ObjectiveTo study the prevalence and trends of lower extremity complications of diabetes over an 8-year period in a single nation.Research design and methodsNationwide data for people with type 2 diabetes (T2D) and diabetic foot complications (DFCs) were analyzed over an 8-year period (2007–2014) from National Health Insurance Research Database using the International Classification of Diseases, Ninth Revision disease coding. The DFCs were defined as ulcers, infections, gangrene, and hospitalization for peripheral arterial disease (PAD). Trends of patient characteristics, foot presentation, and the execution of major procedures were studied, including lower-extremity amputations (LEAs).ResultsAlong with the T2D population increasing over time, the absolute number of people with DFCs increased by 33.4%, but retained a prevalence of around 2% per year. The annual incident of LEAs decreased from 2.85 to 2.06 per 1000 T2D population (p=0.001) with the major LEA proportion decreasing from 56.2% to 47.4% (p<0.001).The mean age of patients increased from 65.3 to 66.3 years and most of the associated comorbidities of diabetes were increased. For example, end-stage renal disease increased from 4.9% to 7.7% (p=0.008). The incidence of gangrene on presentation decreased from 14.7% to 11.3% (p<0.001) with a concomitant increase in vascular interventions (6.2% to 19.5%, p<0.001).ConclusionsDFCs remain a sustained major medical problem. These nationwide long-term data suggest trends toward older people with greater comorbidities such as PAD and renal disease. Nevertheless, promising trends of reducing gangrene on presentation paired with increases in vascular interventions support continued vigilance and rapid, coordinated interdisciplinary diabetic foot care.

The aim of this study was to investigate the risk of fracture and the difference between sexes from a nationwide database of fracture risk among children aged 4-17 years with or without attention deficit hyperactivity disorder (ADHD, ICD-9-CD codes 314). The Longitudinal Health Insurance Database (LHID 2000) was used to analyze fracture characteristics of children from the National Health Insurance that covered 96.1% of the Taiwanese population (N=21.4 million). A total of 7200 ADHD children aged between 4 and 17 years whose diagnosis had been confirmed in at least three outpatient clinics between 1 January 2000 and 31 December 2009 were included, and a cohort of 36 000 children without ADHD matched for age, sex, and urbanization was recruited for analysis. The incidence rate of fractures in ADHD children was 21.0 (95% confidence interval=19.4-22.7) per 1000 person-years, significantly (P<0.001) higher than 15.0 (95% confidence interval=14.4-15.6) in non-ADHDs. After adjusting by age, sex, urbanization level, and geographic region, the statistically significant (P<0.001) hazard ratios (HR) of fracture for ADHD children compared with non-ADHD children included 1.62 in girls and 1.38 in boys, 1.53 in the skull, neck, and trunk (ICD-9-CM 800-809), 1.28 in the upper extremity (ICD-9-CM 810-819), and 1.84 in the lower extremity (ICD-9-CM 820-829). The HR also (P<0.001) increased significantly in all age groups, including 1.35 in 4-6, 1.37 in 7-9, and 1.54 in 10-17 years. ADHD should be listed among risk factors of children's fractures in each sex, all age groups, and all body areas that the parents, teachers, caregivers of ADHD children, and pediatric orthopedists should be aware of. Besides, ADHD girls were more affected than ADHD boys, especially after 10 years of age, whereas the adjusted HR was the highest in the lower extremities. Nationwide analysis matched for age and sex showed that ADHD should be considered the risk factor of children's fracture, especially for girls older than 10 years of age.

IntroductionTherapeutic efficiency of glucagon-like peptide-1 (GLP-1) analog is about 50%–70% in type 2 diabetes mellitus (T2DM). Discovery of potential genetic biomarkers for prediction of treatment efficiency of GLP-1 analog before therapy is still necessary. We assess whether DNA methylation was associated with glycemic response to GLP-1 analog therapy in patients with poorly controlled T2DM.Research design and methodsGenomic DNA was extracted from the peripheral blood of training (n=10) and validation (n=128) groups of patients with T2DM receiving GLP-1 analogs. DNA methylome was analyzed using Infinium Human Methylation EPIC Bead Chip in the training group. The candidate genes were examined using a pyrosequencing platform in the validation group. The association between DNA methylation status and glycemic response to GLP-1 was analyzed in these patients.ResultsThe most differential methylation region between those with a good (responsive) and poor (unresponsive) glycemic response to GLP-1 analog therapy was located on chromosome 5q31.1 (135415693 to 135416613), the promoter of VTRNA2-1 in the training group. The methylation status of the VTRNA2-1 promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of VTRNA2-1 (<40% methylation) was significantly associated with poor glycemic response to GLP-1 treatment (OR 2.757, 95% CI 1.240 to 6.130, p=0.011). Since the VTRNA2-1 promoter region was previously reported maternal imprinting extended to the adjacent centromeric CCCTC-binding factor site that contained an A/C polymorphism (rs2346018), which was associated with methylation density of VTRNA2-1, this A/C polymorphism was also integrated to analyze association with glycemic response to GLP-1 analog therapy. In patients with the A allele of rs2346018 and hypomethylation (<40%) on the VTRNA2-1 promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).ConclusionsThe glycemic response to GLP-1 analog treatment is associated with the methylation status of the VTRNA2-1 promoter and polymorphism of rs2346018.

Cerebral contusions were the primary risk factor for MEMR complaints in chronic complicated mTBI. Early preventive psychological intervention might be necessary for patients with complicated mTBI and cerebral contusions.