bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Behavioral Intervention Produces Comparable Reductions in Regimen-Related Distress in Insulin Users and Nonusers—Twelve-Month Results from COMRADE
Authors: LITTLEWOOD KERRY , PATIL SHIVAJIRAO , CUMMINGS DOYLE M. , LUTES LESLEY , HAMBIDGE BERTHA , CARRAWAY MARISSA , ADAMS ALYSSA , SOLAR CHELSEY , EDWARDS SHEILA , GATLIN PEGGY
Published: June 2018

Complex treatment and monitoring behaviors that accompany insulin use can be associated with higher levels of regimen-related distress (RRD), poor glycemic control, and lower medication adherence. Whether cognitive behavioral intervention can provide comparable impact on distress levels in insulin-using and non-insulin using patients is poorly described. COMRADE was a prospective randomized controlled trial that evaluated the effectiveness of a 16-session severity tailored cognitive behavioral intervention plus lifestyle change counseling (n = 67; IG=intervention group) delivered by trained staff compared to usual care (n = 72; CG=control group), in 139 rural adult patients (mean age = 52.6 ± 9.5 years.; 72% black; BMI = 37.0 ± 9.0) with uncontrolled (mean A1c = 9.6 ± 2.0) type 2 diabetes and co-morbid depressive (PHQ-2) or distress (DDS-2) symptoms at screening in an academic primary care clinic. At baseline and at 12-month follow-up: A1c, RRD (sub-score of DDS-17), self-care behaviors (SDSCA), and medication adherence (ModMAS) were measured using validated instruments. This analysis specifically examined changes in RRD in insulin users (n = 41, 61%) vs. oral medications and lifestyle change users (n = 26, 39%) in the intervention arm only. While A1c was higher in insulin users at baseline as expected, there were no other significant differences between insulin-users and non-users at baseline. Cognitive behavioral intervention produced comparable improvement in RRD (-1.1 ± 1.1 vs. -1.0 ± 0.9; p = 0.6), self-care behaviors (+1.0 ± 1.3 vs. +1.3 ± 1.3; p = 0.4) and medication adherence (+1.0 ± 1.9 vs. +1.0 ± 2.2; p = 0.9) in insulin users vs. non-users. Insulin users had a greater reduction in A1c (-1.1 ± 1.9 vs. -0.6 ± 1.5; p = 0.3). Tailored cognitive behavioral intervention produces comparable improvements in RRD, self-care behaviors, medication adherence and A1c in insulin users and non-users.

Disclosure

K. Littlewood: None. S. Patil: None. D.M. Cummings: None. L. Lutes: None. B. Hambidge: None. M. Carraway: None. A. Adams: None. C. Solar: None. S. Edwards: None. P. Gatlin: None.
Factors Affecting Noninsulin Antidiabetic Drug Adherence in Patients with Type 2 Diabetes
Authors: PETRENCHIK LINDSAY , ELLEN LOH F.
Published: June 2018

Adherence to antidiabetic (AD) medication is a multifactorial phenomenon; however, little is known about which factors are the most contributory. Our objective was to conduct a systematic review aiming to quantify the effect of factors associated with medication nonadherence in patients with type 2 diabetes using non-insulin AD (NIAD) drugs. We conducted a systematic literature search of relevant observational studies published from January 1997 through March 2017. Studies were included if they used medication possession ratio (MPR) or proportion of days covered (PDC) to evaluate adherence associated with factors, were published in the last 10 years, and did not include insulin. The factors identified were then grouped based on the dimensions of medication adherence defined by the World Health Organization (WHO). The search yielded 1studies of which 25 met criteria. Socioeconomic factors associated with increased adherence were older age, male gender, and Caucasian race which were supported by 15, 10, and 8 studies, respectively. Health system related-factors associated with increased adherence were a general practitioner as the initial prescriber and mailed prescriptions, which were supported by 2 and 3 studies, respectively. The most prevalent condition-related factors were no hospitalized in the past year, frequent physician visits, and absence of cancer, each of which were supported by 3 studies. In regards to therapy-related factors, patients prescribed metformin, and who have a higher pill burden are more likely to be adherent, which were supported by 5 and 8 studies respectively. Only one study analyzed a WHO defined patient-related factor, which found a negative relationship between patients’ diabetes-related knowledge and adherence.

In conclusion, the major factors reported to be associated with NIAD nonadherence were younger age, female, non-Caucasian race, not using mailed prescriptions, cancer diagnosis, lower number of comorbidities, and a smaller pill burden.

Disclosure

L. Petrenchik: None. F. Loh: None.
Engaging Hispanic Adolescents with Type 2 Diabetes or Obesity in Personalized Exercise
Authors: FAULKNER MELISSA S. , MICHALISZYN SARA
Published: June 2018

The prevalence of obesity in Hispanic youth (21.9%; Ogden and Flegal, 2015) is the highest of all racial and ethnic groups, increasing their odds for the development of type 2 diabetes (T2D). The purpose of this secondary analysis of a larger trial of a 16-week personalized exercise intervention was to examine differences in exercise adherence and baseline perceptions of benefits and barriers to exercise, exercise self-efficacy and family support to exercise in Hispanic adolescents diagnosed with T2D or obesity. Changes in body mass index, waist circumference, glycosylated hemoglobin (HbA1c), homeostatic model for insulin resistance (HOMA-IR), lipid profile, cardiorespiratory fitness, blood pressure and perception of health were also examined following the intervention. There were 21 adolescents enrolled in the study, 13 with T2D (3 males, 10 females) and 8 who were obese (3 males, 5 females). The personalized programs were based upon individual adolescent choices to promote moderate to vigorous activity (MVPA) and included gym memberships, dance videos, biking, basketball, softball and walking. Adolescents wore the ActigraphTM accelerometer (model GT1M, Pensacola, FL) for tracking exercise throughout the intervention. The completion rate was 88% vs. 59% (67% overall) for obese vs. T2D, with obese adolescents engaging in higher duration of MVPA compared to those with T2D (mean 46.4 ± 33.8 vs. 36.3 ± 16.0 min/day, NS). Perceptions of family support for exercise were associated with benefits of exercise (r = .50, p = .021); barriers to exercise were associated with less MVPA (r = - .56, p = .017). Barriers were significantly higher in those with T2D (p = .01). Despite not meeting recommended activity guidelines, perceptions of health improved for all completing the intervention (p = .01). Future efforts for engaging Hispanic adolescents in regular exercise are warranted to delay the onset of T2D and the development of poor outcomes particularly for those already diagnosed with T2D.

Disclosure

M.S. Faulkner: None. S. Michaliszyn: None.
Impact of Intensive Lifestyle Intervention for Weight Management on Self-Reported Cognitive Function—The Action for Health in Diabetes (Look AHEAD) Randomized Controlled Trial
Authors: DUTTON GARETH R. , ESPELAND MARK , NEIBERG REBECCA H. , CARMICHAEL OWEN , HAYDEN KATHLEEN M. , JOHNSON KAREN C. , JEFFERY ROBERT W. , BAKER LAURA D. , COOK DELILAH , KITZMAN DALANE , RAPP STEVE R.
Published: June 2018

Background: Intensive lifestyle interventions (ILI) to reduce weight and increase physical activity may preserve higher-order cognition in overweight and obese adults with type 2 diabetes (T2D).

Methods: Adults with T2D who enrolled in a randomized clinical trial of a 10-year ILI compared with diabetes support and education (DSE; N=5,084; mean age=58.7 years; mean BMI=35.9 kg/m2; 36.8% racial/ethnic minority) provided self-assessments of difficulty with memory, problem-solving, and decision-making abilities at baseline and over ≥10 years of follow-up. The Health Utilities Index assessed memory and problem-solving; the Beck Depression Inventory-II assessed decision-making. Analyses included the full sample and sub-groups based on baseline weight status and history of cardiovascular disease (CVD).

Results: At baseline, 12%, 16%, and 23% of all participants reported some difficulty with problem-solving, decision-making, and memory, respectively. For those without baseline self-identified cognitive difficulties in a specific domain, ILI was associated with lower odds of decision-making difficulties at follow-up compared to DSE (odds ratio [OR]=0.85, [95% CI 0.75,0.97]). Among those who were not obese, ILI was associated with lower odds of problem-solving difficulties at follow-up (OR=0.69 [0.51,0.95]). For participants with self-identified cognitive difficulties at baseline who had a history of CVD, ILI may have worsened difficulties in problem-solving at follow-up visits (OR=2.95 [1.38,6.31]).

Conclusions: A long-term ILI targeting weight loss and physical activity may protect self-reported higher-order cognitive abilities in adults with T2D without preexisting memory, problem-solving, or decision-making problems. However, among those with preexisting problems, ILI was not protective.

Disclosure

G.R. Dutton: None. M. Espeland: Consultant; Self; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Heart, Lung, and Blood Institute. R.H. Neiberg: None. O. Carmichael: None. K.M. Hayden: None. K.C. Johnson: None. R.W. Jeffery: None. L.D. Baker: None. D. Cook: None. D. Kitzman: Advisory Panel; Self; AbbVie Inc.. Research Support; Self; AstraZeneca. S.R. Rapp: None.
Health Mindset and Health Outcomes for Adolescents with Type 1 Diabetes
Authors: NALLY LAURA , MUELLER CLAUDIA
Published: June 2018

Background: Health mindset theory is a novel approach to the study of health outcomes in pediatric populations. Health mindsets have been found to influence how individuals perceive illness and have been linked to health outcomes in adolescents with T1D. Specifically, individuals with a “fixed” mindset of health view illness more negatively and have worse outcomes than those with a “growth” mindset who believe that health can be improved through effort.

Methods: A cohort of adolescents with T1D was followed across the transition from pediatric to adult care to assess differences in their health outcomes over time. We predicted that having a growth mindset would be a protective factor for young adults as they take greater control over their health care.

Results: Ninety-one participants aged 12-19 with T1D were recruited, with 70 transitioning to adult care during the study period. 61% had a growth mindset while 39% had a fixed mindset of health. Overall, average A1c after transition was lower for participants with a growth vs. a fixed mindset. The most notable difference was found for participants who had the highest A1c before transition (>10%). In this group, growth-mindset adolescents showed a significant improvement in A1c levels compared to those with a fixed mindset (p<.05). Further, a greater percentage of adolescents with a growth (28%) vs. a fixed (9%) mindset was able to reach a target A1c of less than 7%. Age at time of transition (Mean=19 years) was similar for those with fixed and growth mindsets.

Conclusion: In this study of adolescents with T1D, having a growth mindset was linked to better glycemic outcomes after transitioning to adult care. Improvement in A1c was greatest for those young adults with a growth mindset who had the poorest glycemic control before transition. This suggests that health mindset might interact with changes in age or maturity level, particularly for young adults, and so may prove to be a powerful target for efforts to improve health maintenance in this population.

Disclosure

L. Nally: None. C. Mueller: None.
Examination of Accuracy of Self-Reported Blood Glucose Using mHealth Data Collection
Authors: WARNICK JENNIFER , WESTEN SARAH C. , ALBANESE-O'NEILL ANASTASIA , SCHATZ DESMOND , HALLER MICHAEL J. , JANICKE DAVID
Published: June 2018

Introduction: Daily self-monitoring of blood glucose (SMBG) is essential for type 1 diabetes (T1D) management. Adherence to SMBG is often suboptimal during adolescence. SMBG paper diaries are often inaccurate compared to glucometer readings. The current study aimed to compare self-reported SMBG values gathered using ecological momentary assessment via smartphones to glucometer readings.

Methods: Youth (n=54, 11-21 years, 59.3% male) with T1D received 3 text messages/day for 10 consecutive days containing REDCap surveys inquiring to SMBG values. SMBG values from glucometers were obtained during the same period. Based on a previously developed system, paired values were compared and categorized as accurate or discrepant. A discrepancy was categorized as: omission (i.e., glucometer reading with no self-reported SMBG value), addition (i.e., self-reported SMBG value with no glucometer reading), alteration (i.e., self-reported SMBG value different by >10 mg/dL from glucometer value), or digit transformation (i.e., 164 instead of 146). Self-reported values were categorized further to reflect whether patients reported a more clinically favorable or unfavorable profile.

Results: A significant positive correlation was found between glucometer and self-reported SMBG values for all matched pairs (r=.628, p<.001). Out of 817 pairings, 39.3% of the self-reported values were congruent to glucometer readings and 60.7% were discrepant. Of the discrepant, 45% were alterations, 40.9% were additions, 13% were omissions, and .01% were digit transformations. Also, 54.5% of self-reported SMBG appeared clinically favorable, while 45.5% appeared clinically unfavorable.

Conclusions: These findings are consistent with previous studies comparing paper SMBG diaries to glucometers in a pediatric population. Self-reported mHealth data is likely to produce discrepant SMBG values compared to glucometers. Providers are urged to use objective blood glucose devices for clinical decisions.

Disclosure

J. Warnick: None. S.C. Westen: None. A. Albanese-O'Neill: None. D. Schatz: None. M.J. Haller: None. D. Janicke: None.
Grp78 Is Critical for Beta-Cell Maturation and Survival
Authors: SHARMA ROHIT B. , ZHENG XIAOYING , GABLASKI BRIAN , KIM JASON K. , LEE AMY S. , ALONSO LAURA C.
Published: June 2018

Endoplasmic reticulum (ER) stress causes beta cell loss and dysfunction in T1D and T2D. Glucose regulated protein 78 (Grp78) is an abundant, widely expressed ER chaperone with functions including peptide translocation and folding, calcium storage, and regulating activity of the Perk, Ire1 and Atf6 unfolded protein response (UPR) pathways. Whole-body Grp78 deletion in mice is lethal at E3.5 days. Despite its critical importance, the impact of Grp78 deletion in beta cells has not yet been reported. Mice lacking both copies of Grp78 in beta cells (Grp78flox x Ins1CreThor) developed insulin-deficient diabetes by 2 weeks of age; heterozygotes remained normal. Islet architecture was disturbed in KO pups, with fewer beta cells than alpha cells (14.8±1.7% beta cells-KO, 70.5±3.8%-WT), reduced beta cell mass (13.5±1.7mg-KO, 69.7±6.4mg-WT), and abnormal cellular arrangement, with alpha and beta cells interspersed throughout islets. Reduced beta cell number was likely due to increased cell death; TUNEL+ beta cells were increased early, by 2 weeks of age (2.6±0.4%-KO, 0.1±0.0%-WT), whereas proliferation was not reduced until 4 weeks. Intriguingly, when BG was still normal, an increase in bi-hormonal glucagon/insulin cells was observed at 3-5 days (7.1±0.6%-KO, 3.0±0.2%-WT) and 2 weeks (7.7±0.6% in KO, 2.2±0.2% in WT) of age, suggesting defective fetal maturation, de-differentiation or trans-differentiation. Pdx1 staining was heterogeneously lost in insulin+ cells. Acute deletion of Grp78 in ex vivo mouse islet cells, human islet cells and the human EndoC-BH1 beta cell line strongly reduced Grp78 RNA/protein, induced compensatory chaperone Grp94, and activated all three UPR pathways. Grp78 knockdown increased beta cell death (AnnexinV staining, Chop and Txnip) and caused loss of differentiation markers Pdx1, Nkx6.1, Mafa and Neurod1, and induction of Ngn3, a fetal beta cell marker.

In summary, Grp78 is critically important for beta cell survival and plays an unexpected role in maintaining beta cell differentiation markers.

Disclosure

R.B. Sharma: None. X. Zheng: None. B. Gablaski: None. J.K. Kim: None. A.S. Lee: None. L.C. Alonso: None.
The Design and Preliminary Evaluation of a Mobile Health Application TangTangQuan in Management of Type 1 Diabetes in China
Authors: LING PING , LUO SIHUI , YAN JINHUA , ZHENG XUEYING , YANG DAIZHI , ZENG XIFENG , WENG JIANPING
Published: June 2018

Objective: To assess the effectiveness of mobile health application TangTangQuan (TTQ) in management of type 1 diabetes (T1D) in China.

Methods: TTQ is designed to provide diabetes self-management education (DSME) for patients with T1D.The innovation of TTQ is to break the isolation of individual T1D patients by socializing their self-management data, and let them find the “patients like me.” TTQ included four major modules: personal diabetes diary, games for DSME, peer support communities and online education courses. Patients recorded and uploaded their diabetes diary via TTQ, and peer patients or family members were able to make comments, or share their own experiences, or interact with the up loaders under the posts. Free download and registration of TTQ was available in major APP stores for mobiles in China since September 2015. The self-report demographic and clinical data were collected through TQQ.

Results: During September 2015 and December 2017, a total of 7641 patients (M/F, 3716/3925) aged 21.28±14.43 years, with duration of T1D 2.50 (1.00,6.90) years, have signed up and joined the management of TTQ, from 21 provinces in China. Fifty two percent were 18 to 45 years old and 41% were less than 18 years old. Twenty four percent of them were active in peer support communities including sharing their experiences in management of T1D. Among 2903 patients with duration of diabetes ≥1 year who have used TTQ for ≥1 year,435 have continuous record for 1 year of self-meter blood glucose (SMBG) at least 4 times per day in TTQ. Among these patients, SMBG frequency was 2.43/week(1.40,13.13) and 2.88/week(0.63,11.92) (P=0.967), HbA1c was 6.59±1.40% and 6.40±1.39%(P=0.002), the frequency of hypoglycemia was 6.75/week (4.00,11.50) and 6.25/week (2.75,9.67) (P=0.005) before and after one year use of TTQ, respectively.

Conclusions: TTQ has the potential to be a novel intervention for engaging T1D patients and their families in positive communication to support DSME.

Disclosure

P. Ling: None. S. Luo: None. J. Yan: None. X. Zheng: None. D. Yang: None. X. Zeng: None. J. Weng: None.
Neuropathy-Related Unsteadiness and Psychosocial Outcomes in Diabetes—Preliminary Findings
Authors: BROWN STEVEN J. , BOULTON ANDREW J. , VILEIKYTE LORETTA , REEVES NEIL D.
Published: June 2018

Diabetes is a well-established risk factor for psychological distress and reduced quality of life (QoL). This may be part due to biomechanical challenges posed by diabetic peripheral neuropathy (DPN)-related unsteadiness leading to increased risk of falling and reduced physical activity (PA). This cross-sectional study explores relationships between physical (DPN-unsteadiness and PA) and psychosocial outcomes (depression, fear of falling [FoF], and QoL). The preliminary results of 15 type 2 DM people with DPN (age: 67 years; 13M; VPT 24V) indicate that quality of life (NeuroQoL) and depression (Hospital Anxiety and Depression Scale) are strongly associated with objective DPN-unsteadiness (Berg Balance test: r=-.64, p=.01 and r=.63, p=.01; respectively) and FoF (Falls Self-Efficacy Scale: r=.61, p=.02 and r=-.55 p=.03; respectively). Moreover, DPN-unsteadiness (Berg balance score: 47 ±6) and FoF are associated with reduced vigorous exercise PA levels (r=.53, p=.04 and r=-.51, p=.05; respectively), as well as total moderate PA levels (r=-.45, p=.09 and r=.45, p=.09; respectively); measured by General Practice Assessment Questionnaire. Finally, FoF correlates strongly with DPN-unsteadiness (r=-0.79, p<0.001), demonstrating a potential reason why balance impairment may have the negative impact upon PA and QoL. Whilst prospective data are needed to solidify these findings, the preliminary results are robust and support the strong links between the biomechanical impact of DPN and psychosocial outcomes, including depression and fear of falling, and reduced QoL. These data indicate that there is an unmet need for the development of multifaceted interventions that address both psychological distress and biomechanical challenges experienced by patients with this debilitating complication of diabetes.

Disclosure

S.J. Brown: None. A.J. Boulton: None. L. Vileikyte: None. N.D. Reeves: None.
Does Gender Moderate the Relations between Shared Responsibility and Health Outcomes among Adolescents with T1D?
Authors: ABUJARADEH HIBA , SEREIKA SUSAN M. , COHEN SUSAN M. , HELGESON VICKI
Published: June 2018

Shared responsibility (SR) where both parents and adolescents are involved in diabetes management is optimal for reducing psychological distress and improving diabetes outcomes. Few studies examined whether gender moderates the relations between SR and health outcomes. This study examined whether gender moderates the relations of SR to distress and diabetes outcomes during the transition into adolescence. A secondary analysis of longitudinal study of 132 adolescents with T1D and their parents was conducted. Adolescents were 10 to 14 years, 72 girls and 60 boys. All measures were taken annually for 5 years. Both reported on SR. Adolescents reported on distress (depressive symptoms, anxiety, and anger) and self-care. HbA1c was obtained at the clinic visit. Linear mixed models were used to assess if gender moderates the relations between SR and health outcomes.

Results: Concurrent analyses showed that gender moderated the relation between parent-reported SR and HbA1c (p=.007) and child-reported SR and anger (p=.048). At early adolescence, parent-reported SR was associated with lower HbA1c for girls but higher HbA1c for boys. For middle-stage adolescence, SR was associated with higher HbA1c for girls but lower HbA1c for boys. For older adolescents, SR was associated with lower HbA1c for boys but unrelated to HbA1c for girls. Among young and older adolescents, child-reported SR was associated with less anger for boys but unrelated to anger for girls. At middle-stage adolescence, SR was associated with less anger for girls but more anger for boys.

Conclusion: gender moderated the relations between SR and some aspects of health outcomes during transition adolescence in different patterns. SR was associated with better glycemic control among young girls and older boys, and was associated with less anger among boys in general. Healthcare providers need to consider adolescent’s gender when recommending parental involvement in diabetes management for better health outcomes.

Disclosure

H. Abujaradeh: None. S.M. Sereika: None. S.M. Cohen: None. V. Helgeson: None.
Randomized Trial of a Tailored Cognitive Behavioral Intervention in Type 2 Diabetes with Comorbid Depressive and/or Distress Symptoms—Twelve-Month Outcomes from COMRADE
Authors: CUMMINGS DOYLE M. , LUTES LESLEY , PATIL SHIVAJIRAO , HAMBIDGE BERTHA , CARRAWAY MARISSA , LITTLEWOOD KERRY , ADAMS ALYSSA , SOLAR CHELSEY , EDWARDS SHEILA , GATLIN PEGGY
Published: June 2018

Patients with type 2 diabetes (T2D) and co-morbid depressive and/or distress symptoms have poor glycemic control and worse health outcomes. This prospective randomized controlled trial evaluated the effectiveness of a 16-session severity tailored cognitive behavioral intervention plus lifestyle change counseling (n = 67; IG=intervention group) delivered by trained staff compared to usual care (n = 72; CG=control group), in 139 rural adult patients (mean age = 52.6 ± 9.5 years.; 72% black; BMI = 37.0 ± 9.0) with uncontrolled (mean HbA1c = 9.6 ± 2.0) T2D (52% on insulin) and co-morbid depressive (PHQ-2) or distress (DDS-2) symptoms at screening in an academic primary care clinic. At baseline and at 12-month follow-up: height, weight, BP, A1c, diabetes distress (DDS-17), depressive symptoms (PHQ-9), self-care behaviors (SDSCA), empowerment (DES), and medication adherence (ModMAS) were measured using validated instruments. There were no differences between groups at baseline. Between group (IG vs. CG) differences at 12-months follow-up were significant for changes from baseline in diabetes-related distress (-0.83 ± 0.88 vs. -0.15 ± 0.92; p = 0.001), regimen-related distress (-1.12 ± 1.vs. -0.31 ± 1.22; p = 0.001), depressive symptoms (-3.39 ± 5.00 vs. -0.90 ± 6.17; p = 0.01), self-care behaviors (+1.10 ± 1.30 vs. +0.58 ± 1.45; p = 0.03), and medication adherence (+1.00 ± 2.0 vs. +0.17 ± 1.0; p = 0.02). Differences in change in A1c (-0.92 ± 1.81 vs. -0.31 ± 2.04; p = 0.06) were substantially greater in the intervention group and achieved borderline significance. There were no significant differences in glycemic response patterns by race or gender. A tailored cognitive behavioral intervention significantly improves behavioral outcomes and glycemic control in rural black and white patients with T2D and co-morbid depressive and/or distress symptoms.

Disclosure

D.M. Cummings: None. L. Lutes: None. S. Patil: None. B. Hambidge: None. M. Carraway: None. K. Littlewood: None. A. Adams: None. C. Solar: None. S. Edwards: None. P. Gatlin: None.
Hypoglycemia Contributes to Increased CVD Mortality with HbA1c <6.0%
Authors: RHEE MARY , KURGANSKY KATHERINE E. , HO YUK-LAM , GAGNON DAVID R. , RAGHAVAN SRIDHARAN , VASSY JASON L. , CHO KELLY , GONZALEZ ADRIANA , KHAN FARAH N. , STAIMEZ LISA R. , FORD CHRISTOPHER N. , WILSON PETER W. , PHILLIPS LAWRENCE S.
Published: June 2018

Better diabetes control generally reduces development of complications, but those with HbA1c <6.0% have increased cardiovascular (CVD) mortality. Since the cause is unknown, we studied the potential contributions of hypoglycemia, using VA and Medicare databases. 297,263 Veterans with diabetes (ICD-9 codes and diabetes Rx) had ≥4 primary care provider (PCP) visits in 2002-2003, baseline data including age, sex, race, ethnicity, BMI, non-HDL cholesterol, systolic blood pressure (sBP), smoking, ≥1 HbA1c, ≥3 outpatient random plasma glucose (RPG) levels, follow-up through 2012, and survived at least 1 year after A1c measurement. The 40,429 with A1c <6.0% (A1c<6) had mean age 66 year, were 98% male, 16% black and 6.5% Hispanic, had BMI 31, eGFR 71, sBP 139, 81% ever smoked, 51% had CVD at baseline, 48% used sulfonylureas and 13% insulin, with mean HbA1c 5.5%, and RPG 125 mg/dl, while 90,574 with HbA1c 6.0-6.9% (A1c6-6.9) had HbA1c 6.5% and RPG 141 (both p<0.001), but were otherwise clinically comparable. In fully adjusted Cox proportional hazard models, A1c<6 had increased CVD mortality compared to A1c6-6.9 (HR 1.07, p<0.001). However, within 1 year after baseline, A1c<6 also had increased frequency of both outpatient RPG <70 (8.4% vs. 6.0%, p<0.001), outpatient point of care glucose (POCG) <70 (0.34% vs. 0.29%, p=ns), and emergency visits with hypoglycemia (EDHYPO, 0.28% vs. 0.24%, p=ns). Moreover, in Cox models including HbA1c (<6.0 -6.9, -7.9, -8.9, ≥9.0%), hypoglycemia measured by (i) outpatient RPG or POCG levels <70 or (ii) EDHYPO, was independently associated with increased CVD mortality, fully adjusted HR 1.18 and 1.49, both p<0.001. At all HbA1c levels, RPG or POCG <70 predicted CVD mortality more consistently than EDHYPO.

Conclusion: Hypoglycemia-associated CVD mortality occurs in general clinical practice-especially with outpatient glucose <70 mg/dl-and increased mortality with HbA1c <6.0% may be due in part to hypoglycemia. Management should be aimed to optimize control but limit the risk of hypoglycemia.

Disclosure

M. Rhee: None. K.E. Kurgansky: None. Y. Ho: None. D.R. Gagnon: None. S. Raghavan: None. J.L. Vassy: None. K. Cho: None. A. Gonzalez: None. F.N. Khan: None. L.R. Staimez: None. C.N. Ford: None. P.W. Wilson: None. L.S. Phillips: Other Relationship; Self; DIASYST Inc.. Research Support; Self; Amylin Pharmaceuticals, Eli Lilly and Company, Novo Nordisk Inc., Sanofi-Aventis, PhaseBio Pharmaceuticals, Inc., Roche Diabetes Care Health and Digital Solutions, AbbVie Inc., Vascular Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., GlaxoSmithKline plc., Pfizer Inc.. Other Relationship; Self; Novartis Pharmaceuticals Corporation, Merck & Co., Inc..
Proteomic Profile of Circulating Inflammatory Proteins Associated with 10-Year Risk of ESRD in T1 and T2 Diabetes—Enrichment for TNF Receptor Superfamily Members
Authors: NIEWCZAS MONIKA , SKUPIEN JAN K. , NAIR VIJI , SMILES ADAM , PARK JIHWAN , SATAKE EIICHIRO , SIMEONE CHRISTOPHER A. , TSAY JOHN , JU WENJUN , KRETZLER MATTHIAS , SUSZTAK KATALIN , KROLEWSKI ANDRZEJ
Published: June 2018

We conducted an untargeted proteomic profiling of circulating inflammatory proteins using SOMASCAN platform to find those that predicted 10-year ESRD risk in two cohort study. Subjects with Type 1 Diabetes (T1D) served as a discovery cohort and a T2D cohort was used in validation. We identified a kidney risk inflammatory signature (KRIS) that robustly predicted progression to ESRD. The signature comprised 17 proteins out of 194 examined. KRIS was enriched for members of TNFR Superfamily (p=0.007) including TNFR1, TNFR2, TNFRSF19, TNFRSF19L, TNFRSF21 and TNFRSF27. Other KRIS proteins included IL15RA, IL17F, DAF, CLM6, TNFSF15, CCL14, CCL15, CSF1, TIMD3, IL1R1 and IL18R1. Hazard ratio (95% CI) for the top KRIS protein, TNFR1 was 3.6 (2.8, 4.6), p < 10-25. KRIS was neither enriched in receptors for other cytokines nor in cytokine ligands. Pathway analyses pointed to candidate therapeutic targets and aligned them by ranks. Eight proteins are currently targeted with compounds used for other clinical indications. Kidney tissue expression analysis and urinary proteomics suggested a systemic source of KRIS proteins.

In summary, our study identifies and validates a powerful protein signature enriched in TNFRSF members associated with 10-year ESRD risk in diabetes. These findings should inform future drug development strategies.

Disclosure

M. Niewczas: None. J.K. Skupien: None. V. Nair: None. A. Smiles: None. J. Park: None. E. Satake: None. C.A. Simeone: None. J. Tsay: None. W. Ju: None. M. Kretzler: Research Support; Self; AstraZeneca, Novo Nordisk Inc., Boehringer Ingelheim GmbH, National Institute of Diabetes and Digestive and Kidney Diseases, Eli Lilly and Company, Gilead Sciences, Inc. K. Susztak: Research Support; Self; Regeneron Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Merck & Co., Inc., Eli Lilly and Company, Ono Pharmaceutical Co., Ltd.. A. Krolewski: None.
Clinic-Wide Screening of Fear of Hypoglycemia in Mothers and Fathers of Children with Type 1 Diabetes
Authors: MAJIDI SHIDEH , O'DONNELL HOLLY , BENSON KYLIE , DRISCOLL KIMBERLY A.
Published: June 2018

Background: The American Diabetes Association (ADA) recommends anxiety screening in individuals with type 1 diabetes (T1D); however, screening in parents is not addressed. This study describes fear of hypoglycemia (FOH) in parents who were screened as part of their children’s routine T1D clinic visit.

Methods: Mothers (n=234) and fathers (n=79) completed the Hypoglycemia Fear Survey - Parent comprising 3 subscales: Maintaining High Blood Glucose (BG), Worry/Helplessness About Low BG, and Worry About Negative Social Consequences. Scores of ≥7, ≥24, and ≥9, respectively, were used as clinical cutoffs. Higher scores indicate greater fear/worry about hypoglycemia.

Results: Child characteristics were: 53% female; mean age = 13.9±2.2 years; mean A1C = 9.3±2.2%, mean T1D duration = 5.1±4.1 years; 58% CSII. Percentage of mothers and fathers exceeding the clinical cutoffs were: 18%, 14% on Maintaining High BG; 15%, 3% Worry/Helplessness About Low BGs; and 14%, 1% Worry About Negative Social Consequences. Compared to fathers, mothers reported significantly more helplessness about low BGs (t(173.6)=3.24, p=0.001), but not more worry about negative social consequences (t(223.4)=1.42, p=0.16), or engaging in behaviors to maintain high BGs (t(290)=0.68, p=0.50). Parents of older children (≥13 years) worried equally about hypoglycemia (p>0.05), but reported engaging in fewer behaviors to maintain high BGs than parents of younger children (10-12 years) (t(307)=3.27, p<0.001).

Conclusions: FOH is common in both mothers and fathers. Mothers reported more feelings of helplessness than fathers, whereas both mothers and fathers of younger children reported engaging in more behaviors to maintain high BGs than parents of older children. These results support the need to screen parents - not just patients with T1D - for FOH and provide intervention when indicated. Consideration should be given to including recommendations about FOH screening parents in the ADA Medical Standards of Care.

Disclosure

S. Majidi: None. H. O'Donnell: None. K. Benson: None. K.A. Driscoll: None.
Preferences for Health Information and Decision-Making Autonomy among Chinese Patients with T2DM in the mHealth Era
Authors: NIE LISA , XIE BO , YANG YAN , BROWN SHARON A.
Published: June 2018

This cross-sectional survey study explored (1) individual preferences for health information and decision-making autonomy among Chinese patients with type 2 diabetes (T2DM); (2) their use of mHealth in diabetes self-management; and (3) the relationship between their mHealth use and preferences for health information and decision-making autonomy. Sample size: 200 Mandarin-speaking Chinese patients with T2DM; age range: 26-90 years (Mean: 59.91; SD: 12.17); Mean time since diabetes diagnosis: 7.4 years. Data were collected in February 2017 via a paper-and-pen questionnaire at a general hospital in China. The questionnaire was in Chinese, and measured preferences for health information and decision-making autonomy and mHealth use. Key findings: Participants wanted to have a wide range of health information and participation in decision-making. Gender, health status, and knowledge about diabetes were associated with differences in information wanted and participation in decision-making, but age was not. Half (50.5%) of the participants used smartphones to access the Internet and look for health information; 71% used smartphones to receive/read health-related posts; and 24% had at least one health-related application installed on their smartphones. Smartphone use frequency for health information and participation in decision-making had a significant interaction effect (p < .01), the strength of which varied across seven subscales (specific health condition, treatment, laboratory tests, self-management, complementary/alternative medicine, psychosocial aspects, and healthcare providers). The overall health information wanted was positively related to use of smartphones to receive health-related posts (p <.01). This study has implications for research and clinical practice, especially given the shift from disease-centered to patient-centered care and increasing use of mobile technology in health care.

Disclosure

L. Nie: None. B. Xie: None. Y. Yang: None. S.A. Brown: None.
Reasons for Insulin Omission—What Matters Most?
Authors: OSBORN CHANDRA Y. , SEARS LINDSAY E. , HIRSCH ASHLEY , RAYMOND JENNIFER , HEYMAN MARK , HEAD RACHEL , DACHIS JEFF
Published: June 2018

Background: One in 3 people with diabetes (88% with type 2 diabetes [T2D]) do not take insulin as recommended an average ∼3.3 days per month. Insulin omission (IO) is associated with suboptimal A1c. Reasons for IO are multifactorial (e.g., cost, fear, stigma). Unclear are what matters most for reducing IO and improving A1c.

Objective: We assessed 10 reasons for IO among a national sample of people with T2D, and identified reasons that, if addressed, might improve A1c.

Methods: Adults (age 18-75 years) with T2D self-selected to be in a randomized control trial comparing inhalable, ultra-rapid-acting insulin (Afrezza) with One Drop’s digital therapeutics solution vs. injectable, rapid-acting insulin with One Drop. A HIPAA protected, online survey screened potential participants. Eligible persons completed a baseline survey and NGSP certified A1c test. Survey items collected demographics, reasons for IO, and responses to the ARMS-D and SDSCA-IS to assess IO. We used SPSS v25 for psychometric, descriptive, and multivariate statistics, and PROCESS v3 for unadjusted and adjusted mediation models with bootstrapped (10K) CIs.

Results: Participants (N=269) were 50±11 years old, 51% male, 30% non-white, 90% insured, with 13±8 years since a T2D diagnosis, and A1c 8.8%±1.8%. ARMS-D insulin had internal consistency reliability (α=.82), and convergent validity with SDSCA-IS (rho=.46, p<.001). IO was associated with higher A1c (β=.39, p<.001). Cost (coef.=.08; 95% CI:.02-.15), disruption (coef.=.07; 95% CI:.001-.15), fear of side effects (coef.=.15; 95% CI:.07-.26), and burnout (coef.=.11; 95% CI:.05-.19) had indirect effects on higher A1c through IO. Reasons were not directly related to A1c.

Discussion: Cost, disruption, fear, and burnout were associated with IO, and higher A1c through IO. Given time and resources constraints, clinic visits and self-care interventions must prioritize and address modifiable factors contributing to both non-adherence and higher A1c. Such efforts may be more effective than other approaches.

Disclosure

C.Y. Osborn: Employee; Self; One Drop. Research Support; Self; MannKind Corporation. Stock/Shareholder; Self; One Drop. L.E. Sears: Employee; Self; Informed Data Systems Inc.. Research Support; Self; MannKind Corporation. A. Hirsch: Employee; Self; One Drop. Research Support; Self; MannKind Corporation. J. Raymond: None. M. Heyman: Employee; Self; One Drop. R. Head: None. J. Dachis: Stock/Shareholder; Self; One Drop. Board Member; Self; One Drop. Employee; Self; One Drop.
Assessment of Infusion Set Survival of the Newly Developed Lantern Catheter in Type 1 Diabetes by Glucose CLA Technique
Authors: AJSIC AMRA , KRASSER MICHAEL C. , JULIUSSEN RASMUS , SCHØNDORFF PERNELLE K. , HESCHEL MATTHIAS , PÖTTLER TINA , SCHWARZENBACHER DANIELA , AUGUSTIN THOMAS , PIEBER THOMAS R. , TREIBER GERLIES , MADER JULIA K.
Published: June 2018

The catheter-tissue interface is the bottle neck of insulin pump therapy (CSII). Currently infusion sets shall be changed every 2-3 days to avoid lipohypertrophy, fluctuations in insulin absorption and occlusion. Patients would prefer an extended wear time if stable insulin absorption could be achieved. The novel catheter featuring Lantern Technology shall allow more stable insulin delivery via slots in the shaft of the soft cannula even if kinking or clotting occurs. The aim of the present study was to investigate clinical performance of the coated Lantern catheter in 16 patients with type 1 diabetes using CSII over a period of up to 7 days. A combined design comprising inpatient (euglycemic clamps on days 1, 4 and 7) and outpatient phases (insulin pump therapy over 7 days) is chosen to allow assessment of performance and survival time of the Lantern catheter. 16 c-peptide negative patients (age 44.2 ± 15.4 years, BMI 24.5 ± 2.3 kg/m2, HbA1c 55 ± 8 mmol/mol, diabetes duration 20 ± 9 years) completed the 7-day study period. Geometric means of maximum glucose infusion rates (GIR) were similar for days 1, 4 and 7 (6.1 ± 1.5, 7.2 ± 1.3, 5.8 ± 1.4; p=0.14). Time to reach 50% of the maximum GIR were similar over time (31.5 ± 1.6 minutes vs. 29.3 ± 1.3 minutes vs. 27.3 ± 1.3 minutes for days 1, 4 and 7 respectively; p=0.51). Area under the log-transformed GIR curve did not significantly differ for the first 2 hours between days (343.7 ± 1.5 vs. 421.3 ± 1.6 vs. 350.6 ± 1.8; p=0.14; days 1, 4 and 7, respectively); however, there was a trend towards reduced area under the GIR curve over 8 hours over time (874.2 ± 1.4 vs. 744.5 ± 1.7 vs. 509.2 ± 2.0; days 1, 4 and 7, respectively; p<0.05). During outpatient care no severe hypoglycemic event or ketoacidosis occurred. The novel Lantern catheter could be safely used over an extended wear-time of 7 days. There was a trend towards reduced insulin action over time. The findings need to be confirmed in a larger scale trial under routine conditions.

Disclosure

A. Ajsic: None. M.C. Krasser: None. R. Juliussen: Employee; Self; ConvaTec Inc. P.K. Schøndorff: Employee; Spouse/Partner; ConvaTec Inc.. M. Heschel: None. T. Pöttler: None. D. Schwarzenbacher: None. T. Augustin: None. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. G. Treiber: None. J.K. Mader: Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, Novo Nordisk A/S. Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Becton, Dickinson and Company. Speaker's Bureau; Self; Sanofi. Research Support; Self; ConvaTec Inc., Menarini Group. Speaker's Bureau; Self; Medtronic. Research Support; Self; Novo Nordisk A/S, Sanofi.
Effect of Remote Glucose Monitoring Utilizing Computerized Insulin Dose Adjustment Algorithms on A1C Levels—A Preliminary Report
Authors: DAVIDSON MAYER B. , DAVIDSON JOSH
Published: June 2018

Adjusting insulin doses is very challenging for primary care physicians because of infrequent office visits and time constraints at the visit. For patients, frequent office visits are a barrier. We have used FDA-approved, computerized insulin dose adjustment algorithms and remote glucose monitoring to circumvent both of these issues. Diabetic patients in a safety net clinic who took insulin for at least 6 months with A1C levels ?8.0% were enrolled in a study in which an iHealth glucose meter was attached to a smartphone containing an app downloaded from the Web that transmitted the glucose values to a secure, HIPAA-approved server. There the values were analyzed by the algorithms and a report with recommendations for dose changes was generated and sent to a clinic nurse practitioner every 2-3 weeks who could accept or modify the recommendations. A clinic staff individual contacted the patient with the insulin dose changes. Twenty-eight diabetic patients (one type 1) have reached 3 months. Their mean age (± SD) was 55.9 ± 8.6 years, 15 were females and 13 were males. There were 20 Latinos, 4 African-Americans, 3 Caucasians, and 1 Asian. Their insulin regimens were: basal alone - 11, basal/bolus - 14 and self-mixed/split - 3. Non-insulin drugs were not changed. Their baseline A1C levels (± SD) of 10.0% ± 1.2 decreased by 1.9% ± 0.9 to 8.1% ± 1.1 after 3 months. Their total insulin dose increased by 24%. There were no episodes of severe hypoglycemia (requiring 2nd party assistance) nor emergency room visits for hypoglycemia.

Conclusion: Remote glucose monitoring utilizing computerized insulin dose adjustment algorithms to analyze glucose values and generating recommendations for dose changes at more frequent intervals markedly improved A1C levels in poorly controlled diabetic patients in the absence of office visits.

Disclosure

M.B. Davidson: Employee; Self; Insulin Algorithms, Inc. J. Davidson: Employee; Self; Insulin Algorithms.
A Feasibility Study to Detect Neonatal Hypoglycemia Using Real-Time Continuous Glucose Monitoring
Authors: NALLY LAURA M. , BONDY NICHOLAS W. , DOIEV JASMINE , BUCKINGHAM BRUCE , WILSON DARRELL
Published: June 2018

Introduction: Infants of diabetic mothers are at high risk of hypoglycemia (<47 mg/dl) after birth, with rates approaching 50% in the first 48 hours of life (HOL).

Methods: Infants born at ≥34 weeks gestation to mothers with diabetes had a CGM placed after birth and were remotely monitored by research staff during their hospitalization. Clinical staff and families were blinded to CGM data. For CGM readings <45 mg/dl, research staff requested a heelstick blood glucose (BG) using the hospital glucometer.

Results: Eleven infants were studied. Mothers had an average A1c of 5.6% (range 4.7-6.8%) prior to delivery and 82% required insulin. Hypoglycemia (<45 mg/dl) was confirmed in 7 of 11 infants with 14 events at less than 12 HOL, 2 events between 12-24 HOL, and 1 event at >48 HOL. CGM detected hypoglycemia 4 times when the infant was not due for a BG check based on the standard of care. The true positive rate for sensor-detected hypoglycemia was 40% and the false positive rate was 60%. CGM detected 24% of the hypoglycemic events that the usual intermittent pre-prandial BG checks would have missed.

Conclusion: We conclude that CGM is safe and may provide added benefit for detecting hypoglycemia when used early after birth.Table. Neonatal characteristics and duration of hypoglycemia based on CGM readings. Reported as mean ± SD, (range).Neonatal CharacteristicsRemote Monitoring (n=11)Gestational Age (wk)38.4 ± 1.6 (34 - 39.4)Birth weight (kg)3.4 ± 0.6 (2.4 - 4.2)Mean CGM Glucose (mg/dl)64 ± 20 (50 - 114)CGM placed (HOL)2.9 ± 0.6 (1.5 - 3.7)CGM recording started (HOL)6.0 ± 0.7 (5.1 - 7.3)Duration of CGM records (hr) **Median (IQR)31.2 (13.2 - 41.5)Duration of Time BG <45 mg/dl (hr) **Median (IQR)2.7 (0.1 - 5.0)

Disclosure

L.M. Nally: None. N.W. Bondy: None. J. Doiev: None. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. D. Wilson: Research Support; Self; T1D Exchange, Medtronic MiniMed, Inc., Dexcom, Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Insulet Corporation. Advisory Panel; Self; Tolerion.
HbA1c Trends with Treatment Intensification following Inadequate Response to Two Oral Agents in Patients with Type 2 Diabetes
Authors: KIM KIBUM , UNNI SUDHIR , BRIXNER DIANA , THOMAS SHEILA , OLSEN CODY J. , STERLING KIMBERLY L. , MITCHELL MATT , MCADAM-MARX CARRIE
Published: June 2018

Objectives: To describe HbA1c trends 1-year post treatment intensification to insulin or non-insulin agents in patients with insufficient HbA1c control while on 2 oral antidiabetic agents (2 OADs).

Methods: A retrospective cohort study was conducted in a regional health plan claims database from 1/1/2010 to 3/31/2017. Included patients had type 2 diabetes (T2D) and their treatment was intensified with insulin, a GLP-1 receptor agonist (GLP-1RA) or a 3rd OAD within a year from an HbA1c ≥7.0% while on 2 OADs. HbA1c was estimated monthly by intensification with insulin or non-insulin (i.e., GLP-1RA and 3rd OAD) agents using a mixed-effect model.

Results: The study analyzed a total of 3,909 HbA1c measures from 1,226 patients. HbA1c reductions were significant, but most patients continued to have inadequate glycemic control (HbA1c ≥7.0%). Those receiving insulin had a higher baseline HbA1c (p<0.01), but showed more substantial HbA1c decrease vs. those intensified with a non-insulin agent (p<0.01), controlling for baseline HbA1c.

Conclusion: In patients with T2D, intensification following suboptimal glycemic control while on 2 OADs was associated with significant improvement in HbA1c control. Insulin intensification was associated with worse control at baseline, but greater HbA1c reduction than non-insulin intensification. Additional opportunity exists to improve glycemic control.

Disclosure

K. Kim: None. S. Unni: Research Support; Self; AstraZeneca, Sanofi-Aventis. D. Brixner: Research Support; Self; Sanofi. S. Thomas: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C.J. Olsen: None. K.L. Sterling: Employee; Self; Sanofi. Stock/Shareholder; Self; Eli Lilly and Company. M. Mitchell: None. C. McAdam-Marx: Research Support; Self; AstraZeneca, Sanofi.