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Diabetes and Risk of Fracture the Blue Mountains Eye Study

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Diabetes and Risk of Fracture the Blue Mountains Eye Study Epidemiology/Health Services/Psychosocial Research ORIGINAL ARTICLE Diabetes and Risk of Fracture The Blue Mountains Eye Study 1,2 3 REBECCA Q. IVERS, B OPTOM, MPH, PHD PAUL MITCHELL, MD, PHD, FRACO RESEARCH DESIGN AND 2 4 ROBERT G. CUMMING, MB BS, MPH, PHD ANTHONY J. PEDUTO, MB BS, FRANZCR METHODS — The Blue Mountains Eye Study is a population-based survey of vision and common eye diseases in the Blue Mountains, west of Sydney, Austra- lia. Details of the survey methods and pro- OBJECTIVE — To examine associations between measures of diabetes and risk of fracture in cedures have been described previously a population-based sample of older Australians. (16–18). All noninstitutionalized resi- dents aged 49 years or older in two post- RESEARCH DESIGN AND METHODS — This was a prospective study of 3,654 sub- code areas were identified in a census. jects aged 49 years and older who were residents in the Blue Mountains, west of Sydney, Australia. At baseline, subjects were asked questions about history and treatment of diabetes, and From a total of 4,433 eligible residents, fasting blood samples were taken. Photographs were taken of the retina and lens to grade 3,654 (82.4%) attended the baseline eye retinopathy and cataract. Details of fractures (excluding rib and vertebral fractures) were col- examination and interview in 1992 and lected by a combination of self-report and medical record searches; all fractures were radiolog- 1993. ically confirmed. RESULTS — After 2 years of follow-up, we found that several diabetes-related factors were Baseline assessment significantly associated (in multivariate models) with increased risk of all fractures combined, Visual acuity was recorded with current including presence of diabetic retinopathy (adjusted RR 5.4, 95% CI 2.7–10.8), diabetes dura- glasses and after subjective refraction us- Ն Ն tion 10 years (3.3, 1.3–8.2), cortical cataract involving 25% of the lens area (2.5, 1.3–4.7), ing a logMAR (MAR, minimum angle of and insulin treatment (5.9, 2.6–13.5). The proximal humerus was the only individual fracture resolution) chart (19). Contrast sensitiv- site associated with diabetes. Diabetic retinopathy (10.3, 2.2–48.0), diabetes duration (for Ն10 years duration; 11.4, 2.4–54.2), and insulin treatment (18.8, 4.0–88.7) were all associated with ity was measured after refraction for sub- proximal humerus fracture. jects in the first postcode area using the Vectorvision CSV-1000 chart (Vectorvi- CONCLUSIONS — These data suggest a significantly increased risk of fracture associated sion, Dayton, OH) (20). with diabetic retinopathy, advanced cortical cataract, longer diabetes duration, and insulin Each participant had stereoscopic 30° treatment. However, there are some shortcomings in this study that may limit these findings. photographs taken using a Zeiss FF3 Fun- dus camera and Kodachrome 25 slide film Diabetes Care 24:1198–1203, 2001 (Kodak). Photographs were assessed for age-related maculopathy (18) and dia- betic retinopathy (21). The three princi- any studies have examined the re- For instance, the Study of Osteopo- ple cataract types were assessed using the lationship between presence of rotic Fractures, a large prospective study Wisconsin Cataract Grading System M diabetes and bone density. In gen- of older women, found that diabetes was (16,22). Slit-lamp photographs of the lens eral, non–insulin-dependent diabetes has associated with increased risk of foot (11) were taken using a Topcon SL-7E slit- been associated with increased bone den- and proximal humerus fracture (12), but lamp camera (Topcon Optical, Tokyo), sity, (1–4) whereas insulin-dependent not with hip fracture (15). However, two and retroillumination lens photographs diabetes has been associated with de- prospective Norwegian studies found as- were taken using a Neitz CT-R camera creased bone density (5–8). However, sociations between diabetes and risk of (Neitz Instruments, Tokyo). Nuclear cat- fewer studies have examined the risk of hip fracture (13,14). aract was assessed by comparing photo- fracture in people with diabetes. Of Given the conflicting results in previ- graphs from the Topcon camera with a set these, some have found no associations, ous studies, we therefore aimed in this of four Wisconsin standards (22). Pres- (9,10) whereas other larger prospective report to explore the associations between ence and severity of cortical and posterior studies have found strong associations diabetes and risk of fracture in a prospec- subcapsular cataract opacities were grad- between diabetes and risk of fracture tive population-based study of older Aus- ed from Neitz photographs using a circu- (11–14). tralians. lar grid (16,22). ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● At the clinic visit, a questionnaire in- From the 1Institute for International Health; the 2Department of Public Health and Community Medicine, cluding demographic characteristics, the University of Sydney; the 3Department of Ophthalmology, the University of Sydney, Westmead Hospital; medications, visual function, medical his- and the 4Department of Radiology, Westmead Hospital. tory, and self-rating of general health was Address correspondence and reprint requests to Rebecca Q. Ivers, Institute for International Health, P.O. administered. BMI was calculated from Box 576, Newtown, NSW, 2042, Australia. E-mail: [email protected]. Received for publication 31 August 2000 and accepted in revised form 26 March 2001. measured weight and height. A fasting A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion blood sample was taken within 3 months factors for many substances. of the baseline examination, and serum 1198 DIABETES CARE, VOLUME 24, NUMBER 7, JULY 2001 Ivers and Associates was analyzed for glucose. Diabetes was hormone replacement therapy, smoking, there were no other statistically signifi- diagnosed from a self-reported positive physical activity, walking difficulties, and cant associations between either diabetic physician-diagnosis. use of a cane or stick) if they were associ- retinopathy or cortical cataract and the ated with the vision variables and diabetes individual sites of fracture. Collection of follow-up data variables in our data and if they were sta- After follow-up was complete (age- Fracture data were collected in three tistically significantly associated with and sex-adjusted), presence of diabetic ways: self-report, radiology reports, and fracture after adjusting for age and sex. retinopathy was statistically significantly hospital discharge summaries (for hip Variables fulfilling these criteria were re- associated with risk of all fractures com- fracture only). Five-year follow-up clinic tained in multivariable models if their ex- bined, as was treatment with insulin (Ta- visits were conducted between May 1997 clusion changed the relevant vision–hip ble 2). After follow-up, having diabetes and December 1999. At the clinic, sub- fracture RR by Ն10%. Time-dependent duration Ն10 years or insulin treatment jects completed a second detailed ques- covariates for each vision variable were was also associated with increased risk of tionnaire that inquired about fractures introduced into models to test the pro- proximal humerus fracture. sustained since age 49 years, as well as portional hazards assumption. Interac- Table 3 presents associations between details of the fracture(s). We verified all tion terms were introduced into the final both risk factors and all fractures com- self-reported nonrib or nonvertebral frac- models to assess interaction between the bined and fractures of the proximal hu- tures by obtaining the radiology report. In main effects and both age and sex. merus after 2-year follow-up, derived addition, a review was conducted in July Results are presented as RR and 95% from multivariate models. Although 1997 of all radiology reports at the local CI. P values Ͻ0.05 were used to indicate many potential confounders were as- hospital for all subjects in the study. Dis- statistical significance. sessed, only age, sex, and BMI were found charge summaries were also obtained for to actually confound the associations be- all subjects with hip fractures who had RESULTS — At baseline the mean age tween risk factors and risk of fracture. been admitted to the hospital between of the 3,654 study subjects was 66.2 years Many diabetes-related factors were statis- July 1997 and September 1999. Each ra- (range 49–97 years), and 56.7% were tically significantly associated with frac- diology report was reviewed by a special- women. There were 216 (6%) subjects ture risk (after adjusting for age, sex, and ist radiologist (A.P.) who assessed the who reported that they had been diag- BMI): diabetic retinopathy, long duration presence and type of fracture. We were nosed with diabetes by a physician. Of of diabetes, treatment with insulin, high able to obtain films for 25 of the 62 sub- these, 96 (44%), 38 (18%), and 69 (32%) blood glucose, and presence of cortical jects with a radiology report of hip frac- reported having diabetes for, respectively, cataract. ture, and the study radiologist (A.P.) 0–4, 5–9, and Ն10 years. There were Fewer variables were associated with confirmed the hip fracture in all 25 cases. 157 (73%) subjects treated by diet or tab- fractures at 5-year follow-up. After ad- Person-time for hip fracture analyses lets and 47 (22%) treated by insulin. justing for age, sex, and BMI, presence of was calculated from the date of the base- Mean length of follow-up was 5 years diabetic retinopathy was significantly as- line examination to the date of the first hip for hip fractures and 4.7 years for other sociated with risk of all fracture (adjusted fracture, the date of death, or 30 Septem- types of fracture. At the end of follow-up, RR 3.2, 95% CI 1.9–5.5, P Ͻ 0.0001), as ber 1999, whichever came first. For non- there were 59, 53, 26, and 36 subjects was diabetes duration of 5–9 years (3.0, hip fracture analyses, person-time was who had sustained, respectively, a frac- 1.2–7.4, P ϭ 0.02) and insulin treatment calculated from the date of the baseline ture of the hip, distal forearm, proximal (3.8, 2.0–7.1, P Ͻ 0.0001).
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