction % (130) 14.7± % (47) 14.3±2.8 Prticipnts over criterion nd free from mediction % (85) 15.8±3.1,c % (20) 15.7±3 Prticipnts under criterion nd controlled y mediction 250 2% (5) 14.6± % (2) 14.8±3.2 Prticipnts over criterion despite of mediction % (30) 15.8±3.2,c % (7) 15.6±2.9,,c Decresed Prticipnts under criterion nd free from mediction % (159) 15± % (52) 14.5±2.9 Prticipnts over criterion nd free from mediction % (75) 15.1± % (22) 14.7±2.9 Prticipnts under criterion nd controlled y mediction 274 4% (11) 15.3± % (1) 14.6±2.8 Prticipnts over criterion despite of mediction 125 4% (5) 15.4± % (1) 15±2.8 Elevted triglyceride level Prticipnts under criterion nd free from mediction % (153) 14.9± % (63) 14.5±2.9 Prticipnts over criterion nd free from mediction % (81) 15.7±3.2,c % (11) 15.3±3.2 Prticipnts under criterion nd controlled y mediction % (10) 15.1± % (2) 14.7±2.8 Prticipnts over criterion despite of mediction % (6) 15.8± % (0) 14.8±2.7 Arevition: HDL, high-density lipoprotein. In this ssessment, we used the revised ntionl cholesterol eduction progrm dult tretment Pnel III definition. Indictes Po0.05 when compred with prticipnts who were under the criterion nd were free from mediction. Indictes Po0.05 when compred with prticipnts who were over the criterion nd were free from mediction. c Indictes Po0.05 when compred with prticipnts who were under the criterion nd controlled y mediction. syndrome, the men IOP ws lower thn in those metolic syndrome prticipnts who were free from mediction. Next, we seprted prticipnts into four groups s follows to ssess the effect of mediction nd controlling sttes: (1) prticipnts who were under the criterion nd were free from mediction, (2) prticipnts who were over the criterion nd were free from mediction, (3) prticipnts who were under the criterion controlled y mediction, nd (4) prticipnts who were over criterion despite of mediction (Tle 3). IOP ws higher in prticipnts whose lood sugr level ws over the criterion. The mediction nd controlling sttes for lood sugr ws found to hve no effect on IOP. When we turned our ttention towrd lood pressure nd triglycerides, we discovered tht IOP ws lower in prticipnts whose levels were controlled within the criteri y mediction thn in those who hd not received mediction. On the other hnd, HDL criterion ws found to e not ssocited with IOP, regrdless of whether the prticipnts received mediction or not, or whether the prticipnts stisfied the criterion or not. As for the min nlysis, we nlyzed pprently helthy prticipnts (8031 men nd 5972 women) to ssess the direct effects of the metolic syndrome nd its components on IOP. Liner regression nlysis indicted n ssocition etween the verge IOP nd the numer of components of the metolic syndrome, oth in mles ( ¼ 0.17, Po0.001) nd femles ( ¼ 0.13, Po0.001). We clculted the odds rtio of the metolic syndrome, ge, smoking hits, nd temperture for high-oculr using logistic model (Tle 4). The ratpiii-defined metolic syndrome ws sttisticlly significnt explntory vrile oth in mles (odds rtio: 2.02, 95% CI, ) nd femles (odds rtio: 5.28, 95% CI, ). The Jpn Society for The Study of Oesity-defined metolic syndrome ws lso sttisticlly significnt explntory vrile oth in mles (odds rtio: 2.02, 95% CI, ) nd femles (odds rtio: 5.28, 95% CI, ). However, the IDF-defined metolic syndrome ws not sttisticlly significnt explntory vrile in mles. One of the resons for tht ws the fct tht incresed wist circumference ws not sttisticlly significnt explntory vrile in mles. Temperture ws negtive explntory vrile. From the univrite logistic model, we selected ge, mximum temperture, nd the existence of the ratpiiidefined metolic syndrome, or the numer of its components, or ech criterion s n explntory vrile in the multivrite logistic nlyses. We pplied three models of multivrite logistic nlyses to investigte the ssocition of high-oculr with the metolic syndrome (Tle 5). In Model 1, ech component of the metolic syndrome, including incresed dominl circumference, elevted fsting glucose level, elevted lood pressure, decresed HDL Interntionl Journl of Oesity

6 6 Tle 4 Metolic syndrome nd high-oculr K Imi et l The undjusted odds rtio of the metolic syndrome for high-oculr Men (n ¼ 8031) Women (n ¼ 5972) ratpiii-defined MS 2.02 ( ) o ( ) o0.001 IDF-defined MS 1.26 ( ) ( ) o0.001 JASSO-defined MS 1.76 ( ) ( ) o0.001 Numer of components of ratpiii-defined MS 1.37 ( ) o ( ) o0.001 ratpiii nd IDF criteri Incresed wist circumference (X90 cm for men nd X80 cm for women) 1.29 ( ) ( ) o0.001 Elevted fsting glucose level (X100 mg per 100 ml) 2.04 ( ) o ( ) o0.001 Elevted lood pressure (X130/85 mmhg) 1.79 ( ) o ( ) o0.001 Decresed (o40mg per 100 ml for men nd 1.3 ( ) ( ) 0.39 o50 mg per 100 ml for women) Elevted triglyceride level (X150 mg per 100ml) 2.04 ( ) o ( ) o0.001 JASSO criteri Incresed wist circumference (X85 cm for men nd X90 cm for women) 1.19 ( ) ( ) Elevted fsting glucose level (X110 mg per 100 ml) 2.34 ( ) o ( ) o0.001 Elevted lood pressure (X130/85 mmhg) 1.79 ( ) o ( ) o0.001 Anorml cholesterol level (HDL cholesterol o40 mg per 100 ml or triglyceride 1.5 ( ) ( ) levelx150 mg per 100 ml) Current smoker 1.11 ( ) ( ) 0.57 Age (s.d.) 0.97 ( ) ( ) 0.09 Mximum temperture (s.d.) 0.63 ( ) o ( ) o0.001 Minimum temperture (s.d.) 0.63 ( ) o ( ) Arevitions: HDL, high-density lipoprotein; IDF, the new Interntionl Dietes Federtion definition; JASSO, the Jpn Society for the Study of Oesity; MS, the metolic syndrome; ratpiii, the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III definition. Univrite logistic nlysis ws pplied for high-oculr in 8031 mles nd 5972 femles. Dt ws expressed s the odds rtio (95% confidence intervl). The odds of the numer of components men the odds rtio of one component. For ge nd tempertures, the odds of 1 s.d. for high-oculr were expressed. Tle 5 The djusted odds rtio of the metolic syndrome for high-oculr Multivrite nlysis Men (n ¼ 8031) Women (n ¼ 5972) Model 1 Age (s.d.) 0.91 ( ) ( ) o0.001 Mximum temperture (s.d.) 0.64 ( ) o ( ) Incresed dominl circumference 0.9 ( ) ( ) 0.34 Elevted fsting glucose level 1.75 ( ) o ( ) Elevted lood pressure 1.52 ( ) ( ) o0.001 Decresed 1.06 ( ) ( ) 0.45 Elevted triglyceride level 1.7 ( ) ( ) Model 2 Age (s.d.) 0.94 ( ) ( ) o0.001 Mximum temperture (s.d.) 0.64 ( ) o ( ) Numer of components of ratpiii-defined MS 1.37 ( ) o ( ) o0.001 Model 3 Age (s.d.) 0.97 ( ) ( ) Mximum temperture (s.d.) 0.63 ( ) o ( ) ratpiii-defined MS 2 ( ) o ( ) o0.001 Arevitions: HDL, high-density lipoprotein; MS, the metolic syndrome; ratpiii, the revised Ntionl Cholesterol Eduction Progrm Adult Tretment Pnel III definition. Multivrite logistic nlysis ws pplied for high-oculr in 8031mles nd 5972 femles. Dt ws expressed s the odds rtio (95% confidence intervl). The odds of the numer of components men the odds rtio of one component. For ge nd tempertures, the odds of 1 s.d. for high-oculr were expressed. cholesterol level, nd elevted triglyceride level, ws listed s independent vriles. Model 2 replced the dignosis of the metolic syndrome in Model 1 with the numer of metolic syndrome components. In Model 3, ech component of the metolic syndrome ws switched to the dignosis of metolic syndrome. In oth mles nd femles, high-oculr ws correlted positively with the metolic syndrome nd Interntionl Journl of Oesity

7 negtively with mximum temperture. There ws lso significntly positive reltionship etween the numer of metolic syndrome components nd high-oculr. When ech component of the metolic syndrome ws nlyzed, elevted fsting glucose level, elevted lood pressure, elevted triglyceride level, nd mximum temperture were found to e significntly ssocited with highoculr oth in mles nd femles. To clrify the effect of the other two components, incresed dominl circumference nd decresed HDL cholesterol level, for high-oculr, we ctegorized the sujects into one of the two groups. The first group included sujects who stisfied none of the three criteri such s elevted fsting glucose level, elevted lood pressure, nd elevted triglyceride level. The second group included sujects who stisfied t lest one of these three criteri. Metolic syndrome nd high-oculr K Imi et l The prevlence of high-oculr ws not incresed in sujects who hd incresed dominl circumference nd/or decresed mong ech sugroup (Figure 1) Discussion Principl findings In this study, we showed the ssocition etween ratpiiidefined metolic syndrome nd oth IOP nd high-oculr. It hs een reported tht sujects with more metolic syndrome components hd higher IOP. 8 However, we found tht IDF-defined metolic syndrome ws not linked to high-oculr in mles. IDF is different from ratpiii in tht incresed wist circumference is not one of the components, ut is needed to conduct proper 7 5.0% Mle 5.0% Femle 4.0% 4.0% 3.0% P= % 2.0% 1.0% 2.0% 1.0% P= % Norml dominl circumference(-) nd norml Incresed dominl circumference nd/or decresed 0.0% Norml dominl circumference(-) nd norml Incresed dominl circumference nd/or decresed 5.0% Mle 5.0% Femle 4.0% P= % P= % 3.0% 2.0% 2.0% 1.0% 1.0% 0.0% Norml dominl circumference(-) nd norml Incresed dominl circumference nd/or decresed 0.0% Norml dominl circumference(-) nd norml Incresed dominl circumference nd/or decresed Figure 1 When ech component of the metolic syndrome ws nlyzed, three of the five metolic syndrome components (fsting plsm glucose, lood pressure, nd triglycerides) were found to e relted to high-oculr. The study sujects were then ctegorized into one of the two groups. The first group (, ) included sujects who stisfied none of the three criteri such s elevted fsting glucose level, elevted lood pressure, nd elevted triglyceride level. The second group (c, d) included sujects who stisfied t lest one of these three criteri. Figures indicte the prevlence of sujects with high-oculr mong sujects with incresed dominl circumference nd/or decresed, nd those with high-oculr mong sujects with norml dominl circumference nd norml. Two groups of sujects were compred y using the w 2 test, nd Po0.05 ws ccepted s the significnt level. Interntionl Journl of Oesity

8 8 Metolic syndrome nd high-oculr K Imi et l dignosis. Therefore, we lso evluted which components of the metolic syndrome re relted to high-oculr. Interestingly, this study showed tht three of the five components (fsting plsm glucose, lood pressure, nd triglycerides) were ssocited with high-oculr nd tht the other two were not. We lso ssessed the prticipnts who were receiving mediction s sugroup nlysis. The sugroup nlysis indicted tht IOP ws higher in prticipnts who were dignosed s hving metolic syndrome, whether they were receiving mediction or not. When we ssessed the effect of mediction nd the controlling sttes for ech component of the metolic syndrome, the control for lood pressure or triglycerides level y mediction decresed the IOP. However, the mediction for plsm glucose did not present this phenomenon. Limittions of the study High-oculr is concept tht is included in helth checkup progrms, yet it is not necessrily equivlent to OH. To dignose OH, dditionl evlutions including slit-lmp exmintion nd visul-field test re required, yet they were not performed ecuse of economicl nd temporl resons. IOP ws mesured y noncontct tonometer. When compring the noncontct tonometer with the Goldmnn pplntion tonometer, the noncontct tonometer showed slightly higher IOP reding, ut still close to those otined with the Goldmnn pplntion tonometer. 16 Other limittions my include complictions rising from un-mesured fctors such s centrl cornel thickness (CCT) or other known risk fctors for higher IOP. It should e noted tht the results of the sugroup nlysis tht showed tht the mediction for lood pressure or triglycerides could decrese IOP still requires vlidtion y future longitudinl study. Interprettion Severl erlier studies showed tht the rise of IOP is ssocited with dietes mellitus nd systemic hyper, 17,18 wheres other studies hve reported no ssocition. 19 The multivrite nlysis in this study indictes the correltion etween high-oculr nd oth hyperglycemi nd systemic hyper in oth mles nd femles. Although the mechnism ehind how hyperglycemi ffects IOP is uncler, it hs een reported tht there is possily more thn one effect nd tht some effects my operte in opposite directions. 20 It hs een suggested tht the cuse of the rise in IOP in systemic hyper is the excessive production of queous humor or the increse of episclerl vein pressure. 21 The positive reltionship etween IOP nd totl cholesterol hs een reported, 17 wheres to the est of our knowledge, the ssocition etween IOP nd the other lipid metolisms hve not een well discussed. In our multivrite dt, triglycerides were correlted with highoculr. One possile reson for this is tht hypertriglyceridemi is commonly ssocited with dietes nd oesity. Higher IOP hs lso een found to e relted to oesity, 17,22 proly ecuse of excess introritl ft tissue nd n increse in viscosity of the lood, which consequently decreses outflow fcility. 23 Individully, three components of the metolic syndrome, fsting plsm glucose, lood pressure, nd triglycerides, do not ffect IOP elevtion to lrge degree, ut when tken into considertion s whole, they do ffect the development of high-oculr. Therefore, we suspect tht common ckground exists etween high-oculr nd the metolic syndrome. As mentioned ove, the increse in episclerl venous pressure, which is cused y excess oritl ft, my occur with the decrese of outflow fcility. Episclerl venous pressure lso increses the insulin resistnce mechnism, which hs een found in n erlier study to induce the re of sodium when extrcellulr fluid volume is expnded. 24 Recent studies hve suggested tht higher glucose 25 nd the numer of metolic syndrome components 26 were ssocited with thicker CCT. The men CCT of the prticipnts with metolic syndrome who met the three components ws 6 mm thicker thn tht of pticipnts without metolic syndrome. 26 Murse et l. 27 reported tht 10mm increse in CCT led to n IOP 0.29 mm Hg higher when mesured with noncontct tonometer. Accordingly, the influence of CCT to IOP in the metolic syndrome prticipnts who met the three components ws clculted t lmost 0.17 mm Hg, wheres the difference of men IOP etween prticipnts with no component nd prticipnts with three components ws 1.4 mm Hg in this study. We consider CCT to e merely one of the fctors tht elucidte high IOP in the metolic syndrome. Numerous studies hve reported tht there re sesonl vritions of IOP nd tht in winter, IOP rises more thn in summer. 17,28 Our results lso indicte tht mximl temperture is negtively relted to the occurrence of high-oculr. These phenomen show tht IOP is ffected y the endogenous rhythm. 28 Conclusion The prevlence of metolic syndrome ws ssocited with high-oculr, which represents OH in this study. The high IOP relted to the metolic syndrome is not desirle in ptients with not only OH, ut lso norml glucom. It hs een reported tht primry open ngle glucom develops from 1 to 2% of OH cses every yer 7 nd tht the higher IOP the ptients hve, the greter possiility they hve of developing primry open ngle glucom. However, n erlier report hs shown tht norml glucom mkes up 90% of Jpnese primry open ngle glucom cses. 29 Even when IOP is in the norml rnge, the Interntionl Journl of Oesity

9 risk of the progression of visul-field defect in norml glucom increses 10% with ech 1 mm Hg rise in IOP. 30 Therefore, it is importnt to keep the metolic syndrome in mind s considertion when mnging IOP. To improve glucom tretment in ptients with the metolic syndrome, those ptients should e provided with instruction on how to lessen their metolic syndrome component levels. The mediction for lood pressure or triglycerides could decrese high IOP, which often ccompnies the metolic syndrome. However, this possiility requires vlidtion y future longitudinl study. Conflict of interest The uthors declre no conflict of interest. Acknowledgements WE thnk John Bush for his excellent ssistnce in prepring the mnuscript. This study ws supported y grnt from the Gifu Medicl Assocition. References 1 Reven GM. Bnting lecture Role of insulin resistnce in humn disese. Dietes 1988; 37: Ford ES, Giles WH, Dietz WH. 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