Hospitalization and comorbidity in children with type 2 diabetes.

OBJECTIVE: To describe hospitalization rates and reasons for hospitalization in children with type 2 diabetes (T2D) and to compare these rates to a matched cohort without diabetes and to children with type 1 diabetes (T1D). METHODS: Population-based cohorts of 528 children (7-18 years of age) with prevalent T2D, 1519 matched control children without diabetes and 778 children with T1D were identified from a clinical registry and linked to health care records to assess hospitalizations and reasons for hospitalizations using ICD-9CM and ICD-10CA codes. RESULTS: Children with T2D are more likely than their matched controls and children with T1D to be admitted to hospital in the year prior to diagnosis {RR 2.83 (1.77, 4.53) p < 0.0001 and 8.05 (4.05, 16.00) p < 0.0001, respectively}, in the first year post diagnosis {RR 3.19 (2.08, 4.89) p < 0.0001 and 3.04 (1.86, 4.98) p < 0.0001, respectively} and in the 5 year post diagnosis period {RR 1.99 (1.56, 2.53) p < 0.0001 and 1.91 (1.48, 2.46) p < 0.0001, respectively}. Mental illness was the most common cause for hospital admission in both children with T2D and their matched controls. CONCLUSIONS: This differs from children with T1D where endocrine causes constitute the most common reason for hospital admission. This analysis provides novel data on hospitalization rates and diagnoses in the increasing population of children with T2D. This information is important to inform health care programming and health policy planning to best meet the needs of this population.

Mental health comorbidity is common in children with type 2 diabetes.

OBJECTIVE: To describe the prevalence of mental health comorbidity in children with type 2 diabetes compared to a matched population without diabetes and children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Population-based cohorts of 528 youth (7-18 years of age) with prevalent type 2 diabetes, 1519 matched children without diabetes and 778 youth with type 1 diabetes were identified from a clinical registry and linked to provincial health care records to assess the prevalence of mental health comorbidity using ICD-9CM, ICD-10CA and ATC codes. RESULTS: The majority of children with type 2 diabetes were of First Nations heritage. Compared to their matched peers, children with type 2 diabetes where more likely to have a mood or anxiety disorder before and after diagnosis [RR 2.38 (1.63, 3.48) p < 0.001 and 1.70 (1.39, 2.08) p < 0.001 respectively], to attempt/complete suicide [RR 3.18 (1.30, 7.81) p = 0.012 and 2.18 (1.32, 3.60) p = 0.0002 respectively] and be prescribed an antipsychotic [RR 2.33 (1.23, 4.39) p = 0.009 and 1.76 (1.23, 2.52) p = 0.002 respectively]. Following adjustment for age and sex, children with type 2 diabetes, compared to children with type 1 diabetes where more likely to have a mood or anxiety disorder and be prescribed an antipsychotic after diagnosis [RR 1.43 (1.07, 1.91) p = 0.015; RR 2.41 (1.44, 4.06) p = 0.0009 respectively]. CONCLUSIONS: Children with type 2 diabetes have high rates of comorbid mental illness. Programs to provide care, support, and education must address the mental health comorbidity in the context of the demographic, socioeconomic, and psycho-cultural characteristics of the population.

Youth perceptions and experiences of type 2 diabetes: Protocol for a collaborative knowledge translation approach and qualitative study.

AIMS: The aim of this study is to generate an in-depth understanding of youth perceptions and experiences of living with type 2 diabetes to inform knowledge translation, research and intervention development. DESIGN: Interpretive descriptive qualitative study. METHODS: Twenty to 25 youth aged 10-18 years with a diagnosis of type 2 diabetes will be purposively recruited through the Diabetes Education Resource for Children and Adolescents in Winnipeg, Manitoba, and through the Improving Renal Complications in Adolescents With Type 2 Diabetes Through the REsearch [iCARE] cohort. Socio-demographic information will be collected. Semi-structured interviews will occur iteratively with inductive thematic analysis. Data will be professionally transcribed and managed using NVivo 1.0 software. The University Ethics Committee approved this study (May 2020). DISCUSSION: There is a critical gap in understanding youth experiences of type 2 diabetes. Research involving youth with type 2 diabetes is predominantly quantitative in nature, largely reflecting risk factors, underlying mechanisms and treatment outcomes associated with diabetes management. In-depth qualitative research on youth experiences can help identify youth priorities, provide insight into critical misalignments between stakeholder perspectives, and drive forward a more consolidated youth-centred research agenda. IMPACT: Understanding and applying knowledge of youth experiences is critical as the prevalence of, and challenges associated with, youth onset type 2 diabetes continues to increase worldwide. This research will generate a robust interpretive description of youth lived experiences and perceptions of type 2 diabetes where such research is lacking, to inform basic and applied research within an interdisciplinary investigative and clinical research team with relevance to other jurisdictions. In response to calls for youth-oriented research in type 2 diabetes, this work will catalyse collaborative knowledge translation using creative and youth-directed initiatives.

Diabetic ketoacidosis at presentation of type 1 diabetes in children in Canada during the COVID-19 pandemic.

Type 1 diabetes is a common chronic illness in childhood. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes. Early recognition of symptoms of diabetes and immediate initiation of treatment are important factors in preventing DKA at first presentation. We describe the numbers of children presenting with DKA at initial diagnosis across eight Canadian paediatric centres during the COVID-19 pandemic (March 15, 2020 to July 31, 2020) and compare this to the same time period in 2019. Comparing the pre-COVID to the COVID-19 time period, presentation in DKA increased from 36.4% to 55.0% (P<0.0001) and presentation in severe DKA from 37.0% to 48.3% (P=0.044). These findings are concerning and emphasize the importance of awareness of the signs and symptoms of diabetes. In addition, these findings raise concern about access to appropriate and timely care during the COVID-19 pandemic.

Intrauterine exposure to diabetes and risk of cardiovascular disease in adolescence and early adulthood: a population-based birth cohort study.

BACKGROUND: It is unclear whether intrauterine exposure to maternal diabetes is associated with risk factors for cardiovascular disease and related end points in adulthood. We examined this potential association in a population-based birth cohort followed up to age 35 years. METHODS: We performed a cohort study of offspring born between 1979 and 2005 (n = 293 546) and followed until March 2015 in Manitoba, Canada, using registry-based administrative data. The primary exposures were intrauterine exposure to gestational diabetes and type 2 diabetes mellitus. The primary outcome was a composite measure of incident cardiovascular disease events, and the secondary outcome was a composite of risk factors for cardiovascular disease in offspring followed up to age 35 years. RESULTS: The cohort provided 3 628 576 person-years of data (mean age at latest follow-up 20.5 [standard deviation 6.4] years, 49.3% female); 2765 (0.9%) of the offspring experienced a cardiovascular disease end point, and 12 673 (4.3%) experienced a cardiovascular disease risk factor. After propensity score matching, the hazard for cardiovascular disease end points was elevated in offspring exposed to gestational diabetes (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12-1.79) but not type 2 diabetes (adjusted HR 1.40, 95% CI 0.98-2.01). A similar association was observed for cardiovascular disease risk factors (gestational diabetes: adjusted HR 1.92, 95% CI 1.75-2.11; type 2 diabetes: adjusted HR 3.40, 95% CI 3.00-3.85). INTERPRETATION: Intrauterine exposure to maternal diabetes was associated with higher morbidity and risk related to cardiovascular disease among offspring up to 35 years of age.

An evaluation of renin-angiotensin system markers in youth with type 2 diabetes and associations with renal outcomes.

AIMS/HYPOTHESIS: Youth with type 2 diabetes (T2D) have high rates of obesity, hypertension and suboptimal glycemic control. We hypothesized that renin-angiotensin system (RAS) activation is present in youth with T2D and associated with poor glycemic control and renal outcomes. METHODS: Cross-sectional analysis of 183 youth with T2D and 100 controls from the Improving renal Complications in Adolescents with T2D through REsearch cohort. Diabetes youth stratified by urine albumin:creatinine ratio (ACR) < or ≥2 mg/mmol. RAS levels measured with enzyme-linked immunosorbent assay (ELISA) and enzyme activities by synthetic substrates. In T2D, levels log transformed and Tobit linear regressions evaluated for associations with hemoglobin A1c (HbA1c), mean arterial pressure (MAP), estimated glomerular filtration rate (eGFR), ACR. RESULTS: Youth were 14 to 15 years, with diabetes duration 1.7 to 1.8 years; 21.3% albuminuria. Serum: differences in plasma renin activity (<0.0001), and angiotensin converting enzyme (ACE) activity (P = .003) in T2D vs controls. Urine: higher ACE activity and ACE2 protein/activity (all P < .0001) in T2D, higher levels in T2D with albuminuria. Multivariable regressions: higher serum ACE activity (ß = 0.03, SE 0.01;P < .01), urine ACE activity (ß = 0.44, SE 0.18;P < .01), ACE2 (ß = 0.51, SE 0.19;P < .01) positively associated with HbA1c; urine angiotensinogen (AGT) negatively associated (ß = -0.28 [SE 0.06;P < .01]). Higher serum aldosterone (ß = 0.11 [SE 0.04;P < .01]) and urine AGT (ß = 0.32 [SE 0.07;P < .01]) significantly associated with ACR and urine ACE2 (ß = 0.21 [SE 0.13;P < .03]). No associations between RAS markers and eGFR/MAP. CONCLUSIONS/INTERPRETATION: RAS activation present in youth with T2D and associated with higher HbA1c. Higher serum aldosterone and urine AGT associated with albuminuria. The prognostic significance of the combined effect of glycemia and RAS activation on renal outcomes requires additional investigation.

Cardiac structure and function in youth with type 2 diabetes in the iCARE cohort study: Cross-sectional associations with prenatal exposure to diabetes and metabolomic profiles.

OBJECTIVE: This study aimed to determine the degree of left ventricular (LV) dysfunction and its determinants in adolescents with type 2 diabetes (T2D). We hypothesized that adolescents with T2D would display impaired LV diastolic function and that these cardiovascular complications would be exacerbated in youth exposed to maternal diabetes in utero. METHODS: Left ventricular structure and function, carotid artery intima media thickness and strain, and serum metabolomic profiles were compared between adolescents with T2D (n = 121) and controls (n = 34). Sub-group analyses examined the role of exposure to maternal diabetes as a determinant of LV or carotid artery structure and function among adolescents with T2D. RESULTS: Adolescents with T2D were 15.1 ± 2.5 years old, (65% female, 99% Indigenous), had lived with diabetes for 2.7 ± 2.2 years, had suboptimal glycemic control (HbA1c = 9.4 ± 2.6%) and 58% (n = 69) were exposed to diabetes in utero. Compared to controls, adolescents with T2D displayed lower LV diastolic filling (early diastole/atrial filling rate ratio [E/A] = 1.9 ± 0.6 vs 2.2 ± 0.6, P = 0.012), lower LV relaxation and carotid strain (0.12 ± 0.05 vs 0.17 ± 0.05, P = .03) and elevated levels of leucine, isoleucine and valine. Among adolescents with T2D, exposure to diabetes in utero was not associated with differences in LV diastolic filling, LV relaxation, carotid strain or branched chain amino acids. CONCLUSIONS: Adolescents with T2D display LV diastolic dysfunction, carotid artery stiffness, and elevated levels of select branch chain amino acids; differences were not associated with exposure to maternal diabetes in utero.

Neonatal diabetes and protein losing enteropathy: a case report.

BACKGROUND: Neonatal diabetes is a rare form of monogenic diabetes with onset in the first six months of life occurring in 1/100,000 to 1/400,000 births. Both permanent and transient forms have been described. Permanent neonatal diabetes results predominantly from mutations in the KCNJ11 and ABCC8 genes. Less frequently, mutations of the GATA6 gene, located on chromosome 18 cause a form of permanent neonatal diabetes resulting from pancreatic hypoplasia or agenesis. Other anomalies associated with mutations of this gene have also been reported, most commonly congenital heart disease. CASE PRESENTATION: We report the case of a Caucasian male infant diagnosed shortly after birth with neonatal diabetes, truncus arteriosus type III, ventricular septal defect, atrial septal defect, an absent gallbladder and a right inguinal hernia. His diabetes resulted from a de novo mutation of the GATA6 gene resulting in pancreatic hypoplasia. At 20 months of age he developed protein losing enteropathy. This has not previously been associated with GATA6 mutations and it is not known if this association is causal. CONCLUSION: The combination of neonatal diabetes and pancreatic agenesis/hypoplasia should alert the clinician to the possibility of a GATA6 gene abnormality. The association of protein losing enteropathy is unique to the reported case.

Persistent Albuminuria in Children with Type 2 Diabetes: A Canadian Paediatric Surveillance Program Study.

OBJECTIVE: To determine the prevalence and the clinical features associated with persistent albuminuria in Canadian children aged <18 years with type 2 diabetes. STUDY DESIGN: This national prospective surveillance study involved a network of pediatricians and pediatric endocrinologists. Cases of persistent albuminuria in children with type 2 diabetes were reported during a 24-month period from 2010 to 2012. Persistent albuminuria was defined as an elevated albumin-to-creatinine ratio in a minimum of 2 out of 3 urine samples obtained at least 1 month apart over 3-6 months and confirmed with a first morning sample. Descriptive statistics were used to illustrate demographic and clinical features of the population. The prevalence of persistent albumuria was estimated using data from a previous national surveillence study of type 2 diabetes in children. RESULTS: Fifty cases were reported over the 24-month study period. The estimated prevalence of persistent albuminuria in children with type 2 diabetes in Canada was 5.1%. The median duration of diabetes at the time of diagnosis of albuminuria was 21 days (IQR, 0-241 days). Almost two-thirds (64%) were female, 80% were of Canadian First Nations heritage, and 76% were from Manitoba. Exposure to gestational or pregestational diabetes in utero occurred in 65%, and 48% had a family history of diabetes-related renal disease. Structural anomalies of the kidney were found in 37%. CONCLUSION: Persistent albuminuria occurs in youths with type 2 diabetes in the first year after diagnosis, demonstrates regional variation, and is associated with First Nations heritage and exposure to maternal diabetes during pregnancy.

Is the change in body mass index among children newly diagnosed with type 1 diabetes mellitus associated with obesity at transition from pediatric to adult care?

BACKGROUND: Insulin therapy is lifesaving treatment for individuals with type 1 diabetes (T1D). Its initiation maybe associated with significant weight gain because of change from a catabolic to an anabolic state. Excessive weight-gain increases the risk of obesity and is associated with chronic disease. OBJECTIVE: To examine if change in body mass index (BMI) among children in the 6 months after diagnosis with type 1 diabetes mellitus is associated with long-term obesity. METHODS: This was a population-based retrospective study of 377 children (aged 2-18 yr) with type 1 diabetes. Measured heights and weights were used to calculate BMI z-scores based on Centers for Disease Control and Prevention (CDC) cut-points. Generalized Linear Models using BMI group, and age group at diagnosis; postdiagnosis weight change; and sex were applied to assess associations between postdiagnosis weight change and BMI z-score at transition to adult care. RESULTS: Mean BMI z-score increased from 0.28 at diagnosis, to 0.53 at 6 months and 0.66 at transition to adult care. Change in BMI z-scores differed by initial BMI group and magnitude of postdiagnosis weight change. Younger children (<11 yr) had higher (p = 0.004) BMI z-scores at diagnosis but not at last visit (p = 0.1) than older (≥11 yr) children at diagnosis. BMI z-score at diagnosis, postdiagnosis weight change, female sex, and longer duration with TID were associated with higher BMI z-score at time of transition. CONCLUSIONS: BMI z-score at diagnosis was the strongest predictor of BMI z-score at time of transition to adult care, however; its effect was mediated by magnitude of weight change 6 months after diagnosis, sex, and age group at diagnosis.

Higher body mass index associated with severe early childhood caries.

BACKGROUND: Severe Early Childhood Caries (S-ECC) is an aggressive form of tooth decay in preschool children affecting quality of life and nutritional status. The purpose was to determine whether there is an association between Body Mass Index (BMI) and S-ECC. METHODS: Children with S-ECC were recruited on the day of their slated dental surgery under general anesthesia. Age-matched, caries-free controls were recruited from the community. All children were participating in a larger study on nutrition and S-ECC. Analysis was restricted to children ≥ 24 months of age. Parents completed a questionnaire and heights and weights were recorded. BMI scores and age and gender adjusted BMI z-scores and percentiles were calculated. A p-value ≤ 0.05 was significant. RESULTS: Two hundred thirty-five children were included (141 with S-ECC and 94 caries-free). The mean age was 43.3 ± 12.8 months and 50.2 % were male. Overall, 34.4 % of participants were overweight or obese. Significantly more children with S-ECC were classified as overweight or obese when compared to caries-free children (p = 0.038) and had significantly higher mean BMI z-scores than caries-free children (0.78 ± 1.26 vs. 0.22 ± 1.36, p = 0.002). Those with S-ECC also had significantly higher BMI percentiles (69.0 % ± 29.2 vs. 56.8 % ± 31.7, p = 0.003). Multiple linear regression analyses revealed that BMI z-scores were significantly and independently associated with S-ECC and annual household income as were BMI percentiles. CONCLUSIONS: Children with S-ECC in our sample had significantly higher BMI z-scores than caries-free peers.

Children have type 2 diabetes too: an historical perspective.

Prior to 1985, type 2 diabetes was a disease of adults. Simultaneously with the global epidemic of childhood obesity, type 2 diabetes has increased in children. Initially, the presentation of small case series of type 2 diabetes in children was met with skepticism. As the number and size of the case series grew and the first long-term outcomes of end-stage complications in young adults appeared in the literature, the international community took notice with guarded interest. Type 2 diabetes disproportionately affects the children of specific ethnic groups and from disadvantaged socioeconomic environments, especially Indigenous populations. The past decade has seen unprecedented intense global interest in the etiology, treatment, and prevention of type 2 diabetes in children.

Exploring the role of the HNF-1αG319S polymorphism in ß cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models.

The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and private polymorphism in the Oji-Cree population in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene, where a highly conserved glycine residue at position 319 is changed to a serine (termed HNF-1αG319S or simply G319S). Oji-Cree youth who carry one or two copies of the "S-allele" present at diagnosis with less obesity, reduced indicators of insulin resistance, and lower plasma insulin levels at diagnosis, suggestive of a primary defect in the insulin-secreting ß cells. Few studies on the impact of the HNF-1αG319S variant on ß cell function have been performed to date; however, much can be learned from other clinical phenotypes of HNF-1α-deficiency, including HNF-1α mutations that cause maturity-onset diabetes of the young 3 (MODY3). In addition, evaluation of Hnf-1α-deficient murine models reveals that HNF-1α plays a central role in the regulation of insulin secretion by regulating the expression of key genes involved in ß cell glucose-sensing, mitochondrial function, and the maintenance of the ß cell phenotype in differentiated ß cells. The overall goal of this minireview is to explore the impact of HNF-1α-deficiency on the ß cell to better inform future research into the mechanisms of ß cell dysfunction in Oji-Cree youth with T2D.

Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of chronic kidney disease in children. The relevance of timing of diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown. STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS: Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada, identified using administrative data housed at the Manitoba Centre for Health Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and gestational (>20 weeks) DM and relevant confounders (maternal age; renin-angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol, illicit drug, and smoking use during pregnancy; region of residence; and size for gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by International Classification of Diseases codes. RESULTS: 945 case patients with CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%) of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional multivariable logistic regression model, pregestational DM was associated with CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29; 95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA: OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic control and body mass index. CONCLUSIONS: This study suggests that DM in the first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The association between CAKUT and LGA suggests that poor glycemic control increases risk. Screening and intervention studies in women of childbearing age with DM are warranted to determine whether the risk of chronic kidney disease in children can be modified.

Factors Affecting Quality of Life in Adolescents Living With Type 2 Diabetes: A Substudy of the Improving Renal Complications in Adolescents With Type 2 Diabetes Through REsearch (iCARE) Cohort.

OBJECTIVES: Type 2 diabetes (T2D) disproportionately impacts adolescents living in challenging socioeconomic conditions. However, the impacts of T2D on quality of life (QOL) in this context are unknown. Our aim in this study was to evaluate QOL and identify its biological, psychological, and social determinants among adolescents living with and without T2D from similar sociodemographic backgrounds. Relationships between glycemic stability, early complications, and treatments of T2D and QOL were also examined. METHODS: Ninety-two adolescents with T2D and 59 at-risk controls were included from the Improving Renal Complications in Adolescents With Type 2 Diabetes Through Research (iCARE) cohort. The main outcome was QOL (Pediatric QOL Inventory [PedsQL]). Biological covariates included age, sex, body mass index z score, glycated hemoglobin, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. Psychological factors included perceived stress (14-item Perceived Stress Scale) and mental distress (6-item Kessler scale). Social factors included food security (Household Food Security Survey Module) and income quintile. Multivariate linear regression analyses were used to identify factors associated with QOL between adolescents with and without T2D, and within the T2D cohort. RESULTS: Mean total QOL scores among adolescents with T2D were lower than in controls (67.0±14.8 vs 71.7±16.2, p=0.04). Age, sex, and percent Indigenous ethnicity were not significantly different between groups. Mean duration of T2D was 2.3±2.0 years. In the multivariate analysis, QOL was not associated with diabetes status, but negative associations were seen between mental distress (ß=-1.46, p<0.001) and food insecurity QOL (ß=-6.26, p=0.037). No differences were seen between biological factors and QOL in either analysis. CONCLUSIONS: Significant factors associated with decreased QOL in adolescents living with T2D include mental distress and food insecurity, indicating areas for targeted intervention.

Incidence and prevalence of type 2 diabetes in Manitoba children 2009-10 to 2017-18: First Nation versus all other Manitobans.

AIM: To describe the incidence and prevalence of type 2 diabetes in children in Manitoba over a ten-year period. METHODS: Population-based, provincial databases were linked to calculate the incidence and prevalence of type 2 diabetes in children < 18 years of age in Manitoba from 2009-10 to 2017-18. First Nation and all other Manitoban children are described separately. RESULTS: The incidence of type 2 diabetes increased from 16.0/100,000/year in 2009-10 to 31‧1/100,000/year in 2017-18 (p < 0.001). For First Nation children, the incidence increased from 73‧4 to 121‧2/100,000/year (p < 0.001). For all other Manitoban children, the incidence increased from 3‧3 to 10‧7/100,000/year (p < 0.001). The prevalence of type 2 diabetes rose from 66‧4 to 124‧2/100,000/year between 2009 -10 and 2017-18 (<0.001). The prevalence in First Nation children rose from 282‧8 to 517‧9/100,000/year (p < 0.001) and in all other Manitoban children from 18‧4 to 35.0/100,000/year (p < 0.001). CONCLUSIONS: The incidence and prevalence of type 2 diabetes is increasing in Manitoban children. While the greatest increase is seen in all other Manitoban children, type 2 diabetes disproportionally affects First Nation children. Understanding the prevalence and incidence of type 2 diabetes in children is necessary for resource allocation and to inform program planning, aimed at both prevention and management.

DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes.

OBJECTIVE: Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. METHODS: We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. RESULTS: We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth. CONCLUSION: Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Vitamin D status of children with severe early childhood caries: a case-control study.

BACKGROUND: Severe Early Childhood Caries (S-ECC) affects the health and well-being of young children. There is limited research in this area, though evidence suggests that children with S-ECC are at an increased risk of malnutrition. The purpose of this study was to determine the association between vitamin D (25(OH)D) levels and S-ECC. METHODS: This case-control study was conducted from 2009 to 2011 in the city of Winnipeg, Manitoba, Canada. 144 preschool children with S-ECC were recruited from a local health centre on the day of their slated dental surgery under general anesthetic. 122 caries-free controls were recruited from the community. Children underwent a blood draw for vitamin D (25(OH)D), calcium, parathyroid hormone, and albumin levels. Parents completed an interviewed questionnaire assessing the child's nutritional habits, oral health, and family demographics. Analyses included descriptive and bivariate statistics as well as multiple and logistic regression. A p value ≤ 0.05 was significant. RESULTS: The mean age of participants was 40.8 ± 14.1 months. Children with S-ECC had significantly lower mean 25(OH)D (68.9 ± 28.0 nmol/L vs. 82.9 ± 31.1, p < 0.001), calcium (p < 0.001), and albumin (p < 0.001) levels, and significantly higher parathyroid hormone (p < 0.001) levels than those caries-free. Children with S-ECC were significantly more likely to have vitamin D levels below recognized thresholds for optimal and adequate status (i.e. < 75 and < 50 nmol/L, respectively). Multiple regression analysis revealed that S-ECC, infrequent milk consumption, and winter season were significantly associated with lower 25(OH)D concentrations. Low 25(OH)D levels, low household income, and poorer ratings of the child's general health were significantly associated with S-ECC on logistic regression. CONCLUSION: Children with S-ECC appear to have relatively poor nutritional health compared to caries-free controls, and were significantly more likely to have low vitamin D, calcium, and albumin concentrations and elevated PTH levels.

High prevalence of periodontitis in children and adolescents with type 2 diabetes.

BACKGROUND: The aim of the present study was to determine the prevalence of periodontitis in children and adolescents with type 2 diabetes, and if poor glycemic control is associated with increasing prevalence of the disease. METHODS: This is a cross-sectional study involving children and adolescents with type 2 diabetes. A questionnaire related to oral health care history and oral health behaviors was administered to each participant and they then underwent a full-mouth oral evaluation. In addition, clinical and metabolic parameters were extracted from the clinical chart. RESULTS: One hundred and twenty one children and adolescents (8-17 years, 11 months) participated. Overall, 45.5% presented some degree of periodontitis, with 10 (8.3%) mild, 36 (29.8%) moderate, and nine (7.4%) severe. The periodontitis group (PD-group) had higher mean gingival and plaque indexes, periodontal probing depth, and clinical attachment loss than the group without periodontitis (NoPD-group) (p<0.05). A statistically significant relationship between the prevalence of periodontitis and glycosylated hemoglobin (HbA1c) was verified in the bivariate (odds ratio [OR] 1.31 [95% CI, 1.13-1.53], p = 0.001) and multivariate (OR, 1.29 [95% CI, 1.03-1.61], p = 0.03) analysis. For the adjustment variables, associations were verified for duration of diabetes, age, body mass index z-score, lack of running water, insulin use, and acanthosis nigricans. CONCLUSIONS: Children and adolescents with type 2 diabetes presented high rates of periodontitis comparable with that seen in previous studies in youth with diabetes. Uncontrolled HbA1c influences prevalence of periodontal disease. The lack of matched control group and radiographs are limitations of the study. Comprehensive periodontal examination is essential for children and adolescents with type 2 diabetes to prevent, identify, and treat periodontitis early.