Uncontrolled Type Research Articles

Spontaneous Achilles tendon Rupture in Calcaneus Osteomyelitis

Background: Achilles tendon is the most common injured tendon in the lower limb. Spontaneous rupture is attributed to some intrinsic and extrinsic factors in which medications side effect (e.g. corticosteroids and quinolones) is the most common reported cause in the literature. Case presentation: we present a case of 76-year-old female known case of uncontrolled type II diabetes and hypertrophic right Charcot foot. She was diagnosed with chronic foot osteomyelitis for which she received long course of ceftriaxone. Six month following completing the antibiotic course, she presented with fever and malaise with decreased right foot range of motion in the absence of traumatic event. Upon requesting multiple imaging modalities, she was diagnosed with acute Achilles tendon rupture in the setting of acute on top of chronic calcaneus osteomyelitis. Conclusion: AT rupture in the setting of osteomyelitis is a rare entity and has not been reported previously in the literature. This case will bring the attention in evaluating the tendons thoroughly in cases of osteomyelitis.

"It's Not Just Bacteria": A Cavitary Lung Lesion in a Patient Living in the Coachella Valley.

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

Short-Term Effects of Liraglutide versus Vildagliptin on Insulin Secretion and Sensitivity in Type 2 Diabetes: A Single Blinded Randomized Controlled Trial (LIRAVIS Study)

Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m2/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min; p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.

Multidrug-Resistant Escherichia coli Causing Urinary Tract Infections among Controlled and Uncontrolled Type 2 Diabetic Patients at Laquintinie Hospital in Douala, Cameroon.

Urinary tract infections (UTIs) in patients with diabetes are a major public health problem worldwide, particularly in developing countries. This study assessed the resistance profile of Escherichia coli and biochemical abnormalities in controlled and uncontrolled type 2 diabetic patients. A cross-sectional study was conducted at the Douala Laquintinie Hospital from January, 2020, to July, 2021, on the diabetic and nondiabetic participants. The clinical symptoms and biochemical parameters of patient having UTIs were measured using standard methods. E. coli was isolated from urine and an antibiotic susceptibility test was performed using the Kirby-Bauer Agar diffusion method. A total of 851 participants were included with a mean age of 48.54 years. Three hundred and forty-six (40.67%) were nondiabetic, 226 (26.56%) were diabetic patients with balanced blood sugar levels (i.e., glycosylated haemoglobin (HbA1c) is normal), and 279 (32.78%) were diabetic patients with unbalanced blood sugar levels (i.e., patients having an abnormal HbA1c). The prevalence of UTI caused by E. coli was significantly (p < 0.001) higher in diabetics with unbalanced blood sugar levels (15.41%) and diabetics with balanced blood sugar levels (9.73%) compared to nondiabetics (0.87%). Significant (p < 0.001) high frequencies of polyuria (48.39%), proteinuria (29.75%), leukocyturia (27.96%), and polyphagia (8.24%) were observed in diabetic participants with unbalanced blood sugar levels. Significantly (p < 0.001) high average values of aspartate transaminase (25.34; 27.07; 29.93), alanine transaminase (26.08; 27.38; 28.20), creatininemia (8.15; 9.67; 11.31), total cholesterol (1.57; 1.83; 2.63), and atherogenic index (3.81; 6.56; 11.73) were noted in nondiabetics, balanced, and unbalanced blood glucose diabetics, respectively. E. coli showed a high level of resistance to ciprofloxacin (30%), amoxicillin (10.8%), and ofloxacin (9.3%) in diabetic participants with unbalanced blood sugar levels. The antibiotic resistance patterns of the E. coli to triple, quadruple, and quintuple antibiotics were higher when participants had diabetes and even more when diabetes was not controlled. The present findings underline an increased susceptibility of diabetic patients with unbalanced blood sugar levels to multidrug resistant E. coli. Further studies should be conducted to determine the causal association between uncontrolled diabetes and bacterial multidrug resistance.

Early use of airway pressure release ventilation in acute respiratory distress syndrome induced by coronavirus disease 2019: a case report

BackgroundCoronavirus disease 2019 is a highly transmissible and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2, a novel coronavirus that was identified in early January 2020 in Wuhan, China, and has become a pandemic disease worldwide. The symptoms of coronavirus disease 2019 range from asymptomatic to severe respiratory failure. In moderate and severe cases, oxygen therapy is needed. In severe cases, high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation are needed. Many ventilation methods in mechanical ventilation can be used, but not all are suitable for coronavirus disease 2019 patients. Airway pressure release ventilation, which is one of the mechanical ventilation methods, can be considered for patients with moderate-to-severe acute respiratory distress syndrome. It was found that oxygenation in the airway pressure release ventilation method was better than in the conventional method. How about airway pressure release ventilation in coronavirus disease 2019 patients? We report a case of confirmed coronavirus disease 2019 in which airway pressure release ventilation mode was used.Case presentationIn this case study, we report a 74-year-old Chinese with a history of hypertension and uncontrolled diabetes mellitus type 2. He came to our hospital with the chief complaint of difficulty in breathing. He was fully awake with an oxygen saturation of 82% on room air. The patient was admitted and diagnosed with severe coronavirus disease 2019, and he was given a nonrebreathing mask at 15 L per minute, and oxygen saturation went back to 95%. After a few hours with a nonrebreathing mask, his condition worsened. On the third day after admission, saturation went down despite using noninvasive ventilation. We decided to intubate the patient and used airway pressure release ventilation mode. Finally, after 14 days of being intubated, the patient could be extubated and discharged after 45 days of hospitalization.ConclusionEarly use of airway pressure release ventilation may be considered as one of the ventilation strategies to treat severe coronavirus disease 2019 acute respiratory distress syndrome. Although reports on airway pressure release ventilation and protocols on its initiation and titration methods are limited, it may be worthwhile to consider, given its known ability to maximize alveolar recruitment, preserve alveolar epithelial integrity, and surfactant, all of which are crucial for handling the “fragile” lungs of coronavirus disease 2019 patients.

Protocol for a Pilot Randomized Controlled Mixed Methods Feasibility Trial of a Culturally Adapted Peer Support and Self-Management Intervention for African Americans

Due to diabetes disparities commonly seen among African Americans, it is important to address psychosocial and sociocultural barriers to medication adherence among African Americans with diabetes. Building on our prior work testing a culturally adapted peer supported diabetes self-management intervention for African Americans, this study will conduct a pilot randomized controlled feasibility trial that compares the culturally adapted intervention with a standard diabetes self-management program. Using an intervention mixed-methods design, the six-month trial will be conducted at two sites. Twenty-four African Americans with uncontrolled type 2 diabetes will be randomized to the intervention or control arm. Feasibility and acceptability outcomes in four domains (recruitment, intervention acceptability, intervention adherence, retention) will be collected. Primary clinical outcome (A1C), secondary outcome (medication adherence) and patient-specific psychosocial measures will be collected at baseline, 2 months, and 6 months. Document review, interview and focus groups will be used to gather qualitative data on feasibility and acceptability. Expected results are that the trial protocol will be feasible to implement and acceptable for participants, and there will be a signal of clinically meaningful reduction in A1C and improvements in medication adherence. The results of this trial will inform a future powered large-scale randomized controlled trial testing the effectiveness of the culturally tailored intervention.

Analysis of ophthalmic manifestations of invasive rhino-orbito-cerebral mucormycosis in COVID-19 patients in a medical college

To analyze different ophthalmic manifestations of rhino-orbital mucormycosis (ROM) infection in COVID-19 patients. Prospective interventional clinical study.20 microbiologically confirmed ROCM cases with ophthalmic involvement hospitalized between May 2021 and July 2021 in our center were included in this study. Among 20 cases there were 9 female and 11 male with a mean age of 57.5 years. All 20 patients had uncontrolled type 2 diabetes with a mean diagnosis duration of 3.67 years. All patients had COVID-19-associated acute respiratory distress syndrome and received corticosteroids. The mean time interval between COVID-19 diagnosis and ROM diagnosis was 3.46 days. 4 patients (20%) had orbital apex syndrome, and 16 patients (80%) presented with orbital cellulitis. CT scan/MRI revealed sino-orbital involvement in all patients, and 3 of these had cerebral involvement at initial presentation. All 20 patients received intravenous amphotericin B and 7 patients received TRAMB and all 20 patients had undergone radical debridement of involved sinuses. Despite all measures, 3 (7.5%) of 20 patients with cerebral dissemination expired. Severe COVID-19 is associated with a significant incidence of ROM with higher mortality rates due to immune dysregulation and the widespread use of steroids. An aggressive multidisciplinary approach can help to reduce mortality.

Abstract 39

Background: In the urban setting, dinner is the main meal of the day and higher calories later at night may adversely affect glycemic control. We aimed to assess the effect of early dinner on glycemic control in habitual late eaters with uncontrolled T2DM in terms of fasting plasma glucose (FPG) levels and continuous glucose monitoring (CGMS) parameters. Methods: Prospective interventional crossover study recruiting participants from a tertiary care center. We included adult patients with uncontrolled T2DM (HbA1c 7-9% and either FPG ³140 mg/dl or post-prandial glucose ³ 200 mg/dl) who habitually ate their last meal beyond 22:00 hrs, were on a stable lifestyle for the past 3 months and taking metformin and/or DPP4 inhibitors. Other anti-diabetic agents were excluded to avoid hypoglycemia. Late dinner (LD) and early dinner (ED) were defined as the last meal for the day beyond 22:00 hrs andbefore 20:00 hrs respectively. The patients ate LD for 4 days (Days 0-3) and ED for next 7 days (Days 4-10). Patients were admitted overnight for testing on days 0 (LD visit) and 10 (ED visit). Post-prandial (2 hrs post-dinner) and fasting (10 hrs post-dinner) samples were collected for glucose, insulin, lipid profile, hsCRP, IL-6 and malondialdehydelevels. A CGMS was applied for the entire duration and incremental area under curve (iAUC), average blood glucose (ABG) and glycemic variability were calculated. A labelled magnitude satiety scale (LMSS) was provided to document bedtime hunger. Results: 10 patients (7 males, mean age 52.5 years) with T2DM (mean HbA1c 7.54%, mean time of usual dinner 22:33 hrs) were recruited. FPG (119.8 ± 7.3 mg/dl vs 105.2 ± 5.7 mg/dl, P = 0.015), fasting insulin (15.0 ± 4.3 mcIU/ml vs 9.7 ± 2.7 mcIU/ml, P &lt; 0.002) and total cholesterol (162.8 ± 13.4 mg/dl vs 145.6 ± 13.1 mg/dl, P = 0.029) reduced significantly in ED than LD. Post-prandial glucose and insulin and othermarkers did not change significantly. Among CGMS, 10 hr post-dinner iAUC (22587.9 ± 5168.3 mg/dlxmin vs 15886.3 ± 4288.7 mg/dlxmin, P &lt; 0.002) (Fig 1), 10 hrABG (137.5 ± 9.3 mg/dl vs 125 ± 7.9 mg/dl, P &lt; 0.002), 24 hr ABG (132.2 ± 7.5 mg/dl vs 124.8 ± 5.4 mg/dl, P = 0.037) and night meanamplitude of glycemic excursion (83.7 ± 5.8 vs 69.3 ± 7.5, P = 0.027) significantly reduced in ED than LD. The patients ate LD at meantime of 22:28 hrs and ED at meantime of 19:29 hrs. The LMSS showed significantly increased bedtime hunger on days 4 and 5 which reduced to baseline by day 10. Conclusion: This study shows that changing dinner timings without modification of other parametersimproves overall glycemic control, postprandial glycemic excursions, fasting glucose values, night time glycemic variability and insulin sensitivity in T2DM patients.

Stability and Feedback Control of Volterra Type Systems with Time Delay

New results for stability and feedback control of time delay systems were proposed. These results were obtained by using Lyapunov Razumikhin method to approximate the stability of the uncontrolled Volterra type system with delay and designing a state feedback controller using a model transformation technique, the Lyapunov matrix equation and the Razumikhin approach for the stabilization of the controlled Volterra type system with delay. Examples are given to illustrate the effectiveness of the theoretical results.

Platelet indices in controlled and uncontrolled type 2 diabetes mellitus: A cross sectional study

Diabetes is an emerging health problem across the world. Underlying prothrombotic state leads to cardiovascular complications in diabetics especially those with poor glycemic control. Though multiple mechanisms are responsible, platelet activation plays a major role in the pathogenesis of prothrobotic state. Platelet activation causes increase in their size which is represented by Mean Platelet Volume (MPV) whereas variation in their size associated with release reaction is reflected by Platelet Distribution Width (PDW). So MPV and PDW together may help to detect emergence of prothrombotic state at an earlier stage.To find out whether any significant difference exists in platelet count, MPV and PDW in controlled and uncontrolled Type 2 diabetics.It was a hospital based cross sectional study where total 277 patients of Type 2 Diabetes Mellitus were included following predetermined inclusion and exclusion criteria and categorized into controlled (193 subjects) and uncontrolled (84 subjects) groups with HbA1c level ≤ 7% and &amp;#62;7% respectively. Blood from all the participants were analyzed for MPV, PDW and platelet count. Unpaired t-test was done to compare the platelet count and platelet indices among two groups.MPV and PDW were found to be significantly higher (p &amp;#60;0.0001) among uncontrolled group compared to controlled group with Mean MPV 13.47±0.56 fl vs 10.25±1.32 fl and Mean PDW 23.37±2.47% vs 15.57±2.69% respectively. But there was no significant difference in platelet count among two groups. The higher value of MPV and PDW in uncontrolled diabetics indicates that they can be utilized as an inexpensive yet useful method for early detection of thrombotic complication in these patients.

ODP171 Choosing GLP-1RA Over Insulin for Patients with Type 2 Diabetes and Severe Hyperglycemia

Abstract Introduction Although insulin remains the recommended treatment in type 2 diabetes for hyperglycemia with catabolic symptoms, it is also the generally recommended treatment for persistent hyperglycemia or hemoglobin A1c (HbA1c) values above 10% 1 . Recent data has suggested that glucagon like peptide 1 receptor agonists (GLP-1RAs) are also powerful at glucose lowering while additionally offering extra-glycemic benefits such as weight loss with minimal risk of hypoglycemia. Unfortunately, data on initial use of GLP-1RA is limited in patients with very high hemoglobin A1cs. Our objective was to evaluate outcomes in patients with type 2 diabetes and a baseline HbA1c of 10% or greater treated with GLP-1RAs instead of insulin. Methods This study is a small retrospective case series of insulin-naïve patients with uncontrolled type 2 diabetes who were prescribed an injectable GLP-1RA. Patients included had a baseline hemoglobin A1c ≥ 10% without signs of catabolism (weight loss, ketosis, significant polyuria), a minimum of one follow-up visit after initiating GLP-1RA, and at least one HbA1c measurement within six months of initiating treatment. Patients were excluded if they had previously been on insulin or a GLP-1RA in the past 1 year. The primary endpoint was change in HbA1c after 3-6 months of GLP-1 RA use. Results Of the patients initially screened, 7 patients fulfilled criteria and were included in the final analysis. The age range was 45-73 with 4 female patients and 3 male patients. The number of years patients had been diagnosed with type 2 diabetes ranged from 0 to 13 with 1 patient having newly diagnosed diabetes not previously on medications. Of the 6 patients who were on medical treatment at baseline, 3 patients were on monotherapy with either metformin or a sulfonylurea and 3 patients were on 2-4 oral hypoglycemic agents. Patients were continued on their initial medication regimen with the exception of DPP-4 inhibitors which were stopped at the time of GLP-1RA initiation. Mean baseline HbA1c prior to initiation of GLP-1RA was 11.9%. Following 3-6 months of GLP-1RA use, mean HbA1c significantly improved to 7.5% (p value= 0. 0005). All patients showed improvement of HbA1c in response to GLP-1RA initiation (mean HbA1c reduction = 4.4, minimum = 1.9, maximum = 7.5). All patients remained on GLP-1RA without significant side effects. Conclusion In this limited case series of patients with HbA1c ≥ 10%, GLP-1RAs were well tolerated and resulted in significant improvement in HbA1c. Our results suggest that GLP-1RAs should be considered as an alternative treatment option to insulin in non-catabolic patients with very high hemoglobin A1cs.

ODP549 From Positive to Negative, a Histidine to Aspartic Acid Change in SDHB is Breaking Bad in Cardiac Paraganglioma

Abstract Introduction Cardiac paraganglioma (PGL) are extremely rare tumors. They are derived from chromaffin cells of the neural crest. Up to 40% of PGL foster germline mutations, while some bear somatic mutations. Here, we describe a sympathetic paraganglioma presenting as a cardiac mass, found to have a novel mutation of SDHB. Clinical Case A 64-year-old man with uncontrolled type 2 diabetes mellitus presented with chest pain, progressive fatigue and unintentional weight loss. An echocardiogram demonstrated a right atrial mass. Cardiac magnetic resonance imaging showed a 6.9×5.8×4.9 cm mass in the lateral right atrial wall and right atrioventricular groove, encasing the right coronary artery. Surgical removal was attempted and aborted due to involvement of the tricuspid valve. Incisional biopsy was consistent with paraganglioma. Plasma free normetanephrine was elevated at 1.87 nmol/L (ULN 0.89 nmol/L) and plasma free metanephrine was normal at 0.14 nmol/L (ULN 0.49 nmol/L). Chromogranin A was elevated at 1,038 ng/mL (normal &amp;lt;93 ng/mL). Iodine-123 meta-iodobenzylguanidine scan demonstrated increased and persistent MIBG activity of the cardiac mass. Ga-68 DOTATATE PET/CT scan revealed DOTATATE avidity of the mass without evidence of distant metastatic disease. Next-generation sequencing of the specimen revealed a variant of unknown significance of SDHB H244D at a variant allele frequency of 62.2%. This missense mutation replaces the histidine to aspartic acid, resulting in changes in charge of the side chain from positive to negative. Systemic treatment with tyrosine kinase inhibitor (TKI) cabozantinib was initiated due to unresectable tumor. Three month surveillance with Ga-68 PET/CT DOTATATE scan revealed partial response to treatment. Chromogranin A and normetanephrine are trending down, suggesting biochemical response. Conclusion Cardiac PGL are rare and SDHB mutations are associated with worse prognosis. This is the first case of a missense mutation of SDHB at H244D, which may be clinically relevant in characterizing cardiac paraganglioma and potential response to TKI therapy. Presentation: No date and time listed

PSUN264 Insulin Edema: A rare side effect of Intensive Insulin Therapy

Abstract Insulin therapy associated generalized edema is a rare entity. The true incidence is unknown. It has been reported mostly in patients with poorly controlled diabetes mellitus started on intensive insulin regimens. The severity ranges from mild lower extremity swelling to anasarca. Management is primarily supportive with salt restrictions, diuretics and if possible, reduction of insulin doses. We present a case of a 39-year-old African American woman who developed generalized edema after initiation of insulin. She had history of gestational diabetes and presented to the endocrinology clinic to establish care after being hospitalized with Diabetic Ketoacidosis (DKA). She was diagnosed with diabetes mellitus initially during her pregnancy two years prior and was treated with insulin. After pregnancy, she was lost to follow up. She was then admitted to the hospital with severe DKA and was discharged on multiple daily injections of insulin. On the initial encounter in clinic, the patient endorsed developing abdominal distension and lower extremity swelling with insulin use previously so she was not using insulin consistently. Her physical examination was unremarkable. Lab work was significant for hemoglobin A1C of &amp;gt;15%, C-peptide 0.9 ng/mL (1.1-4.4 ng/mL), islet cell antibody 0.09 nmol/L (&amp;lt;0.02 nmol/L), glutamic acid decarboxylase antibody 0.40 nmol/L (&amp;lt;0.02 nmol/L). Her kidney and liver function were normal. She had normal thyroid function and cortisol levels. Her echocardiogram revealed normal cardiac function and she had non proliferative diabetic retinopathy on retinal exam. The patient was started on insulin and a continuous glucose monitor was placed to assess her glycemic patterns. Three days after starting insulin, she developed generalized body swelling involving face, abdomen, and lower extremities. The patient was advised to cut back on salt and started on low dose furosemide. On follow up one month later, her abdominal swelling had improved however she still had pitting lower extremity edema. On follow up two months later the edema completely resolved. Clinicians should be aware of the presentation and management of insulin induced edema. In most of the cases in literature, insulin induced edema started after starting insulin in newly diagnosed Type 1 diabetes or uncontrolled Type 2 diabetes. The pathophysiology is unclear. There is some evidence that insulin deficiency causes a catabolic state and hyperglycemia increases tissue capillary permeability. Re-introduction of insulin causes free water retention and renal excretion of sodium. This along with increased capillary permeability can lead to insulin edema. Water retention caused by the effect of counter regulatory hormones can also play a role. Insulin edema needs to be differentiated from other causes of diffuse edema. Management is generally supportive including temporarily decreasing insulin doses, salt restriction and diuretics as needed. Patient reassurance is important as well to aid in adherence to the prescribed insulin regimen. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP322 Impact of Mifepristone on Liver Function and Resolution of Liver Steatosis in Patients with Cushing Syndrome – A Case Study

Abstract Background Hypercortisolism is a recognized cause of non-alcoholic fatty liver disease (NAFLD). Mifepristone (Korlym®, Corcept Therapeutics), a glucocorticoid receptor (GR) antagonist, is FDA-approved for the treatment of hyperglycemia in patients with endogenous Cushing syndrome (CS). Mifepristone has also shown beneficial effects in preclinical models of fatty liver disease, including reduced liver injury, improved insulin sensitivity, and increased plasma adiponectin concentrations. Here, we report the case of a patient with CS and liver steatosis who was treated intermittently with mifepristone. Clinical Case A 36-year-old woman with CS associated with uncontrolled type 2 diabetes mellitus, obesity, major depressive disorder, hyperlipidemia, hypertension, and liver steatosis was intermittently treated with mifepristone for 3 years. Abdominal imaging was performed several times for abdominal pain. Before treatment with mifepristone was initiated, the patient had a body weight of 198 lbs, BMI of 32kg/m 2, HbA1c of 11.5%, and liver steatosis as noted on abdominal imaging with normal liver function tests (ALT: 40 U/L [normal: 6-42 U/L], AST: 30 U/L [normal: 8-36 U/L]). After 16 months, treatment with mifepristone was discontinued secondary to abnormal uterine bleeding. Imaging performed around the time of discontinuation showed resolution of liver steatosis, which was accompanied by significant reductions in LFTs to levels typically seen in healthy volunteers without liver steatosis (ALT: 10 U/L, AST: 17 U/L). The patient's HbA1c had decreased to 6.8%. Imaging performed 7months after mifepristone discontinuation showed recurrence of liver steatosis, LFTs had returned to pre-treatment values (ALT: 42 U/L, AST: 31U/L), and HbA1c had increased to 9.3%. The patient underwent hysterectomy and restarted mifepristone treatment. One year after resumption of mifepristone, imaging showed that liver steatosis had resolved once again, along with a similar reduction in LFTs as observed before (ALT: 16 U/L, AST: 12 U/L). Fourteen months after restart, mifepristone was discontinued again. Labs and imaging performed 10 months after discontinuation showed, as previously, recurrence of liver steatosis along with elevated LFTs (ALT: 100 U/L, AST: 56 U/L). Data from mifepristone's prospective pivotal study (SEISMIC, NCT00569582) of 50 patients with CS also showed a similar reduction in ALT throughout the study, which was reversed during the 6-week discontinuation follow-up phase of the study. This was followed by a repeat reduction when mifepristone was restarted in the extension study (NCT00936741). Conclusion These results suggest that mifepristone is effective in improving liver function and decreasing liver steatosis in patients with endogenous CS, a trend that is also accompanied by improvement in insulin resistance and glycemic control. Presentation: No date and time listed

ODP620 A Cross-over Trial Using Insulin Glargine And Neutral Protamine Hagedorn Insulin For The Poorly Controlled Patients With Type 2 Diabetes Who Refused Multiple Daily Insulin Injections

Abstract A Cross-Over Trial Using Insulin Glargine and Neutral Protamine Hagedorn insulin for the Poorly Controlled Patients with Type 2 Diabetes Who Refused Multiple Daily Insulin Injections Background: Data in the literature describing the comparison between Neutral Protamine Insulin of Hagedorn (NPH) and glargine insulins are conflicting. While some studies revealed the superiority of Glargine, others had shown comparable results and even NPH superiority figures. We have many patients on NPH basal therapy in our clinical practice and another good number on Glargine. We did observe adverse effects in both groups, but local data and real numbers comparing both regimens are lacking. Objective To compare basal insulin regimen using NPH or Glargine in efficacy, hypoglycaemic events, and weight gain. Design and setting: A prospective interventional crossover study was conducted in Faiha Specialized Diabetes, Endocrine and Metabolism Center from 2018 through 2021, involving patients less than 65 years old with uncontrolled Type 2 Diabetes Mellitus whose HbA1c &amp;gt;10% on oral antidiabetic drugs (OAD); randomized into two groups (G1 &amp; G2), 70 patients in each group had completed the study, one group received NPH and the other received Glargine in addition to their OAD for one year, then they were crossed over for another one year after a period of washout. Results The mean age was 48.9±5.5 and 45.9±4.1 years for G1 and G2, respectively. 36(51.4%) in G1 were women versus 27(38.6%) in G2. In the first phase of the study, HbA1c reduction was 5.5±1.1% for the NPH group and 5.3±1.1% for the Glargine group (p=0.418), there was 1.7±2.7 versus 1.1±2.9 Kg weight gain (p=0.209), 27(39.7%) hypoglycemic event versus 26(37.7%) (p=0.883) and 5 patients(7.4%) achieved HbA1c &amp;lt;7% versus 8(11.6%) (p=0.397) for the patients in NPH and Glargine groups respectively. While in the crossover phase, the data comparing Glargine and NPH groups are as following: 0.6±0.8 versus 0.5±0.9% reduction in HbA1c (p=0.413), 1.7±3.1 versus 0.6±2.2 Kg weight loss (p=0. 035) although the final weight was not much different 77.3±12. 0 versus 77.7±11.5 (p=0.841), 16(27.1%) versus 23(36.5%) hypoglycemic events (p=0.493) and 17(29.8%) versus 11(17.7%) achieved HbA1c&amp;lt;7% (p=0.121) respectively. Conclusion In our study, there was no significant difference in HbA1c reduction, Hypoglycemic events, and weight gain between patients using NPH or Glargine basal insulin regimen. Keywords: Diabetes; Glargine; NPH. Presentation: No date and time listed

ODP302 Cushing's Disease: A Challenging Diagnosis in Patients with Underlying Co-Morbidities

Abstract Introduction Cushing's disease (CD) is a rare endocrine disorder with significant morbidity and mortality. This case is a complicated ACTH (adrenocorticotropic hormone)-dependent hypercortisolism with a negative pituitary MRI inthe setting of underlying liver cirrhosis and chronic kidney disease. Hypercortisolism work up was challenging due to liver and kidney disease. Case Presentation A 42-year-old woman with a history of liver cirrhosis(MELDscore: 19) and stage 3b chronic kidney disease (CKD) presented with nausea, vomiting and abdominal pain. She reported proximal muscle weakness. On examination, she had central adiposity with large purple abdominal striae and proximal muscle wasting. Medical history was pertinent for uncontrolled hypertension and type 2 diabetes mellitus. Due to concern for Cushing's syndrome, an overnight 1 mg dexamethasone suppression test (DST) was performed. She had an inappropriately elevated morning cortisol of 10.1 mcg/dL (n &amp;lt; 1.8 mcg/dL), but suboptimal dexamethasone level of 104 ng/dL (140-295 ng/dL), suggesting incomplete absorption secondary to emesis. A repeat DST was not performed given concerns for reduced dexamethasone clearance with her underlying renal and liver disease. Her 24-hour urine free cortisol (UFC) was elevated at 55 ug/24 hr (6-42 ug/24 hr). A repeat 24-hour UFC was again elevated at 265 ug/24 hr (6-42 ug/24 hr). Three late night salivary cortisol levels were also elevated at 0.231 ug/dL, 0.429 ug/dL and 0.19 ug/dL (n &amp;lt;0. 01-0. 09 ug/dL). Diagnosis of Cushing's syndrome was confirmed. ACTH level obtained was detectable at 70.1 pg/mL (7.2-63.3 pg/mL), suggestive of ACTH-dependent Cushing's syndrome. Pituitary MRI without contrast was obtained due to CKD. MRI reported no pituitary abnormalities. High dose DST was not performed due to concerns for aforementioned reduced dexamethasone clearance and due to lack of availability of CRH (corticotropin-releasing hormone), CRH stimulation testing was not done. She underwent inferior petrosal sinus sampling (IPSS) which showed central to peripheral ACTH ratio of 2.11 at baseline and ratios of 3.53, 3.45 and 3.32 at 5 minutes, 10 minutes and 15 minutes respectively after vasopressin stimulation, solidifying the diagnosis of Cushing's disease. Patient is now scheduled for an exploration of the sella via endoscopic endonasal approach. Conclusion This case highlights the limitations of biochemical tests and imaging modalities in the workup of hypercortisolism, notably in patients with underlying liver and kidney disease. The ordering physician should be mindful of the caveats associated with each biochemical testing. ACTH-dependent Cushing's syndrome can be difficult to diagnose properly in the setting of a negative pituitary MRI. IPSS, although an expensive and invasive test, has the best diagnostic accuracy. This case further demonstrates the importance of performing an IPSS to diagnose CD and distinguish from an ectopic source when imaging is non-diagnostic. Presentation: No date and time listed

THE IMPORTANCE OF B CELLS IN OVERCOMING COVID-19 INFECTION IN COMMON VARIABLE IMMUNODEFICIENCY PATIENTS.

<h3>Introduction</h3> COVID-19 patients exhibit a hyper-inflammatory state. CVID patients have impaired immunoglobulin production and a wide variability in COVID-19 disease course. <h3>Methods</h3> We compared hospitalized patients with CVID and COVID-19 disease (CVID+ COVID-19+) to patients with CVID and another pneumonia (CVID+ COVID-19–) and COVID-19 patients without CVID (CVID– COVID-19+) between March 2020 and September 2021. <h3>Results</h3> 4 female CVID+ COVID-19+ patients received regularly scheduled intravenous immunoglobulin (IVIG) therapy. 1 of 4 died with comorbidities: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and vasculitis treated with hydroxychloroquine, leflunomide, and rituximab. 1 of 6 CVID+ COVID-19– patients died, and was administrated omalizumab and prednisone. 3 of 34 CVID– COVID-19+ patients died; one with significant lung pathology, on home oxygen, and another had uncontrolled type II diabetes, obesity, Behcet syndrome, SLE and RA treated with apremilast, hydroxychloroquine, and rituximab. Mean BMI was 32.1 ± 1.5 for CVID+ COVID-19+, 30.5 ± 5.3 for CVID+ COVID-19– and 37.8 ± 1.5 for CVID– COVID-19+ cases. The number of hospitalizations and comorbidities were greater for COVID-19– cases. Admission LDH was greater in expired cases. Serum IgG for CVID+ patients that died were 852 and 808 mg/dL. <h3>Conclusion</h3> Despite regular IVIG therapy, adequate serum IgG, and convalescent plasma early during hospitalization, the CVID+ COVID-19+ patient that died received anti-CD20, B-cell depleting therapy with rituximab. In addition to immunoglobulin production, B-cells may have a different role in fighting acute COVID-19 infection. B-cell depletion therapy may predispose to worse outcomes and inflammatory markers may aid in prognostication.

Effects of Hydroxychloroquine on Progression of Diabetic Retinopathy in Subjects with Rheumatoid Arthritis and Type 2 Diabetes Mellitus.

The study was conducted to investigate the effects of hydroxychloroquine, an anti-inflammatory drug, which was recently approved and used as an add on oral antidiabetic drug for uncontrolled Type 2 Diabetes Mellitus (DM) on an adequate dose of sulfonylurea and metformin on the progression of diabetic retinopathy (DR) in subjects with Rheumatoid Arthritis and Type 2 Diabetes Mellitus. The primary objective was to evaluate the effect of hydroxychloroquine on the onset of Diabetic Retinopathy (DR) and progression of the disease. Best-corrected visual acuity (BCVA) charts with 3 or more lines worsening of visual acuity and the development of clinically significant macular edema (CSME) were added as secondary objectives as described in the Early Treatment Diabetic Retinopathy Study (ETDRS). This retrospective analysis was done from medical records of all Rheumatoid Arthritis (RA) patients who also had T2DM and were treated with hydroxychloroquine (HCQ) 400 mg OD or 200 mg BID (N=65) and received ophthalmologic care at an endocrinology clinic in India up to a mean follow-up of 3.5±0.5 years and matched subjects taking any other disease-modifying antirheumatic drugs (DMARD) and pioglitazone (N=34). Baseline characteristics were similar in both the groups, with matched glycated haemoglobin (9.1 % and 9.2 % respectively, p=0.127). In both groups, over 3.5 years, HbA1c was reduced significantly. No new cases of DR were detected in the HCQ group, whereas 2 patients had developed DR in the pioglitazone group. At the base line visit, mild non-proliferative Diabetic Retinopathy (NPDR) was present in 18 eyes and 14 eyes in the HCQ and pioglitazone groups, respectively. Progression to moderate NPDR over 3.5 years occurred in 2 out of 18 (11 %) eyes in the HCQ group and 8 out of 14 (57 %) eyes in the pioglitazone group, respectively, representing a significant relative risk reduction (p=.001). No patients had progressed from mild NPDR to severe NPDR in the HCQ group, whereas 2 eyes had progressed from mild NPDR to severe NPDR in the pioglitazone group. None of the patients in either arm developed diabetic macular oedema. Progression of DR from mild to moderate NPDR or severe NPDR may be delayed by HCQ. Large scale randomised prospective clinical trial is required to establish the risk-benefit profiles of HCQ in T2DM.ct.

ODP296 An unusual presentation of Glucagonoma syndrome.

Abstract Introduction Glucagonoma is an uncommon neoplasm of the pancreatic neuroendocrine islet α-cells. At least 50% of cases will have metastatic disease when diagnosed. Glucagonomas can be associated with other tumors in Multiple Endocrine Neoplasia syndrome 1 (MEN 1), but this association is rare and comprises no more than 3% of glucagonomas. Glucagonoma syndrome is a rare paraneoplastic phenomenon characterized by necrolytic migratory erythema (NME), hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, cheilitis, steatorrhea, diarrhea, and venous thrombosis. Case presentation A 55-year-old Caucasian woman was admitted for acute onset of shortness of breath and she was seen by endocrinology team for persistent hyperglycemia. Her medical history revealed a long-standing uncontrolled type 2 diabetes mellitus and an episode of left lower extremity deep-vein thrombosis. Her physical exam revealed tachycardia, otherwise unremarkable, with no skin lesions. Laboratory results showed hyperglycemia (387 mg/dl), Hemoglobin A1C, 9%, and hypoalbuminemia (3.4 g/dl). Her Hemoglobin (13 g/dl), white cell count (6100/μL), and platelet level (19.3 × 104/μL) were within normal limits. The patient underwent CT pulmonary angiogram, which showed a large saddle pulmonary embolism as well as a distal pancreatic mass measuring 4.5×3.4 cm, which contains numerous coarse calcifications. Pancreatic mass was confirmed in a CT abdomen and pelvis with contrast. CA 19-9 was elevated to 51 U/ml (normal range, 0- 35U/ml). The GI team performed an Endoscopic Ultrasound, and samples were sent for FNA and flow cytometry which revealed a 4 cm irregular heterogeneous mass with calcifications at the distal pancreatic body, positive for Pankeratin (CK), Cam 5.2, Synaptophysin, Chromogranin A, and CD56, consistent with Pancreatic neuroendocrine Tumor. Her serum glucagon level was elevated to 447 pg/mL (normal range, 50 -150 pg/mL), while her levels of other hormones, such as somatostatin or gastrin, were within normal limits. Glucagonoma of the pancreas was diagnosed, and a spleen-preserving distal pancreatectomy was performed. Histopathological examination revealed a 5.9 cm alpha-cell pancreatic tumor without lymphovascular or perineural tumor invasion. (AJCC 8th edition staging II, pT3, pN0, MX, G1). Immunohistochemical staining was strongly positive for glucagon. A gallium-68 positron emission tomography (68Ga-PET, Netspot) did not show metastasis. Post resection surveillance showed normalization in Glucagon level and no evidence of recurrence in CT abdomen. Conclusion The diagnosis of glucagonoma is often delayed due to unusual initial manifestations of glucagonoma. Early diagnosis provides a good chance of complete surgical removal as the only curative treatment. Presentation: No date and time listed

ATOS study: effectiveness and safety of insulin glargine 300 U/mL in the real world clinical practice in insulin-naïve type 2 diabetic patients in the Russian Federation

Rationale: Basal insulin glargine 300 U/mL (Gla-300) is a second-generation basal insulin analogue that has comparable efficacy and lower variability compared to the first generation long-acting insulin analogue glargine 100 U/mL.&#x0D; Aim: To assess the effectiveness and safety of Gla-300 in insulin-nave type 2 diabetic patients in the real world practice in Russia.&#x0D; Materials and methods: ATOS (NCT03703869) was a 12-month, prospective observational international multicenter study. The study included 4422 adults ( 18 years) with uncontrolled type 2 diabetes (HbA1c 7 and 11%) with 1 oral anti-hyperglycemic drug and for whom the treating physician had decided to add Gla-300. We performed a post-hoc sub-analysis of the study participants recruited in Russia.&#x0D; Results: The Russian study group included 1493 patients receiving Gla-300. At 6 months, 25.9% of the patients achieved their predefined individualized HbA1c target and 53.3% achieved their HbA1c target at month 12. Their mean ( SD) HbA1c level decreased from 9.3 0.9% at baseline to 7.6 0.7% and 7.2 0.7 at months 6 and 12. The incidence of hypoglycemia was generally low; overall, severe hypoglycemia was reported only in 0.07% and 0.13% of the patients at 6 and 12 months. The baseline average daily dose of Gla-300 was 13.2 4.9 Units; it to 23.6 9.1 and 26.0 9.8 Units at months 6 and 12.&#x0D; Conclusion: In the real world setting, initiation of insulin Gla-300 in type 2 diabetic patients who had been out of their target glucose range with oral hypoglycemic agents is associated with improved glycemic control and low risk of hypoglycemia.