Fracture patterns in adult onset type 1 diabetes and associated risk factors - A nationwide cohort study.

OBJECTIVE: This study aimed to determine the hazard ratios (HR) for various fracture sites and identify associated risk factors in a cohort of relatively healthy adult people with newly diagnosed type 1 diabetes (T1D). METHODS: The study utilized data from the UK Clinical Practice Research Datalink GOLD (1987-2017). Participants included people aged 20 and above with a T1D diagnosis code (n = 3281) and a new prescription for insulin. Controls without diabetes were matched based on sex, year of birth, and practice. Cox regression analysis was conducted to estimate HRs for any fracture, major osteoporotic fractures (MOFs), and peripheral fractures (lower-arm and lower-leg) in people with T1D compared to controls. Risk factors for T1D were examined and included sex, age, diabetic complications, medication usage, Charlson comorbidity index (CCI), hypoglycemia, previous fractures, falls, and alcohol consumption. Furthermore, T1D was stratified by duration of disease and presence of microvascular complications. RESULTS: The proportion of any fracture was higher in T1D (10.8 %) than controls (7.3). Fully adjusted HRs for any fracture (HR: 1.43, CI95%: 1.17-1.74), MOFs (HR: 1.46, CI95%: 1.04-2.05), and lower-leg fractures (HR: 1.37, CI95%: 1.01-1.85) were statistically significantly increased in people with T1D compared to controls. The primary risk factor across all fracture sites in T1D was a previous fracture. Additional risk factors at different sites included previous falls (HR: 1.64, CI95%: 1.17-2.31), antidepressant use (HR: 1.34, CI95%: 1.02-1.76), and anxiolytic use (HR: 1.54, CI95%: 1.08-2.29) for any fracture; being female (HR: 1.65, CI95%: 1.14-2.38) for MOFs; the presence of retinopathy (HR: 1.47, CI95%: 1.02-2.11) and previous falls (HR: 2.04, CI95%: 1.16-3.59) for lower-arm and lower-leg fractures, respectively. Lipid-lowering medication use decreased the risk of MOFs (HR: 0.66, CI95%: 0.44-0.99). Stratification of T1D by disease duration showed that the relative risk of any fracture in T1D did not increase with longer diabetes duration (0-4 years: HR: 1.52, CI95%: 1.23-1.87; 5-9 years: HR: 1.30, CI95%: 0.99-1.71; <10 years: HR: 1.07, CI95%: 0.74-1.55). Similar patterns were observed for other fracture sites. Moreover, the occurrence of microvascular complications in T1D was linked to a heightened risk of fractures in comparison to controls. However, when considering the T1D cohort independently, the association was not statistically significant. CONCLUSION: In a cohort of relatively healthy and newly diagnosed people with T1D HRs for any fracture, MOFs, and lower-leg fractures compared to controls were increased. A previous fracture was the most consistent risk factor for a subsequent fracture, whereas retinopathy was the only diabetes related one. We postulate a potential initial fracture risk, succeeded by a subsequent risk reduction, which might potentially increase in later years due to the accumulation of complications and other factors.

Fracture patterns and associated risk factors in pediatric and early adulthood type 1 diabetes: Findings from a nationwide retrospective cohort study.

PURPOSE: People with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D. METHODS: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls. RESULTS: The crude HRs for any fracture (HR: 1.30, CI95%: 1.11-1.51), lower-arm (HR: 1.22, CI95%: 1.00-1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11-2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70-2.36; MOFs: HR: 1.89, CI95%: 1.44-2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53-2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34-3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20-1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21-1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47-3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10-2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67-0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38-0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0-4 years: HR: 1.20, CI95%: 1.00-1.44; 5-9 years: HR: 1.17, CI95%: 0.91-1.50; <10 years: HR: 0.83, CI95%: 0.54-1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04-1.95). CONCLUSION: The overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones.

Site-Specific Fracture Incidence Rates Among Patients With Type 1 Diabetes, Type 2 Diabetes, or Without Diabetes in Denmark (1997-2017).

OBJECTIVE: To investigate trends in incidence rates (IRs) at various fracture sites for patients with type 1 diabetes and type 2 diabetes compared with patients without diabetes in Denmark in 1997-2017. RESEARCH DESIGN AND METHODS: Patients aged ≥18 years with a vertebral, hip, humerus, forearm, foot, or ankle fracture between 1997 and 2017 were identified from Danish hospital discharge data. IRs per 10,000 person-years were calculated over the study period. Median IRs for the first (1997-2001) and the last (2013-2017) 5 years were compared. We used Poisson models to estimate age-adjusted IR ratios (IRRs) of fractures among patients with type 1 and type 2 diabetes versus patients without diabetes. RESULTS: Except for foot fractures, fracture IRs were higher in patients with type 1 or type 2 diabetes compared with patients without diabetes. Hip fracture IRs declined between the first and last 5 years by 35.2%, 47.0%, and 23.4% among patients with type 1, type 2, and without diabetes, respectively. By contrast, vertebral fracture IRs increased 14.8%, 18.5%, 38.9%, respectively. While age-adjusted IRRs remained elevated in patients with type 1 diabetes compared with patients without diabetes, IRRs in patients with type 2 diabetes converged with those observed in patients without diabetes. CONCLUSIONS: Unadjusted fracture rates are higher in patients with diabetes but have decreased between 1997 and 2017 except for vertebral fractures, which increased in all groups. Fracture rates change after age adjustment.

Sex- and Age Group-Specific Fracture Incidence Rates Trends for Type 1 and 2 Diabetes Mellitus.

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997-2002) to the median IRs of the last 5 years (2012-2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (p-trend <0.05). The median IRs decreased 6.4% in women with T1D (p-trend = 0.35) and 25.6% in women with T2D (p-trend <0.05) but increased 2.3% in women without diabetes (p-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone parameters in T1D and T2D assessed by DXA and HR-pQCT - A cross-sectional study: The DIAFALL study.

INTRODUCTION/AIM: People with type 1 diabetes (T1D) and type 2 diabetes (T2D) have an increased risk of fractures due to skeletal fragility. We aimed to compare areal bone mineral density (aBMD), volumetric BMD (vBMD), cortical and trabecular measures, and bone strength parameters in participants with diabetes vs. controls. METHODS: In a cross-sectional study, we included adult participants with T1D (n = 111, MA = 52.9 years), T2D (n = 106, MA = 62.1 years) and controls (n = 328, MA = 57.7 years). The study comprised of DXA scans and HR-pQCT scans, biochemistry, handgrip strength (HGS), Timed Up and GO (TUG), vibration perception threshold (VPT), questionnaires, medical histories, alcohol use, and previous fractures. Group comparisons were performed after adjustment for sex, age, BMI, diabetes duration, HbA1c, alcohol, smoking, previous fractures, postmenopausal, HGS, TUG, and VPT. RESULTS: We found decreased aBMD in participants with T1D at the femoral neck (p = 0.028), whereas T2D had significantly higher aBMD at peripheral sites (legs, arms, p < 0.01) vs. controls. In T1D we found higher vBMD (p < 0.001), cortical vBMD (p < 0.001), cortical area (p = 0.002) and thickness (p < 0.001), lower cortical porosity(p = 0.008), higher stiffness (p = 0.002) and failure load (p = 0.003) at radius and higher vBMD (p = 0.003), cortical vBMD(p < 0.001), bone stiffness (p = 0.023) and failure load(p = 0.044) at the tibia than controls. In T2D we found higher vBMD (p < 0.001), cortical vBMD (p < 0.001), trabecular vBMD (p < 0.001), cortical area (p < 0.001) and thickness (p < 0.001), trabecular number (p = 0.024), lower separation (p = 0.010), higher stiffness (p < 0.001) and failure load (p < 0.001) at the radius and higher total vBMD (p < 0.001), cortical vBMD (p < 0.011), trabecular vBMD (p = 0.001), cortical area (p = 0.002) and thickness (p = 0.021), lower trabecular separation (p = 0.039), higher stiffness (p < 0.001) and failure load (p = 0.034) at tibia compared with controls. CONCLUSION: aBMD measures were as expected lower in T1D and higher in T2D than controls. Favorable bone microarchitecture and strength parameters were seen at the tibia and radius for T1D and T2D.

Impaired postural control in diabetes-a predictor of falls?

New evidence points toward that impaired postural control judged by center of pressure measures during quiet stance is a predictor of falls in people with type 1 and type 2 diabetes-even in occurrence of well-known risk factors for falls. INTRODUCTION/AIM: People with type 1 diabetes (T1D) and type 2 diabetes (T2D) are at risk of falling, but the association with impaired postural control is unclear. Therefore, the aim was to investigate postural control by measuring the center of pressure (CoP) during quiet standing and to estimate the prevalence ratio (PR) of falls and the fear of falling among people with diabetes compared to controls. METHODS: In a cross-sectional study, participants with T1D (n = 111) and T2D (n = 106) and controls without diabetes (n = 328) were included. Study procedures consisted of handgrip strength (HGS), vibration perception threshold (VPT), orthostatism, visual acuity, and postural control during quiet stance measured by CoPArea (degree of body sway) and CoPVelocity (speed of the body sway) with "eyes open," "eyes closed" in combination with executive function tasks. A history of previous falls and fear of falling was collected by a questionnaire. CoPArea and CoPVelocity measurements were analyzed by using a multiple linear regression model. The PR of falls and the fear of falling were estimated by a Poisson regression model. Age, sex, BMI, previous falls, alcohol use, drug, HGS, VPT, orthostatism, episodes of hypoglycemia, and visual acuity were covariates in multiple adjusted analyses. RESULTS: Significantly larger mean CoPArea measures were observed for participants with T1D (p = 0.022) and T2D (0.002), whereas mean CoPVelocity measures were only increased in participants with T2D (p = 0.027) vs. controls. Additionally, T1D and T2D participants had higher PRs for falls (p = 0.044, p = 0.014) and fear of falling (p = 0.006, p < 0.001) in the crude analyses, but the PRs reduced significantly when adjusted for mean CoPArea and mean CoPVelocity, respectively. Furthermore, multiple adjusted PRs were significantly higher than crude the analyses.    CONCLUSION: Impaired postural control during quiet stance was seen in T1D and T2D compared with controls even in the occurrence of well-known risk factors. and correlated well with a higher prevalence of falls.