Diabetes as a Predictor of Mortality in a Cohort of Blind Subjects

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1 Internatonal Journal of Epdemology Internatonal Epdemologcal Assocaton 1996 Vol. 25, No. 5 Prnted n Great Brtan Dabetes as a Predctor of Mortalty n a Cohort of Blnd Subjects CHRISTOPH TRAUTNER,* ANDREA ICKS,* BURKHARD HAASTERT,* FRANK PLUM," MICHAEL BERGERt AND GUIDO GIANI* Trautner C (Department of Bometrcs and Epdemology, Dabetes Research Insttute at Henrch Hene Unversty, Auf'm Hennekamp 65, Dsseldorf, Germany), Icks A, Haastert B, Plum F, Berger M and Gan G. Dabetes as a predctor of mortalty n a cohort of blnd subjects. Internatonal Journal of Epdemology 1996; 25: Background. There s only a lttle nformaton about survval n newly regstered blnd subjects. Methods. A closed cohort of blnd subjects (n = 2680, 1803 of them women), newly regstered between 1990 and 1993 n the dstrct of Wurttemberg-Hohenzollern, Germany, was observed for up to 48 months. Mortalty was compared to that of the general populaton. Predctors of mortalty wthn that cohort were dentfed by Cox proportonal hazards regresson analyss. Results. Before 1 February 1994, 582 of the subjects had ded. Dabetes had been dagnosed n 772 of the subjects, 226 of them ded. The overall ncdence rate of death was per per year. The probablty of survval after 47 months was 0.64 (95% confdence nterval (Cl) : ) n the non-dabetc, and 0.46 (95% Cl : ) n the dabetc subjects. Predctors of mortalty n the regresson model were age (rsk rato [FIR] per year of age 1.047), sex (RR for men 1.247) and dabetes (RR when blndness was unrelated to dabetes: 1.448, RR when dabetes was the only cause of blndness: 2.253). Compared wth the entre populaton, mortalty was consderably ncreased n the blnd cohort (comparatve mortalty fgure [CMF] 4.79), partcularly n ndvduals wth dabetes (CMF = 6.55). The relatve rsks decreased wth ncreasng age. Conclusons. Overall mortalty n ths cohort was hgh, even hgher than n prevous studes on the mortalty of the blnd. Dabetes ncreased the rsk of death. In addton, the cause of blndness n dabetc ndvduals was a major predctor of mortalty. Keywords: blndness, comparatve mortalty fgure, Cox proportonal hazards regresson, dabetes, mortalty, populatonbased regster, standardzed mortalty rato, survval analyss The objectve of ths study was to estmate the survval functon n a cohort of newly regstered blnd subjects, to dentfy predctors of mortalty, and to compare mortalty n dabetc and non-dabetc subjects wthn ths cohort. Furthermore, t was our purpose to compare the mortalty n ths cohort wth that of the general populaton. There are only a few studes nvestgatng survval n newly regstered blnd subjects. A study of more than polcy holders wth Metropoltan Lfe Insurance who were granted blndness allowances durng revealed 2.5-fold death rates compared wth all polcy holders. 1 In the 1960s, Berkow et al. 2 studed * Department of Bometrcs and Epdemology, Dabetes Research Insttute at Henrch Hene Unversty, Aufm Hennekamp 65, Dsseldorf, Germany. * Department of Ophthalmology, Krefeld Cty Hosptal, (Teachng Hosptal of Henrch Hene Unversty, Dsseldorf) Krefeld, Germany. * Department of Metabolc Dseases and Nutrton, (WHO Collaboratng Center for Dabetes), Henrch Hene Unversty, Dusseldorf, Germany. survval n a seres of 180 blnd dabetc patents who had receved gude dogs. Ther results suggested a very poor lfe expectancy for blnd dabetc ndvduals. Rogot et al? compared death rates n over people frst regstered as legally blnd n Massachusetts between 1940 and 1959 wth those of the general populaton. They found poorer survvorshp n the blnd than n the general populaton up to the age of 75 wth lttle dfference at older ages. Survval n people wth dabetes was extremely low, even lower than n all other blnd people. However, those studes dd not dfferentate among dabetc ndvduals accordng to whether dabetes was the only or a contrbutory cause of blndness, or was unrelated to the blndness. Therefore, survval n the blnd wth dabetes deserves a more detaled nvestgaton. In Germany, almost all blnd people are enttled by law to receve a blndness allowance ndependent of sources of ncome. 4 Because t s a substantal amount (between 500 and 1000 German marks per month), one can assume that almost all the elgble apply for ths blndness allowance and are regstered accordngly. We 1038

2 DIABETES AND MORTALITY IN BLIND SUBJECTS 1039 TABLE 1 Patent characterstcs N Men Women Ded Age (years) Mean (SD) Range All subjects of the cohort" Non-dabetc subjects' Dabetc subjects* Cause of blndness unrelated to dabetes 6 Dabetes contrbutory cause of blndness 11 Dabetes only cause of blndness 6 Unknown cause of blndness (71%) (29%) (34%) (25%) (41%) (1%) (77%) (23%) (36%) (20%) (44%) (0%) (68%) (32%) (33%) (26%) (39%) (1%) (61%) (39%) (34%) (29%) (37%) (0%) (22.1) (24.9) (12.4) (11.4) (9.0) (12.0) (7.5) SD: standard devaton. 8 Per cent of all subjects n the column. b Per cent of all dabetc subjects n the column. used a regster of blndness allowance recpents to study survval n a nearly complete sample of ncdent cases of blndness n one German dstrct. SUBJECTS AND METHODS Defnton and Follow-Up of Study Cohort In one dstrct of Germany (Wrttemberg-Hohenzollern, approxmately 5.4 mllon nhabtants), a lst of all those newly regstered as blnd (blndness allowance recpents) wth the welfare admnstraton between 1 January 1990 and 31 December 1993 was drawn up. All those who appled for regstraton as blnd and met the crtera for blndness accordng to the Federal Mnstry of Labour and Welfare 5 ' 6 (vsual acuty of 1/50 or less n the better eye, vsual feld reduced to a radus of 5 or less, or smlar reducton of vson, e.g. due to central scotoma, makng the person unable to fnd hs or her way) were ncluded. The decson was based on wrtten medcal and ophthalmologcal reports. Each record of an dentfed subject was searched for date of brth, date of regstraton, sex, ophthalmologcal fndngs, and whether dabetes was present. In all cases wth dabetes, an experenced ophthalmologst (FP) determned whether dabetes was the only cause of blndness or one of several contrbutory causes, or whether blndness was not due to dabetes. From the record t was also determned whether the person had ded before 1 February Vtal status could be ascertaned because the blndness allowance s pad every month untl the person des or moves out of the area. Those who moved were censored at the tme of movng. In ths way, a closed cohort of ncdent cases of blndness was generated whch could be followed for up to 48 months. Survval tme was calculated as month of death mnus month of regstraton as blnd. Statstcal Analyss The survval functon was estmated usng the Kaplan- Meer method. 7 Dfferences n survval functons between subgroups were tested by the logrank test. 7 We ftted a proportonal hazards (Cox) model to determne the relatonshp between mortalty as the outcome varable, and age, sex, dabetes and cause of blndness n dabetc subjects as predctor varables. 7 In addton, the mortalty of the study populaton was compared externally to the entre populaton of the federal German state of Baden-Wrttemberg. Mortalty data for ths state were obtaned from the Statstcal Offce. Age- and sex-specfc relatve mortalty rsks were calculated. Usng the drect method of standardzaton, comparatve mortalty fgures (CMF), 8 ' 9 together wth ther 95% confdence ntervals (CI), were estmated accordng to Rothman. 10 In addton, usng the ndrect method of standardzaton, standardzed mortalty ratos (SMR) were calculated. 8 " 10 All calculatons were carred out wth the SAS statstcal package (verson 6.09). The sgnfcance level at all analyses was a = RESULTS There were 2714 people newly regstered as blndness allowance recpents n the defned perod. Because of mssng values on the predctor varables consdered, 34 of them were excluded from the analyss. Therefore, the cohort studed conssted of 2680 subjects, 582 of whom ded up to January The dstrbuton wth respect to sex, age, dabetc status, and cause of blndness n dabetc ndvduals s shown n Table 1. In total, there were person months of observaton. A crude ncdence rate of death of per per year was estmated. The mean observaton tme was 21.4 months (SD 13.1, maxmum 48). Before the end of

3 1040 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY " - ^ I I Dabetc ; subject?"",.! 1 ; 1! Months FIGURE 1 Survval of blnd ndvduals the study perod 47 people were censored. The mean age of the women was 73.9 years (SD 19.4), and of men 63.2 years (SD 25.4). The estmated survval functons are shown n Fgure 1. The probablty of survval after 47 months was 0.64 (95% CI : ) n the nondabetc, and 0.46 (95% CI : ) n the dabetc subjects. In a unvarate analyss, the survval functons were sgnfcantly dfferent between dabetc and nondabetc ndvduals (P < 01). The results of the regresson analyss are shown n Table 2. When all subjects were combned, predctors of ncreased mortalty n the regresson model were age, male sex and dabetes. All of the possble predctors were statstcally sgnfcant. The ncrease n rsk was greater n those dabetc subjects whose cause of blndness was related to dabetes, compared wth dabetc ndvduals wth other causes of blndness. There was only a slght dfference n the rsk rato [RR] (wth wdely overlappng confdence ntervals) between subjects wth dabetes as the only cause, and subjects wth dabetes as a contrbutory cause of blndness. The same pattern was found when men and women were analysed separately. The RR were greater n women than n men, however. Wth fewer deaths n men (179 versus 403 n women) the confdence ntervals are wder and the varables 'blndness unrelated to dabetes' and 'dabetes contrbutory cause of blndness' fal to be statstcally sgnfcant. Comparatve mortalty fgures and SMR are shown n Table 3. Due to zero person-years of observaton n some age- and sex-specfc strata, CMF could not be calculated for some subgroups of dabetc subjects. Mortalty was consderably ncreased n the blnd cohort, manly n those who had dabetes. Dfferences between SMR and CMF n the same subgroup are explaned by the dfferent age dstrbuton of the populaton to whch they are standardzed (the general populaton for CMF, the subgroup consdered for SMR).' (Where possble, the TABLE 2 Predctors of mortalty (Cox regresson model) Predctor varables Both sexes Men only Women only Rsk rato 95% CI P Rsk rato 95% CI P Rsk rato 95% CI P Male sex Age (Rsk change per year of age) Dabetc subjects Cause of blndness unrelated to dabetes Dabetes contrbutory cause of blndness Dabetes only cause of blndness ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) TABLE 3 Comparatve mortalty fgures (CMF) and standardzed mortalty ratos (SMR) CMF 95% confdence nterval SMR 95% confdence nterval All subjects of the cohort Non-dabetc subjects Dabetc subjects Cause of blndness unrelated to dabetes Dabetes contrbutory cause of blndness Dabetes only cause of blndness ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( )

4 DIABETES AND MORTALITY IN BLIND SUBJECTS 1041 comparson of subgroups accordng to CMF s preferable because of the common standard nherent n ths measure.) The SMR and CMF were also analysed separately for men and women (Table 4). The hgher CMF for men are explaned by ther younger mean age. Age-specfc RR of death, compared wth the general populaton, are shown n Table 4. The RR were hgh n the younger age groups and decreased wth ncreasng age. Ths pattern was found n all subgroups (men and women, non-dabetc subjects, dabetc subjects wth cause of blndness related or unrelated to dabetes). In some subgroups, the RR ncreased agan slghtly n the oldest age group. DISCUSSION We compared mortalty n a cohort of newly regstered blnd wth that of the general populaton, and dentfed predctors of mortalty wthn that cohort. Very few people may have become blnd wthout beng enttled to blndness allowance. The rare exceptons nclude blndness due to occupatonal dseases and ndustral accdents, as well as blndness durng mprsonment. Accordng to the professonal assocatons lable for ndustral safety and nsurance, less than 10 people per year become blnd due to occupatonal dseases and ndustral accdents n the whole of Germany. Probably a few subjects meetng the crtera of blndness dd not apply for blndness allowance. Although there s no nformaton about those who dd not apply, due to the unque and substantal fnancal ncentve for regstraton, the regstry can be consdered to nclude a much greater proporton of the blnd than regstres n other countres. 3 " Some subjects had to be excluded for mssng values. Wth these qualfcatons, the study populaton may be consdered to be an almost complete sample of ncdent cases of blndness n the study area durng the perod of observaton. In unvarate analyss, the survval curves show a great dfference between dabetc and non-dabetc ndvduals. Also n the regresson model, ncreasng age and the presence of dabetes ncreased the rsk of death, as would be expected. Dabetes as the cause of blndness further ncreased the rsk of death compared wth subjects who had dabetes but had other causes of blndness. When the study populaton was compared wth the general populaton, the relatve mortalty rsk n the dabetc blnd was consderably hgher than the approxmately twofold mortalty rsk of ndvduals wth type 2 dabetes as compared wth the general populaton."' 12 These fndngs are n accordance wth prevous studes showng a hgh excess mortalty n blnd subjects, especally those who became blnd from dabetc retnopathy. 1 ' 3 As n prevous studes, the excess rsk of death decreased consderably wth ncreasng age. 1 ' 3 Apparently ths pattern has not substantally changed over the last 60 years. However, the RR of death compared wth the general populaton was hgher n our study than n that conducted n Massachusetts (SMR for all blnd subjects: n our nvestgaton, 1.45 n the Massachusetts regstry, although the blnd n Massachusetts were younger than our cohort 3 ). The relatve mortalty rsk was also hgher than n the Metropoltan Lfe Insurance study (SMR 2.47 wth a consderably younger age dstrbuton than n both of the other studes 3 ) under the age of 75 years. Ths dfference may be due to the more rgd defnton of legal blndness n Germany (vson wth correcton of 20/200 or less n the better eye n the USA 3 ) resultng n a selecton of severe cases. Another explanaton may be underascertanment of severe cases, e.g. those lvng n nursng homes, n the Massachusetts study. It s also possble that due to mproved preventon of blndness only people wth the severest underlyng dseases have become blnd n recent years, or that severely ll people lve longer wth a greater cumulatve probablty of becomng blnd. Some lmtatons to the desgn and the results of ths study have to be consdered. We had to rely on the nformaton lad down n the records and provded by the admnstraton. Therefore, the number of varables we could study was lmted. For example, nformaton about possble confounders lke smokng and duraton of dabetes was not avalable. Some msclassfcaton of dabetc status s possble. There are few populaton-based studes of the ncdence and causes of blndness, as well as the rsk of blndness attrbutable to dabetes." Ongong studes of data from blndness allowance regsters' 3 may shed some lght on ths ssue n the future. In the cohort studed here, wth respect to causes of blndness, dagnoses and descrptons of fndngs were gven, but a standardzed classfcaton system was not used. In dabetc subjects we were able to dstngush between those whose blndness was probably due to dabetc retnopathy, and those whose blndness was unrelated to dabetes. We do not report a detaled descrpton of other causes of blndness, however, due to dagnostc uncertanty. A consderable number of dabetc subjects apparently became blnd for other reasons than dabetc retnopathy. Although there may be some msclassfcaton of causes of blndness, our fndngs are plausble gven the age of most subjects studed here. One may conclude that n addton to dabetc status, the cause of blndness n dabetc ndvduals s a major predctor of mortalty.

5 TABLE 4 Age-specfc mortalty rsks of blnd versus general populaton Age" Deaths Relatve mortalty rsk All subjects (95% CI) Non-dabetc (95% Cl) subjects Dabetc subjects All (95% CI) Cause of blndness Blndness (95% CI) Dabetes (95% Cl) Dabetes (95% CI) unrelated contrbutory only to dabetes cause cause Men CMF" SMR C Women II ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) (2.79^*4.63) ( ) ( ) ( ) ( ) ( ) ( ) ;RNATIO z f o JO o 11 2[ w m 5 CMF ( ) ( ) ( ) ( ) SMR ( ) ( ) ( ) ( ) ( ) ( ) ' Age (years) at regstraton as blnd. b Comparatve mortalty fgure. c Standardzed mortalty rato.

6 DIABETES AND MORTALITY IN BLIND SUBJECTS 1043 ACKNOWLEDGEMENTS We thank the welfare admnstraton (Landeswohlfahrtsverband) n Wrttemberg-Hohenzollern for ther support. We are grateful to Karsten Dannehl for developng the documentaton sheet. Ths research project was afflated wth the Publc Health Research Network North Rhne-Westphala (Forschungsverbund Publc Health Nordrhen-Westfalen). We are ndebted to fnancal support from the Brger-Bsng-Stftung, Kaserslautern, and the P Klockner-Stftung, Dusburg (grants made avalable to Prof. M Berger). REFERENCES 1 Metropoltan Lfe Insurance Company. Mortalty of the Blnd. Statstcal Bulletn 1935; 16: Berkow J W, Shugarman R G, Maumenee A E, Patz A. A retrospectve study of blnd dabetc patents. JAMA 1965; 193: Rogot E, Goldberg I D, Goldsten H. Survvorshp and causes of death among the blnd. J Chron Ds 1966; 19: Gesetz ber de Landesbndenhlfe vom 8. Februar 1972, Gesetzblatt Baden-Wurttemberg, 1972, p Rauschelbach H. Bundesmnsterum fur Arbet und Sozalordnung (ed.) Anhaltspunkte fur de arztlche Gutachlertatgket m sozalen Entschadgungsrechl und nach dem Schwerbehndertengesetz. Bonn: Kollen, Aulhorn E, Jaeger W. Blndengeld Rchtlnen der Deutschen Ophthalmologschen Gesellschaft. Klnsche Monatsblatter fur Augenhelkunde 1975; 167 (2). 7 Kalbflesch J D, Prentce R L. The Statstcal Analyss of Falure Tme Data. New York: John Wley & Sons, Breslow N E, Day N E. Statstcal Methods n Cancer Research. Volume I The Analyss of Case-Control Studes. Lyon: Internatonal Agency for Research on Cancer, Breslow N E, Day N E. Statstcal Methods n Cancer Research. Volume II The Desgn and Analyss of Cohort Studes. Lyon: Internatonal Agency for Research on Cancer, Rothman K J. Modern Epdemology. Boston/Toronto: Lttle, Brown and Company, Natonal Dabetes Data Group. Dabetes n Amerca. 2nd edn. Natonal Insttutes of Health, Panzram G. Mortalty and survval n type 2 (non-nsulndependent) dabetes melltus. Dabewloga 1987; 30: Icks A, Trautner C, Berger M, Gan G. Blndness from dabetc retnopathy: age- and sex-specfc ncdence rates. Dabewloga 1994; 37 (Suppl.l): A155 (Abstract). (Revsed verson receved March 1996)

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