bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB110 A Phase 2 Evaluation of a Ready-To-Use Liquid Stable Continuous Subcutaneous Glucagon Infusion for the Treatment of Hypoglycemia Associated Autonomic Failure
Authors: Pettus Jeremy H , Nakhle Samer , Ovalle Fernando , Rickels Michael Roehrhoff , Umpierrez Guillermo Enrique , Junaidi Khaled , Close Nicole C , Nguyen Anh 
Published: May 2020

Abstract
OBJECTIVE:A novel, ready-to-use, liquid stable, continuous subcutaneous glucagon infusion (CSGI; Xeris Pharmaceuticals) was evaluated for the treatment of adults with type 1 diabetes (T1D) with documented Hypoglycemia Associated Autonomic Failure (HAAF).
METHOD:This was a Phase 2 prospective, multi-center, randomized, placebo-controlled, double-blind, parallel trial in T1D adults with documented HAAF, defined as Gold Scale Score ≥4. Subjects were randomized in a 1:1:1 ratio to receive 4 weeks of continuous treatment (via Omnipod pump) with high rate CSGI (80mcg/hour), low rate CSGI, (20mcg/hour) or placebo (matched infusion rates for low and high rate CSGI). The primary endpoint evaluated at 4 weeks was the percent change of the epinephrine hormone response after 30 minutes of induced hypoglycemia. Epinephrine levels and hypoglycemia symptoms were recorded following a stepwise hypoglycemia clamp, and results compared between study treatment arms. Following the first four weeks, subjects continued for an additional 24 weeks to assess their epinephrine hormone response to hypoglycemia measured at 3 months post-treatment (16 weeks), and 6 months post-treatment (28 weeks).
RESULTS:Forty-nine subjects were randomized to receive treatment with high rate CSGI (n=15), low rate CSGI (n=18), or matching placebo (n=16). At the end of study treatment, there were no statistically significant differences between the treatment arms for percent change of epinephrine hormone response during a stepwise hypoglycemia clamp (CSGI vs. placebo; p=0.160). As a result, long-term follow-up of the subjects was stopped early. The long-term follow-up data collected to date will be reported separately. The administration of low and high rate CSGI was associated with mild to moderate nausea (5.9%, 20%, respectively) and vomiting (11.8%, 13.3%, respectively) that was self-limited and required no additional intervention. In this 4-week assessment, CSGI was not associated with pain nor significant injection site reactions, and no SAEs related to CSGI were reported.
CONCLUSION:In this proof-of-concept study, CSGI did not demonstrate statistically significant improvements in plasma epinephrine concentration when compared to placebo at 4 weeks. While there were positive epinephrine and improved hypoglycemia awareness responses observed in some subjects, the equivocal efficacy results observed may be explained by the unanticipated and incomplete elimination of hypoglycemia on CSGI therapy, and those on placebo therapy experienced hypoglycemia improvement. CSGI can be safely used with concomitant diabetes medications, and there were no SAEs related to CSGI. The 4-week administration of both low and high rate CSGI was safe and well tolerated.
MON-LB9 Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS) - Person-Related 6-Month Experience Changes
Authors: Shirin Sonia , Murray Faye , Hajjaran Maryam , Goshtasebi Azita , Kalidasan Dharani , Prior Jerilynn C 
Published: May 2020

Abstract
Endometrial cancer1 and oligomenorrhea2 are common risks for women living with androgenic PCOS (WLWP); cyclic progesterone therapy could prevent both. Cyclic oral micronized progesterone therapy (Cyclic OMP; 300 mg at hs/14 days/cycle) also corrects the neuroendocrine origins of PCOS3. Although vaginal progesterone is used in PCOS ovulation induction 4, and short Cyclic OMP decreases LH and/or Testosterone 5,6, no WLWP person-level prospective data with Cyclic OMP therapy are published.
A WLWP, aged 31, BMI 20.1, with heavy flow and slightly irregular ~35-day cycles, was unable to tolerate birth control pills. She was prescribed Cyclic OMP (300 mg/h.s. cycle days 14-27)7. She began keeping the Menstrual Cycle Diary© (Diary), a 19-item tool (scored 0-4), during her 1st Cyclic OMP cycle and took no other therapy. This pilot study was designed to understand Cyclic OMP-related experience changes in WLWP: 1) by documenting experience changes on the 1st to the 6th complete Diary; and 2) by assessing follicular phase changes in baseline data (no Rx) vs. cycles 3 and 6. We entered data from six consecutive Diaries into an SPSS (Version 24) database. Analysis #1 used Wilcoxon Signed Ranks Tests (for within-person ordinal data) and #2 repeated measures ANOVA. Research question: What Cyclic OMP-related experience changes occurred for a WLWP? On Cyclic OMP, she spontaneously reported improvements in aching joints, sleep and GI problems. We assessed selected, potentially E2-related Diary changes: flow, fluid retention, breast tenderness, stretchy cervical mucus and anxiety. Cyclic OMP was associated with shorter cycle lengths of 28.17+/-0.8 days. Fluid retention (P=0.000), mucus (P=0.048), and breast tenderness (P=0.000) all decreased, but anxiety and flow were unchanged. Follicular phase only fluid retention significantly decreased (F (1.2, 14.7) = 6.7, P =0.017).
Although open-label, these prospective analyses suggest that Cyclic OMP, alone, is related to short-term benefits in androgenic PCOS. Prospective studies and controlled comparative trials of this innovative “luteal phase replacement” PCOS therapy are needed. Reference:1Barry J Hum Reprod Update 2014 20:748. 2Azziz R Nat Rev Dis Primers 2016;2:16057. 3Blank S Hum Reprod Update 2006;12:351. 4Montville C Fertil Steril 2010;94:678. 5Livadas S Fertil Steril 2010;94:242. 6Bagis T J Clin Endocr Met 2002;87:4536. 7Prior J https://hellocluecom/articles/cycle-a-z/the-case-for-a-new-pcos-therapy 2018
SAT-LB70 Relationship Between LC-MS/MS Measurements of PTHrP and Calcium in Patients With Compromised Renal Function
Authors: Kroner Grace , Kushnir Mark , Straseski Joely 
Published: May 2020

Abstract
Elevated concentrations of parathyroid hormone related peptide (PTHrP) may indicate hypercalcemia of malignancy and can prompt investigation into potential malignancy. Early studies using PTHrP radioimmunoassays suggested that PTHrP concentrations in normocalcemic renal failure patients were elevated due to assay cross-reactivity with C-terminal fragments present in this population [1]. At our institution, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for PTHrP targeting a peptide in the middle of the PTHrP sequence (to avoid measuring terminal fragments). Given the high specificity of LC-MS/MS, our objective was to revisit the earlier observation that PTHrP concentrations are elevated in renal failure patients. We used retrospective chart review to investigate 1) whether PTHrP concentrations differed between adult patients with and without renal impairment and 2) how PTHrP and calcium concentrations were related in these patients. We excluded patients with cancer; the participants (n=93, 20-90y, 56% female) were categorized based on eGFR using the 2009 CKD-EPI equation following KDIGO guidelines. We focused on patients with healthy kidney function (n=21, 20-73y, 43% female), stage 4 kidney disease (n=40, 23-90y, 63% female), and end stage renal disease (ESRD, n=19, 27-81y, 58% female), 7 of whom were on hemodialysis. When measured by LC-MS/MS, we observed higher PTHrP concentrations in ESRD and stage 4 patients compared to those with healthy kidney function (p&lt;0.0001 for both). Overall, there was a strong negative correlation between eGFR and PTHrP (ρ=-0.768, p&lt;0.0001). In contrast to the previous study documenting elevated C-terminal fragments of PTHrP in normocalcemic patients, we observed that 80% of patients with elevated PTHrP had hypercalcemia, in agreement with the positive association between concentrations of PTHrP and calcium (ρ=0.295, p=0.0178). No statistically significant difference was observed between distributions of PTHrP concentrations in stage 4 and ESRD patients with and without hypercalcemia. Among ESRD patients, higher PTHrP concentrations occurred in patients on dialysis compared to those not on dialysis (p=0.003). Our data suggest that elevated PTHrP concentrations are not solely due to decreased glomerular filtration; otherwise, patients on hemodialysis would have decreased PTHrP concentrations due to clearance. Considering the specificity of the LC-MS/MS method for the central portion of PTHrP, we conclude that elevated PTHrP concentrations may occur in patients with severe renal dysfunction; PTHrP elevations correlate with hypercalcemia in the majority of these patients. Clinicians should be cognizant of the method used to measure PTHrP when evaluating hypercalcemia, particularly in patients with renal insufficiency.
1) Orloff et al., Kidney International. 1993;43:1371-76.
MON-LB101 5-Year Data of an Aggressive Pharmacological Approach to Moderate and Morbid Obesity: Is Prevention of Bariatric Surgery Feasible in the Long Run?
Authors: Cadegiani Flavio 
Published: May 2020

Abstract
Background: Maintenance of weight loss in patients that undergo weight loss interventions is highly challenging, irrespective of the type of approach to obesity (whether surgical, pharmacological, or non-pharmacological). We proposed a protocol of an aggressive clinical treatment for obesity aiming to prevent the need of bariatric surgery, in patients unwilling to undergo this procedure, by proposing a protocol that included the combination of different anti-obesity medications and non-pharmacological modalities, for longer duration, and with an active approach to prevent weight regain. Our initial 2-year data showed that 93% (40 of 43 patients) with moderate and morbid obesity were able to avoid the need of bariatric surgery, with concomitant improvements of the biochemical profile. However, whether these patients would maintain their successful rates after five years was uncertain. Our objective is to describe the efficacy and safety of a long term (5-year data) pharmacological and multi-modal treatment for moderate and severe obesity. Methods: The 40 patients that were successful in the two-year approach in our obesity center (Corpometria Institute, Brasilia, DF, Brazil) were enrolled. A long-term anti-obesity protocol was employed, with continuous or intermittent use of anti-obesity drugs, trimestral body composition analysis, psychotherapy, visit to a nutritionist every four months, and both resistance and endurance exercises at least four times a week. Body weight (BW), total weight excess (TWE), body fat, markers of lipid and glucose metabolism, liver function, and inflammation were analyzed. Subjects that dropped out were considered as weight regain. Therapeutic success for the 5-year follow-up included as the maintenance of &gt;20% loss of the initial BW loss, and no weight regain (or &lt; 20% of the initial weight loss). Results: A total of 27 patients (67.5%) were able to maintain the body weight, seven dropped out, and six regained more than 20% of the initial weight loss. Of these, 21 (77.8%) had significant further increase of muscle mass and decrease of fat loss, while 17 (63.0%) had further weight loss (p &lt; 0.05), compared to the 2-year data. Improvements on the biochemical profile persisted in all 27 patients, and had significant further improvements in 24 (88.9%) of these patients. Conclusion: The risk of weight regain five years after a weight loss treatment for obesity was significantly lower compared to previous literature, and comparable to the long-term outcomes of bariatric procedures. An aggressive, structured, and long-term clinical weight loss approach has been shown to be feasible, even for morbidly obese patients.
SUN-LB122 Sequential Testing to Assess Insulin Resistance in the Course of Participation in a Diabetes Prevention Program (DPP)
Authors: McPhaul Michael John , Larsen Julia A , Brandon Martha M 
Published: May 2020

Abstract
Obesity has become increasingly prevalent in the United States and diabetes prevalence has increased dramatically. It is estimated that diabetes affects more than 30 million Americans (CDC, 2015). Prediabetes, a condition in which blood sugar or HbA1c levels are elevated but not to levels permitting a diagnosis of type 2 diabetes, is even more prevalent. Prediabetes precedes the development of type 2 diabetes and for this reason, has been identified as a condition at which interventions might be targeted and progression to overt diabetes might be interrupted. The publication of the initial results of the Diabetes Prevention Program (Knowler WC, 2002) demonstrated that lifestyle change and medication could substantially reduce progression to type 2 diabetes. These efforts have stimulated the CDC to implement the National Diabetes Prevention Program. Unfortunately, a substantial proportion of individuals adhering to lifestyle change or medication still progress to overt diabetes and the identification of individuals participating in a DPP at continued risk for the development of type 2 diabetes would be valuable. We designed a protocol to determine whether individuals responding appropriately to a DPP might be distinguished from individuals at continued risk for diabetes progression by sequential assessments of insulin resistance. We recently validated a multiplexed mass spectrometry assay for the measurement of intact insulin and C-peptide (Taylor SW, 2016), used this to model insulin resistance in individuals undergoing formal assessment of insulin resistance using Steady State Plasma glucose (SSPG) measurements (Abbasi F, 2018) and defined an Insulin Resistance Score (IRS) based on this data. To explore the use of this IRS in the context of an established an IRB approved protocol (Quest Testing to Assess Insulin Resistance [Q-TAIR]; Western IRB protocol # 20171395), we enrolled three cohorts totaling 40 individuals. In addition to anthropometric measurements, this protocol permitted assessment of laboratory data for fasting glucose, HbA1c, electrolytes, lipids, and the IRS at baseline, 1, 3, and 6 months, and 1 year. Data collection is complete for cohorts 1 and 2; data collection is still ongoing for cohort 3. Subjects enrolled in the individual cohorts were enrolled in individual participating practices and varied widely in the proportion offered enrollment based on laboratory test results. In keeping with expectations for adherent participants in a DPP, patients lost an average of 11 lbs. In cohorts 1 and 2, initial IRS were top or middle tertile risk in 10 of 17 patients. Importantly, normalization or improvement of laboratory test results at the conclusion of the DPP did not reflect the continued elevation of IRS risk observed in 5 of the 17 patients. These findings suggest the potential utility of the IRS in assessing changes in the degree of insulin resistance in DPP participants.
SUN-281 Pituitary Hyperplasia Secondary to Uncontrolled Primary Hypothyroidism
Authors: Betancourt Jessica Lee 
Published: May 2020

Abstract
Background: There are several recognized causes of hyperplasia of the pituitary gland. These may present as sellar masses and be misdiagnosed as pituitary adenomas. Pituitary hyperplasia can occur in the presence of long standing primary hypothyroidism due to the loss of negative feedback caused by decreased secretion of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland, leading to excessive thyrotropin releasing hormone (TRH) production by the hypothalamus causing Thyrotroph pituitary hyperplasia Clinical case: 51 y/o female with a past medical history that includes anxiety & depression, obesity, pre-diabetes and uncontrolled hypothyroidism due to Hashimoto’s, presented to the Endocrinology clinic for recent diagnosis of pituitary macroadenoma. Patient reported tiredness, decrease energy, myalgias, weight gain, abnormal menstrual periods and frontal headaches. On physical exam, she had a body mass index of 37.39kg/m2, blood pressure of 130/85mmHg, heart rate of 91 bpm. There was no thyromegaly noted on exam. No abdominal striae was noted. Overall, exam was unremarkable. Her neurological exam was normal and there were no obvious visual field deficits. Initial laboratory tests revealed a thyroid stimulating hormone (TSH) &gt;150 uIU/mL (0.46–4.7 uIU/mL), free T4 0.3 ng/dL (0.7–1.3 ng/dL) and positive TPO antibodies. Other endocrine work up including ACTH, cortisol, prolactin, FSH, LH and IGF-1, were normal. An MRI of the pituitary revealed a heterogeneous enhancing mass replacing the pituitary gland in the sella that measured 16 x 17 x 11 mm. She was evaluated by Neurosurgery, for presumed diagnosis of pituitary macroadenoma. However, prompt recognition of uncontrolled primary hypothyroidism causing pituitary hyperplasia lead to medical management, first. She was started on weight based (1.6mcg/kg/day) levothyroxine at 175 mcg per day. Six weeks after thyroid replacement therapy laboratory evaluation showed improvement in thyroid function test with a TSH of 0.8mIU/mL, free T4 2.8ng/dL and total T3 307ng/dL. A repeat MRI of the pituitary showed decrease in size of the pituitary gland measuring 15 x 4 x 10 mm. Conclusion: This case illustrates the importance of early recognition of uncontrolled primary hypothyroidism during the evaluation of a pituitary mass. Complete regression of this pituitary gland abnormality can be achieved with thyroid hormone replacement avoiding the irreversible consequences of inappropriate pituitary surgery.
OR08-02 Do OGTT-based Insulin Secretory Response Measures Approximate 1st Phase Insulin Response in Pregnant Women?
Authors: Powe Camille Elise , Gordesky Larraine Huston , Catalano Patrick M 
Published: May 2020

Abstract
Background: We previously showed that 1st phase insulin response increases dramatically in pregnancy, independent of changes in insulin sensitivity. Measurement of 1st phase insulin response requires the use of hyperglycemic clamps or intravenous glucose tolerance tests (IVGTTs) which are rarely performed in pregnant women. Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy.
Methods: In a secondary analysis of a longitudinal study of glucose metabolism in pregnancy, we examined Pearson correlations between OGTT-based insulin secretory response measures and 1st phase insulin response. Forty women were studied pre-pregnancy; 36 returned in early and late pregnancy (12–14 and 34–36 weeks gestation). At each time point, after overnight fasts, an IVGTT and an OGTT were performed on separate days. The 1st phase insulin response was calculated as the incremental area under the curve during the 1st 10 minutes after intravenous administration of a 0.5 g/kg glucose load (or 19g/m2 body surface area if weight &gt;120% ideal body weight). Homeostatic Model Assessment (HOMAB), Insulinogenic index (IGI), Corrected insulin response (CIR), Insulin area under the curve/Glucose area under the curve (AUCins/AUCglu), and the Stumvoll 1st Phase Estimate (Stumvoll) were calculated from insulin and glucose levels measured fasting and 30, 60, 90, 120, and 180 minutes after an oral glucose load (75 grams pre-pregnancy, 100 grams in pregnancy).
Results: The best OGTT-based measure for estimation of 1st phase insulin response differed across study timepoints. In early and late pregnancy, AUCins/AUCglu had the strongest correlation with 1st phase insulin response (early: R=0.79, P&lt;0.0001; late: R=0.69, P&lt;0.0001), but was not associated with 1st phase insulin response pre-pregnancy (R=0.32, P=0.08). IGI had the strongest correlation with first phase insulin response pre-pregnancy (R=0.50, P=0.005) and was correlated with 1st phase insulin response in late (R=0.68, P=0.0001), but not early (R=0.36, P=0.07) pregnancy. Stumvoll was the only OGTT-based measure that was significantly correlated with 1st phase insulin response at all timepoints (pre: R=0.44, P=0.01; early: R=0.67, P=0.0001; late: R=0.67, P=0.0001). HOMAB was the weakest correlate of 1st phase insulin response, though the correlation was significant in early pregnancy (pre: R=-0.04, P=0.82; early: R=0.33, P=0.05; late: R=0.18, P=0.28).
Conclusion: OGTT-based measures of insulin secretion do not have a consistent relationship with 1st phase insulin response across pre-, early, and late pregnancy. Our findings suggest that Stumvoll can be used in OGTT-based longitudinal studies of insulin secretory response that begin prior to pregnancy and span gestation. For cross-sectional studies in pregnancy, AUCins/AUCglu are the best estimates of 1st phase insulin response.
MON-584 Albuminuria and Obesity - Which Are the Associated Factors?
Authors: Costa Cláudia Fernandes , Salazar Cristina Daniela , Ferreira Maria João Silva , Pedro Jorge Pires , Neves João Sérgio , Maia Isabel , Gonçalves Vanessa Guerreiro , Canha Marta , Viana Sara , Silva Maria Manuel , Mendonça Fernando , Cabral Pedro , Lourenço Rita , Meira Patrícia , Belo Sandra , Varela Ana , Lau Eva , Oliveira Joana , Santos Ana Paula , Torres Isabel , Freitas Paula , Carvalho Davide M ,   Grupo AMTCO
Published: May 2020

Abstract
Introduction
The association between obesity and renal dysfunction has been widely studied. Albuminuria is a cardiovascular risk factor and the most prevalent marker of kidney injury in people with obesity. Despite the higher prevalence of hypertension and diabetes in those patients, other contributing factors are still unknown.
We aimed to explore the factors related to albuminuria in obesity, analyzing its variation after bariatric surgery.
Methods
We evaluated 2518 patients undergoing bariatric surgery, of those, 1243 with preoperative albuminuria measurement were included in this study. Albuminuria was determined by the albumin-creatinine ratio (RAC) in an occasional urine sample (mg/g) or by the 24-hour urine albumin excretion rate (TEA) (mg/24h). Means and medians were compared using Student’s T-test or Mann-Whitney tests, respectively. Spearman correlation was used.
Results Age (ρ = 0.073; p = 0.010), body mass index (BMI) (ρ = 0.139; p &lt;0.001), waist circumference (WC) (ρ = 0.220; p &lt;0.001), glycated hemoglobin (HbA1C) (ρ = 0.221; p &lt;0.001), systolic blood pressure (SBP) (ρ = 0.203; p &lt;0.001), diastolic blood pressure (DBP) (ρ = 0.134; p &lt;0.001), uricemia (ρ = 0.141; p &lt;0.001) and C-reactive protein (CRP) levels (ρ = 0.090; p = 0.017) were positively correlated with albuminuria.Patients with albuminuria (TEA / RAC≥30) had higher BMI (45.0 ± 6.0 vs.43.2 ± 5.6kg / m2; p &lt;0.001), WC (129.3 ± 13.1 vs. 122.0 ± 12.9cm; p &lt;0.001), SBP (142.7 ± 18.0 vs.134.1 ± 16.5mmHg; p &lt;0.001), DBP (88.0 ± 12.6 vs.83, 2 ± 10.3mmHg; p &lt;0.001), uricemia (6.1 ± 1.5 vs.5.4 ± 1.4mg / dL; p &lt;0.001) and CRP (11.3 (16.4) vs.8, 3 (9.6) mg / L; p &lt;0.001).Excluding patients with diabetes and hypertension, BMI and WC remained statistically positively correlated with urinary albumin excretion. After surgery, the decrease of albuminuria was correlated with the reduction of HbA1C (ρ = 0.144; p &lt;0.001) and CRP (ρ = 0.113; p = 0.037).
Conclusion Anthropometric, inflammatory and metabolic factors, namely WC, CRP and uricemia, may be involved in the etiopathogenesis of albuminuria in obese patients. Bariatric surgery is the most effective method to reverse obesity and it has been shown to be a promising therapy on the treatment of associated renal dysfunction.