bluuebunny/crossref_metadata_2025_split huggingface dataset:
1386-P: A Comparison of Ectopic Fat Stores and Insulin Sensitivity among Women With and Without Gestational Diabetes
Authors: VESCO KIMBERLY , LEO MICHAEL C. , FRANCISCO MELANIE , MARSHALL NICOLE E. , ROONEY WILLIAM , BAETSCHER ERIC , VALENT AMY M. , PURNELL JONATHAN Q. 
Published: June 2019

Background: We assessed relationships between ectopic lipid stores [intrahepatic (IHL), intramyocellular (IMCL), and extramyocellular (EMCL)] and parameters of insulin sensitivity in women with gestational diabetes (GDM) compared with BMI-matched controls.
Methods: We performed a case-control analysis nested within a prospective cohort study of 54 pregnant women with normal weight, overweight, and obesity without pregestational diabetes. From the prospective cohort, 7 women developed GDM. Three additional women with GDM were recruited in late pregnancy to increase sample size. All women underwent insulin clamps to assess insulin disposal (Rd) and endogenous glucose production (EGP); 1H magnetic resonance spectroscopy to assess IHL, IMCL, and EMCL content; MRI to assess subcutaneous abdominal (SAT) and visceral adipose tissue (VAT) volume, BODPOD to assess % body fat, fat mass, and fat free mass; and measurement of fasting free fatty acid levels. Measures were performed in early and late pregnancy [mean (minute-max), 15.5 (12.4-17.6) and 34.1 (31.6-37.3) weeks gestation, respectively].
Results: Women with GDM were matched on BMI to women in the prospective cohort who did not develop GDM. In early pregnancy, compared to controls, women with GDM had greater % body fat (P=.02), fasting free fatty acids (P&lt;.01), and insulin resistance (lower Rd, P&lt;.01), but did not significantly differ in amounts of VAT, SAT, IHL, EGP, IMCL, or EMCL. In late pregnancy, cases and controls did not significantly differ by body composition or free fatty acid levels, but insulin resistance remained greater among women with GDM (P=.02).
Conclusion: Women who would be later diagnosed with GDM exhibited greater percent body fat, insulin resistance, and fasting free fatty acid levels early in pregnancy, but not visceral or ectopic fat stores. Accumulation of excess lipids in VAT and ectopic fat stores does not appear to play an important role in distinguishing women who develop GDM from those that do not.

Disclosure
K. Vesco: None. M.C. Leo: None. M. Francisco: None. N.E. Marshall: None. W. Rooney: None. E. Baetscher: None. A.M. Valent: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk A/S.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098707)
1391-P: Longitudinal Changes of Plasma Sphingomyelins during Gestation in Women With and Without Type 1 Diabetes and Preeclampsia
Authors: KELLY CLARE B. , HAMMAD SAMAR M. , KLEIN RICHARD L. , LOPES-VIRELLA MARIA F. , LEYVA MISTI J. , YU JEREMY , JENKINS ALICIA J. , NANKERVIS ALISON J. , HANSSEN KRISTIAN F. , GARG SATISH K. , SCARDO JAMES A. , ASTON CHRISTOPHER E. , LYONS TIMOTHY 
Published: June 2019

Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has significantly higher incidence in women with type 1 diabetes mellitus (T1DM) than in nondiabetic populations (∼20% vs. 5%, respectively). Sphingolipids are key signaling molecules, and have many roles in the structure and regulation of cellular functions. Sphingomyelin (SM) is the most abundant sphingolipid in plasma lipoproteins. There is evidence that altered SM metabolism may contribute to cardiovascular and renal complications in diabetes.
We aimed to determine whether plasma concentrations of 12 SM species were associated with PE in T1DM in a prospective study of pregnancy of 23 T1DM women who developed PE and 24 T1DM who remained normotensive. Additionally, 19 normotensive nondiabetic pregnant women were included for reference. All subjects were free of microalbuminuria and hypertension at enrolment, and all visits (12, 22, 32 weeks’ gestation) preceded clinical PE onset.
Results: There were no cross-sectional differences in total SM, or in any individual SM species, between diabetic women with and without PE, or between normotensive women with and without diabetes at any stage of gestation. With advancing gestation in all groups, C18-SM, C18:1-SM, C20-SM, C20:1-SM, C22-SM, C22:1-SM, C24-SM, and C24:1-SM increased (all p&lt;0.001). LDL- and VLDL-cholesterol also increased, while HDL-cholesterol did not change. In contrast, C14-SM, C16-SM, C26-SM and C26:1-SM decreased (all p&lt;0.001). There were no correlations between any SM species and conventional lipid profiles.
Conclusions: With advancing gestation, plasma concentrations of most SM species increased, as did LDL and VLDL; however, two long-chain and two very long-chain SM species decreased. Although there were no differences in SM according to diabetes or PE status at any time point, further studies should address the significance of differential changes of SM species during pregnancy.

Disclosure
C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None.

Funding
JDRF; Novo Nordisk; National Institutes of Health
1405-P: Glycemic Variability among Pregnant Women with Type 1 Diabetes (T1D) Based on Use of CGM Share Technology
Authors: POLSKY SARIT , SNELL-BERGEON JANET K. , JOSHEE PRAKRITI , DEMMITT JAMIE K. , GARCETTI RACHEL , VIGERS TIM B. , PYLE LAURA 
Published: June 2019

Pregnancies complicated by T1D have more glycemic variability than pregnancies associated with other kinds of diabetes. We examined whether remote monitoring of Continuous Glucose Monitoring (CGM) data by family/friends affects glycemic variability during pregnancy.
Women with T1D were stratified to groups during preconception or the 1st trimester: (1) CGM Alone (n=13): women without Apple devices, or (2) CGM Share (n=15, DexCom, San Diego, CA): women with iPhone and followers with data viewing devices. Data within 12 hours of acetaminophen use were excluded. Linear mixed models were used to compare indices of glycemic variability over time between groups.
A1C decreased in both groups over time and was lower in CGM Share compared to CGM Alone (p=0.0376, Table). Mean sensor glucose was lower in CGM Share than CGM Alone (p=0.0492). Times spent within targeted pregnancy ranges were not different between groups. CGM Alone had a significantly higher High Blood Glucose Index (HGBI) than CGM Share (p=0.0347).
CGM Share was associated with a lower risk of hyperglycemia (as measured by HBGI) than CGM Alone among pregnant women with T1D, but other measures of glycemic variability were similar between groups.

Disclosure
S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US. J.K. Snell-Bergeon: None. P. Joshee: None. J.K. Demmitt: None. R. Garcetti: None. T.B. Vigers: None. L. Pyle: None.

Funding
Dexcom, Inc.; National Center for Research Resources/Colorado Clinical and Translational Science Institute (UL1RR025780)
141-LB: Engineered Silica Particles Work as a Molecular Sieve and Reduce Metabolic Risk Factors in Obese Male Volunteers
Authors: LINDGREN MARIA E. , WAARA ERIK ROLLMAN , BENZIANE BOUBACAR , VALLHOV HELEN , IQBAL NAEEM , JOHNSTON ERIC V. , BENGTSSON TORE 
Published: June 2019

Mesoporous silica particles (MSPs) are thermally and chemically stable porous materials composed exclusively of silicon dioxide. Here we report the results of a First-in-Man clinical trial evaluating engineered MSPs with controlled surface area, pore volume, pore size, particle size and morphology, named SiPore, in obese but otherwise healthy male volunteers (n=20). SiPore is orally ingested and passes through the body without being absorbed and is safely eliminated via the feces. The clinical effects of SiPore were significant reduction in several metabolic and cardiovascular risk factors. HbA1c was reduced by 5% and LDL-C by 15% on average from baseline, both clinically meaningful reductions. Adverse events observed were mild and transient. These promising effects led to further investigations into SiPore’s mode of action.
We hypothesized that SiPore acts as a molecular sieve by sequestration of biomolecules in the gastrointestinal tract, which could explain the observed clinical results. This merited a more detailed analysis of the interaction between SiPore and digestive enzymes. SiPore significantly sequestered amylase and lipase in vitro while MSPs with smaller pore size had no effect. Lipase and amylase were depleted by SiPore from more complex biological matrices, such as porcine pancreatin and mouse intestinal fluid. Moreover, SiPore inhibited the activity of human salivary amylase in human saliva. Further studies of amylase depletion in vitro indicated that the availability of pores of a certain pore size is a critical parameter for enzyme sequestration.
This innovative mode of action, combined with SiPore’s promising safety profile, makes SiPore an exciting candidate for treatment or prevention of metabolic diseases, particularly prediabetes and type 2 diabetes (T2D). SiPore is currently being investigated in an ongoing clinical trial in 40 prediabetic or newly diagnosed T2D subjects (NCT03823027).

Disclosure
M.E. Lindgren: Employee; Self; Sigrid Therapeutics AB. E. Rollman Waara: Employee; Self; Sigrid Therapeutics AB. B. Benziane: Employee; Self; Sigrid Therapeutics. H. Vallhov: Employee; Self; Sigrid Therapeutics. N. Iqbal: None. E.V. Johnston: None. T. Bengtsson: Other Relationship; Self; Atrogi, Sigrid Therapeutics.

Funding
Vinnova (2015-02023)
1414-P: Prolactin as a Potential Modulator for the Adaption to Insulin Resistance in Pregnancy
Authors: FRITSCHE LOUISE , HENI MARTIN , HAERING HANS-ULRICH , FRITSCHE ANDREAS , WAGNER ROBERT 
Published: June 2019

Aims: Plasma prolactin levels are associated with insulin sensitivity and diabetes in an age dependent manner. Pregnancy is a state of physiologically high prolactin concentrations and insulin resistance. Only when beta cells fail to compensate by producing sufficient amounts of insulin, gestational diabetes mellitus (GDM) develops. We aimed to elucidate the relationship of prolactin levels, insulin sensitivity, and the incidence of GDM in pregnancy.
Material and Methods: 321 women from the German Gestational Diabetes study were phenotyped with 5-point 75 g oral glucose tolerance tests during gestational weeks 27.1 ± 2.1 and repeatedly 1 to 10 years after delivery. Prolactin was measured in fasting state.
Results: GDM was diagnosed in 29%. During pregnancy, physiologically high prolactin levels associated negatively with insulin sensitivity. By contrast, prolactin was positively associated with insulin sensitivity after delivery (pinteraction &lt; 0.0001). Despite prolactin’s association with impaired insulin sensitivity in pregnancy, higher prolactin levels were neither associated with AUC-glucose0-120 nor GDM incidence (p&gt;0.14). Prolactin interacted with AUC-glucose0-120 on insulin secretion (disposition index, p=0.01) with higher prolactin levels associating with improved insulin secretion in case of AUC-glucose0-120 above median (p=0.04).
Conclusion: Our findings on countercurrent changes in insulin sensitivity and secretion with higher prolactin levels could indicate a role for this hormone in mounting and compensating for physiologic insulin resistance in pregnant women.

Disclosure
L. Fritsche: None. M. Heni: Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Sanofi. H. Haering: None. A. Fritsche: None. R. Wagner: Other Relationship; Self; Lilly Diabetes, Novo Nordisk A/S.

Funding
German Federal Ministry of Education and Research (01GI0925)
1417-P: Glycemic Control and Insulin Dosing in Pregnancies Complicated by Type 2 Diabetes Mellitus
Authors: NADEAU HUGH C. , MAXTED MARTA E. , MADHAVAN DEVIKA , PIERCE STEPHANIE , FEGHALI MAISA N. , SCIFRES CHRISTINA M. 
Published: June 2019

Type 2 diabetes mellitus (DM) is associated with adverse perinatal outcomes, but insulin requirements and the prevalence of inadequate glycemic control across gestation are not well characterized. We therefore conducted a retrospective cohort study of women with type 2 DM who delivered from 2015 to 2017. Self-monitored blood glucose and insulin doses across gestation were abstracted, and inadequate glycemic control was defined as a mean blood glucose &gt;95 mg/dL fasting or &gt;140 mg/dL 1 hour post-prandial. We compared insulin dosing in early gestation and at delivery by maternal glycemic control. Multivariable logistic regression was used to identify predictors of high insulin requirements at delivery.
Inadequate glycemic control occurred in 96/155 (62%) of women. Maternal BMI, gestational age at first prenatal visit, and duration of diabetes were similar between women with inadequate and adequate control. Baseline HbA1c (8.1 ±2.0 vs. 7.5 ±1.9%, p=0.10) and percent of women receiving medical therapy before initiation of prenatal care (71.3% vs. 69.5%, p=0.81) were also similar between groups. Women with inadequate and adequate control had similar insulin doses in early pregnancy (0.7 ±0.5 vs. 0.7 ±0.5 units/kg, p=0.86), but by delivery women with inadequate control required significantly higher doses (2.3 ±1.2 vs. 1.8 ±1.0 units/kg, p=0.004). The highest quartile of insulin dose at delivery was &gt;2.7 units/kg. Multivariable logistic regression modeling demonstrated that maternal BMI at the first prenatal visit (aOR 1.0, 95% CI 0.99-1.01), non-white race (aOR 0.35, 95% CI 0.16-0.78), and baseline HbA1c (aOR 1.22, 95% CI 1.02-1.46) had poor ability to predict high insulin requirements at delivery (AUC 0.67). Although high insulin requirements may be related to suboptimal glycemic control in women with type 2 DM, it is difficult to identify these women using baseline characteristics. Further studies are urgently needed to optimize insulin dosing in women with Type 2 DM.

Disclosure
H.C. Nadeau: None. M.E. Maxted: None. D. Madhavan: None. S. Pierce: None. M.N. Feghali: None. C.M. Scifres: None.
142-LB: First Non-sulfonylurea Type Inhibitors of SUR1 Showed Superior Efficacy over Sulfonylureas, and Reversed Sulfonylurea Failure
Authors: LIM DONGCHUL , PARK JUNG GYU , KIM DONG WOOK , PARK HEE DONG , KIM YOUNG KWAN 
Published: June 2019

Sulfonylureas (SUs) have been used widely for a long time as a diabetic drug since first discovered in 1942. Because of their good glucose lowering effect and low cost it had been drug of choice until recently. However, SUs are lack of the glycemic durability and lose their efficacy mostly within 1-2 years, resulting in a steady HbA1c rise to or above pretreatment levels. This, so called SU failure, has been the main reason for limiting their use in the clinic. Our efforts for overcoming the SU failure led to the discovery of de novo type sulfonylurea receptor 1 (SUR1) antagonists (e.g., Cpd7). To the best of our knowledge, this is the first report of non-SU type SUR1 antagonists with the superior efficacy to known SU drugs. Molecular modeling with a recently published cryogenic electron microscopy structure of KATP channel showed that Cpd7 occupies the SUR1 binding site in a totally different region from known SUs such as glimepiride with a higher docking score. We hoped that such differences in structure classes and binding patterns lead to improved phenotypic effects. In insulinoma Min6 and INS-1 cells, treating with Cpd7 increased calcium influx and triggered a superior insulin secretion to glimepiride. In mouse oral glucose tolerance test, cpd7 showed a highly effective blood glucose lowering effect at a 30 mg/kg dose. It is well known that chronic glibenclamide treatment in Min6 cells induces unresponsiveness to most of SU drugs. So far no other SUR1 antagonists have been found effective in SU resistance. But we found that Cpd7 overcomes the SU resistance induced by chronic treatment of glibenclamide in Min6 and InS-1 cells. Therefore, it becomes clear that our newly discovered non-SU type SUR1 antagonists can be used for solving the resistance problems caused by the existing SU drugs. We expect that our discovery will lead to the development of a new type of SU drug which gives an alternative treatment option to diabetic patients in the near future.

Disclosure
D. Lim: None. J. Park: Employee; Self; LG Chem. D. Kim: Employee; Self; LG Chem. H. Park: None. Y. Kim: None.
1422-P: Human Milk Composition in Type 2 Diabetes Imparts Higher Insulin Exposure
Authors: RODEL RACHEL , CARLI JAYNE MARTIN , HIRSCH NICOLE , HEISS KRISTY P. , HERNANDEZ TERI L. , KREBS NANCY F. , BARBOUR LINDA (LYNN) A , YOUNG BRIDGET 
Published: June 2019

Little is known about human milk (HM) composition in T2 diabetes (T2DM) and data support that HM insulin may be absorbed from the immature newborn gut and be metabolically active. We characterized HM composition and measured fasting and 90 min postprandial insulin and glucose (gluc) in HM (mid-feed) and plasma in 12 T2DM mothers (BMI 32± 4) after a 60 g carb meal at 2 weeks postpartum. We compared fasting HM samples with 12 normoglycemic (NGT) and 10 GDM mothers who were matched by BMI and infant sex. The study was powered on our hypothesis that fasting HM insulin would be higher in T2DM (2 insulin requiring). All macronutrients and energy density (Miris) in HM of T2DM were in the expected range (mean fat 4.1; protein 1.6; carbs 7.2 g/100mL; energy 74 kcal/100ml) and did not differ postprandially. Notably, paired fasting HM insulin in T2DM was 30.2 and 16.1 μIU/mL higher in the NGT (p&lt;0.01) and GDM groups (p&lt;0.05), respectively (Figure A). HM gluc did not differ by groups. In T2DM, HM gluc (p&lt;0.001) and insulin (p&lt;0.05) increased after the meal. Strikingly, mean fasting insulin was 4-fold higher in T2DM HM vs. plasma (p&lt;0.005; Figure B). These are the first data to show that while HM macronutrients and calories from mothers with T2DM are reassuringly in expected quantities, HM insulin is higher and concentrated in T2DM milk. Given that the newborn gut may be permeable to insulin, potential effects on the newborn pancreas, growth, and the microbiome deserve further study.

Disclosure
R. Rodel: None. J. Martin Carli: None. N. Hirsch: None. K.P. Heiss: None. T.L. Hernandez: None. N.F. Krebs: None. L.A. Barbour: None. B. Young: None.

Funding
Colorado Clinical and Translational Sciences Institute (UL1TR000154); National Center for Advancing Translational Sciences (UL1TR002535); National Institutes of Health (T32DK007658-28), (R01DK101659 to T.L.H.), (F32-HD0978068), (T32-DK007658-21); Thrasher Research Fund; University of Colorado Center for Women’s Health Research
1426-P: Type 1 Diabetes Pregnancies Complicated by Hypertensive Disorders
Authors: SNELL-BERGEON JANET K , PYLE LAURA , SIPPL RACHEL M. , POLSKY SARIT 
Published: June 2019

Women with type 1 diabetes (T1D) are at higher risk for Gestational Hypertensive Disorders (GHD) and cardiovascular disease (CVD) compared to women without diabetes. However, the long-term consequences of GHD complicated by T1D on CVD are unknown. We compared CVD risk factors pre-pregnancy (median follow-up 3 years, IQR 2-4 years) to post-pregnancy (median 2 years, IQR 1-3 years) excluding six weeks post-partum in women with T1D with a first pregnancy complicated by GHD (n=27) vs. those with an uncomplicated pregnancy (n=49), frequency matched for age (mean age 25 years) and diabetes duration (mean duration 12 years). Linear mixed models adjusted for age, diabetes duration, and weeks gestation were used to examine CVD risk factors. Pre-pregnancy, the groups did not differ in age, diabetes duration, body mass index (BMI), lipids, systolic or diastolic blood pressure (BP) (Table). A1c was higher pre-pregnancy in the complicated vs. uncomplicated group (p=0.004); post-pregnancy there was no change in the complicated group but an increase in A1c in the uncomplicated group (p=0.003). Complicated pregnancies resulted in increased systolic (p=0.001) and diastolic BP (p=0.01) post-pregnancy; uncomplicated pregnancies were not associated with significant changes in BP. Women with T1D and a pregnancy complicated by GHD had similar BP but higher A1c pre-pregnancy, and persistently higher BP post-pregnancy, suggesting a need to intervene to prevent CVD.

Disclosure
J.K. Snell-Bergeon: None. L. Pyle: None. R.M. Sippl: None. S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US.

Funding
American Diabetes Association (7-13-CD-10 to J.K.S-B.)
143-LB: Calorie Restriction in Combination with GABA Ameliorates Type 2 Diabetes
Authors: RATHWA NIRALI NANDUBHAI , PATEL ROMA , PRAMANIK SAYANTANI , PARMAR NISHANT R. , A.V. RAMACHANDRAN , BEGUM RASHEEDUNNISA 
Published: June 2019

Dysfunction of adipocytes and β-cells are crucial in the progression of obesity-related insulin resistance and type 2 diabetes (T2D). γ-Aminobutyric Acid (GABA) is a key neurotransmitter and is secreted by β-cells. It exerts protective and regenerative effects on β-cells. At the metabolic level, Calorie Restriction (CR) has been shown to improve insulin sensitivity, reduces Fasting Blood Glucose (FBG) and increases insulin levels. GABA and CR are speculated to show an additive effect on insulin secretion and β-cell regeneration via GABA signaling and enhance insulin sensitivity ameliorating T2D manifestations. We have evaluated the effect of GABA and CR combination on β-cell regeneration and insulin sensitivity in High Fat Diet (HFD) and streptozotocin (STZ) induced late stage T2D mouse model. Our results show favorable changes in the measured parameters. GABA+CR group showed reduced FBG levels and improved whole-body insulin responsiveness indicated by increased insulin levels, insulin sensitivity, and glucose tolerance. The combination therapy improved the lipid profile by significantly reducing triglycerides, total cholesterol, and LDL levels and increased HDL levels. The transcript expression profile of metabolic enzymes in the liver indicates a significant decrease in gluconeogenesis and glycogenolysis. The transcript levels indicate decreased lipolysis and increased fatty acid synthesis in the adipose tissue. The transcript levels of mitochondrial biogenesis in the skeletal muscle indicate increased effect of combination therapy, thereby promoting insulin sensitivity. Also, combination therapy promoted β-cell proliferation.
In conclusion, calorie restriction in combination with GABA ameliorates T2D in the mouse model by inducing β-cell regeneration mediated by GABA and increased insulin sensitivity by CR diet.

Disclosure
N.N. Rathwa: None. R. Patel: None. S. Pramanik: None. N.R. Parmar: None. R. A.v.: None. R. Begum: None.

Funding
Department of Biotechnology, New Delhi, India (BT/PR21242/MED/30/1750/2016)