Pediatric Type 1 and 2 Diabetes Mellitus : Epidemiology, Comorbidities, and Medication Utilization

The numbers of patients with diabetes mellitus (type 1 and type 2) are increasing globally, both in adults and children. Pediatric diabetes mellitus is an important health concern, since this disease has significant effects on health and quality of life, social function, use of medical services and reduced employability in early adulthood resulting in a huge economic burden. The Netherlands is a country with high incidence of pediatric diabetes, but little is known on current trends in pediatric diabetes, comorbidities, and medication utilization in these patients. Therefore, we aimed to study the epidemiology of diabetes mellitus in children, and to investigate screening methods, risk factors, comorbidities, and patterns of medication utilization in this population. In 2011, the age-adjusted incidence rates of pediatric type 1 diabetes (T1D) was 25.2/100,000 (95% confidence interval (CI), 23.7-26.8) person-years (PY) and the prevalence was 174.4/100,000 (95% CI, 170.2-178.5) children. During the period 1998-2011, both incidence and prevalence rates of pediatric T1D in the Netherlands increased by about 3.7% per year. We also observed a shift towards older age at the onset of T1D. From several studies in the current thesis, it appeared that a substantial number of diseases (e.g. mental disorders, anemia, and diseases of the digestive system) and drugs (e.g. ‘‘systemic hormonal preparations’’, medications for ‘‘blood and blood forming organs’’, ‘‘alimentary tract and metabolism’’, and ‘‘anti-infectives for systemic use’’) or the underlying diseases for which these drugs were prescribed were significantly more prevalent among patients who eventually developed T1D compared with diabetes-free controls. Furthermore, children with T1D are at increased risk of developing different chronic comorbidities e.g. thyroid disease, non-infectious enteritis and colitis, cardiovascular disorders, mental disorders, epilepsy, and (obstructive) pulmonary disease. These children received more antibacterials, antimycotics, antivirals, and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems compared to diabetes-free children. In a systematic review of all available population-based studies on the epidemiology of pediatric type 2 diabetes (T2D), we found huge variations in the global rates of this disease which were mainly related to the differences in the study population characteristics and methodological differences. These findings highlighted the importance of continuing to follow global trends in the incidence and prevalence rates of T2D in the young population and to use a valid study design, appropriate diagnostic tools and the same diagnostic criteria as this disease can remain undiagnosed for many years. Therefore it is important to use distinctive tests and appropriate time intervals to screen children at risk for this disease. We identified that screening children at risk for T2D with fasting plasma glucose (FPG) and fasting plasma insulin (FPI) tests identifies all patients with diabetes, and more patients with precursors of diabetes. We also observed that the American Diabetes Association (ADA) recommended screening interval of 3-years for children at risk for T2D is not too long based on the fact that none of our study participants developed this disease in this time interval. From 1998 to 2011, increasing trends were observed in the incidence and prevalence rates of oral anti-diabetic (OAD) medication use among children and adolescents aged 0-19 years in the Netherlands which warrants further research to identify the indications for prescribing these medications and to find optimal treatment in children and adolescents with diabetes

Pediatric Type 1 and 2 Diabetes Mellitus: Epidemiology, Comorbidities, and Medication Utilization

The numbers of patients with diabetes mellitus (type 1 and type 2) are increasing globally, both in adults and children. Pediatric diabetes mellitus is an important health concern, since this disease has significant effects on health and quality of life, social function, use of medical services and reduced employability in early adulthood resulting in a huge economic burden. The Netherlands is a country with high incidence of pediatric diabetes, but little is known on current trends in pediatric diabetes, comorbidities, and medication utilization in these patients. Therefore, we aimed to study the epidemiology of diabetes mellitus in children, and to investigate screening methods, risk factors, comorbidities, and patterns of medication utilization in this population. In 2011, the age-adjusted incidence rates of pediatric type 1 diabetes (T1D) was 25.2/100,000 (95% confidence interval (CI), 23.7-26.8) person-years (PY) and the prevalence was 174.4/100,000 (95% CI, 170.2-178.5) children. During the period 1998-2011, both incidence and prevalence rates of pediatric T1D in the Netherlands increased by about 3.7% per year. We also observed a shift towards older age at the onset of T1D. From several studies in the current thesis, it appeared that a substantial number of diseases (e.g. mental disorders, anemia, and diseases of the digestive system) and drugs (e.g. ‘‘systemic hormonal preparations’’, medications for ‘‘blood and blood forming organs’’, ‘‘alimentary tract and metabolism’’, and ‘‘anti-infectives for systemic use’’) or the underlying diseases for which these drugs were prescribed were significantly more prevalent among patients who eventually developed T1D compared with diabetes-free controls. Furthermore, children with T1D are at increased risk of developing different chronic comorbidities e.g. thyroid disease, non-infectious enteritis and colitis, cardiovascular disorders, mental disorders, epilepsy, and (obstructive) pulmonary disease. These children received more antibacterials, antimycotics, antivirals, and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems compared to diabetes-free children. In a systematic review of all available population-based studies on the epidemiology of pediatric type 2 diabetes (T2D), we found huge variations in the global rates of this disease which were mainly related to the differences in the study population characteristics and methodological differences. These findings highlighted the importance of continuing to follow global trends in the incidence and prevalence rates of T2D in the young population and to use a valid study design, appropriate diagnostic tools and the same diagnostic criteria as this disease can remain undiagnosed for many years. Therefore it is important to use distinctive tests and appropriate time intervals to screen children at risk for this disease. We identified that screening children at risk for T2D with fasting plasma glucose (FPG) and fasting plasma insulin (FPI) tests identifies all patients with diabetes, and more patients with precursors of diabetes. We also observed that the American Diabetes Association (ADA) recommended screening interval of 3-years for children at risk for T2D is not too long based on the fact that none of our study participants developed this disease in this time interval. From 1998 to 2011, increasing trends were observed in the incidence and prevalence rates of oral anti-diabetic (OAD) medication use among children and adolescents aged 0-19 years in the Netherlands which warrants further research to identify the indications for prescribing these medications and to find optimal treatment in children and adolescents with diabetes

Psychiatric medication use before and after the onset of type 1 diabetes in children and adolescents: A population-based cohort study

Background: Several studies showed a bidirectional association between type 2 diabetes and psychiatric disorders in adults. There is limited information available about the association of type 1 diabetes (T1D) and psychiatric disorders in children and adolescents. Objectives: To assess the extent of psychiatric medication use before and after the onset of T1D in children and adolescents compared with a reference cohort without T1D. Methods: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System. All children and adolescents <19 years) with at least two insulin dispensings between 1999 and 2009 were identified as a T1D cohort (N=925) and matched with an up to four times larger diabetes-free reference cohort (N=3591) by age and sex. The period prevalences of psychiatric medication use (psycholeptics (ATC N05) and psychoanaleptics (ATC N06)) were calculated by dividing the number of patients with at least one dispensing by the number of patients available in the cohort during that time. Prevalences were calculated from 5 years before until 5 years after the onset of T1D (the index date in both cohorts) and stratified by age, sex, medication subgroup, and before/after the onset of T1D. Results: The mean age of the study participants was 10.1 years and 51% were boys. The 5-year prevalence of psychiatric medication use before the index date was significantly higher in the T1D cohort than in the reference cohort (7.2 vs. 4.7%, respectively, p=0.002). The same pattern was observed for the period after developing T1D (10.4 vs. 7.9% in the T1D and reference cohort respectively, p=0.015). In both cohorts adolescents (15-19 years) and boys had higher prevalences of psychiatric medication use. This increased prevalence of psychiatric medication use both before and after the index date in T1D cohort was mainly driven by an increased use of psycholeptics (mainly anxiolytics). Conclusions: Children with T1D were more likely to use psychiatric medication in the years before and after the onset of type 1 diabetes. This increased use was mainly driven by psycholeptics both before and after onset of T1D

Psychiatric medication use before and after the onset of type 1 diabetes in children and adolescents : A population-based cohort study

BACKGROUND: Several studies showed a bidirectional association between type 2 diabetes and psychiatric disorders in adults. Because there is limited information on the association between type 1 diabetes (T1D) and psychiatric disorders (including psychiatric medication use) in children and adolescents, we assessed frequency of use of these medications before and after the onset of T1D. METHODS: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System (1999-2009). Children and adolescents (<19 years) with at least 2 insulin dispensings from community pharmacies (T1D cohort, N = 925) were matched by age and sex (reference cohort without insulin use, N = 3591). The 5-year prevalence of psychiatric medication use (psycholeptics [ATC N05] and psychoanaleptics [ATC N06]) before and after onset of T1D were estimated, compared, and stratified by age, sex, and medication subgroup. RESULTS: The mean age of study participants was 10.1 years and 51% were boys. The 5-year prevalence of psychiatric medication use before the index date was significantly higher in the T1D cohort than in the reference cohort (7.2% vs 4.7%, respectively; P = .002) with the same pattern after developing T1D (10.4% vs 7.9%, respectively; P = .015). In both cohorts, adolescents (15-19 years) and boys had higher prevalences of use. This increased prevalence of psychiatric medication use both before and after the index date in T1D cohort was mainly driven by an increased use of psycholeptics (predominantly anxiolytics). CONCLUSIONS: Children with T1D were more likely to use psychiatric medication in the years before and after the onset of T1D which was mainly driven by psycholeptic use