bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-618 A Framework for Understanding and Managing ‘The Diabetes Syndrome’: A Unified Pathophysiologic Approaching the Context of the Beta-Cell Classification of Diabetes
Authors: Schwartz Stanley S
Published: May 2020

We have previously presented a proposal for a new, beta-cell centric classification of diabetes based on a consilience of genetic, metabolic, and clinical research that have accrued since the current classification was instituted. It recognizes that the beta-cell is THE core defect in all patients with diabetes. Differences in the genetics (and epigenetics), insulin resistance, environment and inflammation/immune characteristics resulting in the damage to the beta-cell in each individual will determine the phenotypic presentation of hyperglycemia and allow for a patient-centric, precision-medicine therapeutic approach, part of which we labeled ‘the Egregious Eleven’.

We now recognize the same pathophysiologic mechanisms that account for damage to the beta-cells govern the susceptibility of the cells involved in the complications and other conditions ‘tied to’ diabetes to damage by the abnormal metabolic environment that typifies beta-cell dysfunction and ‘fuel excess’. This abnormal metabolic environment is typified by oxidative stress which alters metabolic pathways (a la Brownlee’s Hypothesis model), alterations in gene expression, epigenetics, and inflammation. This allows us to understand the varied risk of developing complications of diabetes, including malignancies, dementia, NASH, psoriasis with similar levels of glycemic control; how non-glycemic effects of some medications for diabetes result in marked complication risk modification; and the value treating co-morbidities of diabetes in modifying complication risk.

Principles we outlined in using ‘the Egregious Eleven’ model- use agents that preserve beta-cell function, treat with least number of agents that treat most number of mechanisms of hyperglycemia- can be extended to use those agents, in combination, that also engender weight loss, decrease CV outcomes and have real or potential benefits in cancers related to diabetes, dementia risk, NASH, psoriasis. This approach allows for a more accurate assessment of each patient’s disease and effecting true precision medicine

Schwartz, S, et al, Diabetes Care 2016, 39:179–186.

Schwartz SS, et al Trends Endocrinol Metab. 2017;28(9):645–655.
SAT-680 Diabetes Mellitus Induced by Programmed Cell Death-1 (PD-1) Inhibitors: A Case Report
Authors: Abuaisha Munder , Castillo Dan Ran , Imran Maha , Schultz Atara B
Published: May 2020

Introduction:

Immune checkpoint blockade has revealed a remarkable success in the treatment of a range of cancer types. Immune-related adverse events on the endocrine system may be permanent and carry high morbidity and mortality.

Case:

A 35-year-old black male presented to the ED with acute onset diffuse abdominal pain, along with nausea and vomiting. Review of systems was positive for polyuria and polydipsia. The examination was unremarkable apart from a sizeable fungating lesion of the left lower extremity by the ankle measuring 12 x 8 cm. Investigations indicated blood sugars around 600, serum bicarbonate of 19 mEq/L, an anion gap of 19 mEq/L, serum BHB was elevated, and lactate within normal. The patient was diagnosed with DKA, started on an insulin drip, and admitted to the ICU.

Our patient had no known personal or family history of diabetes. A few years ago, he had suffered from a non-healing chronic ulcer in his left ankle secondary to a motor vehicle accident. Three months ago, he had been diagnosed with a well-differentiated squamous cell carcinoma, arising from his chronic non-healing ulcer. One month ago, He had started Pembrolizumab 200mg Intravenously, and he had received a total of two cycles, the last cycle was one week ago. Shortly after he presented to the ED with the above chief complaint.

He made a complete recovery and further investigations revealed HbA1c of 7.2%, C-peptide levels of <0.1 ng/mL, which supports the diagnosis of T1-DM. He was discharged home, and Pembrolizumab was continued.

Conclusion:

Autoimmune T1-DM has been reported after receiving anti-PD-1 therapy. In a recent study included 27 patients with a variety of solid-organ cancers, and all had received anti–PD-1 antibodies treatment, autoimmune, T1-DM diabetes occurred in close to 1% of patients (1). A systematic review and meta-analysis were conducted recently showed that people developed T1-DM within three months of the initial PD-1 inhibitor exposure. Since patients treated with anti–PD-1 antibodies can present with life-threatening DKA, a high index of suspicion is crucial as early detection is the key to successful treatment and prevention of morbidity and mortality. It remains unclear if it is safe to restart the checkpoint inhibitor after an immune-related adverse event, and further studies are necessary in order to resolve this dilemma. A recent retrospective study included patients with melanoma showed that anti–PD-1 therapy could be safely resumed after severe adverse event requiring immunosuppression (2).

References:

1. Stamatouli, A. M. et al. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 67, 1471–1480 (2018).

2. Menzies, A. M. et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann. Oncol. 28, 368–376 (2017).
SAT-356 Reversible Suppression of Serum 1,25-Dihydroxyvitamin D in Williams Syndrome
Authors: Torchinsky Michael Yuri , Bugaieski Eric
Published: May 2020

Background: Hypercalcemia has been reported in 5% to 50% of patients with Williams syndrome; however, observations about the role of 1,25-dihydroxyvitamin D in hypercalcemia related to Williams syndrome have been contradictory. Objective: The objective was to investigate the mineral metabolism in an 11-month-old patient with Williams-Beuren syndrome who had hypercalcemia, hypercalciuria and nephrocalcinosis. Methods: We reviewed test results in an 11-month-old infant with Williams syndrome who developed hypercalcemia following excessive dietary calcium intake that was two to three times higher than recommended for age because he continued receiving a premature formula with high calcium content from birth. Results: Our patient presented with feeding difficulties, daily vomiting, weight loss, and constipation. He had serum total calcium 14.8 mg/dL, phosphorus 4.0 mg/dL, PTH <4 pg/mL, 1,25-dihydroxyvitamin D <8 pg/mL, 25-hydroxyvitamin D 29 ng/mL, PTH-related peptide 3.7 pmoL/L (expected <4.2), alkaline phosphatase 118 U/L, beta-crosslaps 1257 pg/mL, and urinary calcium/creatinine ratio 1.19. XR Skeletal Survey revealed increased bone density in the metaphyseal regions, in particular, above the knee, distal radius and ulna that may result from hypercalcemia; no evidence of rickets, osteoporosis or congenital osteodystrophy was seen. Renal ultrasound revealed increased echogenicity of the renal medullary pyramids consistent with medullary nephrocalcinosis. Hypercalcemia and hypercalciuria were initially treated with IV fluids and Furosemide IV, and resolved only after Pamidronate 0.5 mg/kg/dose IV x 2 doses. After serum calcium normalized, the patient’s symptoms resolved, PTH recovered to 18 pg/mL (expected 10 - 65), and 1,25-dihydroxyvitamin D increased to 27 pg/mL (expected 24 - 86). Chromosomal micro-array analysis showed a 1.9 megabase deletion at 7q11.23 that overlapped the Williams syndrome critical region including the ELN gene, consistent with diagnosis of Williams syndrome. Serum calcium remained normal with dietary calcium restriction using a low-calcium formula and complementary foods. Conclusions: PTH-independent hypercalcemia in our patient with Williams syndrome was due to calcium overload resulting from dietary calcium excess in addition to possibly enhanced intestinal calcium absorption. Serum 1,25-dihydroxyvitamin D was undetectable and returned to normal only with resumption of PTH secretion required for its synthesis after hypercalcemia resolved. The balance between bone formation and resorption was shifted to resorption possibly to remove skeletal calcium excess, based on normal alkaline phosphatase (marker of osteoblast activity) and high collagen beta-crosslaps (marker of osteoclast activity). A premature formula with high calcium content should be switched to a full-term formula when risk for rickets of prematurity clears.
MON-065 Prevention of 6-Mercaptopurine-Induced Hypoglycemia by Levocarnitine Replacement
Authors: Torchinsky Michael Yuri , Miller Mark , Benavides Valeria
Published: May 2020

Background: Symptomatic hypoglycemia has been reported in children less than 6 years of age receiving 6-Mercaptopurine for acute lymphoblastic anemia (ALL); however, the mechanism of 6-Mercaptopurine-induced hypoglycemia has been unclear. Objective: The objective was to investigate the metabolism in a 3-year-old patient with hypoglycemia induced by 6-Mercaptopurine during maintenance therapy for ALL. Methods: We reviewed test results including serum total and free carnitine levels at time of hypoglycemia in a 3-year-old child with ALL who had repeatedly low plasma glucose as a side effect of 6-Mercaptopurine. Hypoglycemia defined as plasma glucose <50 mg/dL was detected using a glucose meter and each time verified in the clinical laboratory. After Levocarnitine was added to 6-Mercaptopurine therapy, the glycemic control was assessed using a glucose meter, the clinical laboratory, and a continuous glucose monitor; serum total and free carnitine levels were repeated when hypoglycemia resolved. Results: Our patient presented with fatigue, tremors and plasma glucose 39 mg/dL to 47 mg/dL, corrected with a sugary beverage. He had plasma ACTH 38 pg/mL, serum cortisol 10 mcg/dL, total carnitine 24 nmol/mL (expected 35 - 84), free carnitine 18 nmol/mL (expected 24 - 63), plasma free fatty acids 1.62 mmol/L (expected >1.5), beta-hydroxybutyrate of 0.2 mmol/L to 0.7 mmol/L (expected >2.0), and urine ketone bodies negative when plasma glucose was between 33 mg/dL and 39 mg/dL. Plasma insulin was undetectable at time of hypoglycemia, and serum glucose increased by less than 30 points in response to Glucagon IV. Serum IGF-1 as measure of growth hormone effect and thyroid function were normal. Hypoglycemia continued to daily recur especially during the night despite bedtime snacks high in complex carbohydrates and was prevented only by Levocarnitine 25 mg/kg/dose every 12 hours PO that raised serum total and free carnitine levels. The patient remained hypoglycemia-free one month after Levocarnitine was added to 6-Mercaptopurine therapy, in particular, he had average glucose 114 mg/dL with standard deviation 30 mg/dL, glucose 70 mg/dL to 140 mg/dL 93% of the time, and glucose <55 mg/dL 0% of the time. Conclusions: Our patient had symptomatic hypoketotic hypoglycemia related to moderately reduced serum total and free carnitine, corrected with Levocarnitine replacement. Increase in plasma free fatty acids without expected increase in plasma and urine ketone bodies may be sign of impaired synthesis of carnitine, which is required for transport of fatty acids into the mitochondria to produce ketone bodies. Measuring serum total and free carnitine in hypoglycemia induced by 6-Mercaptopurine is helpful in identifying children, who may benefit from Levocarnitine replacement.
MON-099 The Association Between C-Reactive Protein, Metabolic Syndrome, and Pre-Diabetes in Korean Children and Adolescents
Authors: Kim Jihyun , Lee Jong Bin , Lim Jung Sub
Published: May 2020

Objective: Cardiovascular disease (CVD) is a leading cause of death worldwide, including in Korea. In adults, the risk for CVD is increased approximately three-fold in subjects with metabolic syndrome (MetS), and the hazard ratio for subjects with MetS has been reported as 1.37 for mortality from CVD after adjustment for other confounders. Furthermore, MetS in childhood predicts adult MetS and T2DM 25 to 30 years later. Because MetS is a state of chronic low-grade inflammation, measurements of the circulating levels of the inflammatory molecules might provide diagnostic and therapeutic approaches to modulate or alter disease progression. High sensitivity C-reactive protein (hsCRP), a biomarker of inflammation, has emerged as an independent predictor of CVD and T2DM development. The aim of this paper is to evaluate the association between hsCRP and MetS and its components in Korean children and adolescents. Methods: We performed a cross-sectional analysis using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016–2017. We analyzed the data of 1,247 subjects (633 males, 14.2 ± 2.7 years) from the KNHANES 2016–2017. MetS were defined by the modified NCEP-ATP III criteria. Results: Among the 1,247 subjects (mean age: 14.2 ± 2.7 years), the prevalence of MetS was 5.8% (7.0% in male subjects and 4.6% in female subjects; p = 0.070). The mean hsCRP level was 0.861 ± 1.567 mg/l (median and interquartile range: 0.370 and 0.430mg/l). Subjects with MetS had higher hsCRP levels than subjects without MetS (geometric mean: 1.08 vs. 0.46 mg/l, p < 0.001). The prevalence of MetS in the lowest, second, third, and highest hsCRP quartiles were 1.8%, 2.4%, 3.5%, and 15.2%, respectively. Compared to the lowest quartile, the odds ratio (OR) for having MetS in the highest quartile was 8.414 (3.272–21.638), adjusting for age and sex. The OR for having abdominal obesity and low HDL-C in the highest quartile were 9.657 (4.818–19.355) and 2.408 (1.286–4.510), adjusting for age, sex, and other components of the MetS. Additionally, the OR for having pre-diabetes (HbA1c ≥ 5.7%) in the highest quartile was 2.061 (1.097–3.870). Conclusion: Serum hsCRP level is positively associated with MetS and pre-diabetes in Korean children and adolescents.
SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer
Authors: Berstein Lev M , Ivantsov Alexander , Vasilyev Dmitry , Iyevleva Aglaya
Published: May 2020

Background and aims : In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7].

References:

1.Talhouk A, McAlpine JN. Gynecol Oncol Res Pract. 2016; 3:14.

2. Talhouk et al., Cancer. 2017; 123(5):802–813.

3. Kommoss FK et al., Br J Cancer. 2018;119(4):480–486.

4. Berstein et al. Future Oncol. 2019; 15(12):1335–1346.

5. Jing X. et al. Immunol Cell Biol. 2019; 97(6):563–576.

6. Zou X. et al. Medicine (Baltimore).2018;97(49):e13273.

7. Bosse T. et al. Am J Surg Pathol. 2018 May;42(5):561–568.
SAT-285 TSH/TSHR Signaling Deficiency Impairs Spatial Learning and Memory
Authors: Luan Sisi , Zhao He , Zhao Jiajun
Published: May 2020

Background: Subclinical hyperthyroidism is associated with cognitive impairment, but the mechanism has remained unclear. As subclinical hyperthyroidism is characterized by significantly decreased TSH levels, this study aimed to investigate whether TSH regulates cognitive function. Methods: The correlation between TSH and cognitive impairment was investigated in a cross-sectional population study. The role of TSH/TSH receptor (TSHR) signaling in spatial learning and memory was further examined by behavior tests in Tshr-/- mice. Dendritic spine, synaptic density and structure of hippocampal CA1 pyramidal neurons were detected by Golgi’s method and electron microscopy. The mRNA and protein expression levels of learning and memory-related genes were assessed by RNA sequencing, real-time PCR, immunoblotting and immunofluorescence approaches. Results: Serum TSH level correlated negatively with cognitive impairment in the current population. Consistently, Tshr deletion in mice led to significantly compromised performance in hippocampus-dependent tasks, reduced dendritic spine density and excitatory synaptic density as well as altered synaptic structure in CA1 subfield of the hippocampus. Furthermore, the mRNA levels of learning and memory-related genes were altered, and protein levels of CREB-regulated genes were downregulated in the hippocampus of Tshr-/- mice. Conclusions: These findings reveal that TSH/TSHR signaling ablation impairs spatial learning and memory, indicating a decline in TSH level might contribute to the increased prevalence of cognitive impairment in subclinical hyperthyroidism patients.
MON-079 Prepubertal Gynecomastia Secondary to Excessive Soy Consumption
Authors: Sea Jessica , Abramyan Mikayel , Chiu Harvey Kenn
Published: May 2020

Enlargement of breast tissue in males, or gynecomastia, is a rare condition in prepubescent boys. While the majority of cases are idiopathic, we describe an 8-year-old patient who developed unilateral gynecomastia secondary to marked dietary soy consumption. Soy products, particularly those consumed by our patient, contain high levels of phytoestrogens which have been documented in limited case studies to contribute to abnormal development of breast tissue in adolescent and adult males. To our knowledge, this is the first documented case of gynecomastia occurring in a prepubescent patient resulting from excessive intake of dietary soy. Importantly, we also report a complete resolution of gynecomastia upon exclusion of dietary products containing significant amounts of soy. While soybeans and soy-derived products can be an important source of nutrition for some, those with abnormal sensitivity to phytoestrogens may benefit from limiting dietary soy consumption to avoid potential adverse effects, including gynecomastia.
SUN-018 No Difference in Breastfeeding Rates in Women with Polycystic Ovary Syndrome
Authors: Bui Leeann , Cooney Laura , Birstler Jen
Published: May 2020

No Difference in Breastfeeding Rates in Women with Polycystic Ovary Syndrome

Objective: Women with PCOS have increased rates of obesity and gestational weight gain compared to women without PCOS, factors which are associated with decreased breastfeeding (BF). Thus, our objective was to evaluate if women with PCOS were less likely to initiate BF.

Design: Cross-sectional analysis of participants in the PRAMS (Pregnancy Risk Assessment Monitoring System) dataset, a national questionnaire from the Centers for Disease Control (CDC) sent to postpartum mothers 2–9 months after delivery. PCOS status and BF were by self-report. Logistic regression was used to assess odds of ever BF. Length of BF was assessed using Cox proportional hazards with right censoring for women who were still BF at the time of follow-up. PRAMS complex survey design was accounted for.

Results: PCOS status was available for 14 states. Median response time was 3.7 months postpartum. Data from 16,036 participants were included which represents 855,302 women due to sample weights. 6.6% of women reported having PCOS and 83.8% reported ever BF. Compared to women with a normal BMI, women who were overweight or obese had decreased odds of BF (OR: 0.7, 95% CI: 0.6–0.9, P=0.01; OR: 0.6, 95% CI: 0.5–0.7, P<0.001 respectively); however, PCOS was not associated with BF (OR: 1.1, 95% CI: 0.9–1.3, P=0.6). In multivariate analysis, women with PCOS still were at no decreased odds of BF after adjusting for age, BMI, race, ethnicity, infertility treatment, and delivery factors (ORadj:1.1; 95% CI: 0.8–1.4; P=0.6). Variables associated with decreased odds of BF included: overweight/obesity, age ≤ 19 yrs (vs. 25–29), Black race, smoking, undesired pregnancy intent, gestational age ≤27 wks, and prior live birth. Variables associated with increased BF included: age 30–39 yrs, hospital stay 1–2 days (vs. 3–5), Hispanic ethnicity, and ≥ 3 life stressors. In multivariable Cox models, women with PCOS did not have a shorter length of BF (HRadj: 0.9, 95% CI: 0.8–1.1, P=0.3).

Conclusion: Given the rise of the national rates of obesity and clear maternal and neonatal benefits to breastfeeding, understanding the predictors of BF success is paramount. In this national survey, women with PCOS were at no decreased odds of BF, despite confirming the association between overweight/obesity and decreased BF. However, our data still supports the clinical relevance of carefully targeting women with PCOS for BF education due to the association of PCOS with increased BMI. Additional prospective studies are needed to fully understand the association between PCOS and BF.
OR32-04 Dynamic Interactions Between Luteinizing Hormone and Testosterone in Healthy Community-Dwelling Men: Impact by Age and Body Composition
Authors: Roelfsema Ferdinand , Liu Peter Y , Takahashi Paul , Yang Rebecca , Veldhuis Johannes D
Published: May 2020

Context. Aging is associated with diminished testosterone (Te) secretion, which could be attributed to Leydig cell dysfunction, decreased pituitary stimulation and altered Te feedback. Objective. The goal was to quantify all three regulatory nodes of the GnRH-LH-Leydig cell- axis in the same cohort of healthy men, by measuring (1) indirectly the strength of the endogenous GnRH signal on the gonadotrope, (2) the strength of Te feedback on LH by ketoconazole (KTCZ), and (3) the effect of LH infusions on Te secretion, in relation to age and body composition.

Design. This was a placebo-controlled, blinded, prospectively randomized cross-over study in 40 men, age 19–73 yr, BMI 20–34.3 kg/m2. A submaximal dose of ganirelix (GnRH antagonist) was used to assess outflow of GnRH, by calculating the difference between LH output during the control and ganirelix arm. Ketoconazole (steroidogenic inhibitor) was used to estimate feedback, by the difference in LH output during ketoconazole and control arm. High-dose ganirelix and repeated 6-min LH (18.75 IU) infusions were used to measure testicular responsivity. Blood sampling was at 10-min intervals. The 4 sessions were concluded with, a single submaximally GnRH stimulus to assess the responsiveness of the gonadotrope during ganirelix inhibition.

Setting. The study was performed in a Clinical Translational Research Unit.

Interventions. In 3 of the 4 experiments subjects underwent 5 h of blood sampling at 10-min intervals, starting at 0800 h. At 1100 h GnRH was injected and sampling was continued for another 2 h. Admission was at 1700 h the day before. At 2000 h they received KTCZ, dexamethasone or ganirelix and/or placebo. KTCZ and dexamethasone (or placebo) were administered again at 0700 when the IV catheter was placed. High-dose ganirelix was used to test the testicular responsiveness, and 7 LH pulses (90 min intervals) were given., with blood sampling from 1500 till 1300 h next day.

Outcome measures. Mean concentrations of LH and (bio)Te, deconvolution analysis, endogenous dose-response LH-bioTe relation, and approximate entropy. Abdominal visceral fat (AVF) was calculated from single slice CT.

Results. There were age-, but not body composition-related decreases in estimated endogenous GnRH secretion, Te’s feedback strength on LH, and Leydig cell responsivity to LH, accompanied by changes in approximate entropy. Bioavailable Te levels were negatively related to both age and AVF, without interaction between these variables. The LH response to a submaximal dose of GnRH was independent of age and AVF.

Conclusion. Advancing age is associated with 1) attenuated bioavailable Te secretion caused by diminished GnRH outflow and not by decreased GnRH responsivity of the gonadotrope, 2) diminished testicular responsivity to infused LH pulses, and 3) partial compensation by diminished Te feedback on central gonadotropic regulation.
MON-612 Vitamin D and Its Relation to Type II Diabetes Control and Complications
Authors: Alswat Khaled Abdullah
Published: May 2020

Vitamin D and its Relation to Type II Diabetes Control and Complications

Background:

Type II diabetes (T2D) prevalence in Saudi Arabia is among the highest in the MENA region according to the recent International Diabetes Federation published statistics. Recent study suggested that around 54% of the screened T2D patients have vitamin D deficiency. Our aim is to assess the prevalence of vitamin D deficiency and its relation to glycemic control and T2D related complications.

Methods:

We conducted a cross-sectional study at the Diabetes Center, Taif, Saudi Arabia for T2D patients whom age > 18 years and were seen in the clinic between Aug2015-Jan2017 and agreed to participate. We excluded those with gestational diabetes and type I diabetes. Baseline characteristics and measurement were obtained by the participated physician. Laboratory data was collected from the patient’s EMR. We considered those whom have vitamin D level below 30 (ng/ml) to be deficient.

Result:

A total of 228 patients with a mean age of 59.1 + 12.5 years, diabetes duration of 10.6 + 8.8 years, BMI of 33.4 + 6.2 kg/m2, heart rate 81.6 + 12.5, systolic BP 130.8 + 19.6, diastolic BP 75.4 + 9.9, fasting glucose 9.4 + 9.5 mmol/l, HbA1c 8.0 + 2.1%, vitamin D 23.2 + 12.3 ng/ml, serum creatinine 73.8 + 22.2, total cholesterol 4.5 + 1.1, LDL 2.7 + 0.9, triglyceride 1.6 + 0.8.

76.3% of the screened patients had vitamin D deficiency. Compared to those with vitamin D deficiency, those with normal vitamin D level less likely to have hypertension (P 0.521), to be male (P 0.028), to have microalbuminuria (P 0.331), and to be diagnosed with neuropathy and retinopathy (P 0.431 and 0.185 respectively). Also those with normal vitamin D were older (P 0.537),has shorter T2D duration (P 0.231), higher BMI (P 0.097), lower pulse rate (P 0.127), lower SBP (P 0.228), higher DBP (P 0.275), lower HbA1c (P 0.027), lower FBG (P 0.093), lower serum creatinine (P 0.039), and lower total cholesterol and LDL (P 0.497 and 0.404 respectively) when compared to those with vitamin D deficiency.

Adjusting for age, gender, diabetes duration, BMI, SBP, DBP, vitamin D supplements and dosage, there was non-significant correlation between HbA1c and vitamin D level.

Conclusion:

Vitamin D deficiency is highly prevalent among our sample of T2D patients. In the non-adjusted modules, vitamin D deficiency were non-significantly associated with more microvascular complications and worse measured cardiovascular markers. Also, T2D patients with vitamin D deficiency had significantly higher HbA1c which were non-significant when adjusted for related variables.
MON-351 Early Diagnosis and Management of Bilateral Transient Osteoporosis of the Hip in Pregnancy
Authors: Kha Christine K , Simon Nicole
Published: May 2020

Introduction: Transient osteoporosis of the hip (TOH) in pregnancy is a rare and under-reported condition. It is clinically characterized by a sudden onset of hip pain in young females without any history of systemic disorders or traumatic injuries (1). Bilateral involvement of the hips, such as in this case report, is less common than unilateral involvement.

Clinical Case: A 33 year old G2P1 female presented to the hospital at 30 weeks gestation for described sharp, bilateral inguinal pain, greater on the left than right, worse with movement, and with progressive difficulty ambulating, of three weeks duration. She had no significant PMH, notably denying thyroid or calcium disorder, nephrolithiasis, osteoporosis, or steroid treatment. She denied tobacco, alcohol, or illicit substance usage. She only took prenatal vitamins. On physical examination, she had reduced active and passive range of motion of both hips, but normal muscle strength and no signs of infection or neurological deficits. Labs including CMP, LFTs, and TFTs were within normal range. 24 hour urine free cortisol was 54 mcg/24h (normal 3.5-45mcg/24h); repeat post-partum was 21 mcg/24h. 25OH-D was 18.3 ng/mL. MRI without contrast demonstrated “extensive abnormal marrow edema within the left femoral head and neck and small effusion, suspicious for transient osteoporosis of the hip. A subtle small focus of edema on the right was also noted. No discrete fracture line or subchondral collapse was noted.”

The patient was managed conservatively with analgesics, thromboprophylaxis, and education regarding reduction of weight bearing activities, rest, and mobility aids with crutches. She was started on vitamin D. Her bilateral hip pain resolved by the 38th week. She had an uncomplicated cesarean delivery at 39 weeks to a healthy male neonate. At the one-month postpartum visit, she was ambulating independently without difficulty. She denied further pain, and passive and active ROM were intact without tenderness.

Conclusion: TOH in pregnancy is usually a self-limiting disorder with no obvious etiology (2). It can present unexpectedly in the third trimester or early postpartum period in a healthy female with an otherwise uneventful pregnancy. In rare instances where fractures of the affected hip occur, surgical intervention may be necessary. MRI has become the diagnostic tool of choice for early diagnosis of TOH. Early diagnosis and optimal management are essential to prevent major complications such as traumatic fractures and deep vein thrombosis, as well as to prevent stress for the mother during the course of pregnancy.

References:

1. Xyda, A. et al., (2008) Postpartum bilateral transient osteoporosis of the hip: MRI findings in three cases. La Radiologia Medica, 113(5),689–694.

2. Asadipooya, K., et al., (2017). Transient osteoporosis of the hip: Review of the literature. Osteoporosis International, 28(6),1805–1816.
SAT-726 Estrogen Receptor Alpha as a Potential Target for Bisphenol A-Mediated Epigenetic Reprogramming: An in Vitro Analysis
Authors: Gallo Morgan , Treviño Lindsey S , Katz Tiffany A
Published: May 2020

Perinatal exposure to bisphenol A (BPA) has been shown to reprogram the hepatic epigenome of rodents and may promote the development of various metabolic diseases later in life, such as nonalcoholic fatty liver disease (NAFLD). This developmental reprogramming is characterized by the creation of “super promoters” at target genes implicated in metabolic pathways. While it is unclear how these “super promoters” are created, their creation is potentially mediated through BPA and estrogen receptor (ER) interaction. In order to test this potential mechanism, in vitro methods were used to examine ER target gene expression via RT-qPCR in 2 human hepatic cell lines transiently transfected with the ER isoform, ER alpha, prior to BPA exposure for various lengths of time. Within individual time points, there were no significant differences in target gene expression levels between cells that had been transfected with ER alpha and the vector control. Gene expression levels in the target genes were visibly increased at the 24-hour exposure mark in both transfection groups in comparison to the 0- and 6-hour time points, however only a fraction of these increases were found to be statistically significant. These gene expression patterns are not only consistent with previous studies examining target gene expression in BPA-treated hepatic cell lines, but more importantly, suggest BPA does not act via ER alpha to orchestrate the epigenetic changes seen in vitro. BPA may interact with a different ER isoform or an unknown target to create the observed “super promoters” at target genes, reinforcing the promiscuity of BPA and other xenoestrogens in facilitating epigenetic modifications, and ultimately, disease phenotypes.
SAT-238 Congenital Nephrogenic Diabetes Insipidus with First Presentation as an Adult: A Case Report
Authors: Liu Yuan-yuan , Sargious Peter , Kline Gregory A , Leung Alexander A
Published: May 2020

Congenital Nephrogenic Diabetes Insipidus with First Presentation as an Adult: A Case Report

Background:

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited condition, usually presenting during the first year of life. It is characterized by a renal insensitivity to arginine vasopressin. About 90% of patients are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. Females are typically asymptomatic. Here, we report female case of NDI initially presenting and diagnosed in an adult woman.

Clinical Case:

A previously well 47-year-old woman of Italian descent underwent an elective laparoscopic repair of an abdominal hernia. Her medical history included obesity and migraine headaches. She was not taking any medications prior to admission. She had a bowel perforation 6 days after surgery, necessitating an emergency right hemicolectomy and small bowel resection. Upon instituting bowel rest with nil per os (NPO), she developed severe hypernatremia (Na+ 163 mmol/L) with polyuria (>6 L/day) and dilute urine (osmolality 174 mmol/kg). Further inquiry revealed that the patient routinely drank at least 10 L/day of fluids throughout her entire adult life. Her family history was remarkable for polydipsia affecting at least additional six people across three generations (including her son, her mother, 3 maternal uncles and 1 nephew). Following administration of desmopressin 1 ug subcutaneously, her urine remained inappropriately dilute (osmolality 160 mmol/kg) with no significant change in urine output (rate 350 mL/h for 3 hours). Her arginine vasopressin level was detectable (3.2 pmol/L, reference range 0.8–3.5 pmol/L), consistent with nephrogenic diabetes insipidus. Subsequent molecular analysis of the AVPR2 gene, located on chromosome Xq28, confirmed a pathogenic mutation (c.253G>A), consistent with a p.Asp85Asn substitution resulting in decreased binding affinity between the V2 receptor and arginine vasopressin. Thus, X-linked NDI was diagnosed according to the patient’s presentation, compatible family history, and genetic analysis. When she was able to eat and drink ad lib again, a low-salt, low-protein diet along with a trial of a thiazide diuretic were recommended. The patient remained well with 3 years of follow-up.

Conclusion:

The diagnosis of congenital NDI may be delayed until adulthood because of a relatively mild phenotype and compensatory drinking behavior, so that the disorder will not be clinically apparent until a person is deprived of free water. Men and women alike can be affected by this X-linked dominant condition which should be considered in any polyuric, hypernatremic hospitalized patient.
SUN-389 Trends in Osteoporosis Treatment Uptake and Persistence Among Postmenopausal Women in the U.S., 2010–2015
Authors: Kim Min , Park Andrew , McGrath Leah , Wiener Catie , Balasubramanian Akhila , McDermott Michele , Deignan Cynthia , Brookhart Alan
Published: May 2020

Background: Over the last several years, the approval of new pharmacotherapies, changes to health plan formularies limiting treatment access, the emergence of new evidence related to medication safety and effectiveness, and updates to clinical practice guidelines may have influenced osteoporosis treatment patterns. Sankey visualizations were used to depict postmenopausal (PM) women’s osteoporosis treatment journeys, from treatment uptake, patterns of transition, to persistence. Methods: We conducted a retrospective analysis of all PM women (aged 55+) who newly initiated five antiresorptive treatments between October 1, 2010 and September 30, 2015 using patient and prescription data from the Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental databases. We identified women who were continuously enrolled in the health plan for one year prior to the date of treatment initiation (index date) and were treatment-free during this period. Treatment states were evaluated cross-sectionally at six-month time points; treatment switches and gaps in therapy between time points were not captured. Persistence was defined as a patient being on the same treatment at a given follow-up time point as compared to the treatment they were on at the index date. Results: Among women newly initiating any of the five antiresorptive therapies, alendronate (53%) remained the most commonly prescribed therapy, followed by ibandronate (13 %), zoledronic acid-ZA (12%), risedronate (11 %), and denosumab (11%). New initiation of alendronate was high across all age, prior fracture history, and osteoporosis diagnosis subgroups (range: 45–68%). From 2010 to 2015, new uptake of denosumab increased by 13%, while ZA uptake declined by 10%. A higher proportion of denosumab users were ≥ 65 years (denosumab: 59%; ZA: 54%; alendronate: 46%) and had a prior history of fracture (denosumab: 30%, ZA: 25%; alendronate: 19%) compared to bisphosphonate users. Two-year persistence was highest among women initiating denosumab (58%), followed by ZA (48%), alendronate (32%), ibandronate (30%), and risedronate (25%). Persistence was lowest for oral bisphosphonate users (alendronate range: 30–33%), irregular among ZA users (range: 29–49%) and higher for denosumab users across all subgroups (range: 46–59%). From 2010 to 2014, persistence improved for all therapies, except among ZA users, which declined by 9%. Conclusions: Little has changed in the prescribing patterns and patient profiles of PM women newly initiating antiresorptive therapies over five years from 2010–2015. Alendronate remained the most commonly prescribed therapy despite lower rates of persistence, with similarly high uptake regardless of risk for fracture. Denosumab was primarily prescribed to women at higher risk for fracture, and persistence was higher compared to other therapies across all subgroups.
SAT-612 Features of the Severity of Cardiovascular Remodeling and Metabolic Disorders in Hypertensive Patients with Obesity in the Presence of Two Unfavorable Genotypes of the ADIPOQ and IRS-1 Genes
Authors: Shalimova Anna , Psarova Valentyna , Kyrychenko Nataliia , Kochuieva Maryna
Published: May 2020

The results of a number of studies have shown that in arterial hypertension (AH), G/T and T/T genotypes of the adiponectin gene (ADIPOQ) and Gly/Arg and Arg/Arg genotypes of the insulin receptor substrate 1 gene (IRS-1) are associated with a greater severity of metabolic disorders and hemodynamic parameters compared with G/G and Gly/Gly genotypes of these genes.

The aim of the study: to evaluate the severity of cardiovascular remodeling and metabolic disorders in hypertensive obese patients in the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes.

Methods: We examined 300 AH patients: 200 patients with AH and obesity, 50 patients with AH and normal body weight, 50 patients with AH and overweight, 40 patients with AH, obesity and type 2 diabetes mellitus (DM2), 30 healthy individuals. The polymorphisms of the ADIPOQ and IRS-1 was assessed by molecular genetic method.

Results: It was found that in all groups of hypertensive patients, regardless of body weight and the presence of DM2, the simultaneous presence of two unfavorable genotypes of the ADIPOQ and IRS-1 genes occurred significantly more often than in healthy individuals: in 41% of AH patients with obesity, 30% of AH patients with normal weight, 40% of AH with overweight, 57.5% of AH with obesity and DM2 vs. 13.3% of healthy individuals. In hypertensive patients, in the presence of overweight and obesity, the frequency of combination of the two unfavorable genotypes of these genes was significantly higher than in AH patients with normal body weight.

Conducting comparative evaluation of AH patients with obesity depending on the presence of two unfavorable genotypes or two protective genotypes of the ADIPOQ and IRS-1 genes showed that carriers of the combination of the G/T + T/T genotype of the ADIPOQ and the Gly/Arg + Arg/Arg genotype of the IRS-1 had a higher body mass index, more pronounced insulin resistance, cardiovascular remodeling, adipokine imbalance, impaired carbohydrate and lipid metabolism.

Conclusions: In AH patients, the frequency of the simultaneous presence of two unfavorable polymorphisms of ADIPOQ and IRS-1 genes was higher than in healthy individuals. In AH patients with overweight and obesity, the frequency of combination of the two unfavorable genotypes of the ADIPOQ and IRS-1 genes was significantly higher than in normal body weight. The presence of a combination of two unfavorable genotypes of the ADIPOQ and IRS-1 genes in patients with AH and obesity was associated with a greater severity of cardiovascular remodeling and metabolic disorders compared with the combination of two protective genotypes of these genes.
SAT-372 A Case of Hypercalcemia Secondary to Rhabdomyolysis Induced by Heroin Use
Authors: Zuniga Gabriela , Garay Paola Andrea Sanchez , Rios Paola , Lichtenberg Robert
Published: May 2020

Background: Rhabdomyolysis is a potential life threatening condition defined as injury of the skeletal muscle, which results in the release of intracellular contents into the circulation. This muscle injury is often associated with the development of myoglobinuria, electrolyte abnormalities, and often ARF; it can be caused by diverse mechanisms including drugs and toxins. We present a case of rhabdomyolysis complicated by hypercalcemia and ARF in a patient with a history of polysubstance abuse after using intravenous heroin.

Case: A 28 y/o male with h/o polysubstance comes to the ED with c/o fatigue, nausea, vomiting and decreased urine output for about 5 days; patient acknowledged using heroin and afterwards he developed weakness and tenderness in upper and lower extremities. Additionally he admitted cocaine and marijuana abuse. On physical exam vital signs were unremarkable and he had some mild tenderness to palpation mostly of the quadriceps bilaterally. Laboratory data was significant for acute kidney injury (cr 11.33 mg/dl, n: 0.7–1.5 mg/dl) and CPK 171920 u/l (n: 22–269 u/l). He received 2 L of NS in the ED and was started on NS at 100cc/hour.

He underwent hemodialysis on day 2; initially he was treated for hypocalcemia with calcium and vitamin D supplementation until day 11 were hypercalcemia (calcium 12.7 mg/dl, n: 8.7–10.3 mg/dl; ionized calcium 1.7 mmol/l, n: 1.12–1.32) was noted; this was associated with concomitant suppression of PTH (5 pg/ml, n: 10–65 pg/ml). He remained asymptomatic from calcium abnormalities during his hospitalization, his urine output recovered progressively, hemodialysis was discontinued on day 13. Upon discharge was recommended to f/u with nephrology.

Discussion: Various neurological and neuromuscular complications of heroin abuse have been described; one of these is rhabdomyolysis; its pathophysiology in heroin abuse is thought to be multifactorial; including acidosis, hypoxia, muscle compression and adulterants found in heroin. Narcotics may also have direct cell toxicity and alter membrane transport. Usually upon initial presentation hypocalcemia is one of the most common electrolyte imbalances seen with rhabdomyolysis. The proposed mechanism is precipitation of serum calcium salts in necrotic muscle. This may be followed by hypercalcemia during the diuretic phase of ARF which appears to be a relatively unusual complication associated with the presence of severe muscle damage due to metastatic calcium salts that are liberated from the necrotic muscle and the return to the serum.

Conclusion: This case report highlights the importance of recognizing potential electrolyte imbalances in patients with rhabdomyolysis; it appears, that concomitant rhabdomyolysis and ARF are needed for a patient to develop hypercalcemia.

Serum calcium should always be routinely measured and the appropriate treatment should be implemented to improve outcomes.
MON-032 Excessive Ovarian Sympathetic Activity Impairs Embryonic Development and Causes Reproductive and Metabolic Dysfunction
Authors: Manti Maria , Pui Han-Pin , Edström Sonja , Risal Sanjiv , Lu Haojiang , Lindgren Eva , Jerlhag Elisabeth , Benrick Anna , Deng Qiaolin , Stener-Victorin Elisabet
Published: May 2020

Nerve growth factor is a member of the neurotrophin family and within the ovary, it plays an important role in sympathetic innervation and in the development and maintenance of folliculogenesis. Despite its critical role, excessive levels of ovarian NGF may lead to ovarian pathology and to the development of features of polycystic ovary syndrome (PCOS), which is the most common endocrine disorder among women of reproductive age. Here, using a transgenic mouse model overexpressing NGF selectively in the ovary (17NF mice), we studied how ovarian sympathetic hyperactivity affects embryonic development and reproductive and metabolic function in adulthood. Firstly, we showed that ovarian NGF excess caused growth restriction in the developing female fetuses, which was driven by defects in the placenta function. Moreover, the 17NF fetuses experienced a reduction of germ cell number along with delayed gonocyte and primary oocyte maturation. The adult 17NF mice displayed irregular cyclicity and aberrant ovarian expression of steroidogenic genes and epigenetic markers. The ovarian sympathetic hyperactivity also led to increased systemic sympathetic outflow, indicated by increased circulating dopamine levels, and to metabolic dysfunction in adulthood. The 17NF mice had increased adiposity, impaired glucose metabolism and decreased energy expenditure. The subcutaneous and parametrial fat depots displayed impaired function due to ovarian NGF excess, wherein the subcutaneous fat increased mass by enhanced preadipocyte differentiation and enlarged adipocyte size, while the parametrial fat had smaller adipocyte size and a modest increase in stimulated lipolysis. These defects also led to hepatic steatosis. Overall, our findings indicate that ovarian sympathetic hyperactivity has deleterious effects on whole-body homeostasis and leads to impaired embryonic development and to reproductive and metabolic defects in adult life.