bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB100 Novel Paradoxical Markers of Weight Loss: Is the Worse Actually the Better? a Retrospectiveanalysisof 1,567 Patientswith Obesity With Successful Clinical Weight-Loss Approaches
Authors: Cadegiani Flavio , da Silva Pedro Luiz H
Published: May 2020

Background:Obesity is a chronic, multi-factorial, and relapsing disorder that has been reported to be a risk factor to more than 200 diseases, among which the majority is direct- or indirectly triggered by the metabolic abnormalities induced by excessive body fat. Indeed, patients with obesity tend to disclose multiple alterations of metabolic markers, which tend to improve with weight loss. Despite the multiple dysfunctions extensively in this population, only mandatory biochemical exams are usually ordered, likely due to limitations in cost and lack of cost-effectiveness, since the majority of the parameters typically altered in obesity does not drive therapeutic choices or influence in an individual-based evaluation.We developed a protocol for obesity treatment that includes a thorough analysis and follow up of the biochemical parameters of patients with obesity, including more than 50 parameters, for more precise diagnosis and response to treatments. Among these parameters, we identified unexpected changes, including some that would initially be related to increased cardiovascular risk or worse prognosis when in an usual context, but which could peculiarly indicate successfulness of weight loss, since these parameters tend to return to normal levels after a period in the new body weight. Our objective is to identify whether these paradoxical changes in biomarkers are linearly correlated with body weight loss, fat loss, mass loss, or whether they were related to the use of any anti-obesity drug. Methods: In a retrospective cohort of 1,567 patients that underwent a clinical weight loss treatment for obesity in a obesity center (Corpometria Institute, Brasília, DF, Brazil), we performed a linear association analysis between body weight and body fat (air displacement pletismography - Bod Pod, CosMed, USA) and 65 parameters, including hormonal, metabolic, inflammatory, and immunologic parameters. We also adjusted for the use of anti-obesity drugs. Results: Homocysteine and triglycerides were identified to increase linearly according to the amount of weight loss (r = -0.77) and fat loss (r = -0.85), but not due to the use of any drug. Folic acid decrease was directly related to fat loss (r = 0.81). Additional findings include more significant decrease of ApoB, compared to LDLc, decreases of GGT, ALT, CRP, ESR, neutrophils, ferritin, fibrinogen, PTH, free T3, uric acid, a and temporary decrease of ApoA and HDLc, all related with body fat loss. Conclusions: Increase of homocysteine resulted from decreased folic acid metabolism, and increased triglycerides may be indirect markers of lipolysis, as no other plausible mechanism could explain these findings.
SUN-299 Flash Glucose Sensor Monitoring for Patients with Endogenous Hyperinsulinaemic Hypoglycaemia
Authors: Arshad Muhammad Fahad , Kaluarachchi Vidumini , Iqbal Ahmed , Munir Alia , Newell-Price John D C
Published: May 2020

Flash Glucose Sensor Monitoring for patients with endogenous hyperinsulinaemic hypoglycaemia

Background:

Flash glucose monitoring systems (FGS) have recently been introduced and measure interstitial glucose using an amperometric electrochemical sensor assay, and are increasingly used to provide a convenient means to monitor levels on a minute-by-minute basis over two weeks in ambulatory patients with diabetes. Although continuous glucose monitoring systems have been previously used in patients with insulinoma,(1) to our knowledge, FGS use has only been described once previously in an adult patient with an insulinoma.(2) Here, we describe use of this system in 6 patients with confirmed endogenous hyperinsulinaemic hypoglycaemia, especially for the critical nocturnal period.

Methods and patients:

FGS data obtained over each 2-week monitoring was reviewed in 6 patients seen between 2018 and 2019: 5 had a biochemically proven insulinoma and 1 had Hirata’s syndrome. In 4 patients, follow-up readings were obtained after adjustment of glucose-raising medication: two on octreotide, one on diazoxide and one on diazoxide and dexamethasone.

Results:

Median age was 63 years (range 37–83). In the 4 patients with more than one 2-week FGS assessment comparison between first and last readings demonstrated that the average duration of hypoglycaemia (<4mmol/L) 126, 171, 173 and 282 minutes improved to 46, 128, 30 and 0 minutes, respectively. The percentage of glucose readings below target (<4mmol/L) improved from 8%, 58%, 4%, and 47% to 1%, 39%, 0%, and 0%, respectively. The mean glucose was 5.9, 3.9, 7.8, and 4.4 mmol/L, which improved to 10.9, 5.0, 7.9, and 7.5 mmol/L respectively. The lowest average glucose was nocturnal (22:00-06:00) (5.8, 3.3, 6.5, and 4.1 mmol/L) which showed significant improvement after adjustment of medications (11.3, 4.2, 7.2, and 5.7 mmol/L). At least 2 of these 4 patients had well documented impaired awareness of hypoglycaemia based on diminished classical adrenergic symptoms. Among the two patients who had only one 2-week FGS assessment, one went on to have curative successful surgery and the second patient who had Hirata’s syndrome did not have significant detectable hypoglycaemia.

Conclusion:

FGS is a convenient tool that may be used to monitor and adjust therapy in patients with endogenous hyperinsulinism. In carefully selected patients, FGS may allow domiciliary glycaemic management avoiding the need for hospital admission for monitoring purposes.

References:

1. Munir, Alia et al. “Continuous glucose monitoring in patients with insulinoma.” Clinical Endocrinology vol.68,6 (2008): 912–918

2. Sugawa, Taku et al. “Hypoglycemia Unawareness in Insulinoma Revealed with Flash Glucose Monitoring Systems.” Internal medicine (Tokyo, Japan) vol. 57,23 (2018): 3407–3412
MON-686 Insulin Autoimmune Syndrome as a Rare Cause of Hypoglycemia
Authors: Mokhtar Marwa , Gul Wajiha , Skarulis Monica
Published: May 2020

Background:

Insulin Autoimmune Syndrome (IAS) or Hirata disease is reported more in Asians. We report the case of a patient with acute onset hypoglycemia secondary to IAS.

Case Presentation:

A 64 year old ARAB male physician presented with 2 weeks history of episodic hypoglycaemia with blood glucose (BG) 40–60 mg/dl, unrelated to food and occurring throughout the day. His attacks were associated with sweating, dizziness and palpitations, relieved by intake of juice. He reported 3 kg weight gain since the beginning of his symptoms.

Past medical history revealed hypertension, past HCV infection with negative PCR and history of allergy to sulfa drugs. His medications included bisoprolol 2.5 mg daily.

Physical exam showed no acanthosis nigericans. Laboratory investigations: Normal hepatic, renal and thyroid functions. 72 Hours fasting test was performed. at hour 3, the BG was 2.27 mmol (40.86 mg/dl), insulin > 1000 mU/ml (N: 2.6–24.9), c- peptide 15 ng/ml (N: 1.1–4.4), negative beta-hydroxybutyrate, with good glycemia response to glucagon 1mg. Urine sulfonylurea (SU) screen was negative. Insulin antibodies titre was high 8.9 nmol/L (N: 0–0.02) and Proinsulin >700 pmol/L (N: 3.6–22). MRI Abdomen showed only 3 mm lesion in the pancreatic head, likely a cyst.

During hospitalization, the patient continued to have episodic hypoglycaemia and received dextrose 10% and octreotide injection. Bisoprolol was changed to amlodipine as it may mask his symptoms.

Episodes of hypoglycaemia improved with octreotide but did not resolve completely. Prednisolone 30 mg daily was started with improvement and was tapered slowly after 16 weeks after mild hyperglycemia developed. Repeat work up showed reduction in insulin 67.4 mcunit/ml, C- peptide 2.66 ng/ml and insulin antibody titres to 0.24 nmol/L and remission of hypoglycemia.

Discussion:

Autoimmune hypoglycaemia is rare resulting from insulin antibodies(IAS), or anti-insulin receptor antibodies (Type B insulin Resistance). IAS can be triggered by drugs or viruses including hepatitis C and is associated with autoimmune diseases and hematologic malignancies. the differential diagnosis of hyperinsulinemic hypoglycemia include insulinoma, the presence of extreme levels of insulin, c-peptide and proinsulin and insulin antibodies is diagnostic of AIS. Short-term treatment with steroids was effective in treating hypoglycaemia and careful follow-up is ongoing. If the patient recurs, rituximab will be employed.

References:

1-CHURCH, D., CARDOSO, L., KAY, R. G., WILLIAMS, C. L., FREUDENTHAL, B., CLARKE, C., HARRIS, J., MOORTHY, M., KARRA, E., GRIBBLE, F. M., REIMANN, F., BURLING, K., WILLIAMS, A. J. K., MUNIR, A., JONES, T. H., FUHRER, D., MOELLER, L. C., COHEN, M., KHOO, B., HALSALL, D. & SEMPLE, R. K. 2018. Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome. J Clin Endocrinol Metab, 103, 3845–3855.
SUN-492 Treatment of Uncontrolled Graves’ Disease Reveals Underlying Thyroiditis
Authors: Sheung Nicole , Belalcazar Ligia Maria
Published: May 2020

Thyrotoxicosis is a life-threatening condition that may result from poor adherence to medical therapy. We describe the case of a patient with Graves’ disease and a history of medication non-compliance who presented with tachyarrhythmia and heart failure (HF). His protracted course after weeks of inpatient treatment with thionamides, iodine, resin and beta-blockers, was followed by a dramatic improvement within days of adding steroids, suggesting the presence of concurrent untreated thyroiditis.

Case Description: A 38-year-old man with an 18-month history of known Graves’ disease presented to the endocrinology clinic requesting thyroidectomy. He complained of 3 weeks of worsening palpitations, shortness of breath, bilateral lower extremity edema, and frequent loose stools. History revealed frequent interruption of thionamide and recent discontinuation of propranolol due to patient’s perceived lack of improvement. Physical exam showed a thin male with a large goiter. He was in moderate distress due to tachypnea. He had atrial fibrillation with rapid ventricular rate (A Fib with RVR) but was not in pulmonary edema. Laboratories showed a suppressed TSH (<0.02 mIU/L [0.45 - 4.70 mIU/L]), a free T4 above the level of detection (>6.99 ng/dL [0.78 - 2.20 ng/dL], and a total T3 level of above 781 pg/mL (97.0 - 170.0 ng/dL). Methimazole 30 mg BID and propranolol 40 mg TID were started, followed within a few hours with potassium iodine (SSKI) 3 drops TID. Although the patient’s HF improved and there was down-trending of free T4, he continued to have A fib with RVR. SSKI and propranolol were increased; diltiazem 90 mg QID and cholestyramine 2g BID were later added. Despite aggressive treatment, the patient continued to have intermittent tachyarrhythmia, postponing his planned thyroidectomy for weeks. Dexamethasone 2mg Q8H was then started aiming to further decrease T4 to T3 conversion. Interestingly, within 48 hours of the start of steroid therapy, his free T4 level markedly decreased and was well within the normal range several days later when he underwent a successful thyroidectomy, with no further tachyarrhythmia recurrence.

Discussion: Thyrotoxicosis is aggressively treated given its high mortality rate. Treatment algorithms guide physicians to categorize hyperthyroidism either as the type associated with increased hormone synthesis and secretion or that which results from increased hormone release due to gland destruction. This thought process may lead, as in our case, to a delay in appropriate therapy and an increased risk of disease complications. Furthermore, providers should not assume that the lack of treatment response in a patient with Graves’ disease is the result of medication non-adherence. The possibility of coexisting thyroiditis and the absence of a treatment regimen that effectively addresses both underlying processes may be the actual cause for the lack of clinical improvement.
SAT-561 Effects of Mineralocorticoid Receptor Antagonists on Primary Aldosteronism Screening
Authors: Tezuka Yuta , Turcu Adina
Published: May 2020

Background: Mineralocorticoid receptor antagonists (MRAs) are the mainstay of medical therapy for primary aldosteronism (PA), and MRAs also benefit patients with other forms of resistant hypertension and cardiovascular disorders. MRAs impact the renin-angiotensin-aldosterone system (RAAS), raising concerns regarding the accuracy of PA screening. The rate of false negative and/or false positive screening for PA in patients taking MRAs has not been systematically evaluated. Herein, we assessed the alterations of both renin and aldosterone after MRA initiation in a large cohort of patients with hypertension.

Patients and Methods: We conducted a retrospective cohort study of patients with hypertension seen in a tertiary referral center. We employed our center’s database search engine to identify adults with hypertension who were treated with MRAs. Of these, we included patients who had renin and aldosterone measured both before and after MRA treatment. We excluded patients with adrenal cortical cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. PA screening was considered positive when plasma aldosterone concentration (PAC) was 10 ng/dL, plasma renin activity (PRA) was 1.0 ng/mL/h, and the aldosterone-to renin ratio (ARR) was 20. Mann-Whitney test and Wilcoxon signed rank test were employed to compare independent or paired groups, respectively.

Results: In total, 109 patients (57 women), mean age 55+/-13 years were included. Of these, 40% had confirmed PA (14% unilateral and 26% bilateral); in 38% PA was excluded; and in the remaining 22%, testing for PA was incomplete. On average, patients were on 3 +/- 1.6 antihypertensive agents; 60% of patients were prescribed beta blockers, 49% K+-wasting diuretics and 35% were on K+ supplements. Both PAC and PRA increased after MRA treatment (from 19.0 [12.6, 26.7] to 26.3 [17.2, 36.2]; and from 0.6 [0.10, 0.80] to 1.00 [0.60, 2.80], respectively, p < 0.0001 for both), while ARR decreased from 42.5 [18.5, 109.8] to 24.0 [10.9, 55.5] (p = 0.003). Of 71 patients with positive PA screening at baseline, 31 (43.7 %) no longer met positive screening criteria during MRA therapy. Conversely, 7 of 38 patients (18 %) with negative screening at baseline met criteria for positive PA screening while on MRA treatment, including 5 patients with a PAC > 20 ng/dL along with suppressed renin. The impact on PA screening accuracy remained similar irrespective of the MRA dose, duration of treatment, changes in concomitant antihypertensive drugs, or hypertension type.

Conclusions: Commonly, MRA treatment leads to renin elevation, ARR reduction, and consequential false negative PA screening. In a minority of patients, MRA therapy can be followed by aldosterone elevations asynchronous from renin, possibly via short feedback loops, mimicking PA. Whenever possible, PA testing should be conducted after MRA discontinuation.
OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model
Authors: Yoshinaga Keiichiro , Zhao Songji , Washino Komei , Aoki Miho , Nishijima Ken-ichi , Shimoyama Saki , Ukon Naoyuki , Gao Fengying , Washiyama Kohshin , Ito Natsue , Yoshioka Naho , Tamura Naomi , Takahashi Kazuhiro , Ito Hiroshi , Higashi Tatsuya
Published: May 2020

Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model.

Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volume was compared among the three groups.

Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P<0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs. 1043.83±320.79%, P<0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P<0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.
OR20-03 Transcriptional Changes in Lipid Metabolism of Adipocytes Derived from Subcutaneous Abdominal Adipose Stem Cells of Normal-Weight Polycystic Ovary Syndrome Women
Authors: Leung Karen Lynn , Sanchita Smriti , Dumesic Phillip , Ding Xiangming , Li Xinmin , Morselli Marco , Pellegrini Matteo , Dumesic Daniel Anthony , Chazenbalk Gregorio Daniel
Published: May 2020

Normal-weight polycystic ovary syndrome (PCOS) women exhibit increased adipose insulin resistance in vivo (1) accompanying enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with greater lipid accumulation per cell in vitro (2). To determine whether this phenomenon is associated with abnormal adipogenic gene transcription during ASC differentiation into adipocytes, SC abdominal ASCs isolated from three non-Hispanic Caucasian normal-weight PCOS women and three age- and BMI-matched controls were cultured in adipogenic differentiation medium for 3–12 days. After RNA isolation, gene expression levels were determined by RNA sequencing at days 3, 7, and 12. Differentially expressed genes were filtered for significance (padj<0.05) and fold change (>2-fold); upstream regulator genes and gene ontology (GO) functions were determined using Ingenuity Pathway Analysis. Gene set enrichment analysis (GSEA) also was used to identify enriched cellular processes (3). Differentially expressed genes in PCOS vs. control cells were either upregulated (466, 768 and 441 genes on days 3, 7 and 12, respectively) or downregulated (742, 974 and 605 genes on days 3, 7 and 12, respectively) over time, with critical genes governing adipocyte cell differentiation in PCOS cells increased 2–6 fold at days 3, 7 and 12 (PPARγ, CEBPα, ADIPOQ, AGPAT2, FABP4, LPL, PLIN1). The predicted upstream regulator genes TGFβ1 (an adipogenic inhibitor) and TNF (a pro-inflammatory adipokine) were significantly reduced in PCOS relative to control cells at all time points. The GO functions lipid oxidation and free fatty acid (FFA) beta-oxidation were enriched amongst upregulated genes in PCOS cells across all time points, while acylglycerol synthesis was increased at days 7 and 12 alone (z>2, p<0.05, all GO functions). In parallel, GSEA showed in PCOS cells significantly increased transcripts related to oxidative phosphorylation, peroxisome activity and adipogenesis at all time points (p<0.05). Thus, adipocytes derived from SC abdominal ASCs of normal-weight PCOS women exhibit early activation of adipogenic genes, potentially underlying their exaggerated lipid accumulation in vitro, as previously described (2). These PCOS-related changes in gene expression involve an increase in both oxidative phosphorylation and FFA beta oxidation, which could disrupt the balance between energy production and lipid storage, particularly when caloric intake exceeds energy utilization. References: (1) Dumesic DA, et al JCEM 2019;104(6):2171–83; (2) Leung KL, et al. JES 2019;3:Supplement 1, SUN-107 (3) Subhramanian A, et al. PNAS 2005;102:43
SAT-739 Membrane Progesterone Receptors (mPRs/PAQRs) Promote Proliferation, Migration and Neurotrophin Expression in Schwann Cell-like Adipose Stem Cells, Potentially Improving Peripheral Nerve Regeneration
Authors: Castelnovo Luca F , Thomas Peter
Published: May 2020

Peripheral nerve injury is a problem affecting millions of people worldwide, causing significant disability and a reduction in the quality of life. The neurons of the peripheral nervous system are characterized by a significant regeneration capability. However, the functional recovery is unsatisfactory in most cases, making the identification of new strategies to improve the regenerative outcome a major medical need. Schwann cells (SCs), the main neuroglial cells of the peripheral nervous system, trans-differentiate after nerve injury towards a phenotype, known as the repair phenotype, that promotes nerve regeneration. Nonetheless, adult human SCs have poor expansion capability in vitro, undermining their potential clinical development. Several studies have shown that mesenchymal stem cells, especially when differentiated into a Schwann cell-like (SCL) phenotype, may represent an alternative to primary SCs, promoting pro-regenerative effects both in vitro and in vivo. Recently, membrane progesterone receptors (mPRs), members of the progestin and adipoQ receptor (PAQR) family, have been shown to be present and active in Schwann cells. Progesterone activates mPRs in SCs to promote cell migration and proliferation, change cell morphology, and modulate the expression of key SC differentiation factors. These findings suggest a possible role for mPRs in nerve repair. The goal of the present project is to study the role of mPRs in the promotion of pro-regenerative effects in mesenchymal adipose stem cells (ASC), both undifferentiated (uASC) and after differentiation toward the SCL phenotype (SCL-ASC). We first characterized uASC and SCL-ASC, confirming that the latter showed increased expression of SC markers like S100B, Sox10, GFAP, P0 and Krox20, alongside a more pronounced spindle-like shape leading to an increased aspect ratio. The differentiation protocol also increased mPR gene expression in SCL-ASC compared to uASC, especially mPRα (PAQR7) and mPRβ (PAQR8). Treatment with the specific mPR agonist Org OD 02-0 (02-0) caused cell elongation in SCL-ASC, mimicking what happens to SCs in vivo when they trans-differentiate towards the repair phenotype. 02-0 treatment also led to increased cell migration and cell proliferation in both uASC and SCL-ASC, consistent with a pro-regenerative role of mPRs. The effect was more rapid and evident in SCL-ASC. Lastly, we analyzed the effect of mPR activation on neutrophin production and release in uASC and SCL-ASC. A significant increase was observed in the expression and release of the brain derived neurotrophic factor (BDNF), whose role in promoting neurogenesis is well established. Our results support the hypothesis that mPRs have an important role in the modulation of uASC and SCL-ASC physiology and their activation may promote nerve regeneration.
OR02-02 Possible Age and Time-Of-Day Differences in the Hypothalamo-Pituitary-Testicular, and Adrenal, Response to Total Overnight Sleep Restriction
Authors: Liu Peter Y , Takahashi Paul , Yang Rebecca , Iranmanesh Ali , Veldhuis Johannes D
Published: May 2020

Introduction: In young men, sleep restriction decreases testosterone and increases afternoon cortisol, leading to anabolic-catabolic imbalance, insulin resistance and metabolic, neurocognitive, reproductive, and other adverse effects. Age-related differences in the hypothalamo-pituitary-testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk, but this possibility has not been previously studied.

Subjects and Methods: Thirty-five healthy young and older men aged 18-30y (n=17) and 60-80y (n=18), underwent blood sampling in the Mayo Clinic Center for Clinical and Translational Science every 10 minutes for 24 hours from 6PM-6PM under two conditions in random order spaced at least 3 weeks apart: awake (no sleep) or sleep (from 10PM to 6AM). Blood was assayed for LH, testosterone (T) and cortisol (F), and then analyzed by automated mathematical deconvolution and with cross approximate entropy statistics to determine hormone secretion and hormone synchrony, respectively. Statistical significance was construed by repeated measures ANOVA using a full factorial model that included age, sleep and the interaction.

Results: Sleep deprivation had multiple effects on 24-hour (6PM-6PM) Te secretion with significant reductions in mean concentrations, basal, total and pulsatile secretion, and pulse frequency (each P<0.05), in the absence of detectable changes in LH. These effects were most apparent in older men and differed according to age for some parameters: pulsatile Te secretion (P=0.03) and T pulse frequency (P=0.02). Time-of-day analyses revealed that sleep restriction significantly reduced Te in the morning (6AM-9AM) and afternoon (3PM-6PM), reduced LH in the morning, and increased F in the afternoon, particularly in older men. Cross-approximate entropy statistics showed that sleep restriction enforced greater LH-Te and Te-LH joint synchrony in the morning (P<0.05 for each), but not in the afternoon.

Conclusion: Sleep restriction decreases morning LH secretion, morning and afternoon Te secretion, and increases afternoon F secretion, especially in older men. This combination of findings could plausibly cause metabolic and reproductive ill-health when accumulated over decades of life, and may explain how chronic sleep loss contributes to metabolic and reproductive diseases that are more prevalent in older men. These preliminary data also suggest a time-of-day dependent uncoupling of the regulatory control of the testicular axis, and of cortisol secretion. Direct verification by interventions that manipulate hormones during the morning and late afternoon in appropriately matched cohorts of young and older men are now required.
SAT-591 Lack of Adipose-Specific Hexose-6-Phosphate Dehydrogenase Improves Fat Metabolic Phenotype and Increases Insulin Sensitivity in Mice
Authors: Wang Jian , Wang Xinxiang , Kim Samuel , Liu Xiwen , Friedman Theodore C , Jiang Meisheng , Liu Yanjun
Published: May 2020

Lack of adipose-specific hexose-6-phosphate dehydrogenase improves fat metabolic phenotype and increases insulin sensitivity in mice.

ABSTRACT

Increased glucocorticoids (GCs) production in adipose tissue promotes the development of visceral obesity and the MS. The action of GCs in adipose tissue is tightly regulated by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH). However, the phenotypic consequences of reduction of fat-specific GC action caused by inactivation of H6PDH specifically in adipose tissue have not been explored. To better understand the physiological effects of adipose H6PDH, we generated a tissue-specific animal model of adipocyte-specific H6PDH deletion under the control of the murine adipocyte-specific adiponectin promoter (H6PDHAcKO mice). H6PDHAcKO mice exhibited complete absence of H6PDH expression and decreased GC production with reduction of 11β-HSD1 in adipose tissue. These mice had decreased abdominal fat mass with decreased adipose lipogenic gene expression associated with reduction of their transcription factor C/EBPs mRNA levels. Moreover, H6PDHAcKO mice also decreased adipose lipolysis and reduced plasma FFA levels. In addition, H6PDHAcKO mice decreased fasting glucose levels and increase tolerance to glucose and insulin. These data suggest that H6PDHAcKO mice may provide a good model for study the potential contribution of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo.
SUN-664 Effects of Acute Hyperglycemia on Monocytes in Type 2 Diabetes
Authors: Zhang Rong Mei , Oh Jisu , Lin Xiaobo , Arbelaez Ana Maria , Bernal-Mizrachi Carlos , Stone Pam
Published: May 2020

Background: Type 2 diabetes is linked to accelerated atherosclerosis, however the mechanisms behind this association are unclear. Inadequate glycemic control is an important contributor for cardiovascular disease (CVD). Episodic hyperglycemia as a surrogate for glycemic variability (GV) promotes monocyte adhesion and increases proinflammatory monocytes within plaques of patients with diabetes. Monocytes are precursors to macrophages which play a vital role in atherosclerosis and are capable of delivering cholesterol content to plaques. Therefore, elucidating the mechanism by which acute hyperglycemia promotes proatherogenic monocytes in diabetes can lead to novel therapies slowing atherosclerosis progression in these patients. Methods: To assess the effects of acute hyperglycemia on monocyte cholesterol metabolism, we isolated monocytes from 28 patients with Type 2 diabetes cultured for 2 and 6 hours in normoglycemic (90mg/dL) or hyperglycemic media (300mg/dL). Cholesterol content was measured by lipid extraction and fluorometric cholesterol oxidase assay. Cholesterol uptake was assessed by incubating monocytes with Dil-oxidized LDL (Dil-OxLDL). Cholesterol synthesis was performed by incubating monocytes with 2-14C-Acetate in both glycemic conditions for 6 hours followed by lipid saponification, and separated via TLC on silica gel plates. Cholesterol efflux was assessed by labeling cells with 3H-Cholesterol-OxLDL in both glycemic conditions for 6 hours followed by APO-A1 or HDL stimulation for 4 hours. Results: Acute hyperglycemia for 2 and 6 hours induced foamy monocytes with increased total cholesterol content (22 and 32%, respectively), cholesterol ester (40% and 43%, respectively), and free cholesterol content (14% and 25%, respectively) due to enhanced DiI-OxLDL uptake. There was no significant increase in monocyte cholesterol synthesis or cholesterol efflux after stimulation with HDL or APO A-1. Conclusions: Increased monocyte cholesterol content during acute hyperglycemia is a potential mechanism promoting atherosclerosis in patients with Type 2 diabetes.
SUN-655 Helicobacter Pylori Infection Is Not Associated with Diabetes Among a Cohort of Diabetic Patients in Alexandria City, Egypt
Authors: Amara Mohamed Fahmy
Published: May 2020

Abstract: Helicobacter Pylori infection is one of the most common bacterial infections in Egypt. A mounting body of evidence suggests the association of H Pylori infection with diabetes. H.Pylori is implicated in increasing insulin resistance and promoting chronic inflammation, resulting in the development of diabetes. This study aimed to estimate the prevalence of H.Pylori infection among a cohort of patients with diabetes in Alexandria city, Egypt and the possible role of this condition in the control of the glycemic profile. We also investigated the correlation between H.pylori infection and the presence of diabetes-related complications (diabetic nephropathy and retinopathy). The study was conducted on 300 subjects classified into three groups; Group (I): 100 patients with type 2 diabetes, Group (II): 100 subjects with type 1 diabetes, Group (III): 100 non-diabetic control subjects. Participants were subjected to detailed history taking and thorough clinical examination. Routine laboratory investigations were done, including HbA1c and fasting plasma glucose. Stool antigen test, on- site Helicobacter Pylori Ag Rapid Test-cassette was done. The mean duration of diabetes in type 2 diabetes was 8.18±5.87 years, while the mean duration in type 1 was 4.88± 3.02 years, which was statistically significante (p< 0.05). The results of the presented study showed that there was no significant difference in the prevalence of Helicobacter Pylori infection between type 1 and type 2 patients with diabetes (31% Vs 38%, p=0.298), moreover; after adjustment for age, there was no significant difference in the prevalence of Helicobacter Pylori infection among either group with diabetes (Group 1 and group 2) compared to the control group, (p= 0.756 and 0.066) respectively. There was no statistically significant association between the presence of Helicobacter Pylori infection in both type 1 and type 2 diabetes, and an elevated HbA1c level above 6.5%.(p= 0.772 and p=0.524) respectively. The prevalence of diabetic nephropathy in patients with type 2 and type 1 diabetes was 5% and 3% respectively, which was non-statistically significant (p=0.721). While the prevalence of diabetic retinopathy was 11% among patients with type 2 compared to 1% among patients with type 1 diabetes, which was statistically significant (p=0.003). There was no statistically significant correlation between Helicobacter Pylori infection and the presence of diabetic nephropathy or diabetic retinopathy. Helicobacter Pylori infection was not associated with diabetes and did not affect the HbA1c level. Helicobacter Pylori infection was not correlated to the presence of either diabetic nephropathy or diabetic retinopathy among both patients with type 2 and type 1 diabetes.

Nothing to Disclose: MA, MM, AH

No Sources of Research Support
SAT-656 Both Neutrophil and Monocyte Ratios to High Density Lipoprotein Cholesterol Are Superior Biomarkers of Metabolic Syndrome
Authors: Ramakrishnan Neeraj , Jialal Ganesh , Jialal Ishwarlal
Published: May 2020

Metabolic Syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder high sensitivity C-reactive protein (hsCRP) is the most widely accepted measure.We examined the ratios between the phagocytes, neutrophils(PMN)and monocytes, to high density lipoprotein (HDL) and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of T2DM, ASCVD, smoking or lipid therapy to determine if they were valid biomarkers of MetS. Patients with nascent MetS(n=58) and matched controls(n=44) were recruited from Sacramento County. Patients with diabetes, cardiovascular diseases, inflammation (hsCRP >10mg/L or leukocytosis), smoking, anti-inflammatory and hypolipidemic drug therapies were excluded. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin adiponectin, leptin and chemerin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin levels. Ratios of PMN and monocytes to HDL-C and Adiponectin were calculated and compared statistically. PMN: HDL-C and Monocyte: HDL-C, increased in patients with MetS compared to controls (p<0.0001 and p=0.001 respectively).Also the PMN: Adiponectin and monocyte: Adiponectin ratios were significantly increased in MetS (p=0.006 and 0.02 respectively). All ratios increased with increasing severity of MetS (p=0.01). Receiver Operating Characteristic (ROC) curve analysis showed that both the PMN/HDL-C and monocyte: HDL-C area under the curve(AUC)(0.85 and 0.84 respectively) significantly added to the CRP AUC(0.75), p=0.01 for both. Neither leukocyte: Adiponectin AUC was significant compared to hsCRP. Also both ratios to HDL-C correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance(HOMA-IR) (p<0.05). Whilst the PMN:HDL-C ratio correlated with leptin, and chemerin the monocyte: HDL-C ratio correlated significantly with chemerin only (p<0.05) Our cross-sectional study indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS, increase with severity of MetS, correlate positively with inflammation and insulin resistance and both ratios appear to be better predictors of MetS than hsCRP. In conclusion, they provide a cost-effective measure of Metabolic Syndrome and should be confirmed in larger data bases and prospective studies.
MON-201 Effects of Incretins on Catecholamine Synthesis by Rat Pheochromocytoma PC12 Cells
Authors: Komatsubara Motoshi , Fujisawa Satoshi , Nada Takahiro , Iwata Nahoko , Otsuka Fumio
Published: May 2020

Incretins, such as gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are metabolic hormones secreted from the intestine to stimulate insulin secretion from the pancreatic β cells. Dipeptidyl peptidase-4 (DPP-4) inhibitors, as anti-diabetic agents, increase the bioavailability of both GIP and GLP-1. Since the receptor expressions of GIP and GLP-1 are detected in various organs, incretins have been suggested to affect many kinds of tissues and organs in addition to their insulinotropic effects. For instance, GIP and GLP-1 have been reported to regulate ovarian steroidogenesis and hypothalamic-pituitary-adrenal axis including secretions of adrenocorticotropin from the pituitary and cortisol from the adrenal cortex. However, the roles of GIP and GLP-1 in the adrenal medulla have not been recognized. Here we focused on the activity of bone morphogenetic protein (BMP)-4, which is expressed in the adrenal medulla and is functionally involved in the control of catecholamine synthesis. We earlier reported that BMP-4 treatment decreased catecholamine synthesis via smad1/5/9 phosphorylation and regulated catecholamine synthesis by cooperating with glucocorticoid and melatonin in rat pheochromocytoma PC12 cells. In the present study, roles of GIP and GLP-1 in the regulation of catecholamine production were studied using PC12 cells by focusing on interaction with BMP-4 and adrenocortical steroids. Both of GIP receptor and GLP-1 receptor expressions were detected in PC12 cells. Of note, treatments with GIP, but not with GLP-1, increased dopamine synthesis and the mRNA levels of catecholamine synthetic enzymes including tyrosine hydroxylase (TH), which is a rate-limiting enzyme for catecholamine synthesis, DOPA decarboxylase (DDC), and dopamine β-hydroxylase (DBH), by PC12 cells. Treatments with GIP enhanced glucocorticoid- and aldosterone-induced TH mRNA levels by upregulating the expressions of glucocorticoid receptor (GR) as well as mineralocorticoid receptor (MR). However, treatment with GLP-1 had no effect on corticosteroid-induced TH mRNA levels or GR/MR expression. On the other hand, treatment with GIP attenuated the inhibitory effect of BMP-4 that enables to decrease TH mRNA levels by suppressing BMP-induced Smad1/5/9 phosphorylation and Id-1 transcription. Furthermore, GIP treatment upregulated the expression of inhibitory Smad7, possibly leading to the suppression of BMP-4 signaling by PC12 cells. Collectively, it was revealed that incretins, in particular, GIP has an inducing effect on catecholamine synthesis through inhibiting BMP activities as well as enhancing corticosteroid actions in adrenomedullar cells.
SUN-693 What Else Should Be Done in Patients with Uncontrolled Type 2 Diabetes and Severe Insulin Allergy?
Authors: Elshimy Ghada , Correa Ricardo Rafael , Techathaveewat Pawarid , Vinales Karyne Lima , Harman Sherman Mitchell
Published: May 2020

Introduction: Insulin allergy in patients with diabetes mellitus is a very rare condition. The immediate vital implications for the patient call for prompt diagnosis and management of insulin allergy. We present a case of a patient that was unable to tolerate the insulin desensitization process, however; he was successfully treated with antidiabetics’ medications following the AACE guidelines for the management of type 2 diabetes (T2DM).Case description:31 years old obese Caucasian male with a BMI of 35, a history of T2DM and insulin allergy who was admitted to the hospital with hyperglycemia and osteomyelitis of the right foot. Endocrinology was consulted for the management of diabetes. Laboratory results showed hemoglobin A1C 11.1%, C peptide level 2.79 with blood glucose 283 mg/dl with negative insulin specific IgG level and elevated Ig E levels. The patient was actually diagnosed with T2DM in 2001, then started on metformin, glyburide initially. Given uncontrolled diabetes he was started on insulin in 2007 however, he developed an allergic reaction to different types of insulin (including anaphylactic reaction) so he was referred to allergy and immunology for further testing and possible desensitization. He had an allergy to human, bovine and porcine insulin. Exclusion of other causes of allergy including latex, protamine, and zinc was performed by the immunologist. Trial of insulin desensitization (using NPH and regular Insulin) failed. He also developed an allergic reaction to different medications including sulfonylurea, SGLT2 inhibitors, DDP4 inhibitors, and alpha-glucosidase inhibitors. During the inpatient setting in 2019, we assessed the patient and considered different options available; bromocriptine versus amylin products versus fish insulin versus IGF1 (as of last resort). Other options were another desensitization process in the ICU setting with transitioning to an insulin pump, however, the patient refused that option. We started the patient on bromocriptine mesylate(cyclocet) with pioglitazone and the A1C improved in the next 3 months from 11.1%-->9.8%. The patient is still following up with us and plans for desensitization once the osteomyelitis of the foot is controlled. Discussion and conclusion: Insulin allergy is a rare but severe condition that calls for immediate work-up. It can be managed well in close cooperation between the endocrinologist and the immunologist. Our patient developed IgE-mediated symptoms occurring immediately after insulin injection and confirmed by intradermal skin testing. Specific immunotherapy has been reported in case reports in the literature and should be considered for these patients Following AACE guidelines for the management of T2DM with the addition of bromocriptine mesylate until desensitization was a beneficial option for our patient.
SUN-621 Body Weight and Body Composition in Patients with Chronic Pancreatitis Are Associated with Islet Function After Total Pancreatectomy and Islet Cell Transplantation
Authors: Harindhanavudhi Tasma , Yang Yi , Hodges Jim , Bellin Melena Dawn
Published: May 2020

Background: Total pancreatectomy with islet autotransplant (TPIAT) is done in patients with chronic pancreatitis to treat intractable pain. In TPIAT, islets are isolated after pancreatectomy and infused into the liver via the portal vein to mitigate post-operative diabetes. Outcomes vary, with ≥60% needing exogenous insulin supplementation to maintain normoglycemia. The current study’s aim was to determine if pre-surgical body composition is associated with islet function and insulin sensitivity after TPIAT.

Methods: We characterized body weight and composition as related to insulin sensitivity and dependence and diabetes outcome in 88 adults who underwent TPIAT for chronic pancreatitis at the University of Minnesota. At baseline, 12 and 18 months after TPIAT, insulin independence was assessed; metabolic testing used mixed meal tolerance testing and frequent sample intravenous glucose tolerance testing. Body composition was measured by Dual X-ray absorptiometry (DXA). Statistical analyses used linear and logistic regression.

Results: At baseline, mean age was 39.9 (SD 11.1) years. 9.1% were underweight (BMI<18.5 kg/m2), 45.5% normal weight (BMI=18.5–24.9), 22.7% overweight (BMI=25–29.9) and 22.7% obese (BMI≥30). Islet equivalent per kg did not differ between body weight categories (p=0.17). Overweight/obese patients had higher peak and AUC c-peptide and lower insulin sensitivity index, as expected. Compared to baseline, android to gynoid fat ratio was lower at 12 (0.80 vs 0.88; p=0.012) and 18 months (0.81 vs 0.88; p=0.041), and lean mass was lower at 18 months (38848 vs 42338 kg; p=0.029). Baseline body weight was positively associated with acute insulin response to glucose (AIRg) at 12 months (effect size 38.5, SE 17.1 mU/L/min; p=0.029) and 18 months (38.3, SE 18.5 mU/L/min; p=0.045), while baseline lean mass was inversely associated with AIRg at 12 (p=0.01) and 18 months (p=0.033). Baseline body weight was positively associated, and fat mass inversely associated with disposition index (Di; islets’ ability to secrete insulin normalized to insulin resistance) at 18 months (p=0.019 for both).

Percent body fat and percent gynoid fat predicted Sg (glucose effectiveness index, i.e., ability of glucose to promote its own disposal and inhibit hepatic glucose production absent an incremental insulin effect) at 18 months (p=0.042 and p=0.019, respectively). Insulin independence at 12 and 18 months was not significantly associated with baseline body weight or body composition.

Conclusions: Overweight/obesity is common in patients with chronic pancreatitis. After TPIAT, patients had lower muscle mass and A/G ratio. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT surgery.