Type 1 Diabetes Adolescents Research Articles

The importance of arterial stiffness in pediatric patients with type 1 diabetes mellitus: What's new?

Youths with type 1 diabetes (T1D) exhibits higher levels of pulse wave velocity (PWV) compared to healthy controls. Higher PWV in T1D subjects is associated with increased hazard of progression in albuminuria, decline in eGFR, cardiovascular (CV) events and mortality. In the recently published work by Georeli et al., increased PWV was associated with poor glycemic control as expressed by time-in-range (TIR) < 50 % in T1D children, adolescents and young adults. This finding is of great interest, since it is well known that glycemic control, as measured by TIR, is an important contributor of CV risk. The duration of TIR < 50 % is not reported by the authors, but is of importance, knowing that CGM provide data for the last 3–6 months, depending on the CGM model. In conclusion, PWV looks promising for risk stratification in T1D, but its exact role in T1D still remains to be fully explored.

Glycemic Variability and Disordered Eating Among Adolescents and Young Adults with Type 1 Diabetes: The Role of Disinhibited Eating.

Background and Aims: Disordered eating behaviors (DEB) are common among individuals with type 1 diabetes (T1D). Glycemic variability, potentially harmful in T1D, may reveal distinct characteristics between those with higher versus lower variability, particularly concerning DEB. Our aim was to evaluate the prevalence of DEB and associated risk factors among adolescents and young adults with T1D and to investigate unique factors associated with DEB across different levels of glycemic variability. Methods: An observational, cross-sectional study was conducted with 147 individuals with T1D, aged 13-21 years. Data were collected from medical charts, personal technological devices for assessing glycemic variability, and self-reported questionnaires, including assessments of DEB. Results: DEB were found in 62 (42.1%) individuals, and 41.5% achieved the glycemic variability (% coefficient of variation) target ≤36%. Among individuals with low glycemic variability, DEB were positively associated with diabetes distress (odds ratio [OR]: 1.14 [95% confidence interval or CI: 1.05-1.22], P < 0.001), longer diabetes duration (OR: 1.34 [95% CI: 1.05-1.70], P = 0.016) and lower socioeconomic-status (OR: 0.53 [95% CI: 0.31-0.90], P = 0.019). Among those with high glycemic variability, body mass index Z score (OR: 3.82 [95% CI: 1.48-9.85], P = 0.005), HbA1c (OR: 4.12 [95% CI: 1.33-12.80], P = 0.014), disinhibited eating (OR: 1.57 [95% CI: 1.14-2.15], P = 0.005), and tendency to lower socioeconomic status (OR: 0.75 [95% CI: 0.56-1.01], P = 0.065). Discussion: DEB are prevalent among adolescents and young adults with T1D and are associated with various risk factors. Factors associated with DEB vary across different levels of glycemic variability. Both low and high glycemic variability are associated with specific risk factors for DEB. One notable risk factor is diabetes-specific disinhibited eating among individuals with high glycemic variability, in contrast to those with low glycemic variability. Given these different risk factors, it may be prudent to adjust intervention programs to reduce DEB among T1D adolescents according to their glycemic variability levels.

Evaluation of optical coherence tomography angiography metrics in children and adolescents with type 1 diabetes: 4-year longitudinal study

PurposeTo evaluate longitudinal changes in optical coherence tomography angiography (OCTA) metrics in children and adolescents with type 1 diabetes (T1D).MethodsThis prospective observational cohort study included thirty-two eyes from thirty T1D children with no history of diabetic retinopathy (DR) who were followed up for 4 years. Participants underwent OCTA examinations at baseline and during follow-up. Quantitative OCTA metrics were measured using a customized MATLAB algorithm. Generalized mixed-effect models were used to determine their relationship with DR development. Systemic parameters and OCTA metrics were screened using least absolute shrinkage and selection operator to identify predictors for visual function.ResultsOver the 4-year period, seven of the included eyes developed DR, and most OCTA metrics decreased with diabetes duration. Higher peripapillary and parafoveal nasal quadrant vessel area density (VAD) in the superficial capillary plexus (SCP) and vessel skeleton density (VSD) in both the SCP and the deep capillary plexus (DCP) were associated with a lower risk of DR in T1D. Parafoveal DCP VSD and VAD in the temporal and inferior quadrants were anticorrelated with changes in best corrected visual acuity.ConclusionsOCTA metrics dynamically change over the duration of diabetes and can be used as biomarkers to improve the risk evaluation of DR development and visual function in T1D children and adolescents.

Microbial taxonomic and functional shifts in adolescents with type 1 diabetes are associated with clinical and dietary factors.

Evidence indicates a link between the pathogenesis of type 1 diabetes (T1D) and the gut microbiome. However, the regulation of microbial metabolic pathways and the associations of bacterial species with dietary factors in T1D are largely unknown. We investigated whether microbial metagenomic signatures in adolescents with T1D are associated with clinical/dietary factors. Adolescents with T1D (case) and healthy adolescents (control) were recruited, and microbiome profiling in participants' stool samples was performed using shotgun metagenomic sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 4 and HUMAnN) was used to assign taxonomy and functional annotations. Clinical (HbA1c) and dietary information (3-day food record) were collected for conducting association analysis using Spearman's correlation. Adolescents with T1D exhibited modest changes in taxonomic composition of gut microbiome. Nineteen microbial metabolic pathways were altered in T1D, including downregulation of biosynthesis of vitamins (B2/flavin, B7/biotin and B9/folate), enzyme cofactors (NAD+ and s-adenosyl methionine) and amino acids (aspartate, asparagine and lysine) with an upregulation in the fermentation pathways. Furthermore, bacterial species associated with dietary and clinical factors differed between healthy adolescents and adolescents with T1D. Supervised models modeling identified taxa predictive of T1D status, and the top features included Coprococcus and Streptococcus. Our study provides new insight into the alteration of microbial and metabolic signatures in adolescents with T1D, suggesting that microbial biosynthesis of vitamins, enzyme cofactors and amino acids may be potentially altered in T1D. Research grants from NIH/NCCIH: R01AT010247 and USDA/NIFA: 2019-67017-29253; and Larry & Gail Miller Family Foundation Assistantship.

Assessment of perceived fear of coronavirus disease 2019 and its relationship to health-related quality of life among type one diabetic children and adolescents during the pandemic in Ismailia City

Background Coronavirus disease 2019 (COVID-19) pandemic affected the world especially those with chronic diseases. Diabetes mellitus (DM) is considered one of the most prevalent noncommunicable diseases. Type 1 diabetes (T1D) is one of the most common endocrine metabolic disorders around the world. This study aimed to assess the perceived fear of COVID-19 and its relationship to HRQoL among children and adolescents with T1D during the pandemic in Ismailia City. Methods This is a retrospective study carried out on T1D children and adolescents during pandemic in Ismailia City and conducted at Suez Canal University endocrinology outpatient clinic, Ismailia City, Egypt from June 30, 2021, to December 31, 2021. All participants were interviewed using a semi-structured demographic and clinical checklist, fear of COVID-19 Scale, and the short form 36 (SF-36) health survey. Blood samples were taken to analyze HbA1c for all patients. Results This study analyzed data from 68 children and adolescents with T1D with age ranged from 10 to 14 years, 58.8% were females and 55.9% had preparatory school education. 38% had BMI more than 30, 38.2% had DM for more than 5 years. HbA1C was more than 8 among 41.2%. 59% had low FCV-19 and 41% had high FCV-19. Mean PCS was 39.1±9.6 and 82% had poor PCS. MCS was ranging from 19 to 36 with a median of 28. Older age, preparatory educated, and larger BMI children had higher fears of COVID-19. Poor DM control, and poor adherence to glucose and diet showed higher FCV-19 scores. Higher PCS was associated with higher FCV-19 score. Using univariate logistic regression, age, HbA1C, type of insulin regimen, family history of DM, and FCV-19 score are predictors for PCS. While age, grade, BMI, HbA1C, adherence to glucose testing, type of insulin regimen, adherence to diet control, and PCS are predictors for FCV-19. Conclusion This study suggested that children and adolescents with T1D showed above-average levels of fear of COVID-19, and it may be associated with lower quality of life, especially physical aspects.

Recurrent depression relates to worse outcomes than single episode depression among Hispanic adolescents with diabetes.

Adolescents with type 1 diabetes (T1D) are at increased risk for depression. A history of recurrent depression (HRD) may relate to worse health outcomes than single-episode depression. However, no study has explored this issue among T1D adolescents. We examined differences in psychosocial and diabetes-related outcomes between T1D adolescents with (G1; n = 33) and without (G2; n = 18) HRD. Participants were 51 youths (aged 12-17 years) enrolled in a depression treatment study. Youths and one caregiver each completed several measures. Using MANOVA, followed by individual ANOVAs, and chi-square tests, we compared groups in continuous and categorical variables, respectively. MANOVA results were significant, F(7, 43) = 3.97, p = .002. Adolescents from G1 obtained higher scores than youths in G2 in self-esteem/guilt problems, cognitive alterations, and sadness due to T1D. Their caregivers reported more burden and rated their offspring as having more internalizing problems, facing more barriers to complying with T1D treatment, and using a medical ID less frequently than their counterparts did. A higher percentage of G1 participants presented clinical anxiety and inadequate glycemic control, and reported a history of major depression. According to caregivers, a higher proportion of G1 members had experienced multiple diabetes-related hospitalizations, were non-compliant with insulin treatment, and lived in homes with a conflictive environment. Our study documents important differences in outcomes between T1D youths with vs. without any HRD. Clinicians may need an intensive and integrative approach to treat mental and physical aspects of health among these patients.

Is there a characteristic pattern of ambulatory blood pressure profile in type 1 diabetic children and adolescents?

To examine the characteristics of ambulatory blood pressure (ABP) including blood pressure variability (BPV) and its association with albuminuria in type 1 diabetic (T1D) children and to identify potential predictors of high-normal albuminuria and microalbuminuria. ABP monitoring was performed in 201 T1D children and adolescents (mean age, 14.7±3.8 years) with T1D duration over 1 year. The level of albuminuria was assessed as the albumin/creatinine ratio (ACR) and patients were further classified as low-normal, high-normal or microalbuminuria. Fifteen T1D children (7.5%) were hypertensive using office blood pressure (BP) and 10 (5%) according to ABP. T1D subjects had elevated 24-hour systolic BP (SBP) and diastolic BP (DBP) (+0.2 and + 0.3 standard deviation score [SDS]) and nighttime SBP and DBP (+0.6 and +0.8 SDS) compared to reference values. Patients with microalbuminuria had significantly higher 24-hour, daytime and nighttime DBP compared to normoalbuminuric subjects. There was a high percentage of nondippers (74.1%). Nighttime diastolic BPV was significantly higher in subjects with high-normal compared to low-normal albuminuria (p=0.01). A weak correlation was found between ACR and daytime DBP SDS (r=0.29, p<0.001 and nighttime DBP SDS (r=0.21, p=0.003). Age and nighttime diastolic BPV were predictors of high-normal albuminuria while nighttime DBP was a strong predictor for microalbuminuria. T1D children have impaired BP regulation although most of them do not fulfill the criteria for sustained hypertension. There is an association between diastolic ABP and diastolic BPV with rising levels of albuminuria pointing to a clear connection between BP and incipient diabetic nephropathy.

36-OR: Bromocriptine Quick Release (BCQR) Improves Vascular Health in Youth with Type 1 Diabetes Even if Normal Weight

Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth. Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p&amp;lt;0.001) and diastolic BP (∆ = -2 mmHg, p=0.039) . BCQR reduced ascending aortic (AA) PWV (∆ = -0.4 m/s, p=0.005) , and increased RAC (∆ = -2.6%, p=0.022) and distensibility (∆ = 0.%/mmHg, p=0.010) . In the thoraco-abdominal aorta, BCQR decreased PWV (∆ = -0.2 m/s, p=0.013) and increased distensibility (∆ = 0.%/mmHg, p=0.032) . Of interest, in the normal-weight participants, BCQR improved systolic BP (∆ = -5 [95.0%CI: -7, -1] mmHg, p= 0.009) , AA PWV (∆ = -0.4 [95.0%CI: -0.7, 0] m/s, p= 0.030) and BrachD (∆ = 0.56 %/mmHg, p=0.023) , and tended to improve AA distensibility (∆ = 0.[95.0%CI: -0.01, 0.19] %/mmHg, p= 0.084) . Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies. Disclosure M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None. Funding JDRF BROM QR THERP3-SRA-2015-125-M-R

Role of optical coherence tomography angiography in early detection of retinal microvascular changes in adolescents with type 1 diabetes

Purpose: Early detection of diabetic retinopathy can prevent progressive visual loss. Evaluate the role of Optical Coherence Tomography Angiography (OCTA) in early detection of diabetic retinopathy (DR) in type 1 diabetes (T1D) adolescents with normal fundus photography. Methods: Cross-sectional study included 150 eyes of 75 T1D adolescents from the Diabetes Endocrine and Metabolism Pediatric Unit, Children hospital, Cairo University. Their ages ranged from 10-18 years and diabetes duration 2 years or more. Fundus photography, OCT and OCTA were done in the diagnostic and laser unit, Ophthalmology department. Results: Twenty-eight patients (37.3%) had abnormalities in the OCTA despite normal fundus examination, photography and OCT. Diabetes duration, DKA at presentation and frequency, elevated blood pressure, limited joint mobility, elevated HbA1c and dyslipidemia had a negative correlation with OCTA measurements (foveal, parafoveal and perifoveal densities). Patients with abnormal OCTA had significantly higher mean age, higher DKA frequency, and lower height SDS (p=0.034, 0.011 and 0.001 respectively). Univariate and multivariate analysis revealed age and DKA at diabetes presentation are significant predictors for abnormal OCTA. Conclusion: OCTA can be used in early detection of diabetic retinopathy in T1D adolescents especially with risk factors (Elevated HbA1c, frequent DKA, decreased height SDS and limited joint mobility).

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound.

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function. 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

Оценка эффективности применения отечественных биосимиляров инсулина для лечения сахарного диабета 1 типа у подростков

Aim: to assess the potential effect of switching from original insulins (lispro and glargine) to Russian biosimilars on glycemic control in adolescents with type 1 diabetes (T1D). Patients and Methods: this 24-week observational clinical trial enrolled 24 adolescents with T1D aged 12–15 (mean age 13.4±1.1 years), 13 boys (54.2%, mean age 13.1±1.1 years) and 11 girls (45.8%, mean age 13.0±0.9 years). Disease duration was 4.0±1.1 years in boys and 4.3±1.8 years in girls. Insulin therapy included original multiple daily injections (MDI) of insulins lispro and glargine. Patients were switched to biosimilars at a ratio of 1:1, doses were adjusted by the patients themselves. Blood sugar levels were measured by flash glucose monitoring (FGM). Time in the target range (TIR), time above the target range (TAR), time below the target range (TBR), and glycated hemoglobin (HbA1c) in the original insulin therapy and 3 and 6 months after switching to Russian biosimilars were evaluated. Results: three and six months after switching of T1D adolescents to Russian biosimilars, no clinically significant worsening of glycemic control parameters was reported, i.e., HbA1c (3 months) 7.6±1.1%, HbA1c (6 months) 7.5±0.9% (p&gt;0.05), TIR (3 months) 65.1±10.6%, TIR (6 months) 66.5±10.7% (р&gt;0.05), TAR (3 months) 26.8±10.9%, TAR (6 months) 25.5±11.1% (p&gt;0.05), TBR (3 months) 8.1±4.3%, TBR (6 months) 7.9±4.5% (p&gt;0,05). No significant differences in the parameters studied between boys and girls 3 and 6 months after therapy switching were reported. No significant changes in the total daily Insulin dose (TDI) were reported, i.e., TDI (3 months) 1.4±0.3 U/kg, TDI (6 months) 1.3±0.3 U/kg. Conclusion: Russian biosimilars of insulins lispro and glargine for T1D in adolescents are not associated with either an increase in TDI or worsening of glycemic control parameters, e.g., HbA1c, TIR, TAR, and TBR. KEYWORDS: type 1 diabetes, insulin, biosimilars, lispro, glargine, glycated hemoglobin, glycemic control, time in the range. FOR CITATION: Platonov V.V., Dubinina T.A., Patrakeeva E.M. et al. Efficacy of Russian insulin biosimilars for type 1 diabetes in adolescents. Russian Journal of Woman and Child Health. 2022;5(2):165–168 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-165-168.

Does introduction of continuous glucose monitoring at diagnosis of type 1 diabetes increase uptake in children and adolescents?

To assess whether introduction of continuous glucose monitoring (CGM) at diagnosis of type 1 diabetes (T1D), leads to greater uptake and continuation at 12 and 24 months, in a population-based pediatric diabetes clinic. All T1D children and adolescents diagnosed in the 12 months following full government subsidization of CGM were offered CGM from diagnosis at Women's and Children's Hospital, SA (Cohort 1). Uptake and continuation of CGM was compared to those diagnosed in the preceding year, who were started on CGM after diagnosis, but otherwise had identical diabetes management (Cohort 2). Demographic and clinical data were collected prospectively. The primary outcome variable was CGM wear >75% of the time at 12 and 24 months. In Cohort 1, 84% were started on CGM at diagnosis. 88% had commenced CGM by 12 months and 90% by 24 months. In Cohort 2, CGM was started on average 10 months after diagnosis (range 1-25 months), with 81% started on CGM within 24 months of subsidization. At 24 months, 78% of Cohort 1 and 66% of Cohort 2 were wearing CGM >75% of the time (p=0.26), higher than the WCH Clinic as a whole (58%). There was no difference in HbA1c between cohorts. Starting CGM at diagnosis of T1D is feasible and well received by families, with high uptake across all ages. Although CGM continuation (wearing CGM >75% of the time) was slightly higher in Cohort 1 than Cohort 2, this did not reach statistical significance.

High Rate of Depression among Saudi Children with Type 1 Diabetes.

Saudi Arabia ranks among the top ten in type 1 diabetes (T1D) prevalence. The psychological burden, including depression, among T1D children, affects short-term and long-term outcomes. In Saudi Arabia, studies on depression among T1D children are limited. We determined the prevalence of depression among T1D children and adolescents in the Saudi Arabia-Qassim region and investigated risk factors for depressive symptoms. This quantitative cross-sectional study was conducted among T1D children and adolescents in the outpatient clinic of Maternity and Children Hospital, Buraydah, Saudi Arabia, between October 2020 and April 2021. Using a validated questionnaire translated into Arabic, we interviewed patients during clinic appointment. Questionnaires on sociodemographic characteristics, clinical data, and Clinical Depression Inventory scale were used to measure depression. There were 148 T1D respondents (children: 58.1%; adolescents: 41.9%). More than half were females (53.4%), with most Saudis (94.6%). Depression prevalence among children and adolescents was 27%. Mild, moderate, and severe depression occurred in 80%, 12.5%, and 7.5% of depressed patients, respectively. Factors significant for depression were female sex (p = 0.014), uncontrolled HbA1c level (p = 0.037), and longer diabetes duration (p = 0.013). Depression among children and adolescents was more prevalent in this study than in previous reports. Early detection of depression will improve diabetes control and quality of life.

Glycemic control, depression, diabetes distress among adolescents with type 1 diabetes: effects of sex, race, insurance, and obesity.

To determine whether diabetes distress or depression screening better predict increased hemoglobin A1c (HbA1c) and to assess interactions with age, sex, race, obesity, and insurance status. Diabetes distress is a negative emotional reaction to diabetes, diabetes complications, self-management demands, unresponsive providers, and/or poor interpersonal relationships. Guidelines recommend annual depression screening, however diabetes distress may be mistaken for depression. Depression (PHQ-9) and diabetes distress (PAID-T) scores from self-administered tests were studied in 313 patients with type 1 diabetes (T1D) between the ages of 13-17. Spearman correlations and robust rank order multivariable regression analysis were used to assess relationships to age, duration, HbA1c. Kruskal-Wallis test was used to assess differences between sexes, races, and insurance status. Receiver operator curves (ROC) were constructed to see whether PAID-T or PHQ-9 scores more closely predicted HbA1c greater than 9%. HbA1c was more strongly correlated with PAID-T (rs = 0.37, p < 0.01), than PHQ-9 (rs = 0.27, p < 0.01) scores. Area under ROC curve for poor HbA1c was 0.75 for PAID and 0.64 for PHQ-9. PAID-T and PHQ-9 scores were increased in females and subjects with public insurance and both were significantly related to HbA1c even when accounting for age, sex, race obesity, and insurance status. PHQ-9 and PAID-T scores correlated with BMI-Z scores in Blacks, but not Whites. Both depression and diabetes distress are associated with increased HbA1c in adolescents with T1D, though distress is more so. Diabetes distress and depression should be routinely assessed in T1D adolescents, particularly those with public insurance.

64-OR: Metformin Improves Cardiac and Aortic Parameters in Adolescents with Type 1 Diabetes

Purpose: People with type 1 diabetes (T1D) have higher rates of cardiovascular disease (CVD) despite modern advances in glucose control. While insulin resistance (IR) is known to relate to CVD in type 2 diabetes, less is understood about IR in T1D-related CVD. We previously found vascular and cardiac dysfunction, including left ventricular (LV) dyssynchrony, in adolescents with T1D. In the Effects of MEtformin on caRdiovascular function in AdoLescents with type 1 Diabetes (EMERALD) study, we also showed that metformin improves BMI, body composition, insulin sensitivity, arterial stiffness, and carotid intimal media thickness in T1D adolescents. We hypothesized that metformin, with insulin-sparing effects, would improve echocardiographically-assessed cardiac and aortic health. Methods: 43 T1D youth ages 12-21 years (mean age 16.8 ± 2.5 years, HbA1c 8.6 ± 1.5%, BMI 25.1 ± 4.3 kg/m2, diabetes duration 7.7 ± 4.2 years) from the EMERALD study who were randomized to 3 months of either 1000 mg BID of metformin (n=23) or placebo (n=20) had echocardiograms with speckle tracking to evaluate traditional echocardiographic measures, cardiac strain and synchrony, and aortic root diameter at baseline and 3 months. One-way ANOVA and paired t-tests were utilized to assess the impacts of metformin. Results: LV diameter (4.45 ± 0.47 vs. 4.26 ± 0.50 cm, p = 0.019) at end-diastole and at end-systole (2.89 ± 0.39 vs. 2.69 ± 0.36 cm, p = 0.022) and LV dyssynchrony (98.0 ± 36.9 vs. 81.7 ± 27.5 milliseconds, p = 0.014) showed significant improvement within the metformin group. Aortic root diameter (2.51 ± 0.39 vs. 2.73 ± 0.28 cm, p = 0.042) was also significantly lower in the metformin vs. placebo group post-treatment. Conclusions: Metformin may be beneficial in improving or reversing early cardiovascular changes in T1D detectable by echocardiogram. A better understanding of T1D-related CVD and the benefits of improving insulin action in T1D longer-term should be investigated further as a target for new treatment modalities. Disclosure A. Nguyen: None. U. Truong: None. M. Schafer: None. A. Baumgartner: None. A. J. Barker: None. K. S. Hunter: None. D. Burkett: None. J. E. Reusch: Advisory Panel; Self; Medtronic. K. J. Nadeau: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.)

Disturbed sleep quality and architecture in adolescents with type 1 diabetes mellitus: Relation to glycemic control, vascular complications and insulin sensitivity

BackgroundInsufficient sleep duration and poor sleep quality have been linked to insulin resistance and impaired glucose metabolism. However, the relation between sleep disruption and type1 diabetes (T1D) hasn’t been thoroughly explored. AimTo study the association between sleep parameters and glycemic control, insulin resistance and micro-vascular complications among adolescent with T1D. MethodologySixty adolescents with T1D were compared to 60 matched controls. Diabetes-duration, insulin-therapy, fundus, Epworth Sleepiness Scale-Child Adolescent and the neuropathy disability score were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin(HbA1c) and urinary albumin-excretion were measured with calculation of the insulin sensitivity score(ISS). Overnight polysomnography(PSG) was done. ResultsAdolescents with T1D had significantly lower sleep efficiency and rapid eye movement(REM) sleep than controls with significantly higher sleep onset latency, non-REM sleep and arousal index(P < 0.001). Although ISS was negatively correlated to total sleep time(P = 0.002); it was positively correlated to sleep efficiency(P < 0.001). HbA1C was negatively correlated to sleep efficiency(<0.001) and REM sleep(P = 0.003) and positively correlated to sleep onset latency(P = 0.005). T1D adolescents with micro-vascular complications had significantly lower sleep efficiency and REM sleep than those without micro-vascular complications. ConclusionPoor sleep quality and architecture among adolescents with T1D are associated with impaired glycemic control, insulin resistance and micro-vascular complications.

Transforming Growth Factor-β1 and Receptor for Advanced Glycation End Products Gene Expression and Protein Levels in Adolescents with Type 1 iabetes Mellitus

Objective:Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-β1 (TGF-β1) are implicated in development and progression of diabetic microand macro-vascular complications, they also have important roles in immune system regulation.Methods:Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-β1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-β1 and soluble RAGE (sRAGE) levels were also determined.Results:TGF-β1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p<0.001, for both). However, TGF-β1 and sRAGE levels were higher in patients than controls (p<0.001, for both). There were significant independent associations of all mRNA and protein levels with T1D. TGF-β1 mRNA was the only marker independently negatively associated with urinary albumin excretion rate in T1D adolescents (p=0.005).Conclusion:Our results indicated gene expression downregulation of TGF-β1 and flRAGE in PBMC of T1D adolescents. TGF-β1 mRNA downregulation may be useful for predicting early elevation of urinary albumin excretion rate.

The Effect of Hypoglycemia on Spectral Moments in EEG Epochs of Different Durations in Type 1 Diabetes Patients.

The potential of using an electroencephalogram (EEG) to detect hypoglycemia in patients with type 1 diabetes (T1D) has been investigated in both time and frequency domains. Under hyperinsulinemic hypoglycemic clamp conditions, we have shown that the brain's response to hypoglycemic episodes could be described by the centroid frequency and spectral gyration radius evaluated from spectral moments of EEG signals. The aim of this paper is to investigate the effect of hypoglycemia on spectral moments in EEG epochs of different durations and to propose the optimal time window for hypoglycemia detection without using clamp protocols. The incidence of hypoglycemic episodes at night time in five T1D adolescents was analyzed from selected data of ten days of observations in this study. We found that hypoglycemia is associated with significant changes (P < 0.05) in spectral moments of EEG segments in different lengths. Specifically, the changes were more pronounced on the occipital lobe. We used effect size as a measure to determine the best EEG epoch duration for the detection of hypoglycemic episodes. Using Bayesian neural networks, this study showed that 30 second segments provide the best detection rate of hypoglycemia. In addition, Clarke's error grid analysis confirms the correlation between hypoglycemia and EEG spectral moments of this optimal time window, with 86% of clinically acceptable estimated blood glucose values. These results confirm the potential of using EEG spectral moments to detect the occurrence of hypoglycemia.

832-P: Resilience Outstrips the Negative Impact of Diabetes Distress on Glycemic Control and Self-Management among Youth with Type 1 Diabetes

Background: Adolescent with type 1 diabetes (T1D) experience increased diabetes distress, which is linked to poor self-management and glycemic control. Resilience might be able to decrease distress and facilitate disease management. Objective: To determine whether resilience buffers the deleterious consequences of distress on glycemic control and self-management. Methods: A convenience sample of 203 eligible adolescents (mean age 14.60 years) was recruited from a national endocrine center. Data were collected on social clinical characteristics, diabetes distress, resilience, self-management and glycemic. We preformed the simple slope and Johnson-Neyman statistical technique to probe moderating effects of resilience. Results: A total of 42.4% of adolescents reported high diabetes distress. Our results indicated that resilience moderated the association that hazards of severe diabetes distress for higher HbA1c (β = 0.148, t = 4.156, p = 0.000) and worse self-management (β = -0.010, t = -3.000, p = 0.003) were only apparent in the context of low resilience. Conclusions: We highlight the interactive relationship between diabetes distress and resilience in relation to glycemic control and self-management. It suggest that resilience is promising intervention target for distressed T1D adolescents with unsatisfactory glycemic control and self-management behavior. Disclosure D. Luo: None. J. Xu: None. M. Zhu: None. H. Wang: None. Y. Wang: None. Y. Shi: None. M. Zhang: None.

MON-LB113 Insulin Resistance in Type 1 Diabetes Managed With Metformin (INTIMET): Rationale and Study Design of a Randomised Placebo-Controlled Trial

Background: Insulin resistance is an under-recognised cardiovascular risk factor in type 1 diabetes (T1D). Individuals with T1D exhibit insulin resistance relative to those without diabetes. In T1D, tissue-specific insulin resistance (muscle, hepatic, adipose) is likely to partly drive increased cardiovascular risk. Adjunctive metformin improves muscle insulin sensitivity in T1D adolescents, but factors that predict responsiveness remain unknown.Objective: To report the rationale and design of the INTIMET study, a double-blind randomised, placebo-controlled trial of metformin in T1D.Methods: Forty adults aged 20-50 years with T1D, and 20 age- gender- and BMI- matched non-diabetic controls will be studied. T1D inclusion criteria are diagnosis > 10 years, HbA1c 9.5% and fasting C-peptide < 0.3nmol/L. Liver and muscle insulin sensitivity will be determined by the 2-stage hyperinsulinemic (20 and 60 mUm2)-euglycemic (5.5 mmol/L) clamp method with deuterated glucose. Subjects with T1D will be randomised to metformin extended-release 1500mg/d or matched placebo for 26 weeks. The primary endpoint is the change in hepatic insulin sensitivity, measured by suppression of endogenous glucose production (EGP) with the low-dose insulin clamp. Secondary endpoints include change in muscle and adipose tissue insulin sensitivity, arterial stiffness, HbA1c, glucose variability, frequency of hypoglycemia, insulin dose, anthropometry, body composition, lipid profile, liver fat and stiffness. Conclusion: The INTIMET study will quantify muscle, liver and adipose insulin-resistance in T1D, determine whether metformin is effective in improving insulin resistance in T1D and identify factors that predict metformin-responsiveness.The trial is registered (Australian New Zealand Clinical Trial Registry, ACTRN12619001440112) and is actively recruiting in Sydney, Australia.