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      Type 1 Diabetes Is Associated With an Increased Risk of Fracture Across the Life Span: A Population-Based Cohort Study Using The Health Improvement Network (THIN)

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          Abstract

          OBJECTIVE

          This study was conducted to determine if type 1 diabetes is associated with an increased risk of fracture across the life span.

          RESEARCH DESIGN AND METHODS

          This population-based cohort study used data from The Health Improvement Network (THIN) in the U.K. (data from 1994 to 2012), in which 30,394 participants aged 0–89 years with type 1 diabetes were compared with 303,872 randomly selected age-, sex-, and practice-matched participants without diabetes. Cox regression analysis was used to determine hazard ratios (HRs) for incident fracture in participants with type 1 diabetes.

          RESULTS

          A total of 334,266 participants, median age 34 years, were monitored for 1.9 million person-years. HR were lowest in males and females age <20 years, with HR 1.14 (95% CI 1.01–1.29) and 1.35 (95% CI 1.12–1.63), respectively. Risk was highest in men 60–69 years (HR 2.18 [95% CI 1.79–2.65]), and in women 40–49 years (HR 2.03 [95% CI 1.73–2.39]). Lower extremity fractures comprised a higher proportion of incident fractures in participants with versus those without type 1 diabetes (31.1% vs. 25.1% in males, 39.3% vs. 32% in females; P < 0.001). Secondary analyses for incident hip fractures identified the highest HR of 5.64 (95% CI 3.55–8.97) in men 60–69 years and the highest HR of 5.63 (95% CI 2.25–14.11) in women 30–39 years.

          CONCLUSIONS

          Type 1 diabetes was associated with increased risk of incident fracture that began in childhood and extended across the life span. Participants with type 1 diabetes sustained a disproportionately greater number of lower extremity fractures. These findings have important public health implications, given the increasing prevalence of type 1 diabetes and the morbidity and mortality associated with hip fractures.

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          Most cited references 36

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          A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.

          Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). To develop an equation to predict GFR from serum creatinine concentration and other factors. Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.
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            Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis.

             P Vestergaard (2007)
            Diabetes affects bone metabolism. The hypothesis was that type 1 (T1D) and type 2 (T2D) affects BMD and fracture risk differently. Pubmed, Embase, and Web of Science were searched using the terms "diabetes", "fracture", and "bone mineral". Hip fracture risk was increased in T1D (RR = 6.94, 95% CI: 3.25-14.78, five studies) and T2D (1.38, 95% CI: 1.25-1.53, eight studies) compared to subjects without diabetes. The increase in relative hip fracture risk was significantly higher in T1D than in T2D. BMD Z-score was decreased in the spine (mean +/- SEM -0.22 +/- 0.01) and hip (-0.37 +/- 0.16) in T1D and increased in the spine (0.41 +/- 0.01) and hip (0.27 +/- 0.01) in T2D. A meta-regression showed that body mass index (BMI) was a major determinant for BMD in both the spine and hip. Glycated haemoglobin (HbA1C) was not linked to BMD. The increase in fracture risk was higher and BMD lower in patients with complications to diabetes. Hip fracture risk is increased in both T1D and T2D, whereas BMD is increased in T2D and decreased in T1D. A common factor such as complications may explain the increase in fracture risk, whereas BMI may ameliorate the increase in fracture risk in T2D.
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              Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

              The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                October 2015
                27 July 2015
                : 38
                : 10
                : 1913-1920
                Affiliations
                1Golisano Children’s Hospital, University of Rochester School of Medicine and Dentistry, Rochester, NY
                2Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
                3Stanford University School of Medicine, Stanford, CA
                4Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
                Author notes
                Corresponding author: David R. Weber, david_weber@ 123456urmc.rochester.edu .
                Article
                0783
                10.2337/dc15-0783
                4580610
                26216874
                © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
                Counts
                Pages: 8
                Product
                Funding
                Funded by: National Institute of Child Health and Human Development http://dx.doi.org/10.13039/100000071
                Award ID: HD-068373
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases http://dx.doi.org/10.13039/100000062
                Award ID: K12-DK-094723
                Award ID: K24-DK-076808
                Award ID: K23-DK-093556
                Categories
                Pathophysiology/Complications

                Endocrinology & Diabetes

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