bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB102 Metformin-Induced Weight Loss in Patients With or Without Type 2 Diabetes/Prediabetes
Authors: Chukir Tariq , Mandel Lindsay , Al-Mulla Nada , Kumar Rekha Babu , Igel Leon I , Waitman Jonathan , Aronne Louis J , Shukla Alpana P
Published: May 2020

Background: Metformin is the first-line pharmacologic treatment for type 2 diabetes (T2DM). Its use has been associated with significant weight loss in patients with obesity with or without T2DM. However, it is unknown whether weight loss outcomes differ with metformin monotherapy in patients with excess weight and euglycemia compared to patients with T2DM/prediabetes (PreDM).

Methods: This is a retrospective study of new patients with overweight/obesity seen at an academic weight management center between 4/1/14-4/1/16. Patients who received metformin as a sole pharmacotherapy were identified, and data pertaining to demographics, medications, comorbidities, and weight changes during 1-year follow-up were obtained from their electronic medical records. Mean and categorical weight losses were compared between patients with and without T2DM/PreDM. We also assessed the rate of metformin discontinuation due to side effects, lack of efficacy or other reasons in the entire cohort.

Results:

Of 1056 patients who were prescribed metformin for weight loss over the 2-year study period and had at least 2 office visits, 99 (9.38%) discontinued the medication due to the following reasons: side effects 59 (60%), lack of efficacy 15(15%) or other reasons 25(25%). A total of 254 patients received metformin as a sole pharmacotherapy for weight loss and had 6 and/or 12-month follow-up visits. In this cohort, the mean age was 53 ± 14 years, 66% were women. The mean BMI was 35 ± 7 kg/m2. The average percent weight loss at 6 and 12 months were similar in patients with euglycemia compared to patients with T2DM/PreDM (6.12% ± 5.68 vs 6.36% ± 6.52 p=0.73 at 6 months; 7.13% ± 6.42 vs 7.23% ± 7.74 p=0.93 at 12 months). The proportion of patients who experienced ≥5% weight loss was similar in both groups at 6-month (54.04 vs 54.55%, p=0.94) and 12-month follow-up visits (63.95 vs 55.42%, p=0.26). The proportion of patients who experienced ≥10% weight loss was also similar in both groups at 6-month (25.81 vs 27.72%, p=0.81) and 12-month follow-up visits (33.72 vs 30.12%, p=0.62).

Discussion: Among patients with obesity, metformin as a sole pharmacotherapy for weight loss achieved significant and comparable weight reduction in patients with or without T2DM/PreDM. Further studies are needed to evaluate the long-term weight loss in patients with euglycemia.
SUN-LB5 GnRHR ECL-2 Epitopes Targeted by Activating Autoantibodies in Polycystic Ovary Syndrome
Authors: Guo Yankai , Deng Jielin , Gege Zhang , Li Hongliang , Weeden Elizabeth A , Aston Christopher E , Burks Heather R , Craig Tasha B , Yu Xichun , Kem David C
Published: May 2020

Background: Activating autoantibodies (AAb) are directed to the gonadotropin releasing hormone receptor second extracellular loop (GnRHR-ECL2) and are pathogenic when induced in rats. We previously reported GnRHR-ECL2-AAb were elevated in sera from patients with PCOS (Rotterdam criteria) compared to ovulatory infertile controls (OIC). Methods:Human studies: ELISA detection of GnRHR Abs used a synthetic h-GnRHR-ECL2 28 mer peptide (LifeTein) as the target antigen. We assayed AAb activity in GnRHR transfected cells using a GeneBLAzer FRET assay (Invitrogen). ELISA AAb epitope locations on the ECL2 were identified on a minipin plate (pins 1-11 containing sequential 2 aa offsetting octapeptides, Mimotope, Inc) using sera from 30 PCOS subjects, 33 OIC and 18 normal controls (NC). Results:Human sera: An ELISA assay for GnRHR-ECL2-AAbs in the PCOS group was markedly higher than the NC group (P<0.0001) and the OIC subjects (P<0.003). The minipin data demonstrated one or more positive OD peaks on pins 4 (20%), 5 (47%) and 8 (47%) which shared L-aa sequences FSQC or CSFSQ. OIC had only 5 subjects with peaks at minipins 4 or 5 and NC had only 3 lower peaks and one with higher OD values over all minipins. GnRHR-AAb Specific Activity (SA) was estimated by measuring serum activity before and after suppression of AAb sensitive activity by addition of retro inverso D-aa (RID) peptides. These were specifically designed to mimic and decoy the AAb L-aa epitope sequences of pins 5 and 8). SA was measured in 10 selected PCOS and 10 OIC subjects who had positive ELISA values. The baseline activity in the PCOS group was significantly higher than OIC (P < 0.01) and dropped 50% with preincubation with peak 5 RID and 25% with peak 8 RID. The addition of both peak 5 and peak 8 RID suppressed the PCOS group activity to OIC levels (P > 0.2). There was no significant change in activity in the OIC subjects by the addition of peaks 5 + 8 RID peptides. Conclusion: These PCOS GnRHR-AAb data confirm the presence of significant activation of the GnRHR by AAb targeted to specific epitope(s) proximate to the disulfide GnRHR-ECL2 linkage to the nearby ECL1. These data are compatible with a pathophysiological role for GnRHR-AAb in PCOS and may provide both diagnostic and therapeutic opportunities.
MON-LB105 Resident Obesity Management: Comfort Correlates With Action
Authors: Hoppenfeld Mita Shah , Abou-Arraj Nadeem E , Hauser Michelle E
Published: May 2020

The projected prevalence of obesity in the US is 50% by 2030.1 Little data exists on resident physician obesity management in their primary care clinics.2 We aimed to explore internal medicine (IM) resident comfort, knowledge, and treatment practice of obesity in primary care.

IM residents at one academic medical center (N=125), at 5 primary care sites were anonymously surveyed about knowledge, comfort, and practice behaviors around obesity management. In this exploratory analysis, respondents self-reported comfort with lifestyle counselling and weight management medication (WMM) prescription on 4-point Likert scales; scores were combined into an overall Comfort Score (CS). Correlation analysis (Pearson’s correlation) compared CS with the following Clinical Actions: referral to lifestyle specialists, lifestyle counseling, WMM prescription, and bariatric surgery referral.

The response rate was 70/125 (56%). Most residents (91%) reported discomfort with prescribing WMMs and most (84%) had never prescribed one. While most residents (81%) were “comfortable” or “somewhat comfortable” with lifestyle counseling, only 33% reported consistently providing it. Of the 31% of residents that correctly identified indications for bariatric surgery, only 9% reported referring patients they considered appropriate for surgery. Notably, a higher CS was significantly correlated with more frequent bariatric surgery referrals (r = 0.29; p = 0.015), lifestyle counselling (r = 0.33; p = 0.004), WMM prescription (r = 0.32; p=0.006), and lifestyle specialist referral (r = 0.25; p = 0.035). Reported barriers to lifestyle counseling were lack of time (93%), poor familiarity with resources (50%), and lack of training in motivational interviewing (36%). Barriers to WMM prescription were unfamiliarity with the medications (84%) and side effect concerns (61%). Finally, 90% desired more training in pharmacotherapy, and 77% wanted more information on referral processes for surgical and medical interventions.

Most residents surveyed do not feel adequately prepared to provide evidence-based management of obesity via lifestyle changes counseling, WMM prescription, or specialty care referral. Comfort and knowledge of system processes/resources and WMMs are critical to resident management of obesity. These are potential targets for educational intervention in residency curricula that may improve care for patients with obesity.

Citations: 1. Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. 2019;381(25):2440-2450. doi:10.1056/NEJMsa19093012. Huang J, Yu H, Marin E, Brock S, Carden D, Davis T. Physicians’ Weight Loss Counseling in Two Public Hospital Primary Care Clinics. Acad Med. 2004. doi:10.1097/00001888-200402000-00012
MON-LB125 Dka From a Ketogenic Diet and Intermittent Fasting or Ketosis-Prone Diabetes?
Authors: Athonvarangkul Diana , Gossmann Mona , Cohen Kenneth
Published: May 2020

Background: Ketogenic diets and intermittent fasting (IF) are popularly used for weight loss. Generation of ketone bodies for fuel from fatty acid oxidation underlies both diets, combined or separately. We present a case of a prediabetic patient admitted for DKA after starting a combination keto/IF diet. Clinical Case: A 63-year-old man with hypertension, prediabetes, and alcohol use was admitted from clinic after receiving lab test results consistent with diabetic ketoacidosis (DKA). Two months ago, he had started a keto diet with IF (5 days/week, 18 hour fast/day) and achieved weight loss of 20 pounds. He reported polyuria and polydipsia, which was attributed to the recent initiation of chlorthalidone. Laboratory testing revealed glucose 519 (</= 199 mg/dL), bicarbonate 12 (20-30 mmol/L), creatinine 1.6 (0.5-1.5 mg/dL), anion gap of 23 (6-16 mEq/L), HbA1c 12.2% (4-5.6%), c-peptide 1.37 (0.80-3.85 ng/mL) with glucose 294, GAD65 Ab <5 (<5 IU/mL), IA2 Ab <5.4 (<5.4 U/mL), Insulin Ab <0.4 (<0.4 U/mL), triglyceride 546 (0-199 mg/dL), LDL-d 176 (0-129 mg/dL), cholesterol 310 (0-199 mg/dL) and HDL 39 (>/= 40 mg/dL). Workup for precipitating causes of DKA was negative including normal lactate, lipase and troponin. The patient was managed with an insulin drip and discharged on subcutaneous insulin (Lantus 45 units/day, Aspart 13 units with meals) and metformin. The patient re-introduced carbohydrates into his diet after meeting with the nutritionist. Eight weeks later, the HbA1c decreased to 6.6% and insulin was significantly reduced to Lantus 25 units/day. Sixteen weeks after discharge, the HbA1c further declined to 5.1% and Lantus was reduced to 10 units/day. Beta cell function at that time was preserved as evidenced by c-peptide 1.82 ng/mL. Insulin therapy was discontinued and the patient was closely monitored for urinary ketones and recurrence of hyperglycemia, neither which have developed. Conclusion: This is a unique case of DKA precipitated by a keto/intermittent fasting diet, without the use of SGLT2 inhibitor. Interestingly, previous metabolic studies show that nutritional ketosis typically generates low levels of serum ketones without a clinically significant anion gap metabolic acidosis. With negative beta cell autoantibodies and preserved beta cell function, this presentation is also consistent with ketosis-prone diabetes type 2B. It is possible that nutritional ketosis triggered the onset of KPD, although the mechanism remains unclear particularly since it is known that lipotoxicity is not pathogenic in the development of KPD. References: 1. Bueno NB et al. Br J Nutr. 2013;110(7):1178-1187. 2. Cahill GF Jr. Annu Rev Nutr. 2006;26:1-22. 3. Gaba R et al. Expert Rev Endocrinol Metab. 2019;14(1):43-48.
MON-LB7 Assessment of Endothelial Dysfunction by Flow Mediated Dilation in Postmenopausal Women
Authors: Chopra Seema , Sharad Piyushi , Bahl Ajay , Sikka Pooja
Published: May 2020

Menopause is defined by the World Health Organization as the permanent cessation of menses as a result of the loss of ovarian follicular Function or surgical removal of ovary. Menopausal health demands priority in Indian scenario due to increase in life expectancy and growing population of menopausal women. It is well known that cardiovascular risk is higher in postmenopausal women than in premenopausal women, but it is unclear how much of the elevated risk is related to aging, menopause itself or presence of other confounding factors. Endothelial dysfunction is one of the most important predictors for determining early atherosclerotic risks as it precedes overt vascular disease by years and may itself be a potentially modifiable risk factor. Although no gold standard for the measurement of endothelial function exists, the measurement of flow mediated dilation (FMD) in the brachial artery, assessed with Doppler ultrasonography, is the most studied method and seems most promising for clinical application.objective - To compare effect of menopause on endothelial dysfunction by brachial artery flow mediated dilation (BAFMD) in postmenopausal women versus menstruating non-diabetic, non-obese females of same age group. Methodology: We conducted a case control study in Departments of Obstetrics & Gynaecology and Cardiology, PGIMER, Chandigarh.Subjects were menopausal women between 45- 55 years of age.Controls included the women of same age group who had not attained menopause.To detect a statistical significant difference of approximately 4-8% between cases and controls,50 women were recruited in both groups with a power of 90% and confidence interval of 95%. The study was approved by the ethics committee of the institute. Effect of menopause on BAFMD, NMD (nitro-glycerine mediated dilation), FRS (Framingham Risk score) and individual components of FRS was studied.Results: A statistically significant negative correlation was found between BAFMD and FRS, BAFMD and age and BAFMD and duration of menopause.On studying the effects of FRS, individual components of FRS and duration of menopause on smooth muscle function, statistically significant negative correlation was found between NMD and FRS and NMD and AgeConclusion:It was concluded that the menopausal status does not affect endothelial function in women who are at low risk of cardiovascular disease but it affects the vascular smooth muscle function. We also found significant correlation between FMD and NMD (p = 0.00) signifying that both endothelial dysfunction and vascular smooth muscle dysfunction are inter-related. On evaluating the strength of correlation of FMD with FRS, different parameters of FRS and duration of menopause, FMD was found to have a statistically significant negative correlation with all these parameters.
MON-LB79 Do Ultrasound Patterns and Clinical Parameters Modify the Probability of Thyroid Cancer Predicted by Molecular Testing in Thyroid Nodules With Indeterminate Cytology?
Authors: Figge James J , Gooding William E , Burman Kenneth D , Mayson Sarah , Scheri Randall P , Sipos Jennifer A , Sippel Rebecca S , Steward David L , Yang Samantha Peiling , Yip Linwah , Nikiforov Yuri E , Carty Sally E
Published: May 2020

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further modify the risk of cancer in nodules predicted to be positive or negative by molecular testing remains unknown. Aim: To test if clinical parameters, including age, gender, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] system vs American College of Radiology TIRADS), radiation exposure, and family history of thyroid cancer (TC) can modify the probability of TC or NIFTP predicted by MT in thyroid nodules with indeterminate cytology. Methods: We studied 257 thyroid nodules from 10 study centers with fine-needle aspiration (FNA) yielding indeterminate cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression were used for data analysis. Results: In this group of thyroid nodules, out of all parameters studied using univariate regression, patient gender, age, and Bethesda category were significantly associated with TC/NIFTP probability (P<0.05 for each). The ATA US patterns showed a positive trend (P=0.1211), whereas TIRADS was not predictive (P=0.3135). A multivariate regression model incorporating the four most informative covariates (gender, age, Bethesda category, and ATA US patterns) (model #1) yielded a C index=0.653; R2=0.108. Male gender and Bethesda category V significantly increased risk, and age demonstrated a nonlinear risk profile. When TSv3 was added to model #1, the C index increased to 0.888; R2=0.572. However, age (P=0.341), Bethesda category (P=0.272), and the ATA US patterns (P=0.264) had limited predictive ability in comparison with TSv3, which dominated the predictive performance (P<0.001). Gender was the only parameter showing tendency for significance beyond MT (P=0.095). The most parsimonious model incorporated gender and TSv3 (C index=0.889; R2=0.588). Conclusions: While often useful in selecting thyroid nodules for FNA, neither the ATA US nor the TIRADS scoring systems were informative in further predicting TC/NIFTP in thyroid nodules with indeterminate FNA cytology. Although age and Bethesda category were associated with TC/NIFTP probability on univariate analysis, they had limited incremental value above the high predictive ability of TSv3. Gender was the only parameter with potential contribution to predicting TC/NIFTP in addition to MT.
SUN-033 A Rare Case: Bone Pain and Continued Linear Growth in a Young Adult Male Due to Aromatase Deficiency
Authors: Lee Ju-Hao , Lee Ni-Chung , Tung Yi-Ching
Published: May 2020

Introduction:

Aromatase, the product of CYP19A1, catalyzes the conversion of androgens to estrogens. 46, XX infants with aromatase deficiency, due to androgen excess, present with ambiguous genitalia at birth. In 46, XY individuals, however, the subtle phenotypic features make the diagnosis even more difficult. Less than 15 male cases were reported in the literature and we present the first case of aromatase deficiency diagnosed in Taiwan.

Clinical Case:

A 23-year-old man, Burman overseas student of Chinese descent, presented to an orthopedist with a two-year history of left ankle pain, which was diagnosed as gout by his previous physician. Unexpectedly, unfused growth plates were discovered so he was referred to our pediatric endocrine clinic for evaluation. Reviewing his past history, we learned he is the third child of consanguineous parents. His mother experienced deepening of voice during this pregnancy which resolved following parturition. He was 177 cm tall at the age of 19. At the time he presented to our clinic, he weighed 95.3 kg and was 183 cm tall. Physical exam showed the ratio of U/L segment to be 0.82, stretched penile length 6.5 cm, bilateral testes > 25 mL, pubic hair at Tanner stage V, and presence of genu valgum. The skeletal age was 14 years and 6 months. Labs showed FSH 19.7 IU/L (0.7–11.1), LH 8.18 IU/L (0.8–7.6), total testosterone 1335 ng/dL (240–871), estradiol <20 pg/mL, DHEA-S 13.41 μmol/L (6.5–14.6), androstenedione 5.73 nmol/L (3.5–9.8) and 17-OH progesterone 6.55 nmol/L (2–10). GnRH (100 μg i.v) stimulation test showed a supranormal basal FSH level and a normal to higher LH response (FSH at baseline/peak were 23.0/38.6 IU/L; LH at baseline/peak were 8.81/47.7 IU/L). Under the clinical suspicion of aromatase deficiency, we performed genetic sequencing of CYP19A1 (NM_031226) and found a homozygous missense variant c.1108G>A (V370M), a previously reported pathogenic mutation.

A diagnosis of aromatase deficiency was made. He also had hypertension (156/87 mmHg), dyslipidemia (T-cholesterol 236 mg/dL, LDL-C 175 mg/dL) and insulin resistance (AC glucose 87 mg/dL, insulin 23.5 μU/mL, HOMA-IR 5.0, Hb1Ac 5.6%). Bone mineral density of lumbar spine (DXA) showed a T-score of -2.8, consistent with the diagnosis of osteoporosis.

Conclusion:

Estrogen is pivotal for epiphyseal closure in both sexes. As demonstrated in this case, estrogen deficiency in men results in tall stature and eunuchoid habitus, while it is also associated with low bone density and metabolic syndrome. The gonadotropin response in this report suggests the inhibitory role of estrogen in the male HPG axis. Clinicians may consider this rare diagnosis for men in their late teens or early twenties, who have spontaneous initiation of puberty, presenting with bone pain and continued linear growth.
MON-LB040 Challenge in Diagnosing and Treating of Mediastinal Paraganglioma
Authors: Alomair Basil , Jammah Anwar
Published: May 2020

Paraganglioma is a rare type of neuroendocrine tumor of the autonomicnervous system.1 It is extremely rarely present in mediastinum (less than2%).2Case report We report a 43 years-old woman, she was referred to our clinic with ahistory of high blood pressure (BP) for two years, accompanied by spellsof sweating, headache, anxiety and palpitation. She was provisionaldiagnosed with essential hypertension and was on four medications onmaximum dose.The patient declined any previous surgical history, and review of systemswas unremarkable. On examination, she was conscious and alert. Her vitalsigns were within normal limit. She reported to our clinic with homereadings of BP ranging from 150-180 mmHg systolic and 90-100 mmHgdiastolic.Initial investigations of basic chemistry, renal profile, hormonal profile,aldosterone, and renin were within the normal range.Serum Normetanephrine was 800 ng/L (normal < 180 ng/L), 24 hoursurine of Normetanephrine was 5205 microgram/24 hours (normal < 600microgram/24 hours), and 24 hours urine Metanephrine was withinnormal. CT scan of the adrenal and MRI abdomen showed normal adrenalglands and no mass in the abdomen. MIBG scan was normal for the wholebody. An unusual location of the Paraganglioma was suspected, andfurther images were carried on. A CT chest showed 4x4 cm posteriormediastinal mass in area of Aortopulmonary window, adherent toposterior wall of Aorta and pulmonary artery. Positron EmissionTomography (PET) scan was done prior to the surgery.Surgical resection of the mass with reconstruction of both pulmonaryartery and pericardium was done without any complications. Moreover,histopathology confirmed the diagnosis of Paraganglioma.The patient was followed up with a CT scan six months post-operativelyas an outpatient, along with 24-hour urine Metanephrine and Normetanephrine. All labs and imaging were normal. The patient hadanother Normetanephrine measurement twelve months later and it wasnormal. Now, she has been followed for seven years with no moresymptoms and normal BP readings. All of her antihypertensive agentswere discontinued. ConclusionWe experience an unusual location of Paraganglioma at the mediastinum,which is representing less than 2% of all Paraganglioma. However, in thepresence of characteristic of Paraganglioma symptoms, a thoroughassessment should be carried out and such location of mediastinumshould be suspected and investigated.References:1. Institute NC. Pheochromocytoma and Paraganglioma Treatment(PDQ®)-Health Professional Version. https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq. Published 2019. Accessed February 1, 2020.2. Paraganglioma: An Uncommon Cause of Mediastinal Mass. -PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/32000513.Accessed February 1, 2020.
SAT-LB49 Persistent vs Recurrent Cushing’s Disease Diagnosed Four Weeks Post-Partum
Authors: Nosova Emily V , Bederson Joshua B , Cheesman Khadeen Christi
Published: May 2020

Background: Cushing’s disease (CD) recurrence in pregnancy has previously been described and is thought to be associated with predictable estradiol fluctuations during gestation. CD recurrence in the immediate post-partum period has been reported once, but never in a patient with documented dormant disease during pregnancy.Clinical Case: A 30 year old woman with recently diagnosed pre-diabetes presented with weight gain, dorsal hump, depression, oligomenorrhea, and lower extremity weakness. Diagnostic tests were consistent with CD. Results included: three elevated midnight salivary cortisols: 0.33, 1.38 and 1.10 ug/dL (<0.010 - 0.090); 1-mg dexamethasone suppression test (DST) with cortisol 14 ug/dL (<1.8); elevated 24-hr urine cortisol 825 ug/24 hr (6-42); and ACTH 35 pg/mL (7.2-63.3). MRI of the pituitary gland revealed a left 4mm focal lesion. After transsphenoidal resection (TSA), day 1, 2, and 3 morning cortisol values were 18, 5, and 2 ug/dL, respectively. Pathology did not show a definitive pituitary neoplasm. She was rapidly titrated off hydrocortisone (HC) by six weeks post-resection. Her symptoms steadily improved. She resumed normal menses and conceived unexpectedly around 3 months post-TSA. She complained of severe fatigue in her late 2nd trimester. Given low 24-hr urine cortisol of 15 ug/24 hr at 36 weeks gestation, she was started on HC. She was induced at 40 weeks gestation for oligohydramnios and subsequently delivered a healthy baby boy. HC was discontinued immediately after delivery. Around four weeks post-partum she developed symptoms concerning for CD. Diagnostic tests showed elevated midnight salivary cortisol of 0.206 and 0.723 ug/dL and 24-hour urine cortisol of 400 ug/24 hr. MRI pituitary illustrated a 3mm adenoma in the left posterior gland which was thought to represent growth of residual tumor not clearly seen on post-op MRI. During repeat TSA, a discrete lesion was found and resected. Pathology confirmed corticotroph adenoma with MIB-1 < 3%. Post-operative day 1, 2, and 3 cortisol levels were 26, 10 and 2.8 ug/dL, respectively. She was tapered off HC within one month. Her symptoms improved only slightly and she continued to report weight gain, muscle weakness, and fatigue. Three months after repeat TSA, biochemical data showed 1 out of 2 midnight salivary cortisols elevated at 0.124 ug/dL and elevated urine cortisol of 76 ug/24 hr. MRI pituitary demonstrated a 3 x 5 mm left enhancement, concerning for residual or enlarged persistent tumor. Conclusion: We describe the first report of recurrent CD that was quiescent during pregnancy, and subsequently diagnosed in the immediate post-partum period. Treatment options for persistent or recurrent CD include aggressive surgical resection, radiation and/or medical therapy. In the context of additional family planning for this otherwise healthy, reproductive-age woman, ideal management options remain uncertain.
MON-215 Clinical Factors Associated with Insulin Secretion and Sensitivity in Patients with Primary Aldosteronism
Authors: Tsurutani Yuya , Katsuragawa Sho , Takiguchi Tomoko , Saito Jun , Omura Masao , Nishikawa Tetsuo
Published: May 2020

Introduction: Primary aldosteronism (PA) is associated with an increased risk of impaired glucose tolerance or type 2 diabetes mellitus. Previous studies have reported that impaired insulin secretion and insulin sensitivity in PA may lead to impaired glucose tolerance. However, the relationship between PA and glucose tolerance, and the factor associated with these glucose metabolism abnormalities is not well understood. In particular, few studies have analyzed the association between aldosterone excess and insulin sensitivity or resistance after the adjustment for other clinical variables. In this study, we analyzed the associations between multiple clinical variables observed in PA and the indices of insulin sensitivity and resistance, using the result of 75 g oral glucose tolerance test (OGTT).Method: This was a retrospective observational study that analyzed the data of 646 patients with PA who underwent adrenal venous sampling and 75 g OGTT. The insulinogenic index and Matsuda index, indices of insulin secretion and sensitivity, respectively, were calculated from the results of a 75 g OGTT. Correlations between these indices and the multiple clinical variables were analyzed. In addition, we performed multiple regression analyses to identify the independent explanatory variables of these indices.Results: Insulinogenic index had positive correlations with the body mass index (BMI), alanine aminotransferase (ALT) level, triglyceride (TGL) level, and potassium level, and negative correlations with both age and plasma aldosterone concentration (PAC). In a multiple regression analysis, both the age (β = -0.231, p < 0.001) and potassium level (β = 0.175, p = 0.002) were selected as the independent explanatory factors. The Matsuda index had positive correlations with the PAC and cortisol level after a 1 mg dexamethasone suppression test (DST), and negative correlations with BMI, ALT level, TGL level, plasma renin activity (PRA), and potassium level. In a multiple regression analysis, BMI (β = -0.216, p < 0.001), ALT level (β = -0.290, p < 0.001), TGL level (β = -0.225, p < 0.001), the cortisol level after 1 mg DST (β = 0.124, p = 0.009), and PRA (β = -0.119, p = 0.019) were selected as the independent explanatory factors.Conclusion: In PA patients, older age and decreased potassium levels were associated with impaired insulin secretion. An increase in the variables associated with metabolic abnormalities such as BMI, ALT, and TGL were associated with decreased insulin sensitivity. In addition, we found that decreased PRA was associated with increased insulin sensitivity.
SUN-LB126 Real-World Safety and Effectiveness of Insulin Glargine 300 U/ML (Gla-300) in People With Type 2 Diabetes Who Fast During Ramadan
Authors: Hassanein Mohamed , Buyukbese Mehmet Akif , Malek Rachid , Pilorget Valérie , Naqvi Mubarak , Berthou Baptiste , Shaltout Inass , Sahay Rakesh Kumar
Published: May 2020

ORION was a prospective, observational study evaluating the safety and effectiveness of the second-generation basal insulin analog Gla-300 in people with type 2 diabetes (T2DM) who fast during Ramadan. Adults with T2DM who intended to fast for ≥15 days during Ramadan, had taken Gla-300 for ≥8 weeks prior to inclusion, and intended to continue its use during Ramadan were enrolled in 11 countries. During Ramadan, Gla-300 treatment was adjusted as per routine practice by the treating physician. Overall, the majority of people (402 [85%]) fasted for the entire Ramadan period and 10.8% fasted for ≥25 days but with at least one missed day. Mean (SD) age was 54.4 (11.0) years, 51.7% were male, BMI was 29.7 (5.3) kg/m2, and duration of diabetes was 10.7 (7.0) years. Risks of diabetes-related complications associated with fasting were assessed by physicians according to IDF-DAR fasting risk category; risk was low/moderate in 82.8%, high in 14.3%, and very high in 2.9% of people. The proportion of people with ≥1 severe and/or documented symptomatic (SMPG ≤70 mg/dL) hypoglycemia event was low (2.2% [event rate: 0.021 per participant-month (PPM)] in pre-Ramadan, 2.6% [0.039 PPM] in Ramadan and 0.2% in post-Ramadan [0.003 PPM]). Overall, 0.8% (0.005 PPM) of participants experienced severe and/or documented symptomatic hypoglycemia at SMPG <54 mg/dL, and only during pre-Ramadan. No participants had severe hypoglycemia during Ramadan or post-Ramadan; 1 participant had severe hypoglycemia pre-Ramadan. Most of those who experienced symptomatic hypoglycemia during Ramadan did so during fasting hours (11/13 people). Reductions were shown pre- to post-Ramadan for mean (SD) HbA1c (8.10 % [1.29] pre-Ramadan to 7.64 % [1.05] post-Ramadan; change of −0.44 % [0.97]), FPG (144.3 [45.8] mg/dL pre-Ramadan to 128.5 [37.8] mg/dL post-Ramadan; change of −13.5 [44.1] mg/dL), and fasting SMPG (130.7 [32.9] mg/dL pre-Ramadan to 126.8 [28.5] mg/dL post-Ramadan; change of −3.3 [26.6] mg/dL). Mean Gla-300 dose was reduced slightly between pre-Ramadan and Ramadan (25.6 [11.9] U/0.32 [0.14] U/kg pre-Ramadan to 24.4 [11.5] U/0.30 [0.13] U/kg in Ramadan) and returned to 26.0 (12.2) U/0.32 (0.14) U/kg in the post-Ramadan period. AE incidence was low (5.5%); 3 (0.6%) participants had an AE of hyperglycemia, 2 (0.4%) during Ramadan. In this study, performed in a real-world setting, incidence of hypoglycemia was low in people with T2DM treated with Gla-300 who fasted for Ramadan, with no incidence of severe hypoglycemia during the Ramadan period; HbA1c, FPG and fasting SMPG reductions were also observed. Supported By: Sanofi
MON-LB120 MODY3 With Insulin Coding Gene Mutation and Craniofacial Microsomia: A Case Report
Authors: Cao Chenxiang , Han Xueyao , Ma Yumin , Bernet Victor Joseph , Xiao Jianzhong
Published: May 2020

Background: Maturity onset diabetes in young 3 (MODY 3) is caused by mutation of the hepatic nuclear factor 1 alpha (HNF-1A) gene. Craniofacial macrosomia (CFM) is associated with an abnormal development of craniofacial structures during the embryonic period. Maternal diabetes and genetic predisposition have been associated with CFM1. There are rare reports about an association of MODY 3 and CFM. Clinical case: An 11-year-old male patient presented with right side CFM (mild mandibular hypoplasia, internal auditory canal absence, severe pinna hypoplasia, abnormal orbital size and location, O3.M0.E3.N0.S02) noted at 8 months of age. Preoperative examination revealed A1c at 10.9%. After short term intensive insulin therapy, he had standard bread meal test: fasting glucose 8.11 mmol/L, insulin 13.9 mIU/L (3-25), C-peptide 1.25 ng/ml (0.81-3.85); 1 hour glucose 10.05 mmol/L, insulin 27 mIU/L, C-peptide 2.42 ng/ml; 2 hour glucose 8.17 mmol/L, insulin 16.09 mIU/L, C-peptide 2.11 ng/ml. GADA, IAA and ICA were negative. The mother was diagnosed diabetes at age 27years, when the patient was 8-month-old, and received insulin therapy. The mother was blind by age 35years due to diabetic retinopathy and died of DKA at 38-years-old. The patient’s 16-year-old brother had left side CFM (O2.M1.E2.N0.S0) and his OGTT was normal. The father was diagnosed with impaired glucose tolerance. The family had whole genome sequencing by Sanger technique, and resequenced the mutation with side primers. The CGA to CAA mutation was present at the 686 loci of exon 3 of HNF1A gene in the patient and mother. The HNF1A exon 3 mutation of CGA to CAA resulted in the change of arginine to glutamine which by the HGMA database is recognized as a reported MODY3 gene mutation. There was a mutation of G to A in the 4 loci of exon 1 of the insulin coding region in chromosome 11 in both the patient and elder brother. Neither elder brother nor father had the CGA mutation of HNF1A. Conclusion: There has not been a previous report of a relationship between HNF1A and CFM. In this case, the elder brother had CFM without a HNF1A mutation which does not support a connection between CFM and HNF1A. The two brothers both had CFM and insulin coding gene mutations which would represent a new association not previously described. Further testing is needed to confirm a relationship between the two. Reference: 1. Chen Q, Zhao Y, Shen G, Dai J. Etiology and Pathogenesis of Hemifacial Microsomia. J Dent Res 2018; 97(12): 1297-305. 2. Gougoutas AJ, Singh DJ, Low DW, Bartlett SP. Hemifacial microsomia: clinical features and pictographic representations of the OMENS classification system. Plast Reconstr Surg 2007; 120(7): 112e-20e.
SUN-LB137 Endocannabinoids Induce Endoplasmic Reticulum Stress in Hepatocytes and Human Coronary Artery Endothelial Cells
Authors: Richter Angela , Parekh Shrina , Kalidas Poonam Kirti , Haas Michael John , Mooradian Arshag D
Published: May 2020

Obesity and diabetes are important risk factors for the development of coronary heart disease and stroke. Plasma endocannabinoid (EC) levels are inappropriately elevated in obesity and diabetes, and are hypothesized to play a causal role in central regulation of weight gain. Importantly, it was recently demonstrated that cannabinoid receptor 1 (CNR1) triggers cell stress and induces apoptosis in kidney tubule cells exposed to palmitic acid and high-glucose (HG). HepG2 and human coronary artery endothelial cells (HCAEC) were treated with tunicamycin (TM), thapsigargin (TG), high-glucose (HG), anandamide (AN), and 2-arachondonyl glycerol (2-AG), and endoplasmic reticulum (ER) stress was measured. In cells treated with TM, AM, and 2-AG and the UPR inhibitors 4-phenylbutyrate (4-PB) and taurodeoxycholic acid (TUDCA), both 4-PB and TUDCA prevented AN and 2-AG from promoting ER stress. ER stress in cells treated with AN and 2-AG, but not TM, was inhibited by the CNR1 antagonist rimonabant. Similar results were obtained with HCAEC. Furthermore, treatment with AN and 2-AG induced inositol requiring enzyme 1α and protein kinase R-like endoplasmic reticulum kinase phosphorylation but had no effect on their expression, while activating transcription factor 6 and binding immunoglobulin protein expression were also induced by AN and 2-AG in both HepG2 and HCAEC. Finally, AN and 2-AG treatment induced CNR1 expression in both cell lines. These results strongly suggest that EC’s promote ER stress and potentially induce liver and endothelial cell dysfunction.
SAT-LB311 Inoperable, Metastatic Pheochromocytoma & Paraganglioma Tumor Size Reduction After Lu-177-dotatate (Lutathera®) Treatment Trial: The Role of Nursing
Authors: Ude Assumpta , Frank Lin , Pacak Karel , Demissie Ejigayehu
Published: May 2020

Tumor Size Reduction after Lu-177-DOTATATE (Lutathera®) Treatment in Patients with Inoperable Metastatic Pheochromocytoma and Paraganglioma: The Role of NursingAssumpta Ude, Frank I. Lin, Karel Pacak, Ejigayehu Demissie. Clinical Center Nursing Department, Molecular Imaging Program NCI, Endocrine Service Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development. Background: Nursing management of patients with metastatic pheochromocytoma (PCC) and paraganglioma (PGL) undergoing treatment trial with radiopharmaceutical medication has unpredictable clinical outcomes. Clinical Case: A 52-year old woman with inoperable metastatic PCC/PGL was admitted into protocol 17-C-0087 after poor response to various chemotherapies. Patient was treated in the endocrine nursing unit with 200 mCi of Lu-177-DOTATATE (Lutathera®) intravenous infusion given by a radionuclide specialist every eight weeks for a total of four doses. Prior to admission, various members of the endocrine clinical nursing leadership team reviewed protocol with the medical and radiation safety team and a clinical research nurse (CRN) to ensure CRNs understand their roles and expectations to ensure patient safety during procedures and treatment. The patient was admitted on the day preceding the treatment and monitored for 48 hours afterwards. The CRN obtained comprehensive diet and medication history to determine if there is anything that may falsely elevate plasma/urinary catecholamines/metanephrines. The CRN ensured correct placement of intravenous (IV) line and proper collection of blood from IV line to increase the reliability of results. The CRN ensured that IV amino acid (Clinisol 15 %) infusion was administered 30 minutes prior to dosing to diminish renal issues. This patient had minimal side effects and no adverse events to therapy. The research team followed up the patient in clinic every month while she was on treatment, then every 3 months in the follow-up period. Recent evaluation showed this patient had stable vital signs, impalpable supraclavicular lymph node, returned to baseline physical activity with significant decrease in the size of the PCC/PGL, and reduction in serum catecholamine/metanephrine levels. Conclusion: The endocrine CRN team is critical in the assessment, monitoring, observation and education of patients and families regarding expectations during therapy which played a significant role in minimizing the patient’s side effects to therapy. Working collaboratively with other members of the multidisciplinary research team also contributed to patient’s favorable outcome.
SAT-LB56 Undernutrition Reduces Transcript Abundance of Kisspeptin and Neurokinin B in Young Male Sheep
Authors: Shuping Sydney L , Renwick Allison N , Harlow Lynn , Sommer Jeffrey R , Merkley Christina M , Nestor Casey
Published: May 2020

Proper energy balance is important to ensure reproductive success. Chronic nutrient restriction is known to suppress hypothalamic-pituitary function, but the central mechanisms whereby undernutrition inhibits GnRH/LH secretion remain largely unknown. KNDy neurons, which co-express kisspeptin, neurokinin B (NKB), and dynorphin, form a unique population of cells in the arcuate nucleus (ARC) of the hypothalamus and play a critical role in GnRH/LH pulse generation. Based on recent evidence from our lab that chronic feed restriction reduces kisspeptin and NKB protein expression in young male sheep, we hypothesized that nutrient restriction would inhibit mRNA abundance for kisspeptin and NKB in the same animals. Fourteen wethers were placed into a fed to maintain body weight group (n=6; Fed) or a feed-restricted to lose 15-20% of pre-study body weight group (FR; n=8). Weekly blood samples (every 12 minutes for 4.5 hours) were taken via jugular venipuncture and plasma was stored at -20°C until the time of radioimmunoassay. Weekly body weights were recorded and feed amounts were adjusted to achieve desired body weights. At Week 13, animals were euthanized following blood collection, brain tissue was perfused with 4% paraformaldehyde, and tissue containing the hypothalamus was collected. Following submersion in 20% sucrose for at least four weeks, hypothalamic blocks were sectioned at 50 µm on a freezing microtome, and stored in a cryopreservative solution until processing. At Week 13, the average percent change in body weight was clearly evident (Fed, 6.79 + 3.4% vs FR, -19.82 ± 1.6%), and mean LH was significantly lower in FR wethers (13.41 + 3.7 ng/ml) compared to Fed controls (26.43 + 2.5 ng/ml). To assess changes in mRNA abundance, we used a relatively new in situ hybridization technique, RNAscope, to quantify mRNA for kisspeptin and NKB in the ARC with probes that were ovine-specific. Results showed that feed restriction reduced the number of kisspeptin mRNA-expressing cells (Fed, 231.2 + 14.4 vs FR, 100.3 + 35.9) and NKB mRNA-expressing cells (Fed, 192.7 + 18.4 vs FR, 97.3 + 21.7) per hemi-section. Furthermore, analysis of kisspeptin and NKB co-expressing cells (30 cells/animal) revealed that feed restriction significantly reduced the average mRNA integrated density for NKB, but not kisspeptin, compared to Fed controls. Together, these findings further support a role for kisspeptin and NKB in the central mechanism governing GnRH/LH secretion during undernutrition in male sheep.
SAT-LB120 A Software Application Delivering Behavioral Therapy Improved Glycemic Control in Adults With Type 2 Diabetes
Authors: Guthrie Nicole L , Appelbaum Kevin J , Berman Mark A
Published: May 2020

Despite advances in pharmacological treatment, half of U.S. patients with type 2 diabetes are not achieving glycemic control (1). Even when glycemic control is achieved via pharmacotherapy, a substantial residual risk to all-cause mortality still exists (2). An overlooked contributor to both poor glycemic control and mortality risk is the need to address the behavioral determinants of type 2 diabetes. We tested a novel software application (app) designed to change behaviors that are root causes of type 2 diabetes and improve glycemic control. If behavioral therapy is effective and can be delivered using software installed on a patient’s smartphone, it may provide a cost-effective means of improving outcomes in this patient population. To study this hypothesis, we examined data from app users with suboptimal glycemic control, as defined by having a 3-day average of self-reported fasting blood glucose (FBG) values ≥ 152 mg/dL, who used the app for 12 weeks. 74 participants residing in 32 U.S. states met inclusion criteria. Their baseline characteristics (means±SD) were an age of 55.2±7.0 years, body mass index 34.7±7.9 kg/m2, 71.6% (53/74) female, current use of 2.2±0.9 antihyperglycemic medications, FBG 199.4±45.1 mg/dL and 10.6±7.1 years since diagnosis of type 2 diabetes. Change in FBG was calculated as the difference between 3-day averages anchored by the first and last values reported. Mean change in FBG was -22.9±42.0 mg/dL (P=0.001, using paired t-test) with an average of 69.0±29.9 days between the first and last value reported. Participants reported an average of 4.4±1.7 FBG values each week over 12-weeks. Participants used the app on average 4.6±1.8 days each week and spent 5.6±8.3 minutes each use. We performed a tertile analysis to examine the relationship between degree of behavioral therapy use and change in glycemic status. The mean changes in FBG in the lowest to highest tertile of behavioral therapy use were -14.4±39.2, -20.4±47.6 and -32.9±38.4 mg/dL (P=0.06, comparing lowest to highest tertile, using a pairwise comparison of the least squares means accounting for baseline FBG and years since diagnosis). These results suggest use of this novel software application is associated with meaningful improvements in glycemic control in a widely distributed treatment population and warrants further study.

Refs: (1) Edelman et al., Diabetes Care 2017 Nov; 40(11): 1425-1432. (2) Rodríguez-Gutiérrez et al., Circ Cardiovasc Qual Outcomes. 2016; 9:504-512.
MON-LB119 Euglycemic Diabetic Ketoacidosis in a Patient on Canagliflozin Presenting With Hypoglycemia
Authors: Inkollu Sindhura , Korem Sindhuja , Ganne Sudha
Published: May 2020

Background: Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newer class of antihyperglycemics that cause reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. Common side effects include yeast and urinary tract infections. The US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors. The mechanisms by which SGLT2 inhibitors cause euglycemic DKA are unclear. SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin and an increase in glucagon production.1 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA. Here, we report a case of euglycemic DKA in a patient on Canagliflozin who presented initially with hypoglycemia.

Clinical case: A 70 year old female presented with altered mental status for 1 day duration. Her past medical history is significant for type 2 Diabetes Mellitus, being managed on Canagliflozin, Glimepiride and Janumet. One week prior to admission she had lumbar spinal fusion surgery. Since then she has been feeling weak and tired with poor oral intake, but continued to use her medications. Initial laboratory findings showed blood glucose of 68 (70-100 mg/dl) without any acidosis. Her altered mental status was attributed to higher opioid doses which she received prior. Oral hypoglycemic agents have been held. On 2nd day of hospitalization, patient became more lethargic and complained of nausea. Laboratory testing revealed a serum glucose of 250mg/dL, serum bicarbonate of 13 (21–31mmol/L), and Anion gap of 25 (3.6–11.0mmol/L). With the suspicion of DKA, a beta-hydroxy butyrate level was obtained which was elevated at 90.10 (0 – 4.16 mg/dL). Venous blood gas analysis was significant for pH 7.23 (7.31-7.41) and pCO2 – 28 (41-51 mmHg). Urinalysis showed ketosis and glucosuria. Patient was diagnosed as euglycemic diabetic ketoacidosis from Canagliflozin in presence of precipitating factors - stress and poor intake. Patient was treated with insulin drip and intravenous fluids with reduction in anion gap and correction of acidosis within 24hrs. There was a gradual improvement in her mental status. She was discharged on subcutaneous insulin, and all other diabetic medications were stopped.

Conclusion: Our case highlights the importance of being vigilant in a patient on Canagliflozin, euglycemic DKA can occur even if they present initially with hypoglycemia and no acidosis.

Reference: 1. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7(2):135-138.