bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Diabetes Outcomes in Rural Dominican Republic
Authors: WALKER ELIZABETH A. , DETHLEFS HENRY J. , DOWD RACHEL A. , SCHECHTER CLYDE , FILIPI CHARLES
Published: June 2018

The Dominican Republic (DR) is a Caribbean country of 10 million with estimated diabetes prevalence at ∼11%. While the public health system has a diabetes program, there are few reliable surveillance data to portray diabetes outcomes in the DR. The HbA1c is not a widely available test for metabolic control in the DR. In 2010, a non-profit group, Chronic Care International (CCI), began a diabetes and hypertension program with 2 clinics in poor, rural DR. CCI developed a model of quality improvement for care and self-management with its Dominican medical team, including doctors, nurses and community health workers. We present process and outcome data collected over 6 years utilizing electronic medical records. In addition to quality improvement analyses, we fit a random-effects linear model to the data to assess trends over time. By May 2017, subjects (N=1,031) were adults: mean age 60.1 years, 45% men, 74% with T2DM. Of those with diabetes (n=758), 76% had an HbA1c <9%, with 86% having had an HbA1c test done in the last 4 mos. Of 650 with hypertension, 64% had a BP < 140/90mmHg. In assessing trends over time, we found the modeled HbA1c trajectory for those with diabetes showed an average decline of 0.13 percentage points per year (95% CI 0.10-0.15) over 6 years. The modeled BMI trajectory for all subjects showed an average decline of 0.kg/m2 per year (95% CI 0.04-0.08) over 6 years. For those with a dx of hypertension, the modeled BP trajectories are biphasic, showing decreases over years 1 and 2, followed by increases. Systolic BP averaged a decline of 3.5mmHg (95% CI 3.0-4.0) per year, followed by an average increase of 1.7mmHg (95% CI 1.3-2.1) per year. Diastolic BP averaged a decline of 2.4mmHg (95% CI 2.1-2.7) per year, followed by an increase of 0.27mmHg (95% CI 0.03-0.5) per year. While decline trends in HbA1c and BMI are encouraging for this model of care in rural areas of this developing country, some challenges in managing BP remain, even with access to several antihypertensive medications. Program sustainability and access to healthy food and exercise are DR priorities.

Disclosure

E.A. Walker: None. H.J. Dethlefs: None. R.A. Dowd: None. C. Schechter: None. C. Filipi: None.
Key Clinical Risk Factors Identify Adverse Glycemia in Hospitalized Patients
Authors: KYI MERVYN , REID JANE E. , GORELIK ALEXANDRA , KUMAR SHANAL S. , GALLIGAN ANNA , ROWAN LOIS M. , NANKERVIS ALISON J. , MARLEY KATIE A. , RUSSELL DAVID M. , WRAIGHT PAUL R. , COLMAN PETER G. , FOURLANOS SPIROS
Published: June 2018

We previously showed that a proactive inpatient diabetes service decreased adverse glycemia (AG) and hospital acquired infections (RAPIDS: ADA2017, 231-OR). To further focus our proactive care on high-risk inpatients, we investigated clinical risk factors associated with AG. We analyzed multiple clinical variables in 643 consecutive inpatients with diabetes or new hyperglycemia (random BG ≥11.1mmol/L). Capillary BG from day 2 of admission until discharge (censored at day 14) were analyzed. AG was defined as BG <4 or >15mmol/L on any day and recurrent AG (RAG) was defined as AG on ≥2 days. A split-sample multivariable logistical regression was performed with internal validation. The patient characteristics included 87% type 2 diabetes, 33% insulin-treated and mean HbA1c 7.6%. AG and RAG occurred in 278 (43%), and 176 (27%) patients respectively. Pre-hospital factors (sulphonylurea or insulin treatment, HbA1c, Charlson index) and in-hospital factors (dysglycemia on day 1, length of stay) were independently associated with both AG and RAG (Table). Glucocorticoid treatment was associated with RAG but not AG. A model using these multiple variables accurately identified AG (ROC-AUC 0.88). Age, diabetes type, creatinine and admission unit were not associated with either AG or RAG. This study identified multiple key clinical risk factors associated with adverse glycemia, and may be used to better concentrate efforts for inpatient diabetes care.

Disclosure

M. Kyi: None. J.E. Reid: None. A. Gorelik: None. S.S. Kumar: None. A. Galligan: None. L.M. Rowan: Speaker's Bureau; Self; AstraZeneca, Sanofi, Novo Nordisk Inc.. A.J. Nankervis: None. K.A. Marley: None. D.M. Russell: None. P.R. Wraight: None. P.G. Colman: None. S. Fourlanos: None.
Documentation of Continuous Subcutaneous Insulin Infusion (CSII) Use in the Emergency Department (ED)
Authors: RUSHAKOFF ROBERT J. , ZOOK JESSICA , MACMASTER HEIDEMARIE W.
Published: June 2018

The Institute for Safe Medication Practices recommends patients on CSII who present to the hospital (inpatient or the ED), should have CSII use and settings verified within 12 hours. Without CSII orders or scheduled glucose checks in the ED, adverse glycemic excursions from insulin pump misadventures can occur, increasing risk of DKA or severe hypoglycemia.

At University of California, San Francisco, (UCSF) 25% of admitted patients enter via the ED with an average door-to-admission of > 12 hours. We have mandatory insulin pump orders for inpatients. To determine the timing of CSII orders, documentation and glucose levels, we performed a retrospective review of patients admitted from the ED who remained on CSII, from June 2012 to August 2016.

32 patients (age 54.3 ± 14.6 years) were admitted to the hospital from the ED who were continued on CSII. We were unable to capture data on ED patients not admitted or who had their CSII discontinued. 37.5% did not have CSII orders written within 12 hours of presentation to the ED. The average time to insulin pump order was 13.3 hours. 43% presented to the ED between1900-0700. The mean time to first glucose was 1.27 hours ± 1.47, and 15.6% had no glucose check within the first 2 hours. <50% had CSII integrity documented (insulin reservoir, site intact, battery capacity) in the first 24 hours. Glycemic control was assessed by 6-hour periods. For these 4 periods: Glucose 80-180 mg/dl (13/32; 12/32; 15/32; 9/32); >180 mg/dl (18/32; 11/32; 12/32; 12/32); <80 mg/dl (0/32; 2/32; 2/32; 2/32); no glucose (0/32; 7/32; 3/32; 9/32). Continuous glucose monitor readings are not part of the patient’s medical record as not approved for clinical decision making.

We found few patients had CSII orders or documentation nor appropriate glucose monitoring in the initial 12 hours after presentation to the ED. We anticipate new ED policies, procedures, and RN protocols, with use of new ED pump order sets and early patient involvement, will improve guideline compliance and patient care.

Disclosure

R.J. Rushakoff: None. J. Zook: None. H.W. Macmaster: None.
HbA1c Screening Characterizes Undiagnosed Dysglycemia in Surgical Patients
Authors: DUGGAN ELIZABETH W. , O'REILLY-SHAH VIKAS N. , TSEGKA KATERINA G. , GALINDO RODOLFO J. , UMPIERREZ GUILLERMO E.
Published: June 2018

Perioperative hyperglycemia is associated with increased morbidity and mortality. We analyzed the prevalence of undiagnosed dysglycemia, prediabetes (pre-DM) and diabetes (DM), in at-risk patients undergoing elective surgery at a large academic medical center.

Methods: As part of a quality improvement project, patients reporting no history of diabetes, and meeting screening criteria (age > 45 years and/or BMI > 25 kg/m2), had an HbA1c measured during their Anesthesia Preoperative visit from 01/2015 to 12/2017. The Emory Clinical Data Warehouse was queried for demographics and blood glucose (BG) during hospitalization. Normoglycemia, pre-DM and DM were defined as HbA1c <5.7%, >5.7% to 6.5%, and >6.5%, respectively.

Results: Among 7,430 patients denying history of DM, 4,204 (57%) met screening criteria. Prevalence of normoglycemia, pre-DM and DM was 69%, 27.2% and 3.9% respectively. Hospital BG was measured in 92% (n = 3,878); stress hyperglycemia (BG > 180 mg/dl) was observed in 6.4% of normoglycemia, 10.6% of pre-DM and 30.5% of DM patients (p <0.001).

Conclusion: A universal pre-operative screening using HbA1C identified a high prevalence of undiagnosed pre-DM (27.2%) and DM (3.9%) in older and overweight adults. Dysglycemic patients were statistically more likely to experience stress hyperglycemia. Future research is needed to assess if intervention can reduce perioperative complications in this population.CharacteristicsNormoglycemiaPre-DiabetesDiabetesp-valueHbA1C, median5.3%5.9%6.7%Patients, n (%)2,892 (69%)1,148 (27.2%)164, (3.9%)Age, (years)57 ± 1461 ± 1261 ± 12P<0.01BMI, (kg/m2)29.0 ± 6.531.1 ± 7.733.6 ± 8.7P<0.01Female Gender, n (%)1,741 (60%)685 (60%)92 (56%)P = 0.53BG> 180 mg/dl, n (%)171 (6.4%)113 (10.6%)50 (30.5%)P < 0.001

Disclosure

E.W. Duggan: None. V.N. O'Reilly-Shah: None. K.G. Tsegka: None. R.J. Galindo: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
The Pro-Diab Perioperative Study—A Structured Perioperative Diabetes Management Plan Improves Medication Usage and Glycemia in Elective Surgery
Authors: DAMIEN QI QI YANG , PEMBERTON ELIZABETH J. , KYI MERVYN , COLMAN PETER G. , FOURLANOS SPIROS
Published: June 2018

The perioperative management of diabetes inpatients is complex, often inconsistent and frequently results in suboptimal glycemia. We designed, implemented and evaluated a structured perioperative diabetes management plan (PDMP) on appropriate diabetes medication usage and glycemia in the perioperative period, in elective non-cardiac surgery patients. A multidisciplinary team developed and implemented a novel structured PDMP at our tertiary hospital. This observational study audited perioperative diabetes management over 4 months pre-implementation (non-structured care) and 4 months post-implementation (structured PDMP care). Primary outcome was appropriate use (documented recommendation, prescription and administration) of diabetes medications in the perioperative period. Secondary outcomes included blood glucose (BG) monitoring practice and glycemia. Pre- and post-implementation groups comprised 138 and 141 patients respectively, all of whom attended preadmission clinic and were admitted on the day of the procedure. The two groups were well matched in clinical characteristics. The PDMP was completed correctly in 107 (76%) patients in the post-implementation group. The appropriate use of diabetes medications increased from 30% to 72% between pre- and post-implementation groups (p<0.001). Appropriate BG monitoring also increased (25% vs. 51%, p<0.001). There was improvement in glycemia with post-implementation group having lower BG in the preoperative period (mean±sd: 10.2±4.6 vs. 8.8±3.9 mmol/L, p=0.001); postoperative period (10.4±3.5 vs. 9.3±3.6 mmol/L, p=0.002); and in the entire perioperative period (10.3±4.1 vs. 9.0±3.8 mmol/L, p<0.001). This practical, implementable and novel structured perioperative diabetes management plan for elective surgery patients significantly improved diabetes medication usage, BG monitoring, and glycemia in the perioperative period.

Disclosure

Q. Qi: None. E.J. Pemberton: None. M. Kyi: None. P.G. Colman: None. S. Fourlanos: None.
Application of a Cloud-Based Medication Adherence Improvement (MAI) System to Assist Diabetic Care in China
Authors: LI YINGJIE , CAO JIUMEI , WANG WEI , WANG ZHEN , LI DONGXING , ZHANG HONGGUANG , LIU KAI
Published: June 2018

Objective: To evaluate the effects on medication adherence by employing a cloud-text messaging platform connecting to the pharmacy Enterprise Resource Planning (ERP) system and diabetic patients.

Methods: We developed a cloud engine housing a continuously growing knowledge database of 5,245 drugs. This database is broken down to 5 different categories of text messages, providing contents of each drug’s 1) indication and dosage, 2) precautions and side effects, 3) relevant disease information, 4) relevant lab test interpretation, and 5) medication reminders. This cloud-based service was offered as Software as a Service (SaaS) by connecting to pharmacies’ ERP, allowing the engine to identify the patients in real-time who filled prescriptions within the drug store and auto-send text messages at dosage-adjusted intervals. During the past 8 months, 9,802 patients at 970 pharmacies in 8 cities received this intervention and medication adherence was measured by Proportion of Days Covered (PDC).

Results: PDC of the study population was improved from 57.9% at baseline to 67.0% at last time, P<0.001. PDC changes were further categorized into various groups by medications of use and intervention durations (Table 1A and 1B), and a global adherence improvement was found.

Conclusion: Text message-based knowledge delivery is an effective way to improve medication adherence for community diabetic patients.

Disclosure

Y. Li: None. J. Cao: None. W. Wang: None. Z. Wang: None. D. Li: None. H. Zhang: None. K. Liu: None.
Culturally-Specific Diabetes Care Reduces Disparities in Metabolic Control
Authors: KAREN LAU KA HEI , POBER DAVID M. , MEHTA SANJEEV N. , HSU WILLIAM C. , KING GEORGE L.
Published: June 2018

Culturally-specific care for Asian Americans (AA) with diabetes may reduce their healthcare disparities and improve outcome. One-year outcomes of an integrated clinic for AA at a tertiary diabetes center previously showed more patients attaining A1C <7% and composite A1C, blood pressure (BP) and cholesterol (ABC) goal than whites in the general Adult Diabetes clinic. In a follow-up study to observe the clinical performance over 4 years, data for patients with T2DM who came during January 1, 2013 to December 31, 2016 were compared among AA in Asian Clinic (AAC, n=162), AA in general Adult Diabetes Clinic (AAD, n=118), and whites in Adult Diabetes Clinic (WAD, n=2846). There was no significant difference in baseline A1C. Patients in AAD were younger (P=0.0003) and diagnosed at an earlier age (P=0.04). Patients in AAC had the lowest BMI of 25.6 kg/m2 (P<0.0001). The majority of patients in AAC use English as a second language and had lower income. After one year, 37% of patients in AAC achieved the ABC goal, compared to 31% in AAD (P=0.29) and 28% in WAD (P=0.03). Clinical outcomes in AAC were compromised in 2014-2015 in parallel to a transient reduction in Asian Clinic providers. The percentage of AAC patients achieving the ABC goal dropped to 29% (P=0.008) and 23% (P<0.001) in 2014 and 2015 respectively. With the restoration of adequate staffing in 2016, the percentage of AAC patients reaching the ABC goal in 2016 increased to 26%, which is comparable to AAD and WAD (P>0.85). Percentage of patients with A1C <7% was not significantly different among groups at the end of the study (P>0.25). Despite financial and language difficulties, staff providing clinical care tailored to the need of AA, the AAC was able to reduce healthcare disparity in metabolic outcomes in Asian Americans with diabetes over a long duration.

Disclosure

K. Lau: None. D.M. Pober: None. S.N. Mehta: None. W.C. Hsu: Board Member; Self; Intarcia Therapeutics, Inc.. Advisory Panel; Self; Twine Health, Inc. G.L. King: Research Support; Self; Sanofi-Aventis.
Hypertension-Associated Medical Expenditures by Diabetes Status among Adult Female Medicaid Enrollees in Alabama
Authors: WANG GUIJING , NG BOON PENG , PARK CHANHYUN , FANG JING , RITCHEY MATTHEW , SOLER ROBIN , SMITH BRYCE , ZHANG PING
Published: June 2018

Little information is available on how diabetes status affects medical expenditures associated with hypertension among Medicaid enrollees. In 2013, Alabama had the highest proportion of Medicaid enrollees who were women and the highest hypertension prevalence in the U.S. We estimated hypertension-associated medical expenditures among adult female Medicaid enrollees by diabetes status in Alabama. We used data for 15,885 female Medicaid enrollees aged 19-64 years from the 2012 Medicaid Analytic extract files. We identified persons with hypertension and diabetes using ICD-9 codes. We used General Linear Models to estimate per person total annual medical expenditures associated with hypertension by diabetes status and hypertension-related conditions including myocardial infarction, congestive heart failure, peripheral vascular disease, chronic pulmonary disease, renal disease, and stroke. Overall hypertension prevalence was 20.8%, with 60.0% and 17.5% among those with and without diabetes, respectively. Annual medical expenditure per enrollee with hypertension was $7,722. After controlling for age, race, and Charlson comorbidity index, hypertension-associated excess annual medical expenditures were $2,540 and $2,926 for persons with and without diabetes (all p<0.01). For persons without hypertension-related conditions, the excess expenditures were $1,931 and $2,533 for those with and without diabetes (all p<0.01). For persons with at least one hypertension-related condition, these excess expenditures increased to $4,217 and $3,264, respectively (all p<0.01). Having hypertension increased medical expenditures greatly regardless of diabetes status. Having a hypertension-related condition further increased hypertension-associated medical expenditures among enrollees, especially in those with diabetes. These results can inform the development and evaluation of strategies to improve management of hypertension by diabetes status.

Disclosure

G. Wang: None. B. Ng: None. C. Park: None. J. Fang: None. M. Ritchey: None. R. Soler: None. B. Smith: None. P. Zhang: None.
Childhood Metabolic Markers Are Associated with Performance on Cognitive Tasks in Young Children—The Healthy Start Study
Authors: SHAPIRO ALLISON L.B. , WILKENING GRETA , TREGELLAS JASON R. , AALBORG JENNY , RINGHAM BRANDY , STAMATOIU ALEXANDRA V. , BANNING ALEXIS , DABELEA DANA
Published: June 2018

A substantial body of literature has implicated metabolic health as a significant contributor to cognitive functioning in adults. However, this has not been investigated among young children whose cognitive functions are still developing. Using data from 4 to 6-year-old healthy children participating in the Healthy Start study, an ongoing pre-birth cohort, we tested the hypothesis that current metabolic parameters (fasting glucose, insulin and Homeostatic Model of Assessment for Insulin Resistance [HOMA-IR] levels) are inversely associated with performance on cognitive tasks, measured via the NIH Toolbox cognition battery. Fully corrected T-scores for inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort test), and language (Picture Vocabulary test) were obtained. General linear models were used to test the associations between child metabolic markers and cognitive test scores. All models were stratified by race/ethnicity (n = 53 non-Hispanic white [NHW]; n = 45 others) and adjusted for APGAR scores at birth. Among NHW children, fasting glucose, insulin, and HOMA-IR were inversely associated with scores for inhibitory control (β = -3.16, β = -4.46; β = -3.90; p<0.for all), while fasting glucose was also associated with lower language scores (β = -3.88, p<0.05). Among children of other racial/ethnic groups, only fasting glucose was significantly associated with lower cognitive flexibility scores (β = -4.19, p<0.05). Our data suggest that metabolic health may impact cognitive development in young children. Further work is needed to replicate these findings and explore the neural underpinnings of these associations.

Disclosure

A.L.B. Shapiro: None. G. Wilkening: None. J.R. Tregellas: None. J. Aalborg: None. B. Ringham: None. A.V. Stamatoiu: None. A. Banning: None. D. Dabelea: None.
Time to Glucose Peak during Oral Glucose Tolerance Test (OGTT) and Pathophysiological Biomarkers of Type 2 Diabetes in Obese Youth
Authors: KIM JOON YOUNG , TFAYLI HALA , BACHA FIDA , MICHALISZYN SARA , ARSLANIAN SILVA A.
Published: June 2018

The time to glucose peak occurring at or after 30 min. during an OGTT identifies physiologically distinct groups of adults with differences in insulin sensitivity (IS) and secretion and risk of prediabetes and type 2 diabetes. We stratified 102 obese nondiabetic youth (age 15.0 ± 0.2 years; 49 M/53 F; 42 black/60 white) to Early-peak (EP) vs. Late-peak (LP) according to time to reach peak glucose (at 30 min. vs. >30 min.) during an OGTT and assessed the relationship to clamp-derived biomarkers of youth type 2 diabetes risk. Hepatic [[6,6-2H2]glucose] and peripheral IS [3-hour hyperinsulinemic (80 mu/m2/min)-euglycemic clamp], insulin secretion [2-hour hyperglycemic (225 mg/dL) clamp], β-cell function (BCF) relative to IS and body composition were compared. The LP group had lower hepatic and peripheral IS, lack of compensatory increase in 1st and 2nd phase insulin secretion and impaired BCF relative to IS compared with the EP group (Table), with similar fasting glucose and insulin, BMI percentiles and % body fat. In obese nondiabetic youth, the time to glucose peak during an OGTT reflects pathophysiological alterations associated with risk of type 2 diabetes. The risk imparted by a Late-peak glucose, independent of fasting glucose and insulin level, is mirrored in lower in vivo insulin sensitivity and impaired β-cell function, two major pathophysiologic biomarkers of youth type 2 diabetes.Variables, mean ± SEMEarly-peak (n=49)Late-peak (n=53)PGlycemic status (NGT/IGT), n (%)40 (82%) / 9 (18%)28 (53%) / 25 (47%)0.003Hepatic insulin sensitivity (mg/kg/min per µU/mL)-120.1 ± 1.714.5 ± 1.10.004Peripheral insulin sensitivity (mg/kg/min per µU/mL)2.55 ± 0.182.03 ± 0.150.0111st-phase insulin secretion (µU/mL)244.3 ± 26.7231.9 ± 26.7NSβ-cell function relative to insulin sensitivity (mg/kg/min)509.9 ± 45.3393.0 ± 33.40.026OGTT 2-hr glucose concentration (mg/dL)120.1 ± 2.8135.5 ± 3.40.001OGTT 2-hr insulin concentration (µU/mL)168.3 ± 22.0226.9 ± 21.80.010

Disclosure

J. Kim: None. H. Tfayli: None. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. S. Michaliszyn: None. S.A. Arslanian: None.
Valine Metabolism Is Altered in Obese Adolescents with Polycystic Ovary Syndrome and Relates to Insulin Sensitivity
Authors: CARREAU ANNE-MARIE , RAHAT HASEEB , REYES YESENIA GARCIA , PYLE LAURA , NADEAU KRISTEN J. , CREE-GREEN MELANIE
Published: June 2018

Polycystic Ovarian Syndrome (PCOS) is common and associated with insulin resistance (IR). The mechanism of IR in PCOS is unclear, likely multifactorial, and may relate to branched-chain amino acids (BCAA) and mitochondrial metabolism. We quantitated differences in BCAA and BCAA breakdown product short chain (C3-C5) acylcarnitines in response to hyperinsulinemia in obese girls with and without PCOS, and assessed the relationship to IR and hyperandrogenism. Obese girls with PCOS [n=15, 14.5 ± 1.6 years, BMI %ile 98.5 ± 1.0] and without PCOS [n=6; 13.2 ± 1.2 years, BMI %ile 98.0 ± 1.1] were studied. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp and a testosterone panel obtained. Nontargeted metabolomics were performed in plasma samples obtained before and after the clamp. T-tests were used for group comparisons, with the Benjamini-Hochberg procedure (false discovery rate (FDR) set to 0.05) to control for multiple testing. Spearman’s correlation coefficient was calculated for BCAA vs. glucose infusion rate (GIR) and free androgen index (FAI). The groups had similar demographic, physical activity, diet attributes, HbA1c and lipids. Girls with PCOS had higher FAI and worse IR than controls. FAI related negatively to short chain acylcarnitines C4 (r = -0.74, p=0.0002) and C3 (r=-0.60, p =0.007). During hyperinsulinemia, girls with PCOS had higher valine (FDR-adjusted p=0.04) and lower valine breakdown product C4 butyrylcarnitine (FDR-adjusted p=0.01). End-clamp valine correlated with GIR (r= -0.59, p= 0.006) as did C4 butyrylcarnitine (r=0.44, p=0.04). Under hyperinsulinemia, a metabolomic signature was revealed in obese girls with PCOS, distinct from that in uncomplicated obesity. Valine was higher in girls with PCOS, while C4 acylcarnitine, its direct mitochondrial metabolite, was lower. Further work is needed to determine if BCAA metabolism is a modifiable target to improve insulin sensitivity or simply a useful biomarker.

Disclosure

A. Carreau: None. H. Rahat: None. Y. Garcia Reyes: None. L. Pyle: None. K.J. Nadeau: None. M. Cree-Green: None.
Maternal Gestational Diabetes and Childhood Obesity—A Large Observational Study
Authors: WANG JING , WANG LEISHEN , ZHANG SHUANG , LIU HUIKUN , LENG JUNHONG , LI WEIQIN , ZHANG TAO , LI NAN , LI WEI , BACCARELLI ANDREA , HOU LIFANG , HU GANG
Published: June 2018

Previous studies found conflicting results about the associations between the exposure to maternal hyperglycemia in utero and the later risks of childhood overweight and obesity. The aim of the present study was to compare the children’s body mass index (BMI) growth between offspring exposed to maternal gestational diabetes mellitus (GDM) and those not exposed, and assess the associations between maternal GDM and their offspring’s overweight and obesity risk. We performed a large observational study in 1156 women and their offspring (578 GDM and 578 non-GDM mother-child pairs, matched by their offspring’s gender and age). The mean values of children were 5.86 years (range 3-9 years old). After adjustment for maternal and children’s characteristics, children born to mothers with GDM during pregnancy had higher mean values of Z scores for BMI-for-age, Z-scores for weight-for-age, waist circumferences, body fat, subscapular skinfold, and suprailiac skinfold, in comparison with their counterparts born to mothers with normal glucose (all P values <0.05). Moreover, maternal GDM was associated with a higher risk of childhood overweight and obesity with multivariate-adjusted odds ratios of 1.42 (95% confidence interval [CI]: 1.02-1.97) and 1.18 (95% CI: 1.11-1.24), respectively, compared with the children of mothers without GDM during pregnancy. Maternal GDM is an independent risk factor of childhood overweight and obesity, and it is associated with children’s faster growth of BMI.

Disclosure

J. Wang: None. L. Wang: None. S. Zhang: Employee; Self; American Diabetes Association. Advisory Panel; Self; Company/ABC. H. Liu: None. J. Leng: None. W. Li: None. T. Zhang: None. N. Li: None. W. Li: None. A. Baccarelli: None. L. Hou: None. G. Hu: None.
Genotype–Phenotype Correlations and Structural Basis of INSR and IGF1R Mutations Causing Severe Insulin/IGF-1 Resistance
Authors: HOSOE JUN , KADOWAKI HIROKO , MIYA FUYUKI , TAKAKURA MINAKA , TSUNODA TATSUHIKO , SHOJIMA NOBUHIRO , YAMAUCHI TOSHIMASA , KADOWAKI TAKASHI
Published: June 2018

Mutations of the insulin receptor (INSR) gene cause severe insulin resistance, resulting in several syndromes with various abnormal phenotypes associated with variable severity of INSR dysfunction. As a member of the insulin receptor family, the IGF-I receptor (IGF1R) shows the same domain structure as INSR containing the fibronectin type III (FnIII) domains where there are an α-β cleavage site and a part of the ligand binding site. Mutations of IGF1R can cause intrauterine and postnatal growth retardation. We compiled 3 mutations of the FnIII-2 and FnIII-3 domains in IGF1R registered in HGMD, ClinVar and UniProt databases as causing growth retardation as well as the SNP with >1% allele frequency in IGF1R from the 1000 Genomes Project data, ESP6500, HGVD and 3.5KJPN, a reference panel of Japanese individuals. We conducted in silico structural analysis of the mutations of the FnIII domains in IGF1R which revealed that the pathogenic mutations were predicted to severely impair stability of the FnIII domains and hydrophobic core formation or affect processing site, while the SNP was predicted not to affect folding of the domains. In addition, IGF-1 proreceptor processing was impaired in cells expressing mutations of FnIII compared to cells expressing WT form. Previously, we performed structural analysis of mutations of the FnIII domains in INSR, which revealed that missense mutations causing the most severe Donohue syndrome were predicted to severely impair hydrophobic core formation and stability of the FnIII domains, while those causing less severe Rabson-Mendenhall syndrome were predicted to lead to localized destabilization and not to affect folding of the FnIII domains. Genotype-structure-phenotype correlations of variants of the FnIII domains in INSR and IGF1R identified in these analyses will enable early diagnosis of pathogenic mutations in INSR and IGF1R and provide a valuable insight into the molecular mechanism of severe insulin or IGF-1 resistance.

Disclosure

J. Hosoe: None. H. Kadowaki: None. F. Miya: None. M. Takakura: None. T. Tsunoda: None. N. Shojima: None. T. Yamauchi: Research Support; Self; Novo Nordisk Inc., Daiichi Sankyo Company, Limited, Sanofi, Takeda, Tanabe-Mitsubishi. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.
Variation in Phenotypic Features of Two Siblings with PC1/3 Deficiency—Obesity and Hyperproinsulinemia
Authors: DAVIS ELISABETH K. , BROADNEY MIRANDA , PERSKY REBECCA , TORKY AHMED , YANOVSKI JACK A.
Published: June 2018

Background: Inactivating mutations in the PCSK1 gene encoding prohormone convertase 1/3 (PC1/3) are associated with failure to thrive (FTT) and diarrhea during infancy, a tendency toward childhood obesity, and the potential for development of endocrinopathies throughout life, including hyperproinsulinemia. We describe two siblings with the same inactivating compound heterozygous mutations (c.625G>A and c.473G>A) in PCSK1, but with phenotypes of differing severity affecting both body composition and glucose homeostasis.

Methods: After sequencing confirmed inactivating PCSK1 mutations, we assessed the siblings for resultant endocrinopathies of PC1/3 deficiency.

Results: The siblings, a 9y male (M) and an 11y female (F), had severe early onset FTT with diarrhea. Currently, M has extreme obesity (BMI=38.2 kg/m2, >99%), diabetes insipidus, central hypothyroidism (FT4 0.7 ng/dL; TSH 4.9 mIU/L with little diurnal variation), and adrenal insufficiency (peak cortisol post-ACTH 10.8 ug/dL). After an overnight fast, glucose was 64 mg/dL and he had dramatic hyperproinsulinemia (5030 pmol/L, normal <8), far exceeding his fasting insulin concentration (360 pmol/L). Glucose tolerance was better than predicted for his degree of obesity (OGTT 2h glucose 79 mg/dL) and proinsulin remained markedly elevated during the OGTT (6610 pmol/L; normal <200).

F was in the 86th percentile for BMI. She had central hypothyroidism (FT4 0.7 ng/dL; TSH 4.7 mIU/L with little diurnal variation) and diabetes insipidus, but had normal adrenal function (peak cortisol post-ACTH 20.3 ug/dL). F also had high fasting proinsulin (1340 pmol/L), out of proportion to fasting insulin (70 pmol/L) and glucose (87 mg/dL) and good glucose tolerance (OGTT 2h glucose 89 mg/dL).

Discussion: PC1/3 deficiency reduces processing of proinsulin to insulin and may thus predispose to fasting or post-prandial hypoglycemia. There is substantial heterogeneity in PC1/3 deficiency even within families.

Disclosure

E.K. Davis: None. M. Broadney: None. R. Persky: None. A. Torky: None. J.A. Yanovski: Research Support; Self; Rhythm Pharmaceuticals Inc., Zafgen.
KIAA2022, a Candidate Gene for Syndromic Diabetes
Authors: STEKELENBURG CAROLINE , BLOUIN JEAN-LOUIS , SANTONI FRED , O'HARE ELIZABETH A. , ZAGHLOUL NORANN A. , SCHWITZGEBEL VALERIE
Published: June 2018

Background/Introduction: Using whole exome sequencing we identified a truncating mutation in the KIAA2022 gene in a child with mental retardation and antibody-negative diabetes. The KIAA2022 gene encodes a large protein of 1516 amino acids, which has no significant homology with other known proteins. KIAA2022 has already been associated to X-linked mental retardation. In this study we analyze the potential contribution of KIAA2022 to diabetes.

Methods: Whole exome capture sequencing was performed using the Illumina HiSeq instrument. We performed qRT-PCR and immunohistochemistry. We used the INS-1E cell line for in vitro and zebrafish and mice for in vivo knock down studies.

Results: We confirmed mRNA and protein expression of KIAA2022 in murine and human islets by qRT-PCR and immunohistochemistry. KIAA2022 partially co-stained with insulin in pancreatic sections. In vitro experiments with INS-1E cells showed that KIAA2022 is highly expressed during cell division and after stress induction by H202. To characterize KIAA2022 function in vivo, we performed knock down studies in zebrafish and found a decrease of the beta cell mass by 40% compared to wild type. The beta cell expansion rate, assessed by culturing zebrafish embryos with and without glucose, lead to a 30% decrease of the expansion rate in the knock-down animals in comparison to the control group. We further used the CRISPR Cas9 technology to disrupt the KIAA2022 gene in mice. The knockout mice showed smaller islets and DNA damage signals in islets in comparison to the control mice. The i.p. glucose tolerance tests at twelve weeks of age showed glucose intolerance in mutant in comparison to wild type mice.

Conclusion: In vitro experiments using INS-1E cells suggest that KIAA2022 may play a role in cell division and in DNA damage signaling or repair. The KIAA2022 knock down experiments lead to a decrease of the beta cell mass and glucose-induced expansion rate in zebrafish and DNA damage signals in beta cells of mutant mice as well as glucose intolerance.

Disclosure

C. Stekelenburg: None. J. Blouin: None. F. Santoni: None. E.A. O'Hare: None. N.A. Zaghloul: None. V. Schwitzgebel: None.
Gluten Intake and Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in Children at Increased Risk of Disease
Authors: LUND-BLIX NICOLAI A. , DONG FRAN , MARILD KARL , BARON ANNA E. , SEIFERT JENNIFER A. , WAUGH KATHLEEN , JONER GEIR , STORDAL KETIL , TAPIA GERMAN , STENE LARS C. , JOHNSON RANDI K. , REWERS MARIAN , NORRIS JILL
Published: June 2018

Background: Few studies have examined gluten intake as a risk factor for islet autoimmunity (IA) and type 1 diabetes (T1D). Our aim was to study the association of gluten intake with development of IA and progression to T1D, accounting for HLA genotype.

Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of T1D based on presence of a first-degree relative with T1D, or HLA genotype. HLA genotypes were categorized in three groups as DR3/4 (DR3/4-DQ2/8), DR3 (DR3/3 or 3/X), and DR4 (DR4/4, 4/X or X/X, where X was neither 3 nor 4). Blood samples were collected at age 9, 15 and 24 months, and annually thereafter. IA was defined by the appearance of at least one autoantibody against insulin, IA-2, GAD or ZnT8 in at least two consecutive blood samples; T1D was defined using ADA criteria. Using FFQs we estimated the gluten intake (g/d) annually from 1 year of age. Cox regression was used to estimate hazard ratios adjusted for potential confounders.

Results: This report includes 1,916 subjects followed from birth to the median age 13.5 y; 178 developed IA and 56 of these progressed to T1D. At the first assessment (median age 1.4 y) the average daily gluten intake was 11.4 g (SD: 5.6). The amount of gluten intake did not predict risk of IA (HR per 4 g 0.93; 95% CI 0.78-1.11) or progression from IA to T1D (HR 1.30; 95% CI 0.94-1.78). Four grams of gluten equal to a slice of bread. However, we found a significant interaction with HLA (p=0.02), where the association between gluten and IA were significantly different between all groups. Moreover, we found a significant interaction for progression to T1D (p=0.04) where in children with IA, gluten intake was associated with T1D among children with DR3/4 (HR 1.66 95% CI 1.10-2.51), but not in children with the other HLA groups.

Conclusion: Gluten intake may have different effects on development of IA and progression from IA to T1D depending on HLA genotype.

Disclosure

N.A. Lund-Blix: None. F. Dong: None. K. Marild: None. A.E. Baron: None. J.A. Seifert: None. K. Waugh: None. G. Joner: None. K. Stordal: None. G. Tapia: None. L.C. Stene: None. R.K. Johnson: None. M. Rewers: None. J. Norris: None.
Novel, Culturally Sensitive Shared Group Appointment Program for Hispanic Pediatric Type 1 Diabetes Patients Is Feasible, Improves Technology Uptake, and Has Promising Results on Better Diabetes Outcomes
Authors: GONZALEZ ANDREA GERARD , BRADY ANDREA CAROLINA , KLINGENSMITH GEORGEANNA J. , PYLE LAURA , THURSTON JESSICA
Published: June 2018

Objective: Hispanic patients with type 1 diabetes (T1D) face cultural and language barriers in care that contribute to a high A1c, infrequent use of diabetes technology and risk of complications. Culturally sensitive programs and shared medical appointments (SMAs) have been recognized as effective models of care. Our aim is to develop a culturally sensitive, cost effective SMA model for pediatric Hispanic T1D patients.

Methods: Hispanic patients, ages 1-20, with T1D (n= 88), and their families were recruited to participate in the SMAs. They received routine care appointments alternating with SMAs that included group diabetes education. Teens, ages 12 to 18 attended a separate educational session from parents. Younger children and parents were seen together. A1c, behavioral tools, and use of diabetes technology were measured at baseline and every 3 months for two years. Satisfaction questionnaires were obtained.

Results: 62% of young children and 48% of teens completed the first 2 years of the SMA model of care. Results showed that there was a significant association between age and change in A1c for SMA participants from baseline to year 1 (p =.001) and baseline to year 2 (p = <.0001). Participants < 12 years old, there was a significant improvement in A1c from baseline to year 1 (p = 0.014) and from year 1 to year 2 (p = 0.007). Participants ≥ 12 years old, also had a change in A1c from year 1 to year 2 (p = 0.008). Technology use increased significantly from baseline to year 2 for participants who were less than 12 years of age (17% to 40% p =.014) and marginally significant for participants who were >11 years of age (10% to 18% p = .083). Participants had a 90% satisfaction rate.

Conclusions: The culturally sensitive SMA proved to be an appreciated, feasible and effective alternative to care for Hispanics with T1D. It may prove to be cost-effective and more effective over the long-term if begun shortly after diagnosis.

Disclosure

A. Gerard Gonzalez: None. A. Brady: None. G.J. Klingensmith: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Foundation. L. Pyle: None. J. Thurston: None.
Comparison of E-Consults and Face-to-Face Care on Costs and Glycemic Control among Veterans with Type 2 Diabetes Mellitus
Authors: KARAJGIKAR NEHA , DETOYA KARLA B. , BEATTIE JANICE N. , LUTZ-MCCAIN STACEY J. , BOUDREAUX-KELLY MONIQUE Y. , BANDI ARCHANA
Published: June 2018

Electronic Consults (EC) offer enhanced access to endocrinologists for patients with type 2 diabetes mellitus (T2DM). The effects of EC on costs of care and glycemic control compared to Face-to-Face (F2F) visits are unknown. A retrospective chart review was conducted for Veterans who received EC (n=440) or F2F (n=397) care for T2DM through the VA Pittsburgh Healthcare System (VAPHS) from 2010 to 2015. Data on demographics, rurality, days to consult completion, and percent (%) A1C at baseline and post-consult at 3-6, and 12 months were collected. A web-based tool calculated the average round-trip distance in miles and travel time in hours from patient’s residential zip code to VAPHS. Annual travel costs for recommended 3 visits per year were estimated at a reimbursement rate of $0.415 per mile. Continuous measures (mean ± standard deviation) were compared using Wilcoxon rank-sum tests. Categorical measures (sex, rurality) were presented as percentages and compared between groups by time point using chi-square tests. Veterans who received EC were predominantly male (98.4%), younger (64.2±8.5 years) and rural (15.8%) than those who received F2F care (95.3% male, p=0.01; 68.1±8.7 years, p<0.0001; 3.7% rural, p<0.0001). The EC cohort had shorter consult completion time than the F2F cohort (EC: 10±10 days, F2F: 37±33; p<0.0001). Mean annual travel-related savings per Veteran in the EC cohort were 431±297 miles, 9.4±7 hours, and $179±123. Mean annual travel burden per Veteran in the F2F cohort were 159±171 miles, 3.5±4 hours and $66±71. EC and F2F cohorts had similar baseline A1C values (10%±1.6). Both cohorts had decline in baseline percent A1C to 3- 6 months (EC: 8.98%±1.54, F2F: 8.75%±1.77, p=0.03) and from baseline percent A1C to 12 months (EC: 8.80%±1.61, F2F: 8.57%±1.72, p=0.002). Electronic consults deliver effective and expedient care by saving money and travel time, and offer long-term, sustainable glycemic control comparable to F2F care for patients in remote areas with T2DM.

Disclosure

N. Karajgikar: None. K.B. Detoya: None. J.N. Beattie: None. S.J. Lutz-McCain: None. M.Y. Boudreaux-Kelly: None. A. Bandi: None.
Dietary Behaviors throughout Childhood Are Associated with Body Mass Index and Estimated Insulin Resistance in Adolescence—A Longitudinal Study
Authors: GINGRAS VERONIQUE , RIFAS-SHIMAN SHERYL , TAVERAS ELSIE M. , OKEN EMILY , HIVERT MARIE-FRANCE
Published: June 2018

Background: Prediabetes is increasingly common in adolescent populations, yet, little is known about the contributing role of dietary behaviors throughout childhood to risk of prediabetes in adolescence.

Objective: We examined longitudinal associations of dietary behaviors throughout childhood with body mass index z-scores (BMI-z) and HOMA-IR index in adolescence.

Design: Among 596 children from Project Viva, a pre-birth cohort from eastern Massachusetts, we examined associations of maternal- or child-reported dietary behaviors annually from ages 4 to 12 years with BMI-z and HOMA-IR in adolescence (median 12.8 years). We used mixed effects models adjusted for: maternal education, pre-pregnancy BMI, marital status and parity, and child’s age, sex, and race/ethnicity.

Results: The frequency of healthful dietary behaviors decreased with advancing age; at age 12, 64% of children ate breakfast daily, 32% ate dinner together with family daily, 59% ate fast food meals <1x/week, and 50% watched television during meals <1x/week. BMI-z (mean 0.44 units, SD 1.06) in adolescence was lower in children who reported daily breakfast eating (β -0.17; 95% CI -0.25, -0.08), daily family dinner (-0.11; -0.17, -0.05), fast food <1x/week (-0.11; -0.18, -0.05) and television during meals <1x/week (-0.07; -0.13, -0.01) throughout childhood. Log-transformed HOMA-IR (mean 0.99, SD 0.62) in adolescence was also lower with daily breakfast (β -0.12; 95% CI -0.17, -0.07), daily family dinner (-0.05; -0.09, -0.01), eating fast food <1x/week (-0.05; -0.09, -0.01) and television during meals <1x/week (-0.05; -0.08, -0.01) throughout childhood. Association of daily breakfast eating with lower HOMA-IR remained significant after further adjustment for child’s BMI-z in adolescence (β -0.08; 95% CI -0.13, -0.04).

Conclusions: Children with healthful dietary behaviors throughout childhood have lower BMI-z and less insulin resistance in adolescence.

Disclosure

V. Gingras: None. S. Rifas-Shiman: None. E.M. Taveras: None. E. Oken: Employee; Spouse/Partner; Novartis Pharmaceuticals Corporation. M. Hivert: None.
Promoting Health Equity in Type 1 Diabetes through Peer Mentorship—Findings from the All for ONE Randomized Controlled Trial
Authors: WALKER ASHBY F. , HALLER MICHAEL J. , GURKA MATTHEW J. , MORRIS HEATHER L. , ANEZ-ZABALA CLAUDIA , BRUGGEMAN BRITTANY S. , GUIFFRE DANIELLE , ROHRS HENRY , ATKINSON MARK A. , SCHATZ DESMOND
Published: June 2018

There are tremendous health disparities in type 1 diabetes (T1D) according to socioeconomic status (SES). Moreover, college students with T1D, regardless of SES, face serious health risks as they transition to independent living. The All for ONE (Outreach, Networks, and Education) program was piloted as a novel intervention where college students with T1D mentored publicly insured teenagers with T1D (n=88, treatment and control). Outcome measures for college students and teens included HbA1c, diabetes knowledge, and the validated College Resiliency and Children’s Hope scales. The intervention included daily text reminders for blood glucose monitoring, weekly text exchanges, social events infused with T1D education, clinic visits with mentors/mentees and a weekly training course for the mentors. Paired t-tests were used to compare changes from baseline to study conclusion among the college students, and ANCOVA was used to compare changes between intervention and control teens adjusting for baseline. Adjusting for baseline, the mean change in HbA1c was +0.09 (9% increase) in the intervention group, compared to +0.28 (31% increase) in the control group (p=0.61). College students had a mean -0.22 (27% decrease) in HbA1c (p=0.38). Treatment group teens were significantly more likely to attend clinic visits during the pilot than control group teens (p = 0.02*). Exit surveys with mentors, mentees and parents expounded on the program’s success with 98% reporting they wanted to participate again if given the opportunity. The main value of the program was listed by mentors as increased networks with other college students with T1D, by mentees as being able to talk to their mentor about the disease, and by parents as giving their child a confidant who understood T1D. This pioneering program concurrently targets two vulnerable populations, establishing critical feasibility for a model that uses routine events of texting, clinic visits, and college curriculum.

Disclosure

A.F. Walker: None. M.J. Haller: None. M.J. Gurka: None. H.L. Morris: None. C. Anez-Zabala: None. B.S. Bruggeman: None. D. Guiffre: None. H. Rohrs: None. M.A. Atkinson: Other Relationship; Self; Patent Issued. D. Schatz: None.
Associations of Executive Function (EF) with Diabetes Management and Glycemic Control in Teens with Type 1 Diabetes (T1D)
Authors: HANSMANN MEREL , GUO ZIJING , VOLKENING LISA , LAFFEL LORI M.
Published: June 2018

Background: Management of T1D requires processes of EF such as planning, problem-solving, and task-completion. This study examined associations of EF with T1D management and outcomes in teens with T1D.

Methods: Teens and their parents completed self-report and parent proxy-report versions, respectively, of the Behavior Rating Inventory of Executive Function (BRIEF). Scores ≥60, as total (Global Executive Composite [GEC]) score or on 2 indices (Behavioral Regulation [BRI] and Metacognition [MI]) indicate EF problems. Parents completed validated surveys assessing teen adherence, teen T1D self-efficacy, parent involvement in T1D care, and diabetes-specific family conflict.

Results: The sample (N=169, 54% male) was 15.9±1.3 (M±SD) years old and had T1D for 8.4±3.7 years; 67% were pump treated, A1c was 8.5±1.2%. Parent reported vs. teen reported GEC scores uncovered 25% vs. 9% of teens with EF problems (p<.001). Teens with EF problems (GEC, BRI, MI) by parent proxy-report were less likely to use pump therapy and had higher A1c, poorer adherence, lower T1D self-efficacy, more parent involvement, and greater family conflict (Table).

Conclusions: Parents appear to be more likely than teens to identify teen EF problems. Screening for executive dysfunction in teens with T1D should be considered in order to identify teens in need of family and healthcare team support.

Disclosure

M. Hansmann: None. Z. Guo: None. L. Volkening: None. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..