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.

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.

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.

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.

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.

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.

24-h ambulatory blood pressure readings and associations with albuminuria in youth with type 2 diabetes: A cross sectional analysis from the iCARE cohort.

AIMS: To evaluate associations between 24-h ambulatory blood pressure monitor (ABPM) data vs. single casual blood pressure (BP) and albuminuria in youth with type 2 diabetes. METHODS: A cross-sectional analysis of youth with type 2 diabetes 10-<18 yrs. from the iCARE cohort. MAIN EXPOSURES: daytime HTN (+/- nocturnal), isolated nocturnal HTN and single casual BP. MAIN OUTCOME: non-orthostatic urine albumin: creatinine ratio (ACR) ≥ 3 mg/mmol and log-transformed urine ACR. Regressions evaluated associations between 1. HTN status based on ABPM and log-transformed urine ACR (continuous) and 2. ABPM-derived BP z-scores and casual BPcentiles and albuminuria status (categorical). RESULTS: Of 281 youth included, 19.6 % had daytime HTN (+/- nocturnal), and 28.5 % isolated nocturnal HTN on 24-h ABPM. In multivariate linear regression, HTN (ABPM) (ß = 0.553; p = 0.001), duration of diabetes (ß = 0.857; p = 0.02), HbA1c (ß = 1.172; p ≤0.0001) and ACEI/ARB use (ß = 3.94; p < 0.0001) were positively associated with log-transformed ACR; (R2 = 0.184). In logistic regression analysis, all ABPM LMS z-scores were positively associated with albuminuria; casual BPcentile was not significant. CONCLUSIONS: Youth with type 2 diabetes have high rates of HTN based on 24-ABPM data. ABPM-derived measures of BP are associated with albuminuria. These data support the routine use of ABPM devices to diagnose hypertension in youth with type 2 diabetes.

Differing clinical features in Aboriginal vs. non-Aboriginal children presenting with type 2 diabetes.

OBJECTIVES: Childhood type 2 diabetes (T2D) is increasing and may present differently across various populations. This study compares clinical features of T2D at diagnosis in Aboriginal children with Caucasian children and children from other high-risk ethnic groups. PATIENTS AND METHODS: This retrospective observational study used data from a Canadian surveillance study where newly diagnosed cases of childhood T2D were reported (n = 227). Using descriptive statistics, clinical features at diagnosis of T2D were compared across different ethnic groups including Aboriginal (n = 100), Caucasian (n = 57), and other high-risk ethnic groups (n = 64). Comparisons were made between Aboriginal children living in central Canada (Manitoba/northwestern Ontario) (n = 74) and Aboriginal children from other regions of Canada (n = 26). RESULTS: Aboriginal children were younger, less obese, and less likely to have polycystic ovarian syndrome and dyslipidemia when compared to Caucasian children and children from other high-risk ethnic groups (p < 0.05). Aboriginal children from central Canada vs. those from other regions of Canada did not differ in age, body mass index z-score, family history of T2D, or presence of acanthosis nigricans. Those from central Canada had lower hemoglobin A1c levels (p < 0.05) and were less likely to have dyslipidemia than Aboriginal children from other regions (p < 0.05). CONCLUSIONS: Clinical features and rates of comorbidity in children with newly diagnosed T2D differ across various populations (Caucasian, Aboriginal, and children who belong to other high-risk ethnic groups) and across distinct Aboriginal populations (those living in central Canada vs. those living in other regions of Canada). Future research should determine specific genetic and environmental factors that contribute to these differences.

The relationship between vitamin D and severe early childhood caries: a pilot study.

INTRODUCTION: Children with Severe Early Childhood Caries (S-ECC) routinely require dental surgery. S-ECC is known to affect childhood health and well-being. The objective of this pilot study was to assess vitamin D [25(OH)D] levels and determine whether differences exist between children with and without S-ECC. METHODS: During July-September 2008, children undergoing surgery for S-ECC < 72 months of age from southern Manitoba were recruited. Age-matched controls were caries-free. Parents completed an interviewed questionnaire. A serum sample was obtained for 25(OH)D and parathyroid hormone (PTH) levels. This study was approved by the University of Manitoba's Ethics Board. Statistics included chi-square analysis, t-tests, and multiple and logistic regression. A p value of <= 0.05 was significant. RESULTS: Thirty-eight children participated (50 % with S-ECC). There was no significant age difference between groups (p = 0.82). The majority of the entire sample (84.2 %) had inadequate vitamin D levels. Children with S-ECC had lower concentrations of 25(OH)D (52.9 ± 15.1 nmol/L vs. 64.4 ± 21.3, p = 0.032) and were at twice the odds of having inadequate levels (<75 nmol/L). Children with S-ECC also had significantly higher PTH levels than caries-free children (53.5 ± 17.6 cm/L vs. 33.9 ± 12.9, p < 0.001). A greater number with S-ECC had elevated PTH levels (68.4 % vs. 21.1 %, p < 0.01). CONCLUSIONS: This pilot study is the first to report differences in 25(OH)D between those with S-ECC and cavity-free controls. Children with S-ECC have lower vitamin D levels and increased PTH levels compared to age-matched controls.

Pregestational Diabetes Exposure In Utero: Validation of a Definition for Use in Administrative Data.

OBJECTIVE: Our aim in this study was to determine the best administrative data case definition for pregestational diabetes exposure. METHODS: We compared the performance of case definitions for pregestational diabetes exposure within the administrative health data housed in the Manitoba Population Health Research Repository at the Manitoba Centre for Health Policy with an identified population of women in whom the diagnosis of pregestational diabetes was known from the clinical database of the Manitoba Diabetes Education Resource for Children and Adolescents (DER-CA) (August 12, 1989 through January 28, 2015). The DER-CA database contains maternal diabetes status during pregnancy and also includes women diagnosed with type 2 diabetes in childhood whose pregnancies were thus all complicated by pregestational diabetes exposure. Linkage of mother-child dyads is possible within the Repository. Diagnosis codes from the International Classification of Diseases---ninth or tenth revision and physician tariff codes were used to identify diabetes in the biologic mothers of children with type 2 diabetes identified from the DER-CA database. The timing of the diagnosis of diabetes in the mother with respect to the gestational age of the pregnancy was determined. RESULTS: The best administrative definition of pregestational diabetes exposure was any incident code for diabetes in the mother before the pregnancy of the index child or within the first 25 weeks of pregnancy (sensitivity: 84.77%; positive predictive value: 92%). CONCLUSION: The definition cited can be used to define pregestational diabetes exposure in studies utilizing administrative data.

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: A cross-sectional study.

Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D. Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D. Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others. Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

Risk factors for medication-induced diabetes and type 2 diabetes.

OBJECTIVE: To compare the prevalence of risk factors in children aged <18 years diagnosed with medication-induced diabetes mellitus versus those diagnosed with type 2 diabetes. STUDY DESIGN: This retrospective observational study used data from a Canadian prospective surveillance study in which clinical features of new cases of type 2 diabetes (n = 225) and medication-induced diabetes (n = 58) were reported over a 2-year period. The presence of risk factors for type 2 diabetes (eg, obesity, family history of type 2 diabetes, ethnicity, acanthosis nigricans, hypertension, polycystic ovarian syndrome) was compared in the 2 groups using descriptive statistics and logistic regression. RESULTS: Compared with the children with type 2 diabetes, the children with medication-induced diabetes were more likely to be Caucasian (P < .0001) and less likely to be obese (P < .0001), to have a positive family history of type 2 diabetes (P = .0001), to have acanthosis nigricans (P < .0001) on clinical examination, and to have an obesity-related comorbidity, such as polycystic ovarian syndrome (P = .04), dyslipidemia (P = .02), hypertension (P = .04), or an elevated alanine aminotransferase level (P = .05). CONCLUSIONS: Evaluating for the typical risk factors for type 2 diabetes is not sufficient to identify all children at risk for developing medication-induced diabetes. Further studies are needed to help inform guidelines on screening for and prevention of medication-induced diabetes in children.