First name
Mary
Middle name
Ellen
Last name
Vajravelu

Title

Visceral adiposity is related to insulin sensitivity and inflammation in adolescents with obesity and mild sleep disordered breathing.

Year of Publication

2022

Number of Pages

1069-1077

Date Published

08/2022

ISSN Number

2191-0251

Abstract

OBJECTIVES: To evaluate the relationships between adipose tissue distribution, insulin secretion and sensitivity, sleep-disordered breathing, and inflammation in obese adolescents.

METHODS: Cross-sectional study of 56 obese adolescents who underwent anthropometric measures, dual-energy X-ray absorptiometry, overnight polysomnography, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test. Correlation and regression analyses were used to assess relationships between adiposity, insulin secretion and sensitivity, measures of sleep-disordered breathing (oxyhemoglobin nadir, SpO; apnea hypopnea index, AHI; arousal index, AI; maximum end-tidal CO; non-REM sleep duration), and inflammation (high-sensitivity C-reactive protein, hsCRP).

RESULTS: Subjects (55% female) were mean (SD) 14.4 (2.1) years, with BMI Z-score of 2.3 (0.4). AHI was >5 in 10 (18%) subjects and 1< AHI ≤5 in 22 (39%). Visceral adipose tissue area (VAT) was positively correlated with OGTT 1 and 2 h insulin and 1 h glucose, and hsCRP (r=0.3-0.5, p≤0.007 for each). VAT was negatively correlated with sensitivity to insulin (r=-0.4, p=0.005) and SpO nadir (r=-0.3, p=0.04) but not with other sleep measures. After adjustment for BMI-Z, sex, population ancestry, age, and sleep measures, VAT remained independently associated with insulin measures and 1 h glucose, but no other measures of glycemia. SAT was not associated with measures of glycemia or insulin resistance.

CONCLUSIONS: Among adolescents with obesity, visceral adiposity was associated with insulin resistance, SpO nadir, and inflammation. The independent association of visceral adiposity with insulin resistance highlights the potential role of VAT in obesity-related chronic disease.

DOI

10.1515/jpem-2021-0745

Alternate Title

J Pediatr Endocrinol Metab

PMID

35822712

Title

Text Messages and Financial Incentives to Increase Physical Activity in Adolescents With Prediabetes and Type 2 Diabetes: Web-Based Group Interviews to Inform Intervention Design.

Year of Publication

2022

Number of Pages

e33082

Date Published

2022 Apr 06

ISSN Number

2371-4379

Abstract

<p><strong>BACKGROUND: </strong>Physical activity is a major component of treatment for adolescents with obesity and prediabetes or type 2 diabetes; however, sedentary behavior remains pervasive. An SMS text message-based intervention paired with financial incentives may be an effective way to promote physical activity in this population.</p>

<p><strong>OBJECTIVE: </strong>This study aims to obtain end-user feedback on SMS text message content and assess the acceptability of a planned SMS text messaging intervention with financial incentives to motivate youth with prediabetes or type 2 diabetes to increase physical activity.</p>

<p><strong>METHODS: </strong>Adolescents with overweight or obesity and prediabetes or type 2 diabetes who attended a large academic pediatric endocrinology clinic were recruited to participate in group interviews (2-4/group) via videoconferencing. Participants were asked to share their thoughts on the use of SMS text messages and financial incentives to remind and motivate them to be more physically active. They rated and provided feedback on specific messages to be used in clinical trials. Participants were also asked about their personal experience with rewards to motivate behavior change and their anticipated reactions to rewards provided for goal attainment (gain-framing) versus those provided and then taken away if a goal was not met (loss-framing). The interviews were conducted by 2 trained interviewers and a note-taker. Content analysis was used to explore themes.</p>

<p><strong>RESULTS: </strong>Group interviews were completed with 20 participants (11/20, 55% women; 15/20, 75% with type 2 diabetes; 5/20, 25% with prediabetes) with a mean age of 15 (SD 1; range 12-18) years and a mean BMI of 41 (SD 5) kg/m (all &gt;95th percentile for age and sex). Most participants were non-Hispanic Black (14/20, 70%) and 10% (2/20) were Hispanics. Participants frequently cited near-continuous smartphone use and agreed that SMS text messages would serve as good reminders to be physically active, but the consensus about the need for short messages was strong. Favorable content included references to what they were likely to be doing when messages were sent (eg, homework or watching television) and messages that were upbeat or informative. Specific physical activity suggestions were rated favorably. Attitudes toward financial incentives varied, with differing opinions about whether loss-framed incentives would be motivating or discouraging. Many participants highlighted the role of intrinsic, rather than extrinsic, motivation in achieving and sustaining behavior change.</p>

<p><strong>CONCLUSIONS: </strong>The engagement of adolescents with obesity and diabetes or prediabetes allowed for the refinement of SMS text messages for our planned intervention, with an emphasis on short, upbeat, relatable, and informative messages. Although an SMS text messaging intervention using financial incentives to motivate youth with prediabetes or type 2 diabetes to be more physically active is theoretically acceptable, the impact on actual activity levels in this population requires prospective evaluation in a clinical trial.</p>

DOI

10.2196/33082

Alternate Title

JMIR Diabetes

PMID

35384850

Title

Real-World Treatment Escalation from Metformin Monotherapy in Youth-Onset Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

Year of Publication

2021

Date Published

2021 May 12

ISSN Number

1399-5448

Abstract

<p><strong>BACKGROUND: </strong>Due to high rates of comorbidities and rapid progression, youth with type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.</p>

<p><strong>OBJECTIVE: </strong>To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with type 2 diabetes in clinical practice.</p>

<p><strong>SUBJECTS: </strong>Commercially-insured patients with incident youth-onset (10-18 years) type 2 diabetes initially treated with metformin only. METHODS: Retrospective cohort study using a patient-level medical claims database with data from 2000 - 2020. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥0.8).</p>

<p><strong>RESULTS: </strong>The cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9-year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=207; 88 to insulin, 164 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07-1.21), medication adherence (HR 4.10, 95% CI 2.96-5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28-2.61), and diabetes-related complications (HR 1.78, 95% CI 1.15-2.74) were positively associated with treatment escalation.</p>

<p><strong>CONCLUSIONS: </strong>In clinical practice, treatment escalation for pediatric type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs, most commonly among older adolescents. This article is protected by copyright. All rights reserved.</p>

DOI

10.1111/pedi.13232

Alternate Title

Pediatr Diabetes

PMID

33978986

Title

Gut Microbiome Profile After Pancreatectomy in Infants With Congenital Hyperinsulinism.

Year of Publication

2021

Number of Pages

89-92

Date Published

2021 Jan 01

ISSN Number

1536-4828

Abstract

<p><strong>OBJECTIVES: </strong>The objective of this study was to characterize gut microbiome profiles of infants with congenital hyperinsulinism (HI) who underwent near-total or partial pancreatectomy for hypoglycemia management, as compared with healthy controls.</p>

<p><strong>METHODS: </strong>A prospective observational cohort study was performed. Subjects were infants (0-6 months) with HI who underwent removal of pancreatic tissue for management of intractable hypoglycemia from February 2017 to February 2018 at the Children's Hospital of Philadelphia. Fecal samples were collected postoperatively, on full enteral nutrition. The gut microbiome of HI subjects was analyzed and compared with age-matched samples from healthy infants.</p>

<p><strong>RESULTS: </strong>Seven subjects with ≥50% pancreatectomy and 6 with &lt;50% pancreatectomy were included. α (within-sample) diversity was lowest among infants with ≥50% pancreatectomy (richness: false discovery rate, 0.003; Shannon index: false discovery rate, 0.01). β (between-sample) diversity (Bray-Curtis dissimilarity, P = 0.02; Jaccard distance, P = 0.001) differed across groups (≥ or &lt;50% pancreatectomy, controls). Bifidobacteria and Klebsiella species were least abundant among infants with ≥50% pancreatectomy but did not differ between infants with &lt;50% pancreatectomy and historical controls.</p>

<p><strong>CONCLUSIONS: </strong>Infants with HI who underwent ≥50% pancreatectomy differed from age-matched infants in gut microbiome profile, whereas those with &lt;50% pancreatectomy more closely resembled control profiles. The durability of this difference should be investigated.</p>

DOI

10.1097/MPA.0000000000001708

Alternate Title

Pancreas

PMID

33370028

Title

Sex-based differences in screening and recognition of pre-diabetes and type 2 diabetes in pediatric primary care.

Year of Publication

2020

Number of Pages

e12699

Date Published

2020 Jul 26

ISSN Number

2047-6310

Abstract

<p><strong>BACKGROUND: </strong>Risk-based screening for type 2 diabetes (T2D) in youth with overweight/obesity is recommended, but rates remain low in practice. Identification of factors impacting provider ordering and patient completion of testing may guide strategies to improve screening.</p>

<p><strong>OBJECTIVE: </strong>To evaluate predictors of hemoglobin A1c (A1c)-based T2D screening in pediatric primary care.</p>

<p><strong>METHODS: </strong>This retrospective cohort study included 10 to 18 year-old patients with overweight/obesity (body mass index [BMI] Z-score ≥1.04) followed in a large academic-affiliated pediatric primary care network, 2009 to 2018. Percentages of patients with ordered and completed A1c were determined, and multivariable Cox proportional hazards regression was used to evaluate independent predictors of screening.</p>

<p><strong>RESULTS: </strong>34 927 (48.0% female; 52.5% with BMI Z-score ≥1.64) youth followed for a median of 3.0 years were included. 21% (7457) of patients had screening ordered and 14% (4966) completed screening during follow-up. In multivariable regression, after controlling for race/ethnicity, BMI, family history of diabetes and age, males were significantly less likely to have ordered screening, but were equally or more likely to complete screening if ordered.</p>

<p><strong>CONCLUSIONS: </strong>Male adolescents were less likely to undergo A1c-based T2D screening due to differential ordering practices. The source of this differential practice should be pursued to avoid under-recognition of cardiometabolic risk in at-risk male youth.</p>

DOI

10.1111/ijpo.12699

Alternate Title

Pediatr Obes

PMID

32715607

Title

Association between Prediabetes Diagnosis and Body Mass Index Trajectory of Overweight and Obese Adolescents.

Year of Publication

2020

Date Published

2020 Apr 21

ISSN Number

1399-5448

Abstract

<p><strong>BACKGROUND: </strong>Prediabetes awareness in adults has been associated with improved weight management. Whether youth with prediabetes diagnosis experience similar improvements is unknown.</p>

<p><strong>OBJECTIVE: </strong>To investigate the association between prediabetes identification and body mass index trajectory in overweight and obese adolescents.</p>

<p><strong>SUBJECTS: </strong>Youth who were followed longitudinally in a large academic-affiliated primary care network and who were overweight/obese while 10-18 years old.</p>

<p><strong>METHODS: </strong>Retrospective cohort study. Subjects were categorized as "screened" if at least 1 hemoglobin A1c (HbA1c) result was available. Time series analysis was used to determine the difference in difference (DID) in body mass index Z-score (BMI-Z) slope before and after HbA1c between: 1) screened youth found to have prediabetes-range HbA1c (5.7-6.4%, 39-46 mmol/mol) versus normal HbA1c, and 2) screened versus age-matched unscreened obese youth.</p>

<p><strong>RESULTS: </strong>4,184 (55.6% female) screened subjects (median follow-up 9.7 years) were included. 637 (15.2%) had prediabetes-range HbA1c. Prediabetes was associated with a greater decrease in BMI-Z slope than normal HbA1c (DID: -0.023/year [95% CI: -0.042 to -0.004]). When compared to age-matched unscreened subjects (n=2,087), screened subjects (n=2,815) experienced a greater decrease in BMI-Z slope after HbA1c than unscreened subjects at a matched age (DID: -0.031/y [95% CI -0.042 to -0.021]).</p>

<p><strong>CONCLUSIONS: </strong>BMI-Z trajectory improved more among youth with prediabetes-range HbA1c but also stabilized in screened youth overall. Prospective studies are needed to identify provider- and patient-level drivers of this observation. This article is protected by copyright. All rights reserved.</p>

DOI

10.1111/pedi.13028

Alternate Title

Pediatr Diabetes

PMID

32314478

Title

Continuous Intragastric Dextrose: A Therapeutic Option for Refractory Hypoglycemia in Congenital Hyperinsulinism.

Year of Publication

2019

Number of Pages

62-68

Date Published

2019

ISSN Number

1663-2826

Abstract

<p>Feeding problems are frequent in infants with congenital hyperinsulinism (HI) and may be exacerbated by continuous enteral nutrition (EN) used to maintain euglycemia. Our center's HI team uses dextrose solution given continuously via gastric tube (intrasgastric dextrose, IGD) for infants not fully responsive to conventional medical therapy or pancreatectomy. Here, we describe our practice as well as growth, feeding, and adverse events in infants with HI exposed to IGD.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort of infants with HI treated with IGD from 2009-2017. Primary outcomes were weight-for-length and body mass index Z-scores (WFL-Z and BMI-Z) in the year following IGD initiation. Secondary outcomes included EN use and adverse events. We used multivariable regression to assess covariates of interest.</p>

<p><strong>RESULTS: </strong>We studied 32 subjects (13 female) with a median age at IGD initiation of 73 days (range 17-367); median follow-up was 11.2 months (range 5.0-14.2). WFL-Z did not change significantly over time (p &gt; 0.05). EN use decreased significantly over time, i.e., at 0 months: 72% (95% CI 53-85) vs. at 12 months 39% (95% CI 22-59). No potential adverse events led to discontinuation of IGD.</p>

<p><strong>CONCLUSIONS: </strong>Over a median follow-up of nearly 1 year, IGD was well-tolerated, with no change in WFL-Z or BMI-Z from baseline.</p>

DOI

10.1159/000491105

Alternate Title

Horm Res Paediatr

PMID

30086540

Title

Identifying Prediabetes and Type 2 Diabetes in Asymptomatic Youth: Should HbA1c Be Used as a Diagnostic Approach?

Year of Publication

2018

Number of Pages

43

Date Published

2018 06 04

ISSN Number

1539-0829

Abstract

<p><strong>PURPOSE OF REVIEW: </strong>Because the incidence of type 2 diabetes and prediabetes in children is rising, routine screening of those at risk is recommended. In 2010, the ADA made the recommendation to include hemoglobin A1c (HbA1c) as a diagnostic test for diabetes, in addition to the oral glucose tolerance test or fasting plasma glucose. Our objective was to assess the pediatric literature with regard to HbA1c test performance and discuss advantages and disadvantages of use of the test for diagnostic purposes.</p>

<p><strong>RECENT FINDINGS: </strong>HbA1c has a number of advantages, including elimination of the need for fasting, lower variability, assay standardization, and long-term association with future development of diabetes. It also has many drawbacks. It can be affected by a number of non-glycemic factors, including red blood cell turnover, hemoglobinopathies, medications, race, and age. In particular, it performs differently in children compared with adults, generally with lower sensitivity for prediabetes (as low as 0-5% in children vs 23-27% in adults) and lower area under the receiver operating characteristic curve (AUC) (0.53 vs 0.73 for prediabetes), and it has lower efficacy at a higher cost, compared with other tests of glycemia. Finally, HbA1c may perform very differently across diverse populations according to race/ethnicity; in Chinese populations, the proportion of individuals classified with prediabetes based on HbA1c predominates compared with IFG (77% for HbA1c vs 27.7% for IFG), whereas in US populations, it is the opposite (24.8% for HbA1c vs 80.1% for FPG). HbA1c is controversial because although it is convenient, it is not a true measure of glycemia. The interpretation of HbA1c results requires a nuanced understanding that many primary care physicians who are ordering the test in greater numbers do not possess. Alternative markers of glycemia may hold promise for the future but are not yet endorsed for use in practice. Further studies are needed to determine appropriate thresholds for screening tests and the long-term impact of screening and identification.</p>

DOI

10.1007/s11892-018-1012-6

Alternate Title

Curr. Diab. Rep.

PMID

29868987

Title

Heart Rate Variability and Cardiac Autonomic Dysfunction: Prevalence, Risk Factors and Relationship to Arterial Stiffness in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

Year of Publication

2019

Date Published

2019 Sep 09

ISSN Number

1935-5548

Abstract

<p><strong>OBJECTIVE: </strong>To determine whether prior type 2 diabetes (T2D) treatment or glycemic control over time are independently associated with heart rate variability (HRV) and whether the presence of cardiac autonomic dysfunction is associated with arterial stiffness in young adults with youth-onset T2D enrolled in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>Heartbeats over 10 min were measured to derive the normal R-Rs (NN intervals). Outcomes included the standard deviation of the NN intervals (SDNN), the root mean square differences of successive NN intervals (RMSSD), percent of NN beats that differ by more than 50 ms (PNN50), and the low-frequency (LF) power domain, high-frequency (HF) power domain, and their ratio (LF:HF). Autonomic dysfunction was defined as ≥3 of 5 abnormal HRV indices compared with obese controls from a separate study.</p>

<p><strong>RESULTS: </strong>A total of 397 TODAY participants were evaluated 7 years after randomization. TODAY participants had reduced HRV (SDNN; 57.9 ± 29.6 ms vs. controls 67.1 ± 25.4 ms; &lt; 0.0001) with parasympathetic loss (RMSSD; 53.0 ± 36.6 ms vs. controls 67.9 ± 35.2 ms; &lt; 0.0001) with sympathetic overdrive (LF:HF ratio; 1.4 ± 1.7 vs. controls 1.0 ± 1.1; &lt; 0.0001). Cardiac autonomic dysfunction was present in 8% of TODAY participants, and these participants had greater pulse wave velocity compared with those without dysfunction ( = 0.0001). HRV did not differ by randomized treatment, but higher hemoglobin A1c (HbA) over time was independently associated with lower SDNN and RMSSD and higher LF:HF ratio after adjustment for age, race-ethnicity, sex, and body mass index.</p>

<p><strong>CONCLUSIONS: </strong>Young adults with youth-onset T2D show evidence of cardiac autonomic dysfunction with both parasympathetic and sympathetic impairments that are associated with higher HbA.</p>

DOI

10.2337/dc19-0993

Alternate Title

Diabetes Care

PMID

31501226

Title

Prevalence of and Risk Factors for Low Bone Mineral Density in Children With Celiac Disease.

Year of Publication

2019

Number of Pages

1509-1514

Date Published

2019 Jul

ISSN Number

1542-7714

Abstract

<p><strong>BACKGROUND &amp; AIMS: </strong>Celiac disease can reduce bone mineral density. We sought to determine the prevalence and risk factors for low areal bone mineral density (aBMD) in children with celiac disease.</p>

<p><strong>METHODS: </strong>We performed a retrospective cohort study of 673 children with celiac disease (63% female; median age at diagnosis, 10.6 y; interquartile range, 7.8-13.9) who underwent dual x-ray absorptiometry (DXA) from 2009 through 2016 at the Children's Hospital of Philadelphia. We collected demographic, clinical, and laboratory data from medical records. We performed logistic regression analysis to identify factors associated with low (Z less than -2) lumbar spine aBMD Z (aBMD-Z) scores at initial and subsequent tests.</p>

<p><strong>RESULTS: </strong>The time between diagnosis of celiac disease and first DXA was 0 days (interquartile range, -11 to 31 d). The mean aBMD-Z score at the children's initial scan was -0.4 ± 1.2; 46 children had aBMD-Z scores less than -2 (6.8%; 95% CI, 5.2%-9.0%). Those who had a second DXA analysis (n&nbsp;= 108; 16.0%) had a significant increase in aBMD-Z score (mean change, 0.29; P&nbsp;= .0005). Higher body mass index (BMI) was associated with lower odds of a low aBMD-Z score at the initial DXA analysis (odds ratio, 0.46, 95% CI, 0.35-0.50). BMI-Z scores greater than -0.4 identified children with a low aBMD-Z at their initial DXA analysis with a 95% negative predictive value.</p>

<p><strong>CONCLUSIONS: </strong>Approximately 7% of subjects with celiac disease had a low aBMD-Z score, determined by DXA, at the time of diagnosis; this value was nearly 3-fold higher than expected from a population of children of this age and sex distribution. BMI-Z scores could be used to identify children with celiac disease at risk for low BMD who should receive DXA screening.</p>

DOI

10.1016/j.cgh.2018.10.035

Alternate Title

Clin. Gastroenterol. Hepatol.

PMID

31230659

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