ResearchPad - complications Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-632 Involvement of NF-κB-p65 in BAG3 Regulation After Stress Stimuli]]> We previously identified the limb salvage QTL1 (LSQ-1) on mouse chromosome 7 as a locus that offered protection against ischemic injury following induction of hind limb ischemia (HLI) a model of experimental peripheral arterial disease (PAD) in mice. To better understand the role of the LSQ-1 locus in post ischemic adaptation we characterized several genes within this locus and identified a number of genes that were important in tissue adaptation to ischemia, including BCL2-associated athanogene 3 (BAG3). BAG3 is an anti-apoptotic protein that plays an important role in cell survival through the regulation of autophagy. BAG3 expression is induced in the gastrocnemius muscles of mice after hind limb ischemia but how ischemia regulates BAG3 expression is poorly understood. Additionally, the activation of NF-κB transcription factor is essential for cell survival after stress stimuli. We hypothesized that BAG3 upregulation following stress stimuli is regulated by NF-κB. We determined whether NF-κB is involved in BAG3-mediated survival of primary human skeletal muscle cells (HSMC) during ischemia and diabetic conditions. Within 6 hours of treatment, ischemia induced BAG3 mRNA (no ischemia vs ischemia: 1.0 ±0.09 vs 1.41±0.02; p<0.01) and protein expression (BAG3/total protein, no ischemia vs ischemia 1.0±0.01 vs 1.38±0.06; p<0.01). Knockdown of BAG3 expression by shRNA induced early cell damage in HMSC under ischemic conditions as measured by HMGB1 expression (HMGB1/total protein; control plasmid vs shRNA, 1.0±0.09 vs 1.71±0.04; p<0.01). Knockdown of p65 subunit of the NF-κB by shRNA significantly diminished BAG3 mRNA expression after ischemia (control plasmid vs shRNA: 2.11±0.18 vs 1.48±0.05; p<0.05). Moreover, treatment of HSMC with 750 uM palmitic acid (PA) and 100nM insulin for 3 days to mimic diabetic conditions significantly increased the expression of BAG3 mRNA (control vs PAL+Ins, 1.0±0.14 vs 2.27±0.08; p<0.01) and protein (BAG3/total protein, control vs PAL+Ins, 1.0±0.03 vs 1.39±0.11, p<0.01). Knocking down p65 attenuated these increase in BAG3 mRNA (PAL+Ins vs shRNA+PAL+Ins, 2.27±0.08 vs 1.56±0.02 p<0.01) and protein (BAG3/total protein; PAL+Ins vs shRNA+PAL+Ins, 1.39±0.11 vs 0.99±0.1; p<0.05) Thus, 1) BAG3 expression is important in cell survival under ischemic conditions, and 2) NF-kB plays a key role in upregulating the expression of BAG3 under diabetic and ischemic conditions.

<![CDATA[SAT-LB110 Sulfonylurea-Induced Hypoglycemia: To Use Octreotide or Not]]> Background: Sulfonylurea poisoning can cause sustained hypoglycemia refractory to intravenous dextrose. Traditional treatment for sulfonylurea induced hypoglycemia includes intravenous dextrose and glucagon as well as diazoxide in refractory cases. Octreotide is recommended for sulfonylurea poisoning in adult and pediatric patients with laboratory evidence of hypoglycemia.

Clinical Case: An 89 year-old female with chronic kidney disease stage III, hypothyroidism, and diabetes mellitus type II, hypertension who presented with intractable nausea and diarrhea. Patient had been taking cefdinir for an UTI the prior week. On CT scan of the abdomen, colitis was demonstrated. Clostridium Difficile Assay was positive. She was incidentally found to have profound hypoglycemia with a blood glucose level of 30 mg/dL. Patient had hypoglycemia unawareness. Despite receiving 4 ampules of dextrose 50%, glucose level did not significantly improve. In the ED, patient was afebrile and hemodynamically stable. Her labs were significant for a hyponatremia of 125 mmol/L with an acute kidney injury [AKI] (Cr 1.94 mg/dL from 1.5 mg/dL). Patient was placed initially on a dextrose 5% normal saline infusion, but glucose levels continued to decline after brief response. Due to poor IV access, internal jugular central line was placed and patient was placed on D10NS infusion with good glycemic response. Patient had taken sulfonylurea despite not eating appropriately for 2 days. After 24 hours on D10 normal saline infusion, patient was able to maintain normal to slightly hyperglycemic levels with consistent carbohydrate diet. Her nausea and diarrhea had considerably improved after starting vancomycin 125 mg every 6 hours. Sulfonyurea was indefinitely discontinued.

Conclusion: Patients presenting with sulfonylurea induced hypoglycemia complicated by poor PO intake, AKI, and infection can be safely treated with supportive measures like proper hydration, and dextrose infusion medication is appropriately metabolized by body without the need for octreotide infusion.

References:Glatstein M, Scolnik D, Bentur Y. Octreotide forthe treatment of sulfonylurea poisoning.Clin Toxicol (Phila). 2012 Nov;50(9):795-804. doi:10.3109/15563650.2012.734626. Epub 2012 Oct 10.

<![CDATA[SAT-LB111 Improving Classification of Diabetes Etiology in Electronic Resources Using Phenotype Algorithms and Polygenic Risk Scores]]> Electronic Health Records (EHR) contain rich data to identify and study diabetes. Many phenotype algorithms have been developed to identify research subjects with type 2 diabetes (T2D), but very few accurately identify type 1 diabetes (T1D) cases or more rare forms of monogenic and atypical metabolic presentations. Polygenetic risk scores (PRS) quantify risk of a disease using common genomic variants well for both T1D and T2D. In this study, we apply validated phenotyping algorithms to EHRs linked to a genomic biobank to understand the independent contribution of PRS to classification of diabetes etiology and generate additional novel markers to distinguish subtypes of diabetes in EHR data. Using a de-identified mirror of medical center’s electronic health record, we applied published algorithms for T1D and T2D to identify cases, and used natural language processing and chart review strategies to identify cases of maturity onset diabetes of the young (MODY) and other more rare presentations. This novel approach included additional data types such as medication sequencing, ratio and temporality of insulin and non-insulin agents, clinical genetic testing, and ratios of diagnostic codes. Chart review was performed to validate etiology. To calculate PRS, we used genome wide genotyping from our BioBank, the de-identified biobank linking EHR to genomic data using coefficients of 65 published T1D SNPS and 76,996 T2D SNPS using PLINK in Caucasian subjects. In the dataset, we identified 82,238 cases of T2D but only 130 cases of T1D using the most cited published algorithms. Adding novel structured elements and natural language processing identified an additional 138 cases of T1D and distinguished 354 cases as MODY. Among over 90,000 subjects with genotyping data available, we included 72,624 Caucasian subjects since PRS coefficients were generated in Caucasian cohorts. Among those subjects, 248, 6,488, and 21 subjects were identified as T1D, T2D, and MODY subjects respectively in our final PRS cohort. The T1D PRS did significantly discriminate well between cases and controls (Mann-Whitney p-value is 3.4 e-17). The PRS for T2D did not significantly discriminate between cases and controls using published algorithms. The atypical case count was too low to calculate PRS discrimination. Calculation of the PRS score was limited by quality inclusion of variants available, and discrimination may improve in larger data sets. Additionally, blinded physician case review is ongoing to validate the novel classification scheme and provide a gold standard for machine learning approaches that can be applied in validation sets.

<![CDATA[MON-667 Prevalence and Predictors of Diabetic Retinopathy Among Type 2 Diabetes Patients at a Tertiary Care Center]]> Objective: Diabetic retinopathy (DR) is one of the most common microvascular complications of type 2 diabetes (T2D). The reported prevalence of DR from different populations in the last decade was 13 - 38.1%. A report from our center 17 years ago showed that DR prevalence was 43.6%. With the all accumulated evidence showing that diabetes control decreases DR risk and the introduction of new drugs that helped better T2D control, we aimed to assess the current prevalence and predictors of DR among patients with T2D attending out-patient department at our tertiary care center. Methods: We conducted a cross-sectional study involving 638 patients. We collected information about their baseline characteristics, confirmed DR with its severity and maculopathy diagnosis, age at T2D diagnosis, duration of T2D, and averages of HbA1C, blood pressure (BP), cholesterol, and vitamin D levels over the previous year. A statistical analysis was performed using the software SPSS 23.0. A multivariate logistic regression analysis examined the independent predictors of DR development. Results: The mean age of the patients was 55.8 ± 10.3 years, and 42.8% were males. The mean BMI was 32.4 ± 12.4 kg/m2 with 58% had obesity. The mean duration of T2D was 11.5 ± 7.7 years, and the mean age at T2D diagnosis was 44.0 ± 9.98 years. The mean HbA1C was 8.3 ± 1.6 % with 77% had average HbA1C above 7% and 51.3% had average HbA1c above 8%. The mean systolic and diastolic BP were 136.37 ± 15.01 mmHg and 74.12 ± 8.078 mmHg, respectively. DR was diagnosed in 223 cases (35%). Of the 638 patients, 24.5% had non-proliferative DR, 9.2% had proliferative DR, and 4.2% had maculopathy. There was no significant difference in DR prevalence between males (36%) and females (34.1%) (P = 0.59). Predictors of DR development were age above 40 years, duration of T2D more than 10 years, early age of T2D diagnosis, average HbA1C more than 8%, and hypertension. Discussion: T2D is a major health challenge to our community with its very high prevalence. The prevalence of DR in T2D patients attending our institution was significant (more than one-third, 35%) in comparison to reports from other centers. However, we showed an improvement in DR development in our patients from 43.6% to 35%, probably due to better T2D and BP control. Similar to previous reports, T2D patients with older age, long T2D duration, younger age at T2D diagnosis, uncontrolled diabetes, and uncontrolled BP were more likely to develop DR. Conclusion: Physicians treating T2D patients should ensure regular retina screening especially for those with risk factors for DR. Also, they should fix the modifiable risk factors of DR; diabetes and BP control. References: (1) Alaboud et al. Saudi Med J 2016; Vol. 37 (12): 1408–1411.doi: 10.15537/smj.2016.12.17062. (2) Lim MC et al. Ann Acad Med Singapore. 2008 Sep;37(9):753–9. (3) Hammes H-P et al. PLoS ONE 10(7): e0132492. doi:10.1371/journal. pone.0132492

<![CDATA[SAT-LB116 Extreme Insulin Resistance: The Diagnostic Challenges When Cost Is a Limitation]]> Introduction: Insulin resistance occurs most commonly in association with obesity but may result from multiple causes, e.g. medications, lipodystrophy, or antibodies to insulin or insulin receptors. We review a case of an unusual presentation of insulin resistance. We highlight challenges of diagnostic testing and treatment when there are cost limitations. Clinical Case:A 41 year old Hispanic male with T2DM and a history of well-controlled BPD on quetiapine only presents for management of diabetes. His current treatment is metformin and a TDD of 170 U human insulin; A1C is 12.2%. He was diagnosed at age 32 via routine lab tests. At diagnosis BW was 96.4 kg, BMI 29, BP 100/70, CHOL 152, TG 247, HDL 35, LDL 68. Physical exam was unremarkable without acanthosis or lipodystrophy. Anti-GAD, anti-islet cell antibodies, insulin and C-peptide levels were ordered, but not obtained due to cost. He was managed with lifestyle modification for 2 years with maintenance of A1C <7%. At age 35 he developed symptomatic hyperglycemia with A1C 9.4% and was started on metformin and glyburide. At age 36 A1C was >11%, with no change in BW. Glargine 5 U was added, and glyburide was changed to glipizide. Glargine was increased to 40 U without changes in glycemia. At age 37 glipizide was stopped, and he could not afford glargine. He was switched to 70/30 human insulin. Insulin dosages were progressively increased to 220 U a day with no change in glycemia. Liraglutide was tried but not continued due to cost, and quetiapine was switched to trazodone without improvement in A1C. LFTs, CBC, HIV, Hepatitis C and B have been negative. The patient has had multiple visits for education with documented adequate disease understanding and performance of injections. Nonadherence was suspected; for its evaluation, the patient was observed in clinic self-injecting 30 U of regular insulin (brought from home); fasting was confirmed for 3hrs post-injection. BG was 327mg/dL pre-injection and 326mg/dL 3hrs post-injection. Insulin antibodies were requested but not obtained due to cost. Insulin receptor antibodies are not commercially available in the US. Potential empiric strategies, e.g. the NIH protocol for insulin type B resistance (rituximab + dexamethasone + cyclophosphamide) was considered but cost is a limitation. We discussed steroids or methotrexate for possible antibody mediated insulin resistance versus a trial of thiazolidinedione, which has been reported to decrease severe insulin resistance in patients with lipodystrophy. The patient opted to initially try a thiazolidinedione. Conclusion:Although poor adherence has not been excluded, the patient appears to have no response to high doses of injected human insulin, suggesting extreme insulin resistance. Cost limitations preclude optimal diagnostic evaluation. Empiric treatment with low cost options potentially may provide diagnostic information as well as efficacious treatment.

<![CDATA[SAT-630 Nutritional Influences on One Carbon Metabolism Exacerbate Diabetic Cardiomyopathy and Nephropathy]]> Choline (Ch) exerts a key role as methyl donor in the one carbon pathway and is an essential nutrient for the optimal development and function of a number of biological systems including the cardiovascular and urinary system. Ch-deprivation has been associated with heart function impairment, insulin resistance, abnormal fat metabolism and acute kidney injury. Diabetes mellitus is a common metabolic disorder with increased prevalence in aging and diabetic patients are of higher risk to develop heart and kidney failure. This study aims to investigate the impact of dietary Ch-deprivation on cardiac and renal function in a streptozotocin (STZ) experimentally induced diabetic setting. Twenty-four male adult Wistar rats, were randomly separated into four groups: control, choline deficient through choline deficient diet (CD), STZ induced diabetic (DM) and diabetic-choline deficient (DM+CD) group. After 5 weeks of dietary intervention, echocardiographic measurements, myocardium and kidney histological examination along with Vascular Endothelial Growth Factor-A (VEGF-A165) and Kidney Injury Molecule-1 (KIM-1) immunohistochemistry expression were performed. DM+CD rats demonstrated an exacerbation of myocardial inflammation and fibrosis accompanied by preserved ejection fraction but with an increased left ventricular (LV) wall tension index and velocity and a decreased LV posterior wall thickness compared to DM group. VEGF-A165 expression both in heart and kidneys was abruptly upregulated in the CD rats with a downward trend under the diabetes mellitus entity reaching significant downregulation in the renal tissue. KIM-1 expression was significantly increased under the insult of both choline deficiency and diabetes mellitus depicting a possible synergistic, though detrimental, effect compared to each condition alone.

In conclusion, five weeks of dietary choline deprivation aggravates the inflammation and fibrosis in the heart and kidneys of diabetic rats leading to organ dysfunction. The structural impairment of the choline deprived diabetic heart with evidence of stiffness and dilation of the left ventricular cavity with preserved systolic function indicates the emergence of a new distinct phenotype of cardiomyopathy that combines features of the restrictive and dilated type at the same time. Moreover, in this setting the kidney injury gets worse implying that diabetic nephropathy might establish earlier and accelerate more quickly in choline deficiency conditions.

<![CDATA[SAT-631 Increased Incidence of Diabetic Nephropathy in Veterans with Severe Insulin Resistance]]> Recently, cluster analysis has been used to classify adult onset diabetes based on pathophysiologic profile. Using autoimmunity status, BMI, insulin resistance, and beta cell function, this classification system can predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. Clinically, patients with severe insulin resistance can be defined as those who require high doses of insulin to achieve glycemic control, such as patients on U-500 insulin requiring more than 200 units of insulin a day. To characterize the clinical and metabolic phenotype of insulin-resistant patients from a South Texas VA diabetes clinic, we evaluated presence of macro or microvascular complications and beta-cell autoimmunity and function in this population. A retrospective cohort study was completed at the South Texas VA Diabetes Clinic. Charts were reviewed for anthropometric measurements, presence of macro and microvascular complications, anti-diabetic medication, lipid profile and HbA1c over 3 visits, autoimmunity (anti-GADab), and beta-cell function (fasting C-peptide). Patients with insulin doses >200 U/day or on U-500 insulin were categorized as “severe insulin-resistant”. Those with insulin doses < 0.5 U/kg/day were categorized as “mild insulin resistance” as a control group. Out of 120 patients, 30 met criteria for severe insulin resistance (n=30, M/F=29/1 age 61±1.6 years (yr), BMI 41±0.9 kg/m2, duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U). 30 patients with insulin use <0.5 U/kg/day met criteria for mild insulin resistance (N=30, M/F: 28/2, age 62±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Prevalence of nephropathy was higher in the insulin resistant group vs the mild insulin resistant group (76% vs 43%, p<0.05). There was no difference in prevalence of retinopathy (p=0.095) or CAD (p=0.6) between the groups. There was no difference in use of ACE-i or SGLT-2i between the groups. Insulin resistant subjects had a higher plasma triglyceride (325±0.3 vs 202±0.3 mg/dl, p=0.04). Prevalence of GAD ab was not different between the groups (3% vs 0%). Fasting C-peptide concentrations were similar in both groups (5.6±0.3 vs 5.2±0.25 ng/ml, p=0.3). HbA1c in the insulin resistant group improved between visits 1 and 3 (p<0.01). Weight increased over three visits in the severe insulin resistant group as opposed to mild weight loss in the mild insulin resistant group.

Our results support the high prevalence of diabetic nephropathy in patients with severe insulin resistance, although it is unclear that insulin resistance is the etiology. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications.

<![CDATA[MON-689 Diabetes Mellitus---Hypoglycemic Response---Empyema]]> Diabetes mellitus---hypoglycemic response---empyema

Case report

A 65-year-old woman was admitted to our department due to high blood glucose for two days on February 29, 2016. Fasting blood glucose was 12.53mmol/L on February 28 without polydipsia, polyuria, polyphagia and weight loss.

In the past medical history, she started to cough in January 2016. On February 2, the routine blood examination showed that white blood cells and neutrophils were higher than normal. Chest X-ray was normal. Moxifloxacin was given and symptoms were relieved slightly.

On examination, the temperature was 36.9℃. Auscultation of the chest was normal. On the evening of admission, body temperature rose to 37.8 C. On March 1st, white cell, neutrophil, erythrocyte sedimentation rate and C-reactive protein were increased. FBG was 10.5mmol/L, and HbA1c was 10.5%. Chest CT was normal. Piperacillin Tazobactam Sodium and Moxifloxacin were given, and insulin was used to lower blood glucose.

On March 2, body temperature was normal. And palpitation, tremor, sweating, fatigue and cold extremities appeared several times. Blood glucose test ruled out hypoglycemia. The above symptoms appeared again at around 4 pm, more serious than before. Gas analysis at 5:12pm showed PH 7.403 and lactic acid 19.27mmol/L. At 6:00pm, blood pressure started to drop. Vasoactive drug was given. In gas analysis at 6:27pm, PH was 7.237, lactic acid 21.05mmol/L. 5% NaHCO3 solution was given to buffer acidosis. Cardiac and respiratory arrested during transferring to ICU. Undergoing cardiopulmonary resuscitation, vasoactive drugs and ventilator-assisted breathing were applied. Hemodialysis was used to counteract lactate acidosis. The bedside chest radiograph showed that the transmittance of left lung was decreased. On March 3, the transmittance of left lung was lower. Doctors prescribed Tylenol and Vancomycin. On March 4, left thoracic puncture and catheterization were performed. The pus was drained out and bacterial cultures were made. Klebsiella pneumoniae was cultured. Sensitive antibiotics therapy was chosen according to pleural cultures. On March 9, left empyema was removed and pericardial fenestration was performed by thoracoscope under general anesthesia. Nutritional support had been given. The patient gradually recovered and was discharged on April 9.


Palpitation, tremor, sweating and fatigue were the first manifestations of the condition change in this diabetic patient. The condition rapidly developed into septic shock and empyema. After active treatment, she was cured and discharged from hospital. Besides hypoglycemia, other diseases such as septic shock also may cause the symptoms of sympathetic excitation, which should be considered in order to avoid delaying the time of treatment. Furthermore, diabetic patients complicating with infection should be actively treated with effective antibiotics.

<![CDATA[MON-668 The Content of Serum Clusterin in Patients with Diabetic Macular Edema Depending on the Kind of Glucose Lowering Therapy]]> Relevance. Insight into the pathophysiology of diabetic macular edema (DME) has led to novel treatments, including anti-VEGF, corticosteroid-based treatment strategies and novel therapies, such as a clusterin blood retina barrier (BRB) cytoprotection. It has been shown the protective effect of clusterin on oxidative stress-induced cell death and its emerging roles in reduction of both BRB breakdown and neural retina damage. Goal. To assess the content of serum clusterin in patients with type 2 diabetes (T2D) and diabetic macular edema depending on the type of glucose lowering therapy. Material and methods. This study was conducted in 82 patients with T2D and DME. The average age of patients was 65.25 ± 10.85 years (±SD) [25; 84], the average duration of diabetes was 14.0 ± 7.05 years (±SD) [1; 35], the average level of HbA1c was 8.40 ± 1.58% (±SD). The criteria for inclusion in the open study was voluntary informed consent, age 18 years and more, the presence of T2DM. Non-inclusion criteria were the presence of endocrine diseases, which can lead to type 2 diabetes, T1D, acute infectious diseases, cancer, decompensation of comorbid pathology, mental disorders, antipsychotics, antidepressants, neurodegenerative diseases of the central nervous system, proteinuria, damage to the optic nerve, glaucoma and mature cataracts. 43 patients received oral glucose lowering drugs (OGLD: sulfonylureas, biguanides), 39 patients received insulin therapy. All patients had instrumental ophthalmological examinations. The concentration of serum clusterin was measured by «Human Clusterin ELISA» kits. Statistical analysis was performed by one-way ANOVA analysis. Results. A study of level variability of blood clusterin in patients with DME showed its dependence from the type of glucose lowering therapy. Comparison of mean values of strum clusterin in patients with DME and T2DM revealed the following statistically significant differences: OGLD 87,08 ± 3,15 mcg/ml [95% CI 82,63 - 91,54 mcg/ml]; insulin therapy 74,79±2,98 mcg/ml [95% CІ 70,58 - 78,99 mcg/ml] (р=0,006). Apparently, clusterin is involved in the pathogenesis of DME and may have a potential in reducing of the pathogenic effect of diabetes on the neurovascular unit. The data obtained make it possible to discuss the neuroprotective role of clusterin in DME with the use of voiced oral hypoglycemic drugs, which usually prescribe for patients with mild form of T2D or for the patients with moderate severity T2D (i. e. at the initial stages of development of diabetes). Conclusion. Against the background of glucose lowering drugs in patients with type 2 diabetes and diabetic macular edema statistically significant (р=0,006) increases the content of serum clusterin compared to insulin therapy.

<![CDATA[MON-701 Uncontrolled Diabetes Presenting as Isolated Sixth Nerve Palsy]]> BACKGROUND Our case report demonstrates acute onset of diplopia due to Isolated Sixth Nerve Palsy (ISNP) secondary to uncontrolled T2DM, presenting as an ophthalmoplegia. The most frequent one, is ISNP with an incidence of 11.3/100.000 1. Vasculopathic ISNP is associated with atherosclerosis in patients older than 50 years 1.

CASE PRESENTATION A 63 year-old male with history of T2DM, HTN, HL, came for evaluation of acute onset double vision 3 days prior. He noted diplopia while attempting to park his car; he saw that tracking to the left with his eyes would elicit double vision. Denied recent travel, trauma, headache or dizziness. He was awake and alert, BP 200/110mmHg, BMI 33. No pathologic murmur. He had PERRLA bilaterally but impaired lateral rectus muscle movement on the left side. Otherwise, EOMI on the right side. No facial asymmetry or ptosis. Overall, findings positive for ISNP. BMP only remarkable for a glucose of 297, HA1c was 10.0. Head CT was negative for any acute intracranial abnormality. Orbital MRI did not show acute infarction or masses. Patient was admitted for acute diplopia due to ISNP. Differential diagnoses were neoplasm, migraine, MS and diabetic neuropathy. Based on the aforementioned data, we suggested that T2DM was the probable cause. Counseling on improving glycemic control was given. Unfortunately, patient was lost to follow up. DISCUSSION ISNP remains an elusive entity; atherosclerotic risk factors such as DM, HTN, HL, hyperhomocysteinemia 2 or viral infections 3 have been reported in association. This type of palsy seems to be more frequent in children and can be recurrent in nature.

In adults, the most likely cause of ISNP seems to be ischemic mononeuropathy or more aggressive etiologies such as temporal arteritis 4. Inconclusive images prove even a higher diagnostic challenge 3. Of note, we found a case demonstrating evidence for Eicosapentaenoic Acid in the improvement of ISNP with recovery in as shortly as 8 weeks. The basis of this treatment lies in the recovery of endothelial function focusing on the anti-platelet and anti-inflammatory effects of the drug2,4. REFERENCES (1). Elder, Christopher, et al. “Isolated abducens nerve palsy: update on evaluation and diagnosis.” Current neurology and neuroscience reports 16.8 (2016): 69. (2). Takenouchi, Yasuhiro, et al. “Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice.” Lipids in health and disease 17.1 (2018): 118. (3). Azarmina, Mohsen, and Hossein Azarmina. “The six syndromes of the sixth cranial nerve.” Journal of ophthalmic & vision research 8.2 (2013): 160. (4). Yanai, Hidekatsu, and Mariko Hakoshima. “Eicosapentaenoic Acid for Diabetic Abducens Nerve Palsy.” Journal of Endocrinology and Metabolism 7.4 (2017): 131–132.

<![CDATA[MON-683 Assessment of Features Associated with Diabetic Foot Risk in General Hospital in Lima-Peru]]> Objectives: To determine the frequency of diabetic foot risk of ulceration and associated factors in patients with type 2 diabetes mellitus.

Methods and materials: We used a cross-sectional descriptive design. Data collection was performed in the foot at risk office at Maria Auxiliadora hospital over a period of 3 years, dating from the october 2016 to september 2019.

Foot risk assessment was based on the International Working Group of Diabetic Foot (IWGDF) system, which evaluates peripheral neuropathy (with monofilament or tuning fork), biomechanical deformity, peripheral arterial disease (altered pulse or ankle branchial index) or a history of foot ulcer1,2. Foot risk frequency was found according to epidemiological characteristics, and the prevalence ratios with 95% confidence interval were calculated to association analysis, we perform bivariate and multivariate analysis using a generalized linear model. This study has the approval of the María Auxiliadora HospitaĹs Ethics Committee.

Results: a total of 402 subjects were included in this study, 63.3% were women, average age 62 yo and diabetes duration <10 years in 56%. 76.6% presented risk to develop ulcer, of which 54.7% presented biomechanical deformation, 37.3% Peripheral Neuropathy (NP), 35.4% Peripheral Arterial Disease (PAD), and 12.7% history of foot ulcer. Patients with foot at risk were associated with older age (RP 1,006, 95% CI 1,001-1.01), and with a score> 5 with respect to <5 in the Total Symptom Score (RP 1.26, 95% CI 1.05-1.51).

Conclusions: 3 of 4 patients have a foot at risk of ulceration, predominantly due to biomechanical deformation and peripheral neuropathy, and this risk was associated with older age and greater pain symptomatology.


1. Bakker K, Apelqvist J, Schaper NC. Practical Guidelines on the management and prevention of the diabetic foot 2011. International Working Group on the Diabetic Foot Guidelines. Diabetes Metab Res Rev. 2012; 28(1):225-231

2. Peters E, Lavery L. Effectiveness of the Diabetic Foot Risk Classification System of the International Working Group on the Diabetic Foot. Diabetes Care. 2001 24:1442–7.

<![CDATA[MON-693 Strongyloides Stercoralis Hyper Infestation Syndrome in Type 2 Diabetes: An ANCA Positive Case Report from India]]> A 53-year old male patient with T2D and hypertension for 13 years, presented to Apollo Sugar Clinic, Raipur with recurrent abdomen pain, but no vomiting, constipation, diarrhea or fever. The patient has a past history of asthmatic bronchitis, recurrent eosinophilia, and one month prior to hospitalization, recovered from erythematous maculopapular serpentine rash measuring 6.0 x 1.5 cm over the abdomen post anti-allergic treatment. The patient was neither suffering from immunosuppressive condition nor was on immunosuppressant therapy, had normal vitals but the laboratory findings revealed high total leukocyte count and raised absolute eosinophil count (52%). The provisional diagnosis was made as hypereosinophilic enteritis in a long-standing T2D and hypertension. Immunological tests antinuclear antibody (ANA) and antineutrophil cytoplasmic antibodies (ANCA) resulted in positive ruling out vasculitis. Stool examination detected rhabditiform larvae of S Stercoralis and diagnosed as Strongyloides hyper infestation syndrome. The patient was managed with IV antibiotics, IV fluids, IV insulin and when abdomen pain reduced started with the oral diet. To remove larvae load, unlike routine treatment, the patient was put on albendazole and ivermectin for three consecutive days. After 15 days follow-up patient was completely asymptomatic; at 6 weeks TLC, stool test, ANCA and ANA titer were negative indicating no parasite load. These antibodies detected could be due to molecular mimicry triggered by parasite antigens which may help in diagnosing and monitoring the disease course. ANA and ANCA positive results have been rarely reported in the past for S stercoralis. This unique case of S stercoralis infestation in T2D may enlighten the health care physicians to investigate for this infestation in immunocompromised T2D patients with pain abdomen. Precise diagnosis with timely management can prevent steroid therapy due to eosinophilic enteritis which can be harmful to the patients.

<![CDATA[SAT-LB117 POEMS Syndrome: Rare Presentation of New Onset Diabetes Mellitus]]> Background: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: osteosclerotic myeloma, Castleman disease, increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. Clinical Case: 45 year old male with no chronic medical issues presented initially to the orthopedic clinic with right hip pain, pelvic MRI showed a right iliac crest lesion. CT Guided biopsy was done and showed plasmacytoma. SPEP showed elevated IgG lambda level in the gamma zone. In the meantime he was complaining of ascending numbness and weakness in hands and feet and he progressively became wheelchair bound. During his treatment and follow ups with Hematology/Oncology he was noted to have elevated blood sugars in the 500s. Hemoglobin A1C was elevated at 9.5 which confirmed the diagnosis of new onset diabetes. He was also noted to have splenomegaly which confirmed the diagnosis of POEMS syndrome. He was started on insulin and he managed to achieve good diabetes control with insulin and dietary changes. He is currently status post stem cell transplantation with a good response and the weakness and polyneuropathy improved with PT and OT. POEMS syndrome has major and minor criteria for diagnosis, mandatory major criteria includes polyneuropathy, monoclonal plasma cell proliferative disorder (almost always lambda). Additional major criteria are sclerotic bone disease, castleman disease, elevated VEGF. Minor criteria are organomegaly, extravascular volume load, endocrinopathy, and skin changes. In order to diagnose the syndrome, mandatory major criteria, and one major and one minor criteria need to be clinically present. Endocrinopathy includes the adrenal, pituitary, thyroid, gonadal, parathyroid, and pancreatic glands. Two-thirds of patients had at least one endocrine abnormality at presentation. Endocrine abnormalities can also develop later, during the course of the disease. Hypogonadism is the most common endocrine abnormality. Elevated levels of follicle stimulating hormone in the absence of primary hypogonadism levels have been reported, hence history and physical examination is crucial to detect the development of endocrinopathies in POEMS syndrome. There are no current guidelines or recommendations about the frequency of screening for endocrinopathies but it is suggested to obtain a baseline of thyroid function test, pituitary, gonadal, and adrenal axis. In addition to baseline parathyroid hormone level, close monitoring of calcium and blood glucose levels once the diagnosis is confirmed in patients with suggestive symptoms. Conclusion: POEMS syndrome is a rare condition that involves multiple endocrine organs, currently there are no guidelines or recommendations to obtain baseline endocrine labs once the diagnosis is confirmed, but it might be appropriate if there is a high clinical suspicion. References: 1. Castillo JJ (2016). “Plasma Cell Disorders”. Primary Care.43(4): 677-691. doi:10.1016/j.pop.2016.07.002. PMID 27866585. 2. Warsame R, Yanamandra U, Kapoor P (2017). “POEMS Syndrome: an Enigma”. Current Hematologic Malignancy Reports.12(2): 85-95. doi:10.1007/s11899-017-0367-0. PMID 28299525. 3. Dispenzieri A (2017). “POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management”. American Journal of Hematology.92(8): 814-829. doi:10.1002/ajh.24802. PMID 28699668. 4. Kaushik M, Pulido JS, Abreu R, Amselem L, Dispenzieri A (2011). “Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome”. Ophthalmology.118(4): 778-82. doi:10.1016/j.ophtha.2010.08.013. PMID 21035860.

<![CDATA[MON-707 Improving Screening for Diabetic Retinopathy in a Resident Based Clinic]]> Introduction Diabetic retinopathy is the leading cause of blindness in US Adults. In order to improve screening rates, we partnered with the Division of Ophthalmology and installed an onsite retinal camera at our primary care clinic. This led to an improvement in EMR reported screening rates from 20.5% to 44% over the first 3 months. We noticed that any fundus photo, whether gradable or not, led to an automatic annotation in EMR (EPIC) health Maintenance that screening had been completed. Abnormal or ungradable (quality too poor to interpret) retinal photos must be followed up with a complete ophthalmologic evaluation. We designed a chart audit to investigate further whether ungradable retinal photos were being followed up appropriately. Methods A retinal camera was installed in the clinic, and patients obtained DR screening during their routine visits from May through October 2018. The nursing staff received training on using the camera and ensuring image quality. These images were then sent to an Ophthalmologist and resulted within the work week. Patients with an abnormal or poor-quality retinal photo were contacted by their resident PCP. We did a retrospective chart review of patients with ungradable photos evaluating whether patients were contacted and whether they followed up with Ophthalmology in the 3 month period after the initial intervention. Results Of the 131 patients who received fundus photos in the study period, 29 (22%) had ungradable photos. Twenty-four of these patients were contacted and ophthalmology consults were placed for 22 patients. Eleven (38%) of these patients went on to complete screening with Ophthalmology within 3 months of the ungradable photo. Eighteen patients, or 62% of ungradeable photos, remained incorrectly identified as having completed retinopathy screening by EMR. Discussion Over reliance on EMR reporting features can lead to incorrect assumptions about DR screening. Based on this analysis, we need to design better interventions for following up on ungradable photos and ensuring appropriate follow up. One such intervention may be changing how EMR reports ungradable photos. EPIC is a widely used EMR in outpatient settings and other practices may be facing similar issues.

<![CDATA[MON-700 Protective Effects of Smoking? Improved In-Hospital Mortality in Smokers Admitted for Diabetic Ketoacidosis]]> PURPOSE: To determine the relationship between tobacco smokers and the rate of hospital readmission within 30 days, mortality, morbidity, and health care resource utilization in patients admitted to the hospital in the United States with diabetic ketoacidosis (DKA). METHOD: A retrospective study was conducted using the AHRQ-HCUP National Inpatient Sample for the year 2014. Adults (≥ 18 years) with a principal diagnosis of DKA and a secondary diagnosis of tobacco dependence or active smokers were identified using ICD-9 codes as described in the literature (1). The primary outcome was in-hospital mortality. Secondary outcomes include readmission rate, length of hospital stay (LOS), total hospitalization costs. Propensity score (PS) using the next neighbor method without replacement with 1:1 matching was utilized to adjust for confounders (2). Independent risk factors for readmission were identified using multivariate logistic regression model (3). RESULTS: In total, 186,824 hospital admissions with a primary diagnosis of DKA were identified, of which 32.44% (47,382) had TD. In-hospital morality among the smoking cohort (0.39%, SD 0.03) was lower than the non-smoking cohort (0.32%, SD 0.04) during the first hospitalization. Similar effects were observed after propensity match - 0.33% (SD 0.18) vs 0.27% (SD 0.03). The mortality rate during next hospitalization was also lower in the smoking cohort (0.72%, SD 0.03) in comparison to their counterpart (1.16%, SD 0.01). Smokers had a higher readmission rate of 17.6% (SD 0.57) than non-smokers (9.6%, SD 0.25). The length of stay among smokers and non-smokers were similar after propensity match - 3.12 days (SD 0.03) vs 3.06 days (SD 0.09), p=0.42, respectively. Total hospital cost was also similar between the two groups, $6,898 (SD $82) vs $7,100 (SD $203), p=0.32, respectively. Based on multivariate logistic regression, female and high Charlson comorbidity index were associated with higher 30-day readmission rate; whereas private insurance and high household income were associated with reduced readmission rate. CONCLUSION: Smoking has been associated with improved survival in patients with DKA (4). Previous studies have shown that glucose concentration were significantly lower at fasting and 120 min in current smokers than non-smokers. However, the effects of cigarette smoking on glucose metabolism and insulin resistance are still disputed.

<![CDATA[SUN-624 Low Risk of Major Adverse Cardiovascular Events After Pancreas Transplantation Alone]]> INTRODUCTION: Type 1 Diabetes (T1D) patients have an increased risk for major adverse cardiovascular events (MACE). Pancreas Transplantation Alone (PTA) in patients with T1D achieves near normal glucose control for a prolonged period but limited data are available to date regarding MACE during a 10 year follow up period after the procedure.

OBJECTIVE: We studied incidence of MACE after PTA in T1D patients over a 10 year follow-up period.

METHODS: Retrospectively, we studied 113 T1D recipients of PTA at Mayo Clinic, Rochester with the procedure performed between January 1998 and August 2018 and follow up of at least 1 year. Data were collected before transplantation and up to 10 year follow up after the first PTA. MACE data were gathered until primary non function, re-transplantation, or complete loss of c-peptide (<0.01ng/ml). We report vascular risk factors including hypertension, hyperlipidemia, smoking and BMI along with MACE (defined as cardiac events as unstable angina, Myocardial Infarction (MI), need for re-vascularization, cardiac death, cerebral events as Transient ischemic attack (TIA), stroke, need for re-vascularization and peripheral arterial disease as need for re-vascularization, gangrene and amputation).

RESULTS: Eighteen subjects had pre-transplant MACE. A total of 14 subjects had graft failure within 24 to 36 hours due to thrombosis, with 3 in pre-transplant MACE cohort and 11 in no MACE cohort. Thus, we followed 99 subjects for the development of post-transplant MACE for a period of 6.3 ± 3.6 years. T1D subjects with MACE (n=15) had baseline characteristics: Age 48± 7.8 years, gender F/M 9/6,, duration of diabetes 33 ± 12 years, BMI 26± 3.1(Kg/m2), HbA1c 9.3 ± 1.5% and C-peptide 0.09 ng/ml. 84 T1D patients without MACE were age 42 ± 10.6 years, gender F/M 55/29, duration of diabetes 26.5 ± 10.7 years, BMI 26 ± 5.2(Kg/m2), HbA1c 6.7 ± 2.5 and C-peptide 0.09 ng/ml. There are a total of 584 person-years of follow up to first MACE event and 632 person-years of graft failure, death or last follow-up. Nine patients developed 11 MACE events post-PTA. Therefore, the event rate is 1.5 MACE events per 100 person-years for first MACE event and the total event rate is 1.7 MACE events per 100 person-years of follow-up. Age, smoking (yes), gender, duration of diabetes, HTN and Hyperlipidemia presence did not show any significant impact on post-transplant MACE outcome based on univariate Cox regression but the pre-transplant BMI (HR = 1.14; CI = (1.04, 1.26); p = 0.008) and pre-transplant HbA1c (HR = 1.26; CI = (1.06, 1.51); p = 0.01) showed statistically significant impact.

CONCLUSIONS: At our center, MACE is low in PTA recipients. There is no impact of presence of pre-transplant MACE on development of post-transplant MACE but pre-transplant BMI and HbA1c account for risk of MACE.

<![CDATA[MON-685 Lipodystrophy, a Forgotten Syndrome]]> Background: Lipodystrophy comprises a group of heterogenous congenital and acquired disorders. These disorders may present as a complete or partial loss of adipose tissue. The magnitude of lipoatrophy correlates with the severity of the associated metabolic disturbances, which include severe insulin resistance, progressive liver disease, severe dyslipidemia, among others. The most prevalent form of lipodystrophy is related to antiviral use in patients with HIV. However, lipodystrophy occurring unrelated to medication side effect is often missed due to the heterogeneity and rarity of this disorder.

Clinical Case: 31 year old female with medical history of type 2 diabetes mellitus, hypertension, mixed dyslipidemia and polycystic ovarian syndrome who was referred to our clinics due to difficult to control hyperglycemia. Family history was limited. She was diagnosed with diabetes mellitus at 12 years old after presenting with polyuria, polydipsia and polyphagia requiring oral antidiabetic therapy. Following poor response, she was started on insulin therapy. At 23 years old, the patient had an episode of pancreatitis associated with hypertriglyceridemia and eruptive xanthomas. Insulin pump therapy with regular U-100 insulin, total daily dose of 308 units, was initiated but failed to improve glycemic control. The patient was referred to our Endocrinology clinics due to high insulin resistance and a glycosylated hemoglobin (A1C) at 12% (n < 6.5%). Physical examination revealed a body mass index of 23 kg/m2, abnormal fat distribution predominantly over the neck and face, and acanthosis nigricans. Abdominal ultrasound revealed fatty liver infiltration consistent with intrabdominal fat deposition. Due to the constellation of the aforementioned findings, the diagnosis of partial lipodystrophy syndrome was presumed. She was started on antidiabetic therapy with metformin, pioglitazone and insulin pump therapy with U-500 insulin, and high-dose statin therapy plus fenofibrate for dyslipidemia. At follow up, the patient showed improvement in glycemic control and an improved lipid profile. She was referred to a geneticist for evaluation.

Conclusion: Lipodystrophy syndromes are a group of heterogenous disorders, which may often be overlooked due to their rarity and lack of familiarity by physicians. The diagnosis of lipodystrophy is based on history, abnormal body fat distribution, and metabolic profile. The metabolic disturbances seen in these patients are mainly due to the lack of adipose tissue, which results in impaired energy storage. Early recognition of these syndromes is important because intensive treatment of hyperlipidemia and diabetes prevents development of severe complications. In this case we highlight this rare condition and the successful use of new therapeutic technology with insulin pumps and U-500 insulin in the glycemic control of a patient with lipodystrophy.

<![CDATA[SAT-LB112 An Unusual Case of Ipilimumab/Nivolumab Induced Fulminant Diabetic Ketoacidosis (DKA) in a Non Diabetic Patient - a Case Report]]> INTRODUCTION

Immune Checkpoint Inhibitors (ICIs) have become a revolutionary milestone in the immune-oncology field and have shown a significant improvement in survival rates and outcomes of advanced malignancies. ICIs including: Ipilimumab (1) - monoclonal antibody that inhibits Cytotoxic T Lymphocyte associated Antigen 4 (CTLA4) - Nivolumab (2) - monoclonal antibody that blocks Programmed Cell Death Ligand 1 (PDL1) - and others turn off the tumor mediated immune system inhibition and boost the immune response against tumor cells resulting in decreased tumor growth. However, targeted immunotherapy has a wide spectrum of immune related side effects (3) that can affect various body organs ranging from mild skin rash to a critical immunotherapy induced pneumonitis and severe colitis. We present a case report of Ipilimumab/Nivolumab induced fulminant DKA in a non-diabetic patient.


We present a case of a 71 year old male with a history of hypertension, hyperlipidemia, hemorrhagic stroke and stage 4 renal cancer with metastasis to the lungs who presented to the Emergency Department with altered mental status for 1 day and respiratory depression. He was accompanied by his wife who provided most of the history and denied any head trauma, seizure, uncontrolled hypertension, recent infections, arrhythmias, endocrine diseases or alcohol/drug use. Initial blood glucose was 1052, pH 7.11, bicarbonate 6, potassium 6.7, CO2 20.1, anion gap of 29 and WBCs 19.3 without any source of infections. Diabetic ketoacidosis (DKA) protocol was started and patient was intubated for worsening respiratory depression. Patient’s wife denied any personal or family history of diabetes mellitus and stated that his Hemoglobin A1c (HbA1c) has always been below 6% during his follow ups. Upon further questioning about any new medications, she stated that 15 years ago he had renal cell carcinoma treated with left radical nephrectomy and was recently discovered to have pulmonary nodules that were biopsy positive for renal cell carcinoma, to which he recently started Ipilimumab and Nivolumab immunotherapy about 2 month and last received doses was 3 days prior to presentation. She also reported one-month history of lethargy, polyuria and polydipsia. HbA1c was found to be 8.0% and lipase enzyme > 4000 u/L without any pancreatic changes or inflammation on Computed Tomography (CT) scan of the abdomen. Insulin autoantibodies, islet cells antibodies and serum C-peptide were undetectable. During the admission DKA and respiratory depression resolved but the patient continued to have hyperglycemia with blood glucose level of 300-400 and was treated with correctional insulin scale. Patient was discharged on long acting and regular insulin after appropriate education.


Ipilimumab and Nivolumab; the novel revolutionary targeted immunotherapy have been approved by the United States Food and Drug Administration in 2011 (4) and 2014 (5) respectively. They enhance the immune response against tumor cells through blocking the immune checkpoints CTLA4 and PDL1 which are activated by the tumor cells as an inhibitory mechanism to interrupt the T lymphocyte - tumor cell destruction pathway (6-7).

Ipilimumab and Nivolumab are used in combination for inoperable or metastatic melanoma (8-9), advanced renal cell carcinoma (10), metastatic squamous non-small cell lung cancer (11) and currently in trials for recurrent small cell lung cancer treatment (12-13). They are also used for primary or metastatic urothelial carcinoma and prostate cancer (14).

As ICIs enhance T lymphocytes immunity by disrupting the inhibitory signaling, they also decrease immune tolerance and, thereby; cause autoimmune toxicities. Yet, ICIs are usually not stopped since their beneficial outcomes seem to outweigh the adverse events. Immunotherapy related adverse events (irAEs) includes: systemic symptoms of fatigue, weakness, muscle and joint pain, dermatological: rash and itchy skin - reported in 10% of patients in trials for melanoma and lung cancer (15) - pneumonitis (16) (4%), gastrointestinal: decreased appetite, abdominal pain, nausea and vomiting, colitis (17) (10%), hepatic toxicity (18) (1-17%), and endocrinopathies: hypothyroidism and hyperthyroidism (19) (8.5% and 3.7% respectively). Severe neurologic disorders including acute demyelination polyneuropathy, ascending motor paralysis and myasthenia gravis have been reported (20). Although there are no guidelines for managing irEAs, most of them are managed with high-dose corticosteroids.

Several cases of autoimmune diabetes mellitus have been reported (2% of cases) as endocrinologic irEAs, most of them were genetically susceptible to type 1 diabetes mellitus. Less than 1% of cases had diabetes mellitus of rapid onset and complete insulin insufficiency leading to fulminant DKA (19). However, the clinical course of their insulin secretion disruption was not well studied.

To our knowledge, the case that we are presenting here is one of a few cases described in literature of fulminant diabetes/DKA caused by immunotherapy. In fulminant diabetes, patients present with severely elevated blood glucose or DKA; however, their HbA1c is unexpectedly low (7-8%) due to the abrupt onset of presentation. C-peptide and Islet cell autoantibodies levels are low or even undetectable which suggest that pancreatic B-cells are totally destroyed via a process that is not completely understood and not similar to the one causing classic autoimmune type 1 diabetes mellitus. In fulminant diabetes/DKA pancreatic islet cells are attacked by autoreactive T lymphocytes. Thiswas initially thought to be a cell-mediated phenomenon; however, some reported cases had 1 or more islet cell autoantibodies which suggests the implication of a humoral immune response component as well. Diagnosis of such an endocrinopathy should be proper and prompt due to the increased risk of death within the first 24 hours.


Identification of rare but serious irAEs like DKA, is very important. This requires a multi-dimensional approach involving effective education about the symptoms of DKA and hyperglycemia in patients receiving immunotherapy along with close monitoring of these patients. More research is needed in this area to clarify the frequency of this entity and its mechanism.


This research was supported (in whole or in part) by HCA Healthcare and/or HCA Healthcare affiliated entity. The views expressed in this publication represent those of author(s) and do not necessarily the official views if HCA Healthcare or any of its affiliated entities.


1-Tarhini A., Lo E., Minor D.R. Releasing the brake on the immune system: Ipilimumab in melanoma and other tumors. Cancer Biother. Radiopharm. 2010;25:601-613. doi: 10.1089/cbr.2010.0865.

2-Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8(3):410-416. doi: 10.7150/jca.17144.

3-Kadono T. Immune-related adverse events by immune checkpoint inhibitors. Nihon Rinsho Meneki Gakkai Kaishi. (2017) 40:83-9. 10.2177/jsci.40.83

4-Lacroix, Marc (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7.

5-“Nivolumab Monograph for Professionals”. Retrieved 14 November 2019.

6-Rotte, A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res 38, 255 (2019) doi:10.1186/s13046-019-1259-z

7-Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol. (2018) 8:86. 10.3389/fonc.2018.00086

8-Johnson DB, Peng C, Sosman JA (March 2015). “Nivolumab in melanoma: latest evidence and clinical potential”. Therapeutic Advances in Medical Oncology. 7 (2): 97-106

9-Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (December 2017). “De-novo and acquired resistance to immune checkpoint targeting”. The Lancet Oncology. 18 (12): e731-e741.

10-Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab vs. sunitinib in first-line treatment for advanced renal cell carcinoma: Extended followup of efficacy and safety results from a randomized, controlled, phase 3 trial. Lancet Oncol. 2019 Aug 16;

11-Sundar R, Cho BC, Brahmer JR, Soo RA (March 2015). “Nivolumab in NSCLC: latest evidence and clinical potential”. Therapeutic Advances in Medical Oncology. 7 (2): 85-96

12-S.J. Antonia, J.A. Lopez-Martin, J. Bendell, P.A. Ott, M. Taylor, J.P. Eder, et al.Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial, Lancet Oncol., 17 (2016), pp. 883-895

13-Clinical trial number NCT00527735 at Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC)

14-“Impact of gemcitabine + cisplatin + ipilimumab on circulating immune cells in patients (pts) with metastatic urothelial cancer (mUC). - 2015 ASCO Annual Meeting - Abstracts - Meeting Library”

15-Nivolumab Label. Last updated November 2015.

16-Tay, Rebecca Y. et al., Checkpoint Inhibitor Pneumonitis — Real-World Incidence and Risk, Journal of Thoracic Oncology, Volume 13, Issue 12, 1812 - 1814

17-Som A, Mandaliya R, Alsaadi D, Farshidpour M, Charabaty A, Malhotra N, Mattar MC. Immune checkpoint inhibitor-induced colitis: a comprehensive review. World J Clin Cases. 2019;7(4):405-418. doi: 10.12998/wjcc.v7.i4.405.

18-Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373: 23-34.

19-de Filette J, Andreescu CE, Cools F, Bravenboer B, Velkeniers B (March 2019). “A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors”. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme. 51(3): 145-156. doi:10.1055/a-0843-3366. PMID 30861560

20-“Two Cases of Myasthenia Gravis Seen With Ipilimumab”. 2014-04-29.

21-Godwin, J.L., Jaggi, S., Sirisena, I. et al. Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer. j. immunotherapy cancer 5, 40 (2017) doi:10.1186/s40425-017-0245-2

22-Gaudy C., Clévy C., Monestier S., et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care. 2015;38(11):e182-e183. doi: 10.2337/dc15-1331.

<![CDATA[SUN-620 Gender Difference in the Outcome of Patients with Diabetes Admitted for Hyperosmolar Hyperglycemia. from the National Inpatient Sample]]> Objective: There is paucity of literature on the impact of gender on outcomes of hyperosmolar hyperglycemic state (HHS) among adult patients with diabetes. The aim of this study was to evaluate the effect of gender on the outcome of these patients. Methodology: The National Inpatient Sample (NIS) was queried for all patients who were admitted with a diagnosis of hyperosmolar hyperglycemic state (HHS) during the years 2005-2014. The primary outcomes of the study were all-cause mortality, acute myocardial infarction (MI), and acute stroke. The secondary outcomes were acute kidney injury (AKI), rhabdomyolysis, acute respiratory failure (ARF), need for mechanical ventilation (MV), length of stay (LOS), and total cost of stay. Results: Overall, 188,725 patients were admitted for HHS. Mean age of males was 53.7, standard error of the mean (SEM: 0.13), and of females was 58.5 (SEM: 0.15), p<0.001. Females were (43.9%), Caucasians were 37.4% while African Americans were 35.2%. Total mortality was 1.1%, MI was 1.3% and stroke was 1.1%. Most common secondary outcome was AKI seen in 31.3% followed by ARF seen in 2.9% of total. The mean cost was 7887 $ (SEM: 84.6) and mean LOS was 4.1 days (SEM: 0.03). Both males and females had equivalent rates of mortality, stroke, ARF and need for mechanical ventilation. Compared to males, females had significantly higher risk for MI 1.6% vs 1.1%, p<0.001, lower risk for AKI 29.3% vs 32.9%, p<0.001, lower risk for rhabdomyolysis 1.1% vs 2%, p<0.001 and higher LOS 4.3 vs 3.9 days, p<0..01 and higher total costs 8165.6 $ vs 7669.3 $, p < 0.001. On multivariable analysis, female gender was independently predictive for higher risk for MI with adjusted odds ratio (aOR) 1.34 [95%CI: 1.08-1.67] p=0.01 and lower risk for rhabdomyolysis with aOR 0.52 [95%CI: 0.42-0.63] p<0.001 and lower risk for AKI with aOR 0.74 [95%CI: 0.7-0.78] p<0.001. In addition, female gender correlated with higher cost and length of stay. Conclusion: Females with hyperosmolar hyperglycemic state are at higher risk for MI and lower risk for AKI and rhabdomyolysis.

<![CDATA[SUN-616 Poor Diagnostic Concordance Between Fasting Plasma Glucose and Glycosylated Hemoglobin in a Black South African Population]]> Background: While elevations in fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) are both recognized by the American Diabetes Association (ADA) as diagnostic of hyperglycemia, previous comparisons of these tests have demonstrated discordant individual classifications and population estimates. This may be due to additional postprandial glycemia reflected by HbA1c and, in African-descent populations, to non-glycemic factors that contribute to higher HbA1c at any given level of glycemia. We hypothesized that glycemic classifications based on FPG or HbA1c would differ in a Black South African population and investigated factors associated with discordance.

Methods: 889 Black adults with previously undiagnosed diabetes, aged 40-79 years, from the population-based Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) cohort were included. Concordance between ADA FPG (normoglycemia [NG] <100 mg/dl, prediabetes [pre-DM] 100-125 mg/dl, diabetes [DM] ≥ 126 mg/dl) and HbA1c (NG <5.7%, pre-DM 5.7-6.4%, DM ≥ 6.5%) classifications was assessed using Cohen’s kappa statistic and logistic regression models were used to identify predictors of discordance.

Results: Median age was 55 years (IQR 49-62) and 49.3% of the sample was male. Median glucose was 86.4 mg/dl and median HbA1c was 5.4%. Pre-DM, as defined by HbA1c, was present in 204 participants (22.9%), while FPG-defined pre-DM was present in 122 (13.7%). DM defined by HbA1c was present in 146 (16.4%), while FPG-defined DM was present in 36 (4.0%). Concordance between the two tests was poor (kappa statistic 0.18; 95%CI 0.13-0.24). Self-reported history of tuberculosis (OR 1.90, p=0.026) and higher HbA1c (OR 4.70, p<0.001) were associated with increased likelihood of discordance, whereas higher fasting glucose was associated with decreased likelihood of discordance (OR 0.58, p<0.001). There was no association between discordance and hemoglobin, HIV status, BMI, waist circumference or hip circumference.

Conclusion: FPG and HbA1c exhibit poor concordance in classifying hyperglycemia in this Black South African population, with HbA1c-based definitions identifying higher prevalences of pre-DM and DM. Further work is needed to confirm whether these discrepancies are due solely to elevations in postprandial glucose. In the interim, clinicians should consider confirming elevated HbA1c concentrations with oral glucose tolerance testing, particularly in those with a history of tuberculosis, prior to making a diagnosis of DM in this population.