Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance.

SUMMARY: We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants. LEARNING POINTS: Insulin receptor (INSR) gene variants can be a cause of monogenic diabetes in children and adolescents. Genetic evaluation should be considered in children and adolescents with type 2 diabetes (T2D), particularly where there is an atypical presentation and/or positive family history. Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.

Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes.

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8-15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.

Demographic and clinical characteristics of a population-based pediatric cohort of type 1 and type 2 diabetes in Western Australia (1999-2019).

OBJECTIVES: To determine demographic and clinical characteristics of youth diagnosed with type 1 (T1D) or type 2 (T2D) diabetes aged ≤15 years from 1999 to 2019 in Western Australia, and examine time to first diagnosis of diabetes complications. METHODS: A retrospective cohort study was conducted of patients identified from the population-based, prospective Western Australian Children's Diabetes Database and longitudinal data extracted for available demographic and clinical variables. Patients were followed from diagnosis to transition to adult services, death, or December 31, 2019. Cox proportional hazards regression models were used to analyse time to first diagnosis of hypertension, high cholesterol or microalbuminuria, after adjusting for sex, age at diagnosis, time period of diagnosis, hemoglobin A1c , and body max index Z-score. RESULTS: 2438 eligible patients were identified (2209 [91%] T1D: 229 [9%] T2D). The mean age at diagnosis was lower in patients with T1D (8.5 [±4.0] vs. 12.7 [±2.0] years). A higher proportion of patients with T2D were female (58% vs. 47%) and of Aboriginal ethnicity (59% vs. 2%). The median HbA1c (interquartile range) at diagnosis was lower 8.9% [6.7, 11.5] (74 mmol/mol [50, 102]) versus 11.6% [10.1, 13.3] (103 mmol/mol [87, 122]) and mean body max index Z-score higher (2.05 [±0.66] vs. 0.37 [±0.95]), in patients with T2D compared to T1D. Patients with T2D had a higher risk of hypertension, high cholesterol, and microalbuminuria (aHR 3.39 [95%CI:2.04, 5.63], 2.69 [95%CI:1.21, 5.98], and 19.79 [95%CI:10.99, 35.64] respectively).

Families' knowledge, attitudes, and experiences of the tissue donation process.

CONTEXT: Most existing research on the experiences of donor families has been focused on organ donation, with few studies pertaining specifically to the experiences of tissue donor families. Further investigation into tissue donation in Australia is needed in order to improve the process, support, and potential rate of tissue donation consent. OBJECTIVE: To assess the experiences of families of recent tissue donors, to compare changes in the tissue donation process with previously published research, and to identify areas for improvement. DESIGN: Cross-sectional survey by postal questionnaire. SETTING AND PARTICIPANTS: Families who consented to tissue donation through DonateLife Western Australia (the coordinating organization for deceased organ and tissue donation in Western Australia) between 2004 and 2009 were invited to participate. MAIN OUTCOME MEASURES: Donor families' experience, knowledge, and attitudes toward tissue donation and their satisfaction with the approach and quality/effectiveness of support services provided to donor families. RESULTS: One hundred one (39%) of the 256 questionnaires were completed. Most respondents were satisfied with how they were approached, whether by phone or in person. Most participants who received ongoing support after donation (91%) found it beneficial. Nearly half (46%) of respondents supported the use of tissue for research; however, only 28% could recall the topic being discussed at the time of donation. Only 40% of respondents knew of the differences between organ and tissue donation before the donation process. Overall, respondents rated the experience of donating tissue as positive.