Effects of 12-Week Freestyle Libre 2.0 in Children with Type 1 Diabetes and Elevated HbA1c: A Multicenter Randomized Controlled Trial.

Objective: To investigate whether intermittently scanned continuous glucose monitoring (isCGM) reduced glycated hemoglobin (HbA1c) compared with capillary self-monitored capillary blood glucose (SMBG) in children with type 1 diabetes (T1D) and elevated glycemic control. Research Design and Methods: This multicenter 12-week 1:1 randomized, controlled, parallel-arm trial included 100 participants with established T1D aged 4-13 years (mean 10.9 ± 2.3 years) naive to isCGM and with elevated HbA1c 7.5%-12.2% [58-110 mmol/mol] [mean HbA1c was 9.05 (1.3)%] [75.4 (13.9) mmol/mol]. Participants were allocated to 12-week intervention (isCGM; FreeStyle Libre 2.0; Abbott Diabetes Care, Witney, United Kingdom) (n = 49) or control (SMBG; n = 51). The primary outcome was the difference in change of HbA1c from baseline to 12 weeks. Results: There was no evidence of a difference between groups for change in HbA1c at 12 weeks (0.23 [95% confidence interval; CI: -0.21 to 0.67], P = 0.3). However, glucose-monitoring frequency increased with isCGM +4.89/day (95% CI 2.97-6.81; P < 0.001). Percent time below range (TBR) <3.9 mmol/L (70-180 mg/dL) was reduced with isCGM -6.4% (10.6 to -4.2); P < 0.001. There were no differences in within group changes for Parent or Child scores of psychosocial outcomes at 12 weeks. Conclusions: For children aged 4-13 years with elevated Hba1c isCGM led to improvements in glucose testing frequency and reduced time below range. However, isCGM did not translate into reducing Hba1c or psychosocial outcomes compared to usual care over 12-weeks. The trial is registered within the Australian New Zealand Trial Registry on February 19, 2020 (ACTRN12620000190909p; ANZCTR.org.au) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1237-0090).

Inequity in access to continuous glucose monitoring and health outcomes in paediatric diabetes, a case for national continuous glucose monitoring funding: A cross-sectional population study of children with type 1 diabetes in New Zealand.

Background: Continuous glucose monitoring (CGM) improves glycaemia for people affected by type 1 diabetes (T1D), but is not funded in Aotearoa/New Zealand. This study explores the impact of non-funded CGM on equity of access and associated glycaemic outcomes. Methods: Cross-sectional population-based study collected socio-demographic (age, gender, prioritised ethnicity, socioeconomic status) and clinical data from all regional diabetes centres in New Zealand with children <15 years with T1D as of 1st October 2021. De-identified data were obtained from existing databases or chart review. Outcomes compared socio-demographic characteristics between those using all forms of CGM and self-monitoring of blood glucose (SMBG), and association with HbA1c. Findings: 1209 eligible children were evaluated: 70.2% European, 18.1% Maori, 7.1% Pacific, 4.6% Asian, with even distribution across socioeconomic quintiles. Median HbA1c was 64 mmol/mol (8.0%), 40.2% utilised intermittently scanned (is)CGM, and 27.2% real-time (rt)CGM. CGM utilisation was lowest with Pacific ethnicity (38% lower than Maori) and the most deprived socioeconomic quintiles (quintile 5 vs. 1 adjusted RR 0.69; 95% CI, 0.57 to 0.84). CGM use was associated with regional diabetes centre (P < 0.001). The impact of CGM use on HbA1c differed by ethnicity: Maori children had the greatest difference in HbA1c between SMBG and rtCGM (adjusted difference -15.3 mmol/mol; 95% CI, -21.5 to -9.1), with less pronounced differences seen with other ethnicities. Interpretation: Inequities in CGM use exist based on prioritised ethnicity and socioeconomic status. Importantly, CGM was independently associated with lower HbA1c, suggesting that lack of CGM funding contributes to health disparity in children with T1D. Funding: Australasian Paediatric Endocrine Group (APEG), Canterbury Medical Research Foundation, Starship Foundation.

The OPTIMISE study protocol: a multicentre optimisation trial comparing continuous glucose monitoring, snacking habits, sleep extension and values-guided self-care interventions to improve glucose time-in-range in young people (13-20 years) with type 1 diabetes.

Purpose: The OPTIMISE study uses a Multiphase Optimisation Strategy (MOST) to identify the best combination of four interventions targeting key diabetes self-care behaviours for use in clinical practice to improve short-term glycaemic outcomes. Methods: This 4-week intervention trial will recruit 80 young people (aged 13-20 years) with type 1 diabetes ≥ 6 months duration), and pre-enrolment HbA1c ≥ 58 mmol/mol (7.5%) in the prior 6 months. Both main intervention and interaction effects will be estimated using a linear regression model with change in glucose time-in-range (TIR; 3.9-10.0 mmol/L) as the primary outcome. Participants will be randomised to one of 16 conditions in a factorial design using four intervention components: (1) real-time continuous glucose monitoring (CGM), (2) targeted snacking education, (3) individualised sleep extension, and (4) values-guided self-care goal setting. Baseline and post-intervention glucose TIR will be assessed with blinded CGM. Changes in self-care (snacking behaviours, sleep habits and duration, and psychosocial outcomes) will be assessed at baseline and post-intervention to determine if these interventions impacted behaviour change. Discussion: The study outcomes will enable the selection of effective and efficient intervention components that increase glucose TIR in young people who struggle to achieve targets for glycaemic control. The optimised intervention will be evaluated in a future randomised controlled trial and guide the planning of effective clinical interventions in adolescents and young adults living with type 1 diabetes. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 7 October 2020 (ACTRN12620001017910) and the World Health Organisation International Clinical Trails Registry Platform on 26 July 2020 (Universal Trial Number WHO U1111-1256-1248).

Use of intermittently scanned continuous glucose monitoring in young people with high-risk type 1 diabetes-Extension phase outcomes following a 6-month randomized control trial.

AIMS: To describe the impact of a 12-month intervention using intermittently scanned continuous glucose monitoring (isCGM) on glycaemic control and glucose test frequency in adolescents and young adults with type 1 diabetes (T1D) and high-risk glycaemic control (HbA1c ≥75 mmol/mol [≥9.0%]). METHODS: In total, 64 young people (aged 13-20 years, 16.6 ± 2.1 years; 48% female; 41% Maori or Pacific ethnicity; mean diabetes duration 7.5 ± 3.8 years) with T1D were enrolled in a 6-month, randomized, parallel-group study comparing glycaemic outcomes from the isCGM intervention (n = 33) to self monitoring blood glucose (SMBG) controls (n = 31). In this 6-month extension phase, both groups received isCGM; HbA1c , glucose time-in-range (TIR), and combined glucose test frequency were assessed at 9 and 12 months. RESULTS: At 12 months, the mean difference in HbA1c from baseline was -4 mmol/mol [-0.4%] (95% confidence interval, CI: -8, 1 mmol/mol [-0.8, 0.1%]; p = 0.14) in the isCGM intervention group, and -7 mmol/mol [-0.7%] (95% CI: -16, 1 mmol/mol [-1.5, 0.1%]; p = 0.08) in the SMBG control group. No participants achieved ≥70% glucose TIR (3.9-10.0 mmol/L). The isCGM intervention group mean rate of daily glucose testing was highest at 9 months, 2.4 times baseline rates (p < 0.001), then returned to baseline by 12 months (incidence rate ratio = 1.4; 95% CI: 0.9, 2.1; p = 0.091). CONCLUSIONS: The use of isCGM in young people with high-risk T1D resulted in transient improvements in HbA1c and glucose monitoring over a 9-month time frame; however, benefits were not sustained to 12 months.

Impact of high-risk glycemic control on habitual sleep patterns and sleep quality among youth (13-20 years) with type 1 diabetes mellitus compared to controls without diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1D), glycemic control and sleep have a bidirectional relationship, with unhealthy glycemic control impacting sleep, and inadequate sleep impacting diabetes management. Youth are at risk for poor quality sleep; however, little is known about sleep among youth with high-risk glycemic control. OBJECTIVE: To assess differences in habitual sleep timing, duration, and quality among youth with T1D and controls. SUBJECTS: Two-hundred-thirty youth (13-20 years): 64 with T1D (mean age 16.6 ± 2.1 years, 48% female, diabetes duration 7.5 ± 3.8 years, HbA1c 96 ± 18.0 mmol/mol [10.9 ± 1.7%]), and 166 controls (mean age 15.3 ± 1.5, 58% female). METHODS: Comparison of data from two concurrent studies (from the same community) using subjective and objective methods to assess sleep in youth: Pittsburgh Sleep Quality Index evaluating sleep timing and quality; 7-day actigraphy measuring habitual sleep patterns. Regression analyses were used to compare groups. RESULTS: When adjusted for various confounding factors, youth with T1D reported later bedtimes (+36 min; p < 0.05) and shorter sleep duration (-53 min; p < 0.05) than controls, and were more likely to rate subjective sleep duration (OR 3.57; 95% CI 1.41-9.01), efficiency (OR 4.03; 95% CI 1.43-11.40), and quality (OR 2.59; 95% CI 1.16-5.76) as "poor" (p < 0.05). However, objectively measured sleep patterns were similar between the two groups. CONCLUSIONS: Youth with high-risk T1D experience sleep difficulties, with later bedtimes contributing to sleep deficit. Despite a lack of objective differences, they perceive their sleep quality to be worse than peers without diabetes.

Fatal perinatal mitochondrial cardiac failure caused by recurrent de novo duplications in the ATAD3 locus.

BACKGROUND: In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosis. A contributing factor is the difficulty with repetitive regions of the genome, such as those generated by segmental duplications. The ATAD3 locus is one such region, in which recessive deletions and dominant duplications have recently been reported to cause lethal perinatal mitochondrial diseases characterized by pontocerebellar hypoplasia or cardiomyopathy, respectively. METHODS: Whole exome, whole genome and long-read DNA sequencing techniques combined with studies of RNA and quantitative proteomics were used to investigate 17 subjects from 16 unrelated families with suspected mitochondrial disease. FINDINGS: We report six different de novo duplications in the ATAD3 gene locus causing a distinctive presentation including lethal perinatal cardiomyopathy, persistent hyperlactacidemia, and frequently corneal clouding or cataracts and encephalopathy. The recurrent 68 Kb ATAD3 duplications are identifiable from genome and exome sequencing but usually missed by microarrays. The ATAD3 duplications result in the formation of identical chimeric ATAD3A/ATAD3C proteins, altered ATAD3 complexes and a striking reduction in mitochondrial oxidative phosphorylation complex I and its activity in heart tissue. CONCLUSIONS: ATAD3 duplications appear to act in a dominant-negative manner and the de novo inheritance infers a low recurrence risk for families, unlike most pediatric mitochondrial diseases. More than 350 genes underlie mitochondrial diseases. In our experience the ATAD3 locus is now one of the five most common causes of nuclear-encoded pediatric mitochondrial disease but the repetitive nature of the locus means ATAD3 diagnoses may be frequently missed by current genomic strategies. FUNDING: Australian NHMRC, US Department of Defense, Japanese AMED and JSPS agencies, Australian Genomics Health Alliance and Australian Mito Foundation.

Young people with a variation in sex characteristics in Aotearoa/New Zealand: identity, activism and healthcare decision-making.

Young people born with variations in sex characteristics (VSC) or disorders of sex development (DSD) face numerous challenges in navigating issues relating to identity and to their lived and embodied experience. There is limited published research amplifying the voices of young people with a VSC, especially from Aotearoa/New Zealand. This qualitative study provides an up-to-date picture of the lived experience of 10 young people with a VSC in Aotearoa/New Zealand. The research was conducted in collaboration with the advocacy group, Intersex Youth Aotearoa, and explored the level of support provided by health services, peers and advocacy groups in relation to the ways the participants viewed themselves and their bodies, and their health related decision-making. Findings reveal the pressure on young people with a VSC to conform to cultural and societal norms, specifically, heteronormative and traditional constructs of how male and female bodies should look in Aotearoa/NZ society. Such views, often held and perpetuated by health professionals and parents, contributed to complexities surrounding identity, agency and acceptance of difference experienced by these young people. The implications of these findings are discussed, including the need for better psychological and peer support for young people.

Youth and non-European ethnicity are associated with increased loss of publicly funded insulin pump access in New Zealand people with type 1 diabetes.

AIMS: Continuous subcutaneous insulin infusion (CSII) has been publicly funded in New Zealand for people living with type 1 diabetes since 2012. The aim of the current study was to investigate the loss of access, once obtained, to public-funded CSII. The frequency and socio-demographics of access, and loss, to CSII spanning the period 2012 to 2018 were examined. METHODS: Nationally held data collections including the New Zealand Virtual Diabetes Register were used to calculate the overall and subgroup proportions using and ceasing CSII. A logistic regression model was used to estimate odds ratios for pump use for the predictor variables (sex, age group, ethnicity and deprivation index) and to calculate odds ratios for pump cessation for the same demographic factors. RESULTS: Once CSII access is obtained, approximately 4% per year cease CSII in a subsequent year. This cessation of publicly funded CSII was not distributed equally among the population, showing over-representation in youth (aged 10-29 years) and non-Europeans, in particular Maori and Pasifika. Compounding this, it remains less likely for people with diabetes to initially access publicly funded CSII in New Zealand if they are non-European and more socio-economically deprived. CONCLUSIONS: In New Zealand, Maori and Pasifika, as well as youth, are over-represented in the cessation of CSII in comparison with Europeans and all other age groups. These groups are also less likely to gain initial access to public funding. Efforts to understand and reduce these disparities are needed, including review of current public funding access criteria.

Cutaneous adverse events in a randomized controlled trial of flash glucose monitoring among youth with type 1 diabetes mellitus.

BACKGROUND: The literature regarding flash glucose monitoring (FGM)-associated cutaneous adverse events (AE) is limited. OBJECTIVES: This study among youth participating in a 6 month randomized controlled trial aimed to compare cutaneous AE between FGM and self-monitored blood glucose (SMBG) use and evaluate premature FGM sensor loss. METHODS: Patients aged 13 to 20 years with type 1 diabetes were randomized to intervention (FGM and usual care) or control (SMBG and usual care). Participants self-reported cutaneous AEs electronically every 14 days. Reports were analyzed to determine frequency, type, and severity of cutaneous AEs, and evaluate premature sensor loss. RESULTS: Sixty-four participants were recruited; 33 randomized to FGM and 31 to control. In total, 80 cutaneous AEs were reported (40 in each group); however, the proportion of participants experiencing cutaneous AEs was greater in the FGM group compared to control (58% and 23% respectively, P = .004). FGM participants most frequently reported erythema (50% of AEs), while controls most commonly reported skin hardening (60% of AEs). For FGM users, 80.0% of cutaneous AEs were mild, 17.5% moderate, and 2.5% severe. Among controls, 82.5% of cutaneous AEs were mild and 17.5% moderate. One participant ceased using FGM due to recurring cutaneous AEs. Additionally, over 6 months, 82% of FGM participants experienced at least one premature sensor loss, largely unrelated to a cutaneous AE. CONCLUSIONS: Cutaneous FGM-associated AEs are common, and mostly rated as mild. However, the majority of users continued FGM despite cutaneous AEs. Awareness of cutaneous complications and mitigation measures may reduce cutaneous AEs and improve the overall experience of FGM.

Effect of 6 Months of Flash Glucose Monitoring in Youth With Type 1 Diabetes and High-Risk Glycemic Control: A Randomized Controlled Trial.

OBJECTIVE: To investigate whether intermittently scanned continuous glucose monitoring (isCGM) significantly improves glycemic control compared with capillary self-monitored blood glucose (SMBG) in youth with type 1 diabetes and high-risk glycemic control. RESEARCH DESIGN AND METHODS: This multicenter 6-month randomized, controlled, parallel-arm trial included 64 participants aged 13-20 years with established type 1 diabetes and glycated hemoglobin (HbA1c) ≥9% (≥75 mmol/mol). Participants were allocated to 6-month intervention (isCGM; FreeStyle Libre; Abbott Diabetes Care, Witney, U.K.) (n = 33) or control (SMBG; n = 31) using minimization. The primary outcome was the difference in change in HbA1c from baseline to 6 months. RESULTS: There was no evidence of a difference between groups for changes in HbA1c at 6 months (adjusted mean 0.2% greater improvement for isCGM [95% CI -0.9 to 0.5] [-2.1 mmol/mol (95% CI -9.6 to 5.4)]; P = 0.576). However, glucose-monitoring frequency was 2.83 (95% CI 1.72-4.65; P < 0.001) times higher in the isCGM group compared with that in the SMBG group at 6 months. The change in the Diabetes Treatment Satisfaction Questionnaire mean item score also favored isCGM at 6 months (P = 0.048), with no significant differences between groups for fear of hypoglycemia and quality of life (both general and diabetes specific) (all P > 0.1). CONCLUSIONS: For youth with high-risk glycemic control, isCGM led to improvements in glucose testing frequency and diabetes treatment satisfaction. However, these did not translate to greater improvement in glycemic control over usual care with SMBG at 6 months.

The 'flash' adhesive study: a randomized crossover trial using an additional adhesive patch to prolong freestyle libre sensor life among youth with type 1 diabetes mellitus.

AIMS: Although strategies to prevent premature sensor loss for flash glucose monitoring (FGM) systems may have substantial benefit, limited data are available. This study among youth with high-risk type 1 diabetes evaluated whether an additional adhesive patch over FGM sensors would reduce premature sensor loss frequency and not cause additional cutaneous adverse events (AEs). METHODS: This is a six-month, open-label, randomized crossover trial. Participants were recruited at completion of prior 'Managing Diabetes in a Flash' randomized controlled trial and allocated to three months of Freestyle Libre FGM sensors with either standard adhesive (control) or additional adhesive patches (RockaDex, New Zealand) (intervention), before crossing over to the opposite study arm. Participants self-reported patch use or non-use, premature sensor loss and cutaneous AEs fortnightly via an electronic questionnaire. RESULTS: Thirty-four participants were enrolled: mean age (± SD) 17.0 (± 2.2) years; mean HbA1c (± SD) 89 (± 16) mmol/mol (10.3% ± 1.4%). The response rate of questionnaires was 77% (314/408). Premature sensor loss was reported in 18% (58/314) of questionnaires: 20% (32/162) from intervention and 17% (26/152) from control (p = 0.56). Thirty-eight percent (118/314) of questionnaires were non-compliant to protocol allocation. However, per-protocol analysis showed similar findings. No significant difference in AEs was reported between compliant adhesive patch use and non-use (6% [5/78] and 3% [3/118], respectively, p = 0.27). CONCLUSIONS: The adhesive patch investigated in this study does not appear to prevent premature FGM sensor loss. However, the low risk of AEs and low cost of an adhesive patch suggest an individualized approach to their use may still be warranted. Further research is needed to explore alternative strategies to prevent sensor loss.

Impact of type 1 diabetes mellitus, glucose levels, and glycemic control on sleep in children and adolescents: a case-control study.

STUDY OBJECTIVES: To assess differences in habitual sleep patterns and sleep states between children and adolescents with type 1 diabetes mellitus (T1DM) and control subjects, and to explore the relationships between sleep, glucose levels, and glycemic control. METHODS: Participants included 82 children (5-18 years); 41 with T1DM (cases), and 41 healthy control subjects group matched for age and sex. Sleep was measured by 7-day actigraphy and single-night home-based polysomnography (PSG) recordings. Hemoglobin A1c (HbA1c) and 7 days of continuous glucose monitoring (CGM) data were collected in cases. Regression analyses were used to model all within- and between-group comparisons adjusted for age, sex, and BMI z-scores. RESULTS: There were no significant differences in sleep duration, efficiency, or awakenings as measured by actigraphy and PSG between cases and controls, nor sleep states measured by PSG. However, cases had significantly later sleep onset and offset than controls (both p < 0.05), partially moderated by age. Cases with suboptimal glycemic control (HbA1c ≥ 58 mmol/mol [≥7.5%]) had significantly shorter actigraphy-derived total sleep time (TST) (mean difference = -40 minutes; 95% confidence interval = -77, -3), with similar differences in TST measured by PSG. Cases with mean CGM glucose levels ≥10 mmol/L (≥180 mg/dL) on PSG night had significantly more stage N3 (%) sleep and less stage REM (%) sleep (both p < 0.05). CONCLUSIONS: Short- and long-term suboptimal glycemic control in T1DM children appears to be associated with sleep alterations. Pediatric diabetes care teams should be aware of potential interrelationships between sleep and T1DM, including management and glycemic control.

Effect of 6 months' flash glucose monitoring in adolescents and young adults with type 1 diabetes and suboptimal glycaemic control: managing diabetes in a 'flash' randomised controlled trial protocol.

BACKGROUND: Teenagers and young adults with type 1 diabetes (T1D) experience significant burden managing this serious chronic condition and glycaemic control is at its unhealthiest during this life stage. Flash glucose monitoring (FGM) is a new technology that reduces the burden of glucose monitoring by easily and discreetly displaying glucose information when an interstitial glucose sensor worn on the upper arm is scanned with a handheld reader, as opposed to traditional capillary glucose sampling by finger prick (otherwise known as self-monitored blood glucose, SMBG). The effectiveness of this technology and impacts of its long-term use in youth with pre-existing suboptimal glycaemic control are unknown. This study therefore aims to investigate the effectiveness of FGM in addition to standard care in young people with T1D. METHODS: This is a two phase study programme including a multi-centre randomised, parallel-group study consisting of a 6-month comparison between SMBG and FGM, with an additional 6-month continuation phase. We will enrol adolescents with T1D aged 13-20 years (inclusive), with suboptimal glycaemic control (mean glycated haemoglobin (HbA1c) in past 6 months ≥75 mmol/mol [≥9%]). Participants will be randomly allocated (1:1) to FGM (FreeStyle Libre; intervention group) or to continue SMBG with capillary blood glucose testing (usual care group). All participants will continue other aspects of standard care with the study only providing the FreeStyle Libre. At 6 months, the control group will cross over to the intervention. The primary outcome is the between group difference in changes in HbA1c at 6 months. Additional outcomes include a range of psychosocial and health economic measures as well as FGM acceptability. DISCUSSION: >If improvements are found, this will further encourage steps towards integrating FGM into regular diabetes care for youth with unhealthy glycaemic control, with the expectation it will reduce daily diabetes management burden and improve short- and long-term health outcomes in this high-risk group. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry on 5 March 2018 ( ACTRN12618000320257p ) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1205-5784).

A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

OBJECTIVE: To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. STUDY DESIGN: A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. RESULTS: Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). CONCLUSIONS: A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies.

Pedometers and text messaging to increase physical activity: randomized controlled trial of adolescents with type 1 diabetes.

OBJECTIVE: To assess whether pedometers and text messaging increase physical activity in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: A 12-week randomized controlled trial was conducted. A total of 78 subjects participated in the trial (mean +/- SD age 14.4 +/- 2.37 years, 36 [47%] male). Intervention participants wore an open pedometer and received regular motivational text messages. Control participants received usual care. Primary outcomes were daily step count (4-day closed pedometer) and physical activity questionnaire. RESULTS: Baseline median step count was 11,063 steps/day (range 1,541-20,158). At 12 weeks, mean daily step count reduced by 840 (95% CI -1,947 to 266) in the control group and by 22 (-1,407 to 1,364) in the intervention group (P = 0.4). Mean self-reported moderate or vigorous physical activity increased by 38.5 min/week in the control group and by 48.4 in the intervention group (P = 0.9). CONCLUSIONS: A 12-week intervention using pedometers and text messaging as motivational tools in adolescents with type 1 diabetes did not increase physical activity.

Hs-CRP is associated with weight, BMI, and female sex but not with endothelial function in children with type 1 diabetes.

BACKGROUND: Atherosclerosis is an inflammatory process, and high-sensitivity C-reactive protein (Hs-CRP), a marker of inflammation, predicts cardiovascular events in adults. Vascular endothelial and smooth muscle dysfunction, measurable precursors of atherosclerosis, begin in childhood. Therefore, we sought to determine if Hs-CRP is associated with vascular endothelial and smooth muscle dysfunction in children with type 1 diabetes mellitus (T1DM) and healthy control subjects. METHODS: Hs-CRP and endothelial function assessed by flow-mediated dilatation (FMD) and smooth muscle function assessed by glyceryl-trinitrate (GTN)-induced dilatation were measured in 121 subjects with T1DM aged 14.1 (2.9) yr, of whom 31 were also studied at 4 and 8 wk, and in 33 healthy controls aged 14.2 (3.6) yr. RESULTS: Hs-CRP did not differ between subjects with T1DM and healthy, age-matched controls. In both controls and subjects with T1DM, Hs-CRP did not relate to FMD or GTN at baseline or at intervals over 8 wk in T1DM. Hs-CRP did not change over time. In T1DM, but not healthy controls, Hs-CRP related to body mass index (BMI) z-score (r = 0.47, p < 0.001), weight z-score (r = 0.41, p < 0.001), and female sex (p = 0.008). CONCLUSIONS: Hs-CRP is not associated with early vascular dysfunction in children with T1DM. However, in children and adolescents with T1DM, Hs-CRP was associated with female sex and children with higher BMI, suggesting that these groups may be at greater cardiovascular risk. Maintenance of a healthy BMI may be important in the prevention of vascular disease of T1DM.

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetes.

Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C-->T, 1298A-->C in MTHFR, and 66A-->G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06-1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG.

Unrecognised hypoglycaemia in children and adolescents with type 1 diabetes using the continuous glucose monitoring system: prevalence and contributors.

AIM: To determine prevalence of hypoglycaemia, and contributing factors, in children with type 1 diabetes, using the Medtronic MiniMed continuous glucose monitoring system (CGMS). METHODS: Fifty-one children and adolescents with diabetes were studied with the CGMS. The studies were analysed for frequency and duration of hypoglycaemia (below 3.5 and 2.5 mmol/L). Contributing clinical factors were determined. Occurrence of nocturnal hypoglycaemia was related to bedtime and fasting home glucose recording. RESULTS: Hypoglycaemia was common, with 1 (0-4.2) (median (range)) episode per patient per 24 hours, and 0.33 (0-2) episodes per patient per night. Nocturnal episodes were longer than daytime episodes [97.5 (5-720) versus 35 (5-295) minutes for episodes below 3.5 mmol/L, P < 0.001; and 75 (10-640) versus 25 (5-200) minutes for episodes below 2.5 mmol/L, P < 0.001], and less likely to be recognised by the subject (P < 0.001 for episodes below both 3.5 and 2.5 mmol/L). Nocturnal hypoglycaemia was more common with a bedtime glucose recording <6 mmol/L, but also occurred frequently in subjects with glucose recordings >10 mmol/L. No bedtime glucose value reduced the risk of nocturnal hypoglycaemia to <10%. CONCLUSION: Hypoglycaemia, assessed using the CGMS, is common in children with type 1 diabetes and can be prolonged (although is predominantly mild). Bedtime home glucose recordings are poorly predictive of hypoglycaemia during the following night. Continuous glucose monitoring has proven very useful in management of individual patients, particularly adolescents experiencing difficulties with adherence to diabetes management.

Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus.

BACKGROUND: Endothelial dysfunction, a precursor of vascular disease, begins early in type 1 diabetes mellitus and is associated with folate status. METHODS: A randomized, double-blind, placebo-controlled study of folate (5 mg daily) and vitamin B6 (100 mg daily) in 124 children with type 1 diabetes determined the immediate and 8-week effects of these vitamins, alone and in combination, on endothelial function. Endothelial function, assessed as flow-mediated dilation and glyceryltrinitrate-induced dilation with high-resolution ultrasound of the brachial artery, was measured at baseline, at 2 and 4 hours after the first dose (n = 35), and at 4 and 8 weeks of treatment (n = 122). RESULTS: Flow-mediated dilation normalized in all treatment groups. From baseline to 8 weeks, flow-mediated dilation improved with folate from 2.6% +/- 4.3% (mean +/- SD) to 9.7% +/- 6.0%, with vitamin B6 from 3.5% +/- 4.0% to 8.3% +/- 4.2%, and with folate/vitamin B6 from 2.8% +/- 3.5% to 10.5% +/- 4.4%. This improvement in flow-mediated dilation occurred within 2 hours and was maintained at 8 weeks for each treatment. Flow-mediated dilation in the placebo group, and glyceryltrinitrate-induced dilation in all groups, did not change. Increases in serum folate, red cell folate, and serum vitamin B6 levels related to increases in flow-mediated dilation. Improvement in flow-mediated dilation was independent of changes in total plasma homocyst(e)ine, glucose, hemoglobin A1c, and high-sensitivity C-reactive protein levels. Baseline red cell folate levels and baseline diastolic blood pressure were related inversely to improvement in flow-mediated dilation. Serum triglyceride and low-density lipoprotein cholesterol inversely related to baseline flow-mediated dilation. CONCLUSIONS: High-dose folate and vitamin B6 normalized endothelial dysfunction in children with type 1 diabetes. This effect was maintained over 8 weeks, with no additional benefit from combination treatment.

Dietary fats do not contribute to hyperlipidemia in children and adolescents with type 1 diabetes.

OBJECTIVE: To determine the relative influence of diet, metabolic control, and familial factors on lipids in children with type 1 diabetes and control subjects. RESEARCH DESIGN AND METHODS: We assessed fasting serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein (apo)-A1, and apoB in 79 children and adolescents with type 1 diabetes and 61 age- and sex-matched control subjects, together with dietary intakes using a quantitative food frequency questionnaire. RESULTS: Total cholesterol, LDL cholesterol, apoB, HDL cholesterol, and apoA1 were significantly higher in children with diabetes. Children with diabetes had higher percentage energy intake from complex carbohydrates (P = 0.001) and fiber intake (P = 0.02), and they had lower intake of refined sugar (P < 0.001) and percentage energy from saturated fat (P = 0.045) than control subjects. Total cholesterol (beta = 0.43, P < 0.001), LDL cholesterol (beta = 0.4, P < 0.001), and apoB (beta = 0.32, P = 0.006) correlated independently with HbA(1c) but not dietary intake. HDL cholesterol (beta = 0.24, P = 0.05) and apoA1 (beta = 0.32, P = 0.004) correlated independently with HbA(1c), and HDL cholesterol (beta = -0.34, P = 0.009) correlated with percentage energy intake from complex carbohydrates. Triglycerides correlated independently with percentage energy intake from complex carbohydrates (beta = 0.33, P = 0.01) and insulin dose (beta = 0.26, P = 0.04). Subjects with diabetes and elevated LDL (>3.35 mmol/l, >130 mg/dl), for whom dietary therapy would be recommended, had significantly higher HbA(1c) (P = 0.007), but they had higher intake of complex carbohydrates than subjects with LDL cholesterol <3.35 mmol/l. CONCLUSIONS: Lipid abnormalities remain common in children and adolescents with type 1 diabetes who adhere to current dietary recommendations, and they relate to metabolic control but not dietary intake.