bluuebunny/crossref_metadata_2025 huggingface dataset:
1299-P: Ecological Momentary Assessment (EMA) of Positive and Negative Affect, Social Context, and Blood Glucose (BG) in Teens with Type 1 Diabetes
Authors: SHAPIRA AMIT , VOLKENING LISA K. , BORUS JOSHUA , LAFFEL LORI M.
Published: June 2020

Aim: Affect and social context are associated with diabetes self-care in teens with T1D. We used EMA to examine associations of affect and social context with BG levels in teens with T1D.

Methods: Over 2 weeks, 32 teens reported positive (POS) and negative (NEG) affect (Positive and Negative Affect Schedule) and BG levels on handheld computers 4 times/day, coordinated with daily BG checks; at 3/4 times, teens also reported attitudes toward social context (i.e., strong desire to blend in, strong desire to impress others). Z-scores were calculated for NEG and POS subscales to reflect deviations from each teen’s overall affect. BG values were classified: 1) time in range (TIR) 70-180 mg/dL; 2) low <70 mg/dL; 3) serious low <54 mg/dL; 4) high >180 mg/dL; 5) serious high >250 mg/dL. Separate logistic generalized estimating equations, adjusted for age, sex, T1D duration, pump therapy, and A1c, determined associations between affect, social context, and BG ranges.

Results: Teens (44% male) were ages 14-18 years with T1D duration of 8.8±4.2 (M±SD) years; 63% were pump treated and A1c was 8.8±1.4%. Median 2-week EMA response rate was 72%. Average NEG and POS affect scores were 1.4±0.5 and 2.4±1.1, respectively. Teens reported a desire to impress others 8% of time and desire to blend in 9% of time. Teens reported 51% TIR, 6% low (2% serious low), and 44% high (19% serious high) BG. In adjusted models, more NEG affect was associated with lower odds of reporting a serious low BG (OR= 0.5, 95% CI: 0.3-0.9, p=.03) and higher odds of reporting a serious high BG (OR= 1.2, 95% CI: 1.1-1.4, p=.0002). NEG affect was not associated with TIR, low BG, or high BG. Neither POS affect nor social context were associated with any BG ranges.

Conclusions: In our sample, NEG affect was associated with BG >250 mg/dL. Teens with T1D who experience NEG affect may not attend to diabetes self-care. Interventions targeting NEG affect may help improve diabetes self-care behaviors in teens with T1D.

Disclosure

A. Shapira: None. L.K. Volkening: None. J. Borus: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding

JDRF International; National Institutes of Health (P30DK036836, K12DK094721)
13-LB: Leptin Treatment Prevents Impaired Hypoglycemic Counterregulation Induced by Exposure to Recurrent Hypoglycemia or Caloric Restriction
Authors: MCDOUGAL DAVID , DUVALL MARINA , SIKAFFY HUNTER X. , JARIWALA RAJVI , MORRISON CHRISTOPHER , HILL CRISTAL M.
Published: June 2020

Background: Hypoglycemia-associated autonomic failure (HAAF) is a significant barrier to achieving optimal glucose levels in persons with diabetes. Our group and others have demonstrated that low leptin levels are concurrent with impaired hypoglycemic counter-regulation in two separate animal models of HAAF: six days of 60% caloric restriction (CR) in mice and 3 days of recurrent hypoglycemia (3dRH) in rats. In this study, we tested whether leptin treatment during CR or 3dRH could prevent the development of HAAF.

Methods: In experiment one, 3 groups of mice (two CR groups and one ad-lib fed control group) received either twice daily leptin (0.5-1μg/g, IP) or PBS. In experiment two, 3 groups of rats (two 3dRH and one control) received daily leptin or PBS injections (0.3-0 .7 mg/kg, IP). One day following the CR or 3dRH paradigms, all animals underwent a hypoglycemic ITT and levels of glucagon, leptin, epinephrine (rats), and corticosterone were assessed 60 min following insulin treatment.

Results: As expected, PBS treated CR mice and 3dRH rats had significantly reduced glucagon levels and epinephrine levels relative to controls (24 ± 5 vs. 95 ± 20 pmol/L and 57 ± 12 vs. 110 ± 9 ng/mL, respectively). In contrast, there was no differences in the glucagon levels of leptin treated CR mice and epinephrine levels of leptin treated 3dRH rats relative to their respective control groups. Leptin levels in both CR groups were reduced relative to controls (0.9 ± 0.3 and 0.2 ± 0.1 vs. 3.0 ± 0.5 ng/mL, respectively), while corticosterone was unchanged. Glucagon, corticosterone, and leptin levels were similar across groups in the 3dRH paradigm.

Discussion: Utilizing two separate animal models of HAAF, we established that leptin treatment can prevent the loss of hypoglycemic counter-regulation. Future studies investigating whether combining leptin treatment with insulin therapy could significantly reduce hypoglycemic complications in diabetes patients are warranted.

Disclosure

D. McDougal: None. M. DuVall: None. H.X. Sikaffy: None. R. Jariwala: None. C. Morrison: None. C.M. Hill: None.

Funding

American Diabetes Association (1-15-JF-37 to D.M.); National Institutes of Health (U54GM104940)
13-OR: Piloting the Problem Areas in Diabetes Scale in Clinical Practice: The DiaPROM Pilot Trial
Authors: HERNAR INGVILD , GRAUE MARIT , RICHARDS DAVID , STRANDBERG RAGNHILD B. , LØVAAS KARIANNE F. , MADSEN TONE VONHEIM , TELL GRETHE S. , HAUGSTVEDT ANNE
Published: June 2020

Background: Diabetes distress is a potential barrier to self-management and satisfactory glycaemic control. A structured focus on diabetes distress using the Problem Areas in Diabetes (PAID) scale may improve the health of people with diabetes. We designed the DiaPROM trial, evaluating the effect of using electronically captured PAID in clinical practice, to reduce diabetes distress among adults with type 1 diabetes.

Methods: In this pilot trial, we aimed to evaluate PAID scores pre and post intervention and identify patients with elevated scores. We randomly assigned participants (18-≤40 yrs) at an outpatient clinic to standard care or an intervention were physicians referred individuals with a PAID score ≥30 or single item(s) ≥3 (moderately high distress) to minimum two nurse appointments. Following a communication manual based on empowerment and self-determination theory, reported problem areas were reviewed and discussed.

Results: We recruited 79 adults with type 1 diabetes (age 27.2 ±5.0 yrs, diabetes duration 13.7 ±7.0 yrs, HbA1c 65.4 ±14.5 mmol/mol). In the intervention group (n=39), baseline PAID score was 27.7 ±16.8; 23 (59%) participants qualified for additional follow up and 17 (44%) accepted referral, attending a mean of 2.2 ±1.1 appointments. At 12 month follow up, the intervention group (n=31) mean score was 21.7 ±14.4 (mean change 3.7 ±13.0), with 13 (42%) reporting moderately high distress. The control group (n=40) scored 24.1 ±14.3 at baseline and 26.2 ±14.5 at 12 months (n=36), with respectively 19 (48%) and 20 (56%) patients reporting moderately high distress. Between-group difference at 12 months was 5.5 (95% CI 0.25, 10.7).

Conclusion: Half of the participants reported diabetes distress levels qualifying for additional follow up, which has consequences for scaling a future RCT. Although the study was not powered to estimate intervention effects, we identified a promising PAID score reduction in the intervention group which was not observed for the controls.

Disclosure

I. Hernar: None. M. Graue: None. D. Richards: None. R.B. Strandberg: None. K.F. Løvaas: None. T. Madsen: None. G.S. Tell: None. A. Haugstvedt: None.
1311-P: Number of Daily Meals and Snacks Impacts Glycemic Outcomes in Youth with T1D
Authors: LA BANCA REBECCA O. , VOLKENING LISA K. , DASSAU EYAL , MEHTA SANJEEV N. , LAFFEL LORI M.
Published: June 2020

Aim: Most youth with T1D meet neither nutrition guidelines nor glycemic goals. We assessed macronutrient content of meals/snacks and impact of daily number of meals/snacks on glycemic outcomes in youth with T1D over 1 year.

Methods: Youth completed 3-day food records (2 week days/1 weekend day) and wore 3-day masked CGM (iPro™) every 3 months for 1 year. Diet data were reviewed by 2 RDs and analyzed using Nutrition Data System for Research (NDSR). Glycemic outcomes were A1c and CGM metrics (glucose % time in range [TIR] 70-180 mg/dL, % time [T] <70, %T>180, and glucose CV [SD/mean]). Longitudinal mixed models assessed effect of number of daily meals/snacks on glycemic outcomes.

Results: Youth (N=136, ages 8-17, 48% male) were ages 12.8±2.5 years with T1D duration 5.9±3.1 years and daily insulin dose 0.9±0.3 U/kg; 73% used insulin pumps. Number of meals/snacks ranged from 1-9 with most youth (69%) reporting 3-4 meals/snacks daily. Macronutrient intake varied by meal/snack (Figure). An increase of 1 meal/snack per day led to a 0.1% decrease in A1c (p=.001), 2.4% (35 minutes/day) more TIR (p=.0006), and 3.1% (45 minutes/day) less T>180 (p=.0001); T<70 and CV were unchanged.

Conclusions: In youth with T1D, eating frequent meals/snacks may lead to lower A1c, more TIR, and less hyperglycemia. These findings may be due to dividing energy intake across the day with more frequent bolus dosing, given predominance of carbohydrates in meals/snacks.

Disclosure

R.O. La Banca: None. L.K. Volkening: None. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. S.N. Mehta: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding

National Institutes of Health (P30DK036836, K12DK094721)
1318-P: Characteristics of Autoimmune Thyroid Disease in African American and Caucasian Children with Type 1 Diabetes Mellitus
Authors: BEJJANI MIREILLE EL , ZIDAN MARWAN , ZIDAN HANAA
Published: June 2020

Background: Patients with type 1 diabetes mellitus (T1DM) are at increased risk of autoimmune thyroid disease (AIT). In the pediatric age group, the prevalence of AIT varies across a wide range (3-50%), depending on the population studied. There is very limited data describing the association of T1DM and AIT disease in African-American (AA) children.

Objective: Characterize the association between T1DM and AIT in AA and Caucasian children presenting to the same medical center.

Methods: After IRB approval, the medical records of 130 AA and 130 Caucasian children with T1DM presenting to the Children’s Hospital of Michigan were reviewed. Data collected included age, gender, ethnicity, presence of AIT evidenced by positive anti-TPO or anti-TG antibodies, TSH, free T4, anti-islet, anti-insulin and anti-GAD antibodies. Comparison was drawn between the two ethnicities in regards to the prevalence of AIT as well as predisposing factors for the onset of AIT.

Results: 12.3% of AA with T1DM developed AIT versus 23.8% of Caucasian. This difference was statistically significant with a p-value of 0.023. In the Caucasian group, female was a risk factor for developing AIT (37.9% in females vs. 12.5% in males, p-value 0.001) while gender was not a significant risk factor for AA patients (p-value 0.790). The presence of anti-insulin antibodies was a risk factor for Caucasians (p-value 0.024) but not for AAs (p-value 0.185). The survival analysis showed mean time for onset of AIT in AA with T1DM is 15.1 years vs. 11.7 years in Caucasians (Log Rank p-value 0.025).

Discussion: Our study shows a significantly lower prevalence AIT in AA compared to Caucasian children with T1DM. Female gender and anti-insulin antibody are risk factors for Caucasians but not in AAs. Differences could be secondary to different genes implication given the different genetic background. Further investigation can lead to a better understanding of T1DM and thyroid autoimmunity in the AA population.

Disclosure

M. El Bejjani: None. M. Zidan: None. H. Zidan: Speaker’s Bureau; Self; Novo Nordisk Inc.
1321-P: Lower Use of Technology in Youth with Type 1 Diabetes in Locations Distant from Specialty Care
Authors: COBRY ERIN C. , REZNICK-LIPINA TYLER , PYLE LAURA , SLOVER ROBERT H. , THOMAS JOHN F. , ALONSO GUY T. , WADWA R. PAUL
Published: June 2020

Pediatric patients with type 1 diabetes (T1D) who live far from a diabetes specialty clinic have fewer clinical visits. Telemedicine can increase visit frequency, but the impact on adoption of diabetes technology, such as insulin pumps and continuous glucose monitoring (CGM), is unclear.

Pediatric patients with T1D in Colorado and Wyoming who received diabetes care from our center via telemedicine were eligible to participate. As part of an ongoing telemedicine study, medical records were reviewed to ascertain technology use, and data were compared to patients whose care did not involve the use of telemedicine.

Patients (N=149, age 12.0 ± 4.3 yrs, T1D duration 2.7± 4.2 yrs, HbA1c 8.9 ± 1.8%, gender 60% male, race/ethnicity 74% non-Hispanic white, insurance status 68% private) who utilized telemedicine between 2012 and 2019 were included. Compared to the general clinic (N=2672), technology use was lower (pump: 64% vs. 77%, p = 0.001; CGM: 35% vs. 79%, p <0.001; pump and CGM: 30% vs. 56%, p <0.001). Use of technology among telemedicine patients was not associated with gender, T1D duration, insurance or distance from the main clinic but was associated with race/ethnicity and lower HbA1c (Table).

Diabetes technology use is lower in pediatric T1D patients using telemedicine. Additional research is needed to explore potential reasons for this discrepancy and methods to improve the use of diabetes technology in these patients.

Disclosure

E.C. Cobry: None. T. Reznick-Lipina: None. L. Pyle: None. R.H. Slover: None. J.F. Thomas: None. G.T. Alonso: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company, Medtronic. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk Inc., Tandem Diabetes Care.

Funding

National Institutes of Health (K12DK094712); National Center for Research Resources (UL1TR002535)
1323-P: Frequency of Diabetes Team Contacts in Children and Adolescents Using Insulin Pumps
Authors: BABALOLA FUNMBI , MILLER MICHAEL , ENS ANDREA , GALLEGO PATRICIA H. , STEIN ROBERT I. , CLARSON CHERIL
Published: June 2020

Type 1 diabetes (T1D) management has become increasingly technologically advanced with the use of insulin pumps, continuous glucose monitoring and diabetes data management software. These technologies are underutilized although there is evidence for improvement in A1C when adults review blood glucose trends with their diabetes team in between clinic visits. The primary objective of this study was to assess if a correlation exists between A1C within target (≤ 7.5%) and frequency of contact of pediatric patients with the diabetes team between clinic visits. Secondary objectives included determining barriers to contact and change in A1C from baseline to end of study. T1D patients using an insulin pump for one year or more were approached to participate. Participants completed a questionnaire to assess diabetes management over the past year. A1C and contact with the diabetes team between clinic visits for insulin adjustments in the past year were collected. One hundred and seventy six participants were enrolled, 46% female, with a mean age of 12.9 (± 3.8) years. Mean duration of T1D was 6.7 (± 3.7) years with a mean duration of pump use of 4.5 (± 3.1) years. Mean A1C at baseline was 8.1% (± 1). One hundred and sixteen (66%) patients contacted the diabetes team for insulin adjustments between clinic visits with a mean of 1.2 (± 1.7) contacts, 90% by e-mail. There was no significant relation between target A1C and frequency of contact (p>0.05). Decreased frequency of contact was associated with increased age (r=0.20, p = 0.01) and longer duration of pump use (r=0.17, p = 0.02). Barriers to contact included being too busy (41%) and technical problems with software (39%).

In conclusion, there was no significant relationship between frequency of contact of pediatric patients with the diabetes team and A1C. The low frequency of contact raises the importance of defining strategies to increase patient contact which has the potential to improve diabetic control.

Disclosure

F. Babalola: None. A. Ens: None. P.H. Gallego: None. R.I. Stein: None. C. Clarson: None.
1325-P: Study on the Mechanism of Activating Macrophages TGR5 on Glucose Metabolism during Pregnancy
Authors: LI JUNXIAN , LIU FANG
Published: June 2020

Purpose: To explore a new mechanism of improving glucose homeostasis in pregnancy through activation of Takeda G protein-coupled receptor 5 (TGR5) in bone marrow derived macrophages (BMDM) from gestational diabetes mellitus (GDM) model mouse and observation the changes of macrophages migration, inflammatory factors and chemokines expression and secretion, and the expression of Proprotein Convertase 1/3 (PC1/3).

Methods: INT-777 was used as TGR5 agonist and LPS was used as inducer for macrophage polarization to M1. Primary bone marrow cells were extracted from GDM model mouse and were induced into macrophages. The macrophages activity and migration were detected by cck-8 tests and Transwell assay respectively when macrophages were treated with INT-777. The expression and secretion levels of inflammatory factors and chemokines in macrophages were detected by real-time PCR, cytometric bead array and ELISA, and the expression levels of PC1/3 was detected by Western blot when macrophages were treated both with INT-777 and lipopolysaccharide (LPS).

Results: TGR5 activation of macrophages by INT-777 increased cell activity (P < 0.01) and decreased cell migration (P < 0.001). Moreover, the mRNA levels of inflammatory cytokines and chemokines including IL-1β, IL-6, TNF-α, CCL2, CCL4, CCL5 and CCL7 mRNA were significantly decreased (All P < 0.05), the secretion levels of inflammatory cytokines and chemokines including IL-6, TNF-α, MCP-1, CCL2, CCL3 and CCL4 were significantly decreased (All P < 0.05) and the expression of PC1/3 was increased (P < 0.05) in INT-777 + LPS treated macrophages, compared with LPS treated macrophages only.

Conclusions: Activation of TGR5 in BMDM can effectively inhibit the macrophage polarization to M1, including inhibiting inflammatory factors expression and secretion. Moreover, activation of TGR5 can inhibit macrophage chemokine expression and secretion, cell migration and can upregulate PC1/3 expression.

Disclosure

J. Li: None. F. Liu: None.

Funding

National Natural Science Foundation of China (81770802)
1327-P: Maternal Diabetes Suppresses Neural Tube Closure Gene Shroom3 through DNA Hypermethylation and Thus Disrupts Planar Cell Polarity
Authors: XU CHENG , YANG PEIXIN
Published: June 2020

Neural Tube Defects (NTDs) are among the most frequent and severe malformations associated with maternal diabetes. DNA hypermethylation inhibits gene expression. Our recent studies have revealed a group of neural tube closure-related genes are downregulated by maternal diabetes. Planar cell polarity (PCP) is conserved in metazoans and is essential for development, deficiencies of PCP genes result in NTDs. Shroom3 encodes a PDZ-domain-containing protein that regulates cell shape in epithelium. Shroom3 interacts with PCP genes, loss of function of Shroom3 leads to NTDs. We hypothesize that DNA hypermethylation induced by maternal diabetes is responsible for the downregulation of Shroom3, which disrupts the PCP pathway leading to NTD formation. We found global DNA methylation levels were increased about 3 times and all 3 DNA methyltransferase levels were increased in the embryos from diabetic dams compared to the nondiabetic control group. Conditional double knockout of Dnmt3a/Dnmt3b gene in the developing neuroepithelium ameliorated maternal diabetes-induced NTDs, while overexpression Dnmt3b in the neuroepithelium induced NTDs in a dose dependent manner. Expression levels of PCP genes and Shroom3 were reduced by maternal diabetes and Dnmt3b transgenic overexpression. Similarly, PCP protein subcellular expression patterns were also disrupted. DNA methyl-sequencing revealed maternal diabetes-induced hypermethylation in the Shromm3 gene promoter. De-methylation rescued Shroom3 promoter activity suppressed by high glucose. Our study reveals that diabetes-induced DNA hypermethylation inhibits Shroom3 gene expression and Shroom3 deficiency mediates the teratogenic effect of maternal diabetes by disrupting PCP and resulting in NTDs. Since de-methylation can rescue Shroom3 activity, our findings suggest that targeting DNA hypermethylation could be therapeutically effective in treating maternal diabetes-induced NTDs.

Disclosure

C. Xu: None. P. Yang: None.

Funding

National Institutes of Health (R01DK083243, R01DK101972, R01HL131737, R01HL134368, R01DK103024)
1332-P: Lactation Improves Glucose Homeostasis by Enhancing ß-Cell Mass and Function through Serotonin Production
Authors: MOON JOON HO , KIM HYEONGSEOK , JANG HAK CHUL , KIM HAIL
Published: June 2020

Parous women who did not lactate have increased risk of diabetes compared to nulliparous women, but this risk is normalized by lactating for >3 months. However, the mechanism of the beneficial effects of lactation has not been elucidated. Therefore, we compared metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. For the human study, we recruited gestational diabetes and gestational impaired glucose tolerance women, and performed 75 g oral glucose tolerance test at postpartum 2 months and annually thereafter. Both lactating and non-lactating women showed normal glucose tolerance after 2 months of lactation. However, after a mean 3.6 years from delivery, lactated women maintained similar glucose tolerance whereas glucose tolerance deteriorated over time in non-lactated women. The Disposition index was improved in previously lactated women, suggesting improved β cell function after several years of delivery. For the mouse study, nine-week-old female C57BL/6J mice were mated to give birth and pups were either left (Lactating) or removed (Non-lactating) from the cage at the day of delivery. At 3 weeks after delivery, lactating mice had improved glucose tolerance and increased β cell mass compared to non-lactating mice. Lactating mice maintained high serum prolactin levels, which induced serotonin production in β cell via PRLR-STAT5-TPH1 cascade. Serotonin facilitated β cell proliferation and enhanced β cell function in lactating mice. Amelioration of glucose tolerance and β cell function were maintained for several months after the cessation of lactation in mice. These beneficial effects of lactation, however, were diminished in β cell-specific Tph1 knockout mice. We demonstrated a novel mechanism of 5-HT derivatives acting as a direct anti-oxidant to enhance β cell survival upon oxidative stress.

In conclusion, serotonin contributes to the beneficial metabolic effects of lactation by enhancing β cell mass and function.

Disclosure

J. Moon: None. H. Kim: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. H. Kim: None.

Funding

National Research Foundation of Korea (2017H1A2A1042095, 2013H1A8A1003985, 2018R1A6A3A01012333, 2015M3A9B3028218, 2018R1A2A3074646)
1335-P: Hepatic Prolactin Receptor Signaling Is Critical for Protecting against Gestational Diabetes
Authors: ZHU CUILING , YAMAUCHI JUN , PAN CHENGLIN , GAO JINGYANG , QU SHEN , BANERJEE RONADIP R. , DONG H. HENRY
Published: June 2020

Gestational diabetes mellitus (GDM) is characterized by fasting hyperglycemia and glucose intolerance during pregnancy, but with poorly understood mechanisms. We found that prolactin receptor (Prlr) is markedly upregulated in liver of pregnant female mice. These findings have spurred the hypothesis that hepatic Prlr signaling is pivotal for physiological adaptation of hepatic metabolism to gestation. To address this hypothesis, we generated liver-conditional L-Prlr-KO mice, followed by determination of glucose and lipid metabolism in female L-Prlr-KO vs. age-matched female WT mice prior to and during gestation. Hepatic Prlr depletion did not impact glucose and lipid metabolism in virgin L-Prlr-KO mice. However, pregnant L-Prlr-KO mice developed GDM, as evidenced by the induction of glucose intolerance, fasting hyperglycemia, higher HOMA-IR levels and abnormal glucose-stimulated insulin secretion at gestational day 15.5. We reproduced these findings in female L-Prlr-KO mice in the 1st, 2nd and 3rd pregnancy, with the severity of GDM exacerbated by transient high fat feeding prior to conception in female L-Prlr-KO mice. Hepatic Prlr depletion did not affect litter size, but pups born to L-Prlr-KO mice had significantly lower birth weight. We recapitulated this finding in newborns derived from the 1st, 2nd and 3rd pregnancy in L-Prlr-KO mice. Hepatic Prlr depletion also resulted in increased triglyceride and cholesterol levels in liver, characteristic of nonalcoholic fatty liver disease and consistent with increased insulin resistance in pregnant L-Prlr-KO mice. Multiparous L-Prlr-KO mice developed postpartum prediabetes. Our studies unveiled an unprecedented role of hepatic Prlr signaling in regulating maternal hepatic metabolism to protect against GDM.

Disclosure

C. Zhu: None. J. Yamauchi: None. C. Pan: None. J. Gao: None. S. Qu: None. R.R. Banerjee: None. H. Dong: None.

Funding

National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)
1341-P: Comparison of the Effects of Metformin and Exenatide on Pregnancy Rate and Outcomes in Overweight or Obese PCOS Women
Authors: LI RENYUAN , ZHENG SIYUAN , MAI TINGTING , XUE JIAO , ZHANG YING
Published: June 2020

The majority of PCOS are overweight or obese (OW/OB) with increased infertility and risk of pregnancy complications. Evidences show that in PCOS, metformin and exenatide have impact on insulin resistance and body weight with seldom information about pregnancy and its outcome. This study was designed directly to compare the effect of two treatments on pregnancy rate and outcomes in OW/OB PCOS. This prospective clinical trial randomized 160 OW/OB PCOS with infertility, without diabetes into metformin and exenatide treatment for the first 12 weeks. Afterward, all were treated with metformin alone until week 52. If patients failed spontaneous pregnancy during the second 12 weeks, assisted reproduction technique (ART) could be offered until week 52. The spontaneous and total pregnancy rates were recorded within 52 weeks. Pregnancy outcomes were followed until the deliveries. Baseline characteristics were similar between two groups. At week 24, higher spontaneous pregnancy rate was observed in exenatide group, although at week 52, the total pregnancy rates were similar between two groups. Meanwhile, no significant difference of pregnancy outcomes was implicated between two groups (Table 1). In OW/OB PCOS, 12 weeks exenatide treatment had improved spontaneous pregnancy rate compared with metformin treatment, without benefit effects on total pregnancy rate and overall pregnancy outcomes.

Disclosure

R. Li: None. S. Zheng: None. T. Mai: None. J. Xue: None. Y. Zhang: None.

Funding

National Natural Science Foundation of China (81200607)
1347-P: Contraception Preferences in Women with Diabetes
Authors: WALKER SHANNON L. , ANGUZU RONALD , EGEDE LEONARD E. , PALATNIK ANNA
Published: June 2020

Objective: Effective contraception use in women with diabetes until glucose control is achieved is one of the key factors for optimizing pregnancy outcomes in this high-risk population. The objective of this analysis was to examine whether contraception utilization varied by presence of maternal diabetes.

Methods: Data from the 2011-2017 National Survey of Family Growth were analyzed using cross-sectional methodology. Women age 18-44 were included in the analysis. Maternal diabetes was defined as either the presence of pre-gestational diabetes or diagnosis of gestational diabetes. Bivariate and multivariable logistic regression analyses were run to evaluate the association between the use of contraception by contraception type (sterilization, long-acting reversible contraception (LARC), other hormonal method, barrier method and none) and maternal diabetes status.

Results: A total of 28,454 women were included in the analysis, with 3,003 (10.5%) women with diabetes during pregnancy. Women with diabetes were less likely to use LARC (7.2% vs. 10.7%) or barrier methods (14.4% vs. 17.6%) compared to controls (p<0.001 for both comparisons). The utilization rates of sterilization and other hormonal methods did not differ between the groups. In multivariable logistic regression, controlling for maternal age, race/ethnicity, body mass index, insurance, education, marital status, family income and diagnosis of sexually transmitted infection, maternal diabetes remained to be significantly associated with lower utilization rates of LARC (aOR=0.73, 95% CI 0.55-0.97) and barrier methods (aOR=0.76, 95% CI 0.59-0.97).

Conclusions: In this cohort, women with diabetes were less likely to choose LARC and barrier methods for contraception. As LARC is one of the more effective and safest options of contraception in this high-risk population, further research is required to understand the causes behind this variation in contraception utilization.

Disclosure

S.L. Walker: None. R. Anguzu: None. L.E. Egede: None. A. Palatnik: None.
1349-P: Incidence of Diabetes in Women with Gestational Diabetes Mellitus Diagnosed by the IADPSG vs. Two-Step Criteria
Authors: BALAJI BHAVADHARINI , READ STEPHANIE , BERGER HOWARD , FEIG DENICE , SHAH BAIJU R. , LIPSCOMBE LORRAINE
Published: June 2020

Background: In Canada, the 2-step approach for the diagnosis of gestational diabetes (GDM) continues to be used, due to uncertain treatment benefit at the lower diagnostic thresholds recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). GDM diagnosed by 2 step criteria is associated with an elevated risk of subsequent diabetes; however, the impact of GDM based on IADPSG criteria on future diabetes risk is unknown.

Aim: To evaluate the risk of future diabetes associated with a GDM diagnosis using the 2 step and IADPSG criteria.

Methods: Using Ontario population-based databases, we evaluated the incidence of diabetes in women with a live birth recorded between April 2011 and March 2014 and available prenatal glucose tolerance test records. Women were categorized according to their prenatal glucose tolerance results as no GDM, GDM based on 2-step criteria, and GDM based on IADPSG criteria (positive by IADPSG, negative by 2 step criteria). They were followed until April 2018 for a diagnosis of diabetes. Risk of diabetes associated with GDM based on each definition was compared to no GDM using a multivariable Cox proportional hazards model.

Results: Of the 104,942 women included in the study, 5,371 (5.1%) had GDM by 2 step criteria and 2,436 (2.3%) had GDM based on IADPSG criteria. There were 821 (0.78%) diabetes cases over 329 771 person-years of follow-up. After adjusting for age, body-mass index, history of GDM, gestational weight gain, birth weight, income, and ethnicity, diabetes risk was significantly higher for both GDM women by 2 step criteria (HR 14.1; 95% CI 11.7-16.9) and for GDM based on IADPSG criteria alone (HR 3.1; 95% CI:2.0-4.7) compared to no GDM.

Conclusion: While the relative risk of diabetes compared to normal glucose tolerance is higher for women diagnosed with GDM using the conventional 2 step criteria, GDM based on IADPSG criteria also confers a significant 3-fold increase in diabetes risk.

Disclosure

B. Balaji: None. S. Read: None. H. Berger: None. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. B.R. Shah: None. L. Lipscombe: None.
135-OR: The Effect of Fixed-Dose Combination of Insulin Degludec and Liraglutide on Serum Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus
Authors: PAPPA ELENI , KOSTARA CHRISTINA , TELLIS CONSTANTINOS , TSELEPIS ALEXANDROS D. , BAIRAKTARI ELENI , TSIMIHODIMOS VASILIS
Published: June 2020

Aim: Administration of fixed-dose combination of Insulin Degludec and Liraglutide (IDegLira) has been associated with changes in the lipid-profile of diabetic patients. We assessed the effect of IDegLira on serum apolipoproteins, apoB-containing lipoprotein subclasses and HDL lipidome in patients with type 2 diabetes mellitus (T2DM).

Methods: Sixty uncontrolled patients with T2DM on oral antidiabetic drugs were included. Of them, thirty received IDegLira and the remaining Insulin Degludec(IDeg). Lipid and carbohydrate metabolism parameters were assessed before and following 3-month-treatment. ApoB-containing lipoprotein subclasses levels were measured by LDL-Lipoprint method, whereas HDL lipidomic analysis via 1H-NMR spectroscopy.

Results: Administration of IDegLira resulted in a significant reduction of total (TC) and LDL cholesterol (LDLC) by 14.68mg/dl and 10.45mg/dl, respectively. ApoA1 and apoB decreased in patients treated with IDegLira. A non-significant change in small-dense LDLC (sdLDL-C) levels was observed that was significantly correlated with changes in TG levels (r=0.468, p=0.007). Furthermore, IDegLira administration resulted in significant enrichment of HDL particles’ core in esterified cholesterol and depletion of TGs content. IDegLira induced an atheroprotective shift in fatty acid pattern of HDLs characterized by a statistically significant lower content in saturated and higher in unsaturated fatty acids (linoleic acid, eicosapentaenoic and arachidonic acids and docosahexaenoic acid). No significant changes were observed in the IDeg group.

Conclusions: Administration of IDegLira is accompanied by changes in HDL lipdome, a decrease in TC, LDLC, apoA1 and B, while the levels of sdLDL were only reduced in patients experiencing a decrease in TGs. The contribution of these changes to cardiovascular risk reduction after treatment with liraglutide in clinical trials cannot be excluded.

Disclosure

E. Pappa: None. C. Kostara: None. C. Tellis: None. A.D. Tselepis: None. E. Bairaktari: None. V. Tsimihodimos: None.
1358-P: Point of Care OGTT for the Screening of Gestational Diabetes: A Feasible Proposal for Low-Resource Settings
Authors: GALLARDO HECTOR , LOMELIN-GASCON JULIETA , MARTINEZ LUIS A. , MONTOYA ALEJANDRA , REYES-MUÑOZ ENRIQUE , TAPIA-CONYER ROBERTO C.
Published: June 2020

Due to the ubiquity of risk factors associated with gestational diabetes (GDM) in Mexican women and the low availability of the Oral Glucose Tolerance Test (OGTT), we compared the efficacy of two point of care (POC) models for GDM detection against the plasmatic 2hr OGTT-75gr in primary health care clinics in Mexico. We evaluated 328 pregnant women without previous diabetes diagnosis from a prospective cohort study “Cuido mi embarazo”; all of them were tested with the gold standard plasmatic 2hr OGTT-75gr for the diagnosis of GDM based on the ADA 2019 criteria. Simultaneously, we measured with a glucometer (ACCU-CHEK instant®) the glucose concentration either by capillary whole blood (172 measures) or from venous whole blood (156 measures). We evaluated the diagnostic accuracy by calculating the sensitivity, specificity, and ROC curve of each of the glucometer test results compared to the plasmatic test. For the first model, POC venous OGTT, the incidence of GDM was 41.66% compared to 7.05% of the plasmatic test. The ROC area under the curve for GDM prediction was 0.81 (95% CI 0.77-0.85), with a sensitivity of 100% and specificity of 62.8%. The low specificity is dependent on the fasting venous value of 64% since it was compared to 95% and 97% specificity of the 1hr and 2hr values, respectively. The second model, POC capillary OGTT, had an incidence of GDM of 30.23% compared to 8.13% of the plasmatic test. It had lower sensitivity (78.57%) and higher specificity (74.1%) compared to the first model, having an overall 0.76 (95% CI 0.65-0.88) ROC area under the curve for GDM prediction. We propose POC venous OGTT as a feasible diagnostic alternative for low resource settings where laboratory infrastructure is not available. Its positive bias could be beneficial since the treatment and control of early cases is related to better health outcomes for the moms and their babies. Further analysis is needed to improve GDM, POC screening interventions.

Disclosure

H. Gallardo: None. J. Lomelin-Gascon: Other Relationship; Self; Lilly Global Health Partnership. L.A. Martinez: Other Relationship; Self; Lilly Global Health Partnership. A. Montoya: None. E. Reyes-Muñoz: None. R.C. Tapia-Conyer: None.

Funding

Eli Lilly and Company
1359-P: Neck Circumference: A Useful Tool for the Diagnosis of Gestational Diabetes and Risk of Adverse Outcomes in Overweight Pregnancy
Authors: DUALIB PATRICIA , CARVALHO CAMILA R.D. , MATTAR ROSIANE , DIB SERGIO A. , PITITTO BIANCA ALMEIDA
Published: June 2020

Introduction: Few studies addressed the role of neck circumference (NC) as a risk factor during overweight pregnancy.

Objective: To evaluate the association of NC with GDM and adverse outcomes in overweight and obese women.

Methods: This longitudinal study included 132 (BMI>25kg/m2) pregnant women. Standardized questionnaire and biochemical/physical evaluation were performed when they were admitted at GDM outpatient clinic (2018-2019): during the 1st to 3rd trimester (without and with DMG according to the IADPSG criteria). Fifth-five women were evaluated regarding hypertension in pregnancy, type of delivery and neonatal complications (death, intensive care unit admission and hypoglycemia). ANOVA, Chi-square test and logistic regression were performed.

Results: Women with (n=61) and without (n=71) GDM had similar mean(SD) pre-gestational BMI [30.3(4.0)vs29.4(3.5)Kg/m2,p=0.16], familiar history of diabetes, physical activity, schooling, lipid profile, TSH levels and blood pressure. Women with GDM were older [32(6)vs28(6)yrs,p<0.001] and had greater NC [36.0(2.7)vs34.5(1.8)cm,p<0.001] than those without GDM. NC was similar in women with GDM diagnosed in first or third trimester [p=0.4] and was correlated with FPG [r0.29,p=0.01] and systolic [r0.28,p=0.001] and diastolic [r0.25,p=0.004] blood pressure. In logistic regression analysis, NC was associated with GDM [OR1.25,95%CI1.03to1.52] adjusted for age, physical activity, schooling and familiar history of diabetes. In ROC analysis, the area under the curve was 0.655 and the cut-off value of 34.5cm had 0.70 of sensitivity and 0.51 of specificity for GDM. Women who had NC≥34.5 vs. <34.5cm had higher frequencies of hypertension [32.3vs4.2%,p=0.01] and C-section [58.1vs29.2%,p=0.03] but not neonatal complications [45.2vs25.0%,p=0.12].

Conclusions: In a group of overweight or obese pregnant women the NC can be a useful tool for identifying GDM and obstetric adverse outcomes.

Disclosure

P. Dualib: None. C.R.D. Carvalho: None. R. Mattar: None. S.A. Dib: None. B. Almeida Pititto: None.

Funding

Fundação de Amparo a Pesquisa do Estado de São Paulo (18/14795-9)
136-OR: Lipid Profile in Men with Hypogonadism and Type 2 Diabetes Improves during Long-Term Treatment with Testosterone Undecanoate Injections (TU) in Comparison to an Untreated Control Group: Update of Real-World Registry Data
Authors: SAAD FARID , HAIDER KARIM S. , HAIDER AHMAD
Published: June 2020

Background: Previous studies reported inconsistent effects of testosterone therapy on the lipid profile in men with hypogonadism.

Methods: Of 356 men with hypogonadism and T2DM, 178 received TU 1000 mg/12 weeks (T-group), 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups.

Results: Mean follow-up 8.2±2.9, baseline age 61.5±5.4 (T-group) and 63.7±4.9 (CTRL) years. Total cholesterol (mmol/L) decreased by 2.9±0.1 (from 8.3±1.1 to 5.2±0.3) at 11 years in T-group and increased by 1.1±0.1 (from 7.1±1.2 to 8.1±1.3) in CTRL. Estimated adjusted difference between groups: -4.0 (p<0.0001 for all). HDL (mmol/L) increased by 0.5±0.0 (from 1.0±0.4 to 1.6±0.4) in T-group and decreased by 0.3±0.0 (from 1.1±0.5 to 0.9±0.5) in CTRL, difference between groups: 0.8 (p<0.0001 for all). LDL (mmol/L) decreased by 1.9±0.1 (from 4.7±0.9 to 2.6±0.2) in T-group and increased by 0.9±0.1 (from 4.1±1.4 to 4.9±1.5) in CTRL, difference between groups: -2.8 (p<0.0001 for all). Triglyceride (mmol/L) decreased by 1.1±0.0 (from 3.5±0.6 to 2.2±0.1) in T-group and increased by 0.5±0.0 (from 3.1±0.6 to 3.7±0.6) in CTRL, difference between groups: -1.7 (p<0.0001 for all). Non-HDL (mmol/L) decreased by 5.5±0.3 (from 9.6±4.3 to 3.4±0.8) in T-group and increased by 4.9±0.3 (from 8.0±3.9 to 11.3±6.8) in CTRL, difference between groups: -10.4 (p<0.0001 for all). Remnant cholesterol (mmol/L) decreased by 1.4±0.1 (from 2.6±1.0 to 1.0±0.2) in T-group and increased by 0.5±0.1 (from 2.0±1.0 to 2.3±0.7) in CTRL, difference between groups: -1.9 (p<0.0001 for all).

Conclusions: Long-term treatment with TU in men with hypogonadism and T2DM progressively improved the lipid profile, which worsened in controls.

Disclosure

F. Saad: Consultant; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Bayer AG. K.S. Haider: None. A. Haider: None.

Funding

Bayer AG
1364-P: Barriers and Facilitators of Diabetes Self-Management among Pregnant Women with Preexisting Type 2 Diabetes: A Scoping Review
Authors: PHONYIAM RATCHANOK , BERRY DIANE C.
Published: June 2020

Background: Pregnant women with pre-existing type 2 diabetes (T2DM) are at risk for poor maternal and neonatal outcomes. Previous systematic reviews in women with T2DM have focused on physical activity, blood glucose monitoring, and insulin injections. The purpose of this review was to examine the barriers and facilitators of diabetes self-management.

Method: PubMed, CINAHL, and EMBASE databases were searched using PRISMA-ScR guidelines from January 1, 2009, to July 30, 2019. Inclusion criteria included manuscripts written in English and qualitative studies. Themes were compared and contrasted to identify areas of congruence and discrepancy.

Results: The review included ten manuscripts with 241 pregnant women with pre-existing T2DM, and eight family members were enrolled with sample sizes ranging from 5-89. First, barriers to knowledge about diabetes in pregnancy, physical activity, dietary control, medication adherence, financial constraints, stress, lack of social support, and cultural beliefs. Second, stress related to the diagnosis, infant outcomes, and cultural expectations. Third, barriers to access to care and disrespect from health care providers. Fourth, a loss of self-control. Fifth, facilitators of diabetes self-management in pregnancy were related to support from family, financial support, support from health care providers.

Discussion: Pregnant women with pre-existing T2DM have multiple barriers. Only one manuscript incorporated family members. Further qualitative research may need to seek the perspectives of family members about diabetes self-management in pregnancy and examine how they can provide support to the women.

Conclusion: This supports an integrative model of maternity care to overcome critical barriers and optimize key facilitators to enhance diabetes self-management behaviors and improve maternal and neonatal health outcomes.

Disclosure

R. Phonyiam: None. D.C. Berry: None.
1369-P: Is Weight Loss after a Pregnancy Complicated by Diabetes Associated with Improved Subsequent Pregnancy Outcomes?
Authors: YU LULU , HERRICK CYNTHIA J. , DUCKHAM HILLARY E. , CARTER EBONY B.
Published: June 2020

Objective: To determine whether inter-pregnancy weight loss is associated with improved perinatal outcomes among pregnancies complicated by recurrent diabetes.

Methods: We performed a retrospective cohort study of all women with at least 2 singleton pregnancies complicated by gestational (GDM) or type 2 (T2DM) and cared for by the Resident Diabetes in Pregnancy Clinic at a large tertiary referral center from 2007-2017. Women whose initial pregnancy weight decreased between pregnancies were compared to those whose weight stayed the same or increased. Demographic characteristics were compared between groups and logistic regression was used to control for potential confounding variables including maternal age, race, and depression.

Results: There were 62 pregnancies complicated by recurrent diabetes during the study period. Weight loss between pregnancies occurred in 24 women. Women with pregnancies with inter-pregnancy weight loss were older (31.6 vs. 27.6, p=0.01) and had higher early pregnancy Edinburgh Postnatal Depression Scale scores (median 7; IQR 5,8 vs. median 2; IQR 1, 3, =0.01). Adjusted analyses using logistic regression demonstrated no significant association between inter-pregnancy weight loss and adverse maternal/neonatal outcomes including large for gestational age, small for gestational age, cesarean section, shoulder dystocia, birth injury, NICU admission>24 hours, and preterm birth.

Conclusions: Inter-pregnancy weight loss was not associated with improved maternal or neonatal outcomes among pregnancies complicated by GDM or T2DM. Future studies are needed to identify the impact of depression on gestational weight gain/loss and subsequent pregnancy outcomes.

Disclosure

L. Yu: None. C.J. Herrick: None. H.E. Duckham: None. E.B. Carter: None.

Funding

American Diabetes Association/Pathway to Stop Diabetes (1-19-ACE-02 to E.B.C.); Robert Wood Johnson Foundation (74250); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD095075)
1376-P: Association of Continuous Glucose Monitoring (CGM)-Derived Parameters with Adverse Pregnancy Outcomes in Pregnant Women with Type 1 Diabetes
Authors: LUO SIHUI , LING PING , DING YU , ZHENG XUEYING , YANG DAIZHI , ZHOU YONGWEN , YAN JINHUA , WENG JIANPING
Published: June 2020

Background: The relation of CGM derived parameters and adverse pregnancy outcomes (APOs) in pregnant women with type 1 diabetes (T1D) is not completely clear.

Methods: During 2015 - 2018, data were prospectively collected from pregnancies of women with pregestational T1D receiving intermittent CGM in 11 centers in China. Characteristics and CGM derived parameters were compared between the women who had severe APOs and those who did not. Severe APOs were defined as maternal death, neonatal death, congenital anomaly, pregnancy loss in 2nd/3rd trimester and neonatal admission to intensive care unit.

Results: Data of 84 pregnant women with pregestational T1D were collected. Among them, 56 had received CGM in the 1st trimester, 55 in the 2nd trimester, and 59 in the 3rd trimester. 30 of these 84 women had severe APOs. Compared with women without severe APOs, women who had severe APOs had lower age at diagnosis, longer diabetes duration at conception. For CGM derived parameters, women who had severe APOs had significantly higher mean glucose (MG), MG at wake, MG at night, and time above range (TAR, >7.8mmol/L) throughout all 3 trimesters, compared with women who did not have. Details see Table.

Conclusions: Higher MG, MG at wake, MG at night, and TAR throughout pregnancy were associated with the presence of severe APOs in women with T1D. These parameters should be closely monitored.

Disclosure

S. Luo: None. P. Ling: None. Y. Ding: None. X. Zheng: None. D. Yang: None. Y. Zhou: None. J. Yan: None. J. Weng: None.

Funding

National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011)