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

ABSTRACT

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 11 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.