Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

INTRODUCTION: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. ß-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. MAIN RECOMMENDATIONS: This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.

Whole exome sequencing reveals copy number variants in individuals with disorders of sex development.

Complete androgen insensitivity syndrome (CAIS), where 46,XY individuals present as female, is caused by variants in the androgen receptor gene (AR). We analyzed the DNA of a patient with suspected CAIS using a targeted gene sequencing panel and whole exome sequencing (WES) but did not detect any small nucleotide variants in AR. Analysis of WES data using our bioinformatics pipeline designed to detect copy number variations (CNV) uncovered a rare duplication of exon 2 of AR. Using array comparative genomic hybridization, the duplication was found to span 43.6 kb and is predicted to cause a frameshift and loss of AR protein. We confirmed the power of our WES-CNV detection protocol by identifying pathogenic CNVs in FSHR and NR5A1 in previously undiagnosed patients with disorders of sex development. Our findings illustrate the usefulness of CNV analysis in WES data to detect pathogenic genomic changes that may go undetected using only standard analysis protocols.

Hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN syndrome): an extreme subphenotype of polycystic ovary syndrome.

HAIR-AN-a syndrome of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN)-is a specific subphenotype of polycystic ovary syndrome (PCOS), and it is seen in almost 5% of all women with hyperandrogenism. An adolescent girl aged 11 years old was referred with adrenarche, hyperandrogenism and obesity commencing at age 8. Clinical and biochemical investigations confirmed significant hyperandrogenism and insulin resistance, and a diagnosis of HAIR-AN syndrome was made after exclusion of other differential diagnoses. HAIR-AN syndrome is an important diagnosis for the adolescent gynaecologist to be aware of, and it requires a multidisciplinary approach, including endocrinology input, for optimal management. Weight loss, lifestyle modification and combined hormonal pill and metformin are considered first-line treatment.

Muscular strength, aerobic capacity, and adipocytokines in obese youth after resistance training: A pilot study.

BACKGROUND: Exercise has shown positive training effects on obesity-related inflammation, however, resistance training has shown mixed results concerning adipocytokine levels. AIMS: The purpose of this pilot study was to explore the effects of resistance training on blood adipocytokine concentrations in obese youth, with specific examination of the relationship between these biomarkers and improved fitness (i.e., aerobic capacity, muscular strength). METHODS: Fourteen obese adolescents (16.1 ±1.6 y; BMI: 32.3 ±3.9 kg/m(2)) participated in a 16-week resistance training intervention. Body composition, fasting blood concentrations of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), adiponectin, and leptin were measured pre- and post-training. Aerobic capacity was assessed via a maximal discontinuous exercise test. The rate of gain in muscular strength was calculated as the slope of progression in 1-repetition maximum throughout the intervention. RESULTS: Resistance training increased lean mass (total, trunk) and decreased per cent body fat (total, trunk). The training also caused moderate clear decreases in IL-6 and TNF-ɑ concentrations. A small increase in adiponectin was also observed before and after intervention. When the group was stratified by changes in aerobic capacity, there were substantially larger decreases in leptin levels for those with improved capacity. Correlation analyses also revealed a negative relationship between log-transformed leptin and aerobic capacity at rest. Improvement in quadriceps strength was positively correlated with IL-6 and TNF-ɑ, while improvement in shoulder adductor strength was positively correlated with IL-6 only. CONCLUSION: Resistance training improved adipocytokine markers, which were partially associated with improved physical fitness. Specifically, the relationship between strength improvements and IL-6 and TNF-ɑ suggests an exercise-induced signalling pathway that results in overall adaptive decreases in systemic inflammation in obese youth.

Relation of reduced preclinical left ventricular diastolic function and cardiac remodeling in overweight youth to insulin resistance and inflammation.

Insulin resistance (IR) and inflammation are associated with an increased risk of cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic function, which may be evident in obese children and adolescents. However, the precise metabolic basis of the impaired LV diastolic function remains unknown. The aims of this study were to evaluate cardiac structure and LV diastolic function by tissue Doppler imaging in overweight and obese (OW) youth and to assess the relative individual contributions of adiposity, IR, and inflammation to alterations in cardiac structure and function. We studied 35 OW (body mass index standard deviation score 2.0±0.8; non-IR n=19, IR n=16) and 34 non-OW youth (body mass index standard deviation score 0.1±0.7). LV diastolic function was reduced in OW youth compared with non-OW controls, as indicated by lower peak myocardial relaxation velocities (p<0.001) and greater filling pressures (p<0.001). OW youth also had greater LV mass index (p<0.001), left atrial volume index, and LV interventricular septal thickness (LV-IVS; both p=0.02). IR-OW youth had the highest LV filling pressures, LV-IVS, and relative wall thickness (all p<0.05). Homeostasis model of assessment-insulin resistance and C-reactive protein were negative determinants of peak myocardial relaxation velocity and positive predictors of filling pressure. Adiponectin was a negative determinant of LV-IVS, independent of obesity. In conclusion, OW youth with IR and inflammation are more likely to have adverse changes to cardiovascular structure and function which may predispose to premature cardiovascular disease in adulthood.