Serum Beta-hydroxybutyrate Research Articles

PSUN249 Starvation Ketoacidosis as the Presenting Finding of Glycogen Storage Disorder Type III

Abstract A 30-year woman with a history of heart transplantation and a history of post-transplant diabetes mellitus presents with severe euglycemic ketoacidosis. Initial concern was for diabetes related ketoacidosis given history of diabetes however blood glucose was within goal range in the absence of pregnancy and use of sodium glucose transporter type 2 inhibitor use. Initial laboratory evaluation showed a serum glucose of 177 mg/dL, a serum beta hydroxybutyrate of greater than 12.66 mmol/L, serum lactate of 0.6 mmol/L, with a calculated anion gap of greater than 30 mmol/L. C-peptide levels were repeatedly normal and appropriate for blood glucose level ranging between 2.8 ng/mL and 7.5 ng/mL ruling out insulin deficiency as causative. It was discovered that the patient had intentionally fasted for greater than 18 hours and thus had not used the premixed insulin regimen prescribed. Metabolic disturbance corrected with a dextrose and insulin infusion. Evaluation for inborn error of metabolism showed: acylcarnitine panel returned normal making an inborn error of fatty acid metabolism unlikely. The mitochondrial DNA mutation panel was negative for point mutations or deletions. Further testing for urinary organic acids did not reveal elevation of 3-hydroxybutyric acid suggesting SCOT enzyme levels were sufficient in our patient. Review of pathology records for heart transplantation completed for idiopathic cardiomyopathy 20 years prior to this presentation showed high levels of glycogen deposition prompting evaluation for glycogen storage disorders. Results revealed a heterozygous abnormality at exon 9 of the AGL gene; AGL gene c.1139A>G (p.Glu380Gly). This is not a reported pathologic mutation, and given the heterozygosity of the mutation in this autosomal recessive condition, it is felt that either environmental factors or the presence of other unrecognized genetic mutations allowed for the phenotypic expression of GSDIII with euglycemic starvation ketoacidosis. The patient was treated with dietary counseling regarding ketone suppression with basal insulin during periods of fasting and preference to avoid periods of prolonged fasting with frequent carbohydrate-containing meals. Conclusion This case represents a novel, potentially pathologic defect in the AGL gene. This finding should prompt further investigations into genetic variabilities that may lead to this phenotypic expression. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

LBSUN290 A Rare, Sordid Tale Of The Two Most Dreaded Adverse Effects Of SGLT-2 Inhibitors Occurring Concurrently - Acute Pancreatitis And Euglycemic Diabetic Ketoacidosis - Within Days Of Initiating Empagliflozin Therapy.

Abstract Introduction Empagliflozin is an anti-diabetic agent belonging to the class of SGLT-2 inhibitors, which was approved by the U. S. Food and Drug Administration (FDA) in 2013. It has emerged as a popular choice of second line diabetic therapy owing to benefits of reduction in cardiovascular adverse events and delayed progression of kidney disease. However, in 2015, FDA issued a safety warning in connection to its use with euglycemic ketoacidosis and subsequently in 2016, started investigating its link with pancreatitis. We present a case of a type 2 diabetic started on Empagliflozin therapy 4 days prior to his presentation to the ER with nausea, vomiting and diarrhea when he was found to have concurrent euglycemic DKA and acute pancreatitis. Case presentation A 49 year old male with a history of diabetes mellitus type 2 presented to the ER with nausea, vomiting, diarrhea and fatigue. He reported these symptoms since starting a new anti-diabetic agent Empagliflozin four days ago. He denied fever, chills, chest pain, shortness of breath, abdominal pain, and urinary symptoms. He denied heavy alcohol use or binge drinking. Lab tests showed: WBC count 18.7 k/mm cu (4 -11), Glucose 229 mg/dL (70 - 99), Bicarbonate 7 mmol/L (21 - 31), Anion gap 30 mmol/L (6 -14), Lactate 1.8 mmol/L (0.7 - 2.5), Serum beta hydroxybutyrate level >4 mM (0. 02 - 0.27), Lipase 866 IU/L (11 - 82) and Venous blood pH 6.98 (7.30 - 7.45). Repeat blood glucose measurements remained < 250 mg/dl. Urinalysis showed > 500 mg/dl glucose. CT abdomen and pelvis showed moderate fat stranding consistent with acute pancreatitis. He was started on insulin infusion and admitted to the intensive care unit. He was subsequently discharged on a basal-bolus regimen with instructions to discontinue Empagliflozin. Discussion Acute pancreatitis and euglycemic DKA are grave clinical entities, associated with significant mortality. Our patient presented with nausea, vomiting, diarrhea and fatigue; he denied the characteristic abdominal pain yet was noted to have pancreatitis by laboratory and imaging studies. It is extremely important that pancreatitis be considered and ruled out in patients presenting with non-specific symptoms while on SGLT-2 inhibitor therapy. In addition, a high radar of suspicion should be maintained in both inpatient and outpatient settings for euglycemic DKA in patients on SGLT-2 inhibitor therapy presenting with non-specific symptoms, even in the absence of a classic identifiable triggering event, especially as there is evidence to suggest that pancreatitis may actually serve as a triggering factor for euglycemic DKA suggesting that, due to a cause-effect phenomenon, these two conditions may co-exist more often than expected. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes.

To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n=12) or placebo (n=11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater. During the 7- to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( -27.6 vs. -4.4mg/dL [-1.5 vs. -0.2 mmol/L]; P=0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants. When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

Metabolic profile and productivity of dairy Holstein cows milked by a pasture-based automatic milking system during early lactation: Effects of cow temperament and parity

This study aimed to evaluate the influence of temperament and parity on milk production and metabolic responses of Holstein cows in a pasture-based automatic milking system. Thirty-five primiparous and 58 multiparous cows were classified as ‘calm’, ‘intermediate’ or ‘reactive’ in each of the temperament tests conducted: milking reactivity (MR), race time (RT), flight speed, and flight distance. The milk yield and milk composition, as well as the blood biochemistry, were measured during the first 10 weeks of lactation. Primiparous cows produced less milk than multiparous cows (24.0 ± 0.8 vs. 34.2 ± 0.6 L/d, respectively, P ˂ 0.0001), while the serum beta-hydroxybutyrate concentration differences according to parity were not detected. Multiparous cows that were classified as ‘reactive’ on MR and RT tests produced 3 kg/d more milk and had greater concentrations of milk components than ‘calm’ cows (P ≤ 0.05). There was no such relation in primiparous cows. Also, cows scored ‘reactive’ on RT showed greater milking frequency (2.50 ± 0.05 vs. 2.35 ± 0.04 milking/d; P = 0.01) and blood beta-hydroxybutyrate concentrations (1.28 ± 0.09 vs. 0.92 ± 0.10 mmol/L; P = 0.04) than RT ‘calm’ cows. In conclusion, the cows' temperament was associated with milk production and metabolism, which depended on parity and the temperament tests used. Although productive performance was different between parities, lipomobilization was not.

Oversupplying metabolizable protein during late gestation to beef cattle does not influence ante- or postpartum glucose-insulin kinetics but does affect prepartum insulin resistance indices and colostrum insulin content.

The objective of this study was to evaluate whether oversupplying metabolizable protein (MP) during late gestation influences glucose and insulin concentrations, and insulin resistance (IR) in late gestation and early lactation. Crossbred Hereford, first-lactation heifers were individually fed diets to supply 133% (HMP, n = 11) or 100% (CON, n = 10) of their predicted MP requirements for 55 ± 4 d (mean ± SD) prior to calving. All heifers received a common lactation ration formulated to meet postpartum requirements (103% MP and 126% ME). After feed was withheld for 12 h, cattle underwent an intravenous glucose tolerance test (IVGTT) on days -6.7 ± 0.9 and 14.3 ± 0.4 by infusing a 50% dextrose solution (1.36 g glucose/kg BW0.75) through a jugular catheter with plasma collected at -10, 0 (immediately after infusion), 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, and 120 min, respective to the infusion. Glucose and insulin concentrations were assessed. Insulin resistance indices (homeostasis model of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], revised quantitative insulin sensitivity check index [RQUICK], and RQUICKI incorporating serum beta-hydroxybutyrate concentrations [RQUICKIBHB]) were calculated from measurements of serum non-esterified fatty acids and beta-hydroxybutyrate and plasma glucose and insulin concentrations on days -34 ± 4, -15 ± 4, 7 ± 1, 28 ± 3, 70 ± 3, and 112 ± 3. Colostrum samples were collected within an hour of calving (prior to suckling) and analyzed for insulin concentration. Data were analyzed as a randomized block design using the PROC GLIMMIX of SAS, accounting for repeated measurements when necessary. Baseline (-10 min) plasma glucose and insulin concentrations were elevated (P ≤ 0.038) for HMP heifers during the antepartum IVGTT, but not (P ≥ 0.25) during the postpartum IVGTT. Plasma glucose and insulin concentrations throughout the antepartum or postpartum IVGTT did not differ (P ≥ 0.18) by prepartum treatment, nor did other glucose and insulin IVGTT parameters (i.e., max concentration and time to reach max concentration, nadir values, clearance rates and half-lives, area-under-the-curve, and insulin sensitivity index; P ≥ 0.20). Antepartum IVGTT IR indices indicated that HMP heifers were more (P ≤ 0.011) IR than their counterparts. Similarly, the prepartum HOMA-IR was greater (P = 0.033) for HMP heifers, suggesting increased IR. Postpartum IR indices did not (P ≥ 0.25) indicate that prepartum MP consumption impacted postpartum IR. Colostrum insulin concentration was increased (P = 0.004) by nearly 2-fold for HMP relative to CON heifers. These data demonstrate that prepartum MP overfeeding alters baseline glucose-insulin concentrations in late-pregnant beef heifers and increases colostrum insulin content without having carry-over effects on postpartum glucose-insulin concentrations and IR.

Phase I single center trial of ketogenic diet for adults with traumatic brain injury.

Traumatic Brain injury (TBI) is a major cause of mortality and morbidity in the United States. Ketogenic diet (KD) has been shown to have neuroprotective effects in acute brain injury, but limited data about its use in adult TBI patients is available. The objective of this study is to investigate the feasibility and safety of ketogenic diet (KD) for adult TBI patients in the Neuroscience Intensive Care Unit (NSICU). TBI patients admitted to NSICU between June 2019 to March 2021 were enrolled in this single-center, open label, single-arm prospective intervention study. The primary feasibility outcome was achievement of ketosis (detection and maintenance of serum beta-hydroxybutyrate (BOB) levels above normal); secondary outcomes included laboratory and clinical adverse effects related to KD. 10 adults with TBI with Abbreviated Injury Score (AIS)-Head ≥3 and ventriculostomy catheter to monitor intracranial pressure met inclusion/exclusion criteria and were placed on KD. Mean age was 47 years, and all patients were male. Eight out of 10 patients achieved ketosis within mean 2.2 days. KD was initiated within 8-33h (average 23h) of hospital admission. No clinical adverse effects were noted, 2 patients developed hypertriglyceridemia and 1 patient developed hypoglycemia. Serum glucose showed a decreasing trend in most patients. This pilot study shows that KD is feasible in the management of TBI patients. A randomized controlled trial (RCT) is justified to further understand the optimal serum BOB levels, dose and duration of KD in TBI and its effect on the outcome. CLINICALTRIALS. NCT03982602, Registered 06/11/2019, https://clinicaltrials.gov/ct2/show/NCT03982602?term=brain+injury&cond=ketogenic+diet&draw=2&rank=3.

SEVERE LACTIC ACIDOSIS SECONDARY TO ACUTE ALCOHOL INTOXICATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Alcoholic ketoacidosis is one of the several etiologies where serum lactate level rarely exceeds 3 mmol/L. We present to you an interesting case of severe lactic acidosis (24 mmol/L) in a patient with acute alcohol intoxication. CASE PRESENTATION: Patient is a 62-year male who presented with intractable abdominal pain for 2 days. Past medical history was significant for alcohol use disorder. On presentation, patient had tachycardia, tachypnea, was restless with slurred speech with mild abdominal tenderness. Laboratory findings were remarkable for leukocytosis of 22.7, serum bicarbonate of 4 mmol/L, serum glucose 104 mg/dL, serum lactate 24 mmol/L. ABG showed pH of < 7.00, pCO2 12 mmHg, HC03 4.6 mmol/L. Anion gap was 41.0. Serum ethanol level was elevated at 0.185 g/dl. Patient was started on bicarbonate infusion, IV thiamine with 5% dextrose fluid and CIWA protocol. Serum beta hydroxybutyrate was elevated at 2.9, serum osmolality was elevated at 344 with osmolar gap of 13. LFT was deranged with unremarkable liver ultrasound. Patient was admitted to the ICU. Serum isopropanol, methanol, and ethylene glycol were negative. Infectious workup including blood culture, urine culture, pneumonia workup were negative. Acetaminophen and salicylate levels were normal. Urine drug screen was unremarkable. No history of GI malabsorption (short-bowel syndrome), renal failure or recent phenobarbital administration. Lactic acidosis was therefore attributed to alcoholic ketoacidosis in a setting of alcoholic hepatitis. Patient gradually improved with final pH 7.38, lactate 1.80 and serum HC03 24.6 by day 2. DISCUSSION: Lactate level of > 4 mmol/L with arterial pH < 7.35 suggests lactic acidosis. Lactic acidosis is broadly classified into type A which occurs due to impaired systemic tissue oxygenation and type B due to toxin induced cellular metabolism impairment and regional ischemia, commonly in alcoholism, HIV, antiretroviral medications, beta adrenergic medications, D lactic acidosis (short-bowel syndrome), diabetes mellitus, metformin, malignancy. Alcoholic ketoacidosis remains important etiology as if missed may result in fatal consequences including sudden death. Occasionally, alcoholic ketoacidosis can be misdiagnosed as diabetic ketoacidosis with subsequent mismanagement resulting in increased morbidity and mortality. CONCLUSIONS: Alcoholic ketoacidosis typically presents with metabolic acidosis but rarely with lactate > 3mmol/L in absence of other contributing factors. Oftentimes, the diagnosis is missed or misdiagnosed as diabetic ketoacidosis resulting in mismanagement contributing to increased morbidity and mortality. REFERENCE #1: Adeva-Andany, M., et al. 'Comprehensive Review on Lactate Metabolism in Human Health'. Mitochondrion, vol. 17, July 2014, pp. 76–100. PubMed, doi:10.1016/j.mito.2014.05.007. REFERENCE #2: Kreisberg, R. A. 'Lactate Homeostasis and Lactic Acidosis'. Annals of Internal Medicine, vol. 92, no. 2 Pt 1, Feb. 1980, pp. 227–37. PubMed, doi:10.7326/0003-4819-92-2-227 REFERENCE #3: Madias, N. E. 'Lactic Acidosis'. Kidney International, vol. 29, no. 3, Mar. 1986, pp. 752–74. PubMed, doi:10.1038/ki.1986.62 DISCLOSURES: No relevant relationships by Luna Khanal, source=Web Response No relevant relationships by Adarsha Ojha, source=Web Response

Method comparison of beta-hydroxybutyrate point-of-care testing to serum in healthy children.

Ketone production is a physiological phenomenon that occurs to avoid irreversible neurological damage from hypoglycemia, thereby serving as a marker of metabolic stress. The primary ketone body, beta‐hydroxybutyrate (BHB), guides the diagnostic evaluation and management of many hypoglycemic disorders. Serum and point‐of‐care (POC) BHB values were not been compared in children without diabetes or metabolic disorders. We aim at comparing the serum and point‐of‐care BHB values in healthy children after an overnight fast. Eligible participants were ≤18 years of age prospectively recruited from elective procedures through our surgery centers. Exclusion criteria included a history of diabetes, hypopituitarism, adrenal, metabolic or inflammatory disorders, dietary restrictions, trauma, or use of medications that might affect blood glucose. The main outcome measure was comparing serum and POC BHB levels after a period of fasting. Data from 94 participants (mean age 8.29 ± 5.68 years, 54.3% male, 45.7% female, BMI mean 19.28 ± 5.25 kg/m2) were analyzed. There was a strong correlation between serum BHB (mean 0.25 ± 0.23 mmol/L) and POC BHB (mean 0.18 ± 0.20 mmol/L) (r s = 0.803, p < 0.0001). The majority (96.81%) of values for serum BHB compared with POC BHB fell within 0.1 ± 0.1 mmol/L. The average of difference between serum and POC BHB (the bias) was 0.064 mmol/L (95% CI 0.047–0.081), and percentage error was 3.19%. Point‐of‐care BHB is accurate and comparable to serum BHB levels in our cohort of children after an overnight fast.SynopsisPoint‐of‐care BHB agrees with serum values in healthy children.

Alpelisib-Induced Diabetic Ketoacidosis- A Case Report

Background: Alpelisib, in combination with Fulvestrant, was approved in 2019 by the Food and Drug Administration for treatment of HR+, HER2- advanced or metastatic breast cancer in patients with PIK3CA mutation. a This combination is currently on phase III of study. One of the most common side effects is hyperglycemia. Rarely, this can be severe enough to induce diabetes ketoacidosis, which is an indication for interrupting Alpelisib treatment. Clinical Case: A 78 year old female presented to our emergency department with altered mentation. Her past medical history is significant for metastatic breast cancer, with known PIK3CA mutation, started on alpelisib three months prior. Concomitantly, despite not carrying a diagnosis of diabetes mellitus, the patient was started on metformin, due to the known side effect of hyperglycemia. Upon admission, the patient was found to be tachycardic and otherwise hemodynamically stable. Pertinent laboratory studies revealed an initial serum glucose of 600 (nl 70–100) mg/dL, potassium of 5.4 (nl 3.5–5.1) mmol/L, serum carbon dioxide of 8 (nl 21–32) mmol/L, calculated anion gap of 25 (nl <12) mEq/L, and a serum beta-hydroxybutyrate > 4.50(nl 0.02–0.27) mmol/l. ABG revealed a pH of 7.11, PaO2 of 102, pCO2 of 11, and a lactate of 4.0 mmol/L. Glycated hemoglobin was 10.7% (nl <6.5%). EKG revealed sinus tachycardia with PACs, abnormal anterolateral T wave inversion, and a QTc of 519 msec. Initial troponin was elevated at 0.15 with a max troponin at 1.40 ng/mL. Urinalysis revealed glucosuria. Chest x-ray showed no acute cardiopulmonary process. Blood cultures were negative to completion. Patient was admitted for diabetic ketoacidosis and was started on DKA protocol which included aggressive hydration with sodium chloride and insulin drip. Alpelisib was discontinued immediately. Upon resolution of the anion gap metabolic acidosis, the patient’s encephalopathy significantly improved. She was transitioned to subcutaneous insulin. During the same hospitalization, the patient’s serum glucose rapidly normalized and she did not require insulin at the time of discharge. Conclusion: Diabetic ketoacidosis is an unusual but life-threatening side effect of Alpelisib, even in patients without an underlying diagnosis of diabetes mellitus. This case suggests that such patients should have a close monitoring of glycemic control and intensification of their anti-diabetic medications if required, to prevent hyperglycemic crises.

A Moderate‐Protein and Controlled‐Phosphorus Ketogenic Food Improves Lipid Metabolism in Dogs while Preventing Elevations in Circulating Urea and Phosphorus

Objective Ketogenic foods (KF) limit digestible carbohydrate (carb) and offer benefits to disease management including cancer, diabetes, renal failure and cognition. While companion dogs are susceptible, their metabolic response to ketogenic foods that vary in protein/fat ratio is not known. We sought to compare metabolic effects of two KF varying in protein/fat, and further compare their effects to a standard adult food (CON). The first KF (KFA) was commercially available and the second (KFB) was developed for this experiment as a moderate protein, controlled phosphorus (Pi) food to make it amenable to at-risk populations. Methods Dogs housed in pairs, with daily group exercise in outdoor grassy runs. All dogs returned to the colony healthy after the study; no invasive procedures. Fasted blood collections under approved protocols. Macronutrients (P/F/C; % energy): CON (21/32/48); KFA (52/42/5); KFB (26/68/5). Food ash, Pi (dry mass, DMB): CON (ash 4.9%, Pi 0.68%), KFA (ash 8.6%; Pi 1.2%), KFB (ash 4.9%, Pi 0.58%). Prospective randomized crossover trial (n = 16). CON the wash-in food followed by KFA then KFB in randomized order (5 wk feeding each). Foods by AOAC methods. Serum beta-hydroxybutyrate (BHB) by enzymatic reaction. Clinical measurements by Cobas. Fatty acid (FA) elongase (ELO) and desaturase (ACD) substrate/product ratios by GC-FID from serum FA. Linear mixed modeling for diet effects. Least-squared means with pooled variance presented. Significance at a = 0.05. Results Ketogenic ratios (KR) of the foods: CON (KR 0.46), KFA (KR 0.97), KFB (KR 1.63). Clinical blood values remained in normal ranges. Despite only 5% carb as energy, the KFA food was not ketogenic; KFA (KFA 101.2 ± 0.09 uM) did not elevate serum BHB above that of the CON food containing 48% starch as energy (CON 93.6 ± 0.09 uM). In contrast, the KFB food was ketogenic; increasing BHB (KFB 143.8 ± 0.09 uM) relative to both KFA and CON. Serum glucose was not different. The KFA elevated insulin and glucagon relative to CON; the KFB food not different from KFA or CON. The KFA increased blood urea and Pi above KFB and CON; KFB food was not different from CON. Liver enzymes ALP and AST were lowest when dogs were fed KFB. Both KFA and KFB decreased serum triglycerides (TG) by 30% compared to the CON food, but increased total cholesterol. The KFB decreased the product/substrate ratios of d-9 (16:1/16:0, 18:1/18:0) and d-5 ACD (20:4n6/20:3n6) but increased that of d-6 ACD (18:3n6/18:2n6, 20:3n6/18:2n6). KFB also increased apparent these ratios for ELOs elov5 (20:3n6/18:3n6) and elov6 (18:0/16:0). Conclusions: A low-carb, moderate protein, controlled Pi ketogenic food increased circulating ketone BHB 40% above that of a low-carb food that contained 80% more protein. Moderating protein and reducing Pi in the KFB prevented elevations in blood urea and Pi that occurred with KFA. Thus, high levels of protein and ash may limit a food's ketogenic potential and it's use in renal patients. The TG-lowering effect of ketogenic foods observed in humans was mirrored in this canine study; we further found that KFB altered fatty acid metabolism. These results will further enable the personalization of nutritional recommendations for ketogenic foods to benefit a broad spectrum of health states.

Influence of Different Lactation Stages on Circadian Rhythmicity of Metabolic Biomarkers in Dairy Cows: A Pilot Study.

Simple SummaryCircadian rhythms are present in most species and play an important role in their metabolism. Metabolic biomarkers, which are commonly used to assess the health status, are also affected by those rhythms. In this study, we investigate the influence of lactation and time on four metabolic biomarkers in dairy cows. Our findings provide new insights into the physiology of circadian rhythms in dairy cows, which enables novel metabolic monitoring approaches.Currently, subclinical metabolic imbalances at the individual cow and herd level are detected by measuring biomarkers in single blood samples. However, diurnal variations have not been fully described yet but need to be considered when sampling for a robust ad consistent analysis. The study describes the influence of lactation phases on circadian rhythms and diurnal variations for non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), total bilirubin (tBIL) and aspartate aminotransferase (AST) in dairy cows. In an observational pilot study, we used 16 clinically healthy Simmental dairy cows subdivided in four different lactation stages (dry-off, fresh, high and late lactating). Every cow was monitored for 24 h, with blood sampling and assessment of clinical parameters every 2 h. Time and lactation stage influence the concentration of the biomarkers NEFA, BHB and tBIL in serum. Further, circadian rhythmicity was found in high lactating cows for NEFA peaking at 5:39 am and BHB peaking at 4:20 pm. We suggest blood sampling for single-point measurements within three hours after the first feeding until two hours after the last feeding of the day. The results provide a new insight into the physiology of circadian rhythms in dairy cows and enable improved metabolic monitoring.

Euglycemic diabetic ketoacidosis associated with SGLT2i use: Case series.

Euglycemic diabetic ketoacidosis (EuDKA) associated with Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) use has been described but remains poorly understood. Data on Emergency Department (ED) presentation, resource utilization, and safety outcomes for these patients are lacking. We report a case series of patients diagnosed with EuDKA in the ED. An electronic medical record search identified adult patients presenting to a large tertiary ED with EuDKA. They were screened for concurrent use of SGLT2i. Clinical presentation, resource utilization, safety, and disposition data were collected and described. Five patients were included for analysis. Median age [range] was 57 [43-73] years. Presenting symptoms included nausea, vomiting, fatigue, and altered mental status. Initial results included: serum glucose 191mg/dL [176-215], venous pH7.01 [6.95-7.30], serum HCO3 8mEq/L [6-13], anion gap 27 [26-31], serum beta-hydroxybutyrate 9.9mmol/L [9.2-12.3], and urine ketones 150 [150-150]. Patients remained on an insulin infusion for 18.77h [11.25-56.48]. There were zero episodes of hypoglycemia and one episode of hypokalemia while on insulin infusion. Time to resolution of metabolic acidosis was 23.82h [15.45-24.77]. We report a case series of ED patients with EuDKA associated with SGLT2i use, and describe presentation characteristics, resource utilization, and safety outcomes. Emergency physicians should be aware of the association between SGLT2i use and EuDKA. An appropriate work-up should be pursued for patients taking an SGLT2i who present with symptoms suggestive of DKA, including nausea, vomiting, malaise, and altered mental status, or are noted to have an unexplained elevated anion gap metabolic acidosis.

MOVEMENT DISORDER AS A MANIFESTATION OF DIABETIC KETOACIDOSIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Movement disorders are well-defined presentation of non-ketotic hyperglycemia (NKH) but are rarely associated with diabetic ketoacidosis (DKA). Here we present a rare case of movement disorder in DKA. CASE PRESENTATION: A 50-year-old female with a past medical history of HIV, migraine and hypertension presented to our tertiary care center with a chief complaint of sudden onset involuntary movement of her right upper extremity. She reported 4 days of generalized weakness as well. On physical examination, she was alert and well-oriented with choreiform movements localized to her right upper extremity. Decreased muscle strength (3/5) of her right upper extremity was also noted. No other neurological deficits were observed. Laboratory evaluation revealed serum glucose 1147 mg/dl, sodium 136 mEq/L, potassium 6.3 mEq/L, HCO3 16 mEq/L, chloride 93 mEq/L, creatinine 2.17 mg/dl, TSH 0.88 mIU/L, calcium 9.1 mg/dl and HbA1C 14%. Urinalysis revealed 1+ ketones and serum beta-hydroxybutyrate was positive. CT head was unremarkable. Patient was treated with tissue plasminogen activator (tPA) due to clinical suspicion of stroke and was started on IV fluids and insulin. MRI brain was negative for any acute ischemic process and MR angiogram of head was normal. Her serum glucose gradually normalized with insulin drip. Involuntary right upper extremity movement gradually improved as serum glucose normalized and completely resolved on 3rd day. Patient was back to her baseline with no residual weakness on 6th day of presentation. DISCUSSION: Sudden onset chorea is an uncommon presentation of DKA. Mechanism of DKA induced movement disorder remains unclear although several hypotheses have been proposed to explain the pathophysiology of movement disorder in NKH. Most patients show hemichorea-hemiballism with upper extremity involvement similar to our patient[1,3]. Characteristics MRI findings in basal ganglia were reported but imaging finding is not a prerequisite for the diagnosis of hyperglycemic movement disorder as seen in our patient[3]. Chorea is associated with a large number of hereditary and systemic diseases such as stroke, hyperthyroidism, NKH, hypocalcemia, and renal failure. It is the most common movement disorder to occur as a result of stroke. A variety of drugs have been reported to cause chorea[2]. Significant rapid improvement in symptoms after blood glucose control and anion gap closure in our case proves the role of DKA in movement disorder. CONCLUSIONS: Movement disorders are presenting symptoms for a variety of medical conditions and disorders. It can manifest as a presenting complaint in DKA. Early recognition and appreciation of these disorders will help clinicians narrow the diagnosis and avoid inadvertent use of medications. Reference #1: Jagota P, Bhidayasiri R, Lang AE. Movement disorders in patients with diabetes mellitus. Journal of the Neurological Sciences. 2012 Mar 15;314(1):5–11. Reference #2: Barton B, Zauber SE, Goetz CG. Movement Disorders Caused by Medical Disease. Semin Neurol. 2009 Apr;29(2):97–110. Reference #3: Lee S-H, Shin J-A, Kim J-H, Son J-W, Lee K-W, Ko S-H, et al. Chorea-ballism associated with nonketotic hyperglycaemia or diabetic ketoacidosis: Characteristics of 25 patients in Korea. Diabetes Research and Clinical Practice. 2011 Aug;93(2):e80–3. DISCLOSURES: No relevant relationships by Anisha Adhikari, source=Web Response No relevant relationships by Prashank Neupane, source=Web Response No relevant relationships by Bharadwaj Satyavolu, source=Web Response No relevant relationships by Zed Seedat, source=Web Response

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study.

Concussion is the most common form of mild traumatic brain injury (mTBI). Although most patients' symptoms resolve within a month, patients with post-concussion syndrome (PCS) may continue to experience symptoms for years and have limited treatment options. This pilot study assessed the feasibility and symptom-related effects of a ketogenic diet (KD) in patients with PCS symptoms. The Ketogenic Diet in Post-Concussion Syndrome (KD-PCS) was a single-arm trial of a 2-month KD high in non-starchy vegetables and supplemented with medium-chain triglyceride (MCT) oil. Macronutrient targets were ≥70% fat, ≤10% carbohydrate, and the remainder as protein as energy. We assessed feasibility by daily self-reported measure of urine acetoacetate and collection of 3-day food records and serum beta-hydroxybutyrate at multiple timepoints. We assessed symptoms by administering the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Modified Balance Error Scoring System (M-BESS) at baseline and month 2 and the Post-Concussion Symptom Scale (PCSS) at baseline, month 1, and month 2. Fourteen participants enrolled in the KD-PCS. Twelve participants completed the study and 11 implemented the KD (73% fat, 9% carbohydrate, and 18% protein) and achieved ketosis. One participant complained of MCT-related diarrhea that resolved and another reported nausea and fatigue that resulted in withdrawal from the study. Among compliant participants, the visual memory domain of the ImPACT improved by 12 points (p = 0.02) and PCSS scores improved by 9 points, although not statistically significant. This pilot trial suggests that the KD is a feasible experimental treatment for PCS and justifies further study of its efficacy.

Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: a randomized controlled clinical trial

IntroductionDespite recent interest in the use of ketogenic diets (KDs) for cancer, evidence of beneficial effects is lacking. This study examined the impact of a randomly assigned KD on quality of life, physical activity and biomarkers in patients with breast cancer.MethodA total of 80 patients with locally advanced or metastatic breast cancer and without a history of renal disease or diabetes were randomly assigned to either a KD or a control group for this 12-week trial. Concurrent with the first, third, and fifth chemotherapy sessions, quality of life, physical activity, and biomarkers (thyroid function tests, electrolytes, albumin, ammonia, ALP, lactate and serum ketones) were assessed. Dietary intake was also recorded on admission and the end of the treatment.ResultsNo significant differences were seen in quality of life or physical activity scores between the two groups after 12 weeks; however, the KD group showed higher global quality of life and physical activity scores compared to the control group at 6 weeks (P = 0.02 P = 0.01). Also, serum lactate and ALP levels decreased significantly in the KD group compared to the control group at the end of the intervention (10.7 ± 3 vs 13.3 ± 4, 149 ± 71 vs 240 ± 164, P = 0.02 and P = 0.007, respectively). A significant inverse association was observed between total carbohydrate intake and serum beta-hydroxybutyrate at 12 weeks (r = − 0.77 P < 0.001). No significant differences between groups were observed in thyroid hormones, electrolytes, albumin, LDH or ammonia. Compliance among KD subjects ranged from 66.7 to 79.2% as assessed by dietary intake and serum ketones levels of > 0.5.ConclusionAccording to our results, besides a higher global quality of life and physical activity scores compared to the control group at 6 weeks, KD diet combined to chemotherapy in patients with breast cancer does not bring additional benefit about quality of life and physical activity at 12 weeks. However, decreases seen in levels of lactate and ALP in the KD group suggest that a KD may benefit patients with breast cancer.Trial registrationThis trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT20171105037259N2 https://www.irct.ir/trial/30755

1129-P: Effect of Sotagliflozin Added to Insulin Therapy on Beta-Hydroxybutyrate in Patients with Type 1 Diabetes

Objective: To evaluate the effect of sotagliflozin (SOTA), a dual SGLT 1 and 2 inhibitor, on beta-hydroxybutyrate (BHB) over 52 weeks in adults with type 1 diabetes (T1D) on insulin therapy. Methods: Analyses were performed on pooled data from two, 52-week, placebo-controlled studies in 1575 adult patients with T1D on optimized insulin therapy, who were randomly assigned 1:1:1 to placebo (PBO), SOTA 200 mg, and SOTA 400 mg. Descriptive statistics were performed on serum BHB using results from scheduled visits at baseline and Weeks 4, 12, 24, and 52. A 2-sample Wilcoxon rank sum test was performed to test the distribution of change in BHB from baseline between SOTA and placebo. The proportion of patients experiencing ≥1 measurement meeting predefined limits of DKA risk based on BHB levels (≥0.6 mmol/L “ketonemia” and ≥1.5 mmol/L “impending DKA”) was assessed. Results: Median baseline BHB was 0.13 (IQR 0.10, 0.20), 0.13 (IQR 0.10, 0.22), and 0.14 mmol/L (IQR 0.10, 0.23) in the PBO, SOTA 200-mg, and SOTA 400-mg groups, respectively. While the median change in BHB was 0 mmol/L with PBO, median BHB increased from baseline by 0.03 to 0.05 mmol/L with SOTA, and generally remained stable over 52 weeks (p&amp;lt;0.001 vs. PBO at each time point). Per the predefined limits of DKA risk based on BHB levels, a BHB level ≥0.6 mmol/L was experienced by 19.8, 46.9, and 45.5% and a BHB level ≥1.5 mmol/L in 2.1, 6.3, and 8.2% of patients on PBO, SOTA 200 mg, and SOTA 400 mg, respectively. Approximately 2/3 of the BHB ≥0.6 mmol/L events were observed by Week 16 and ∼2/3 of the BHB ≥1.5 mmol/L events were observed by Week 24. Conclusion: Treatment with SOTA was associated with small increases in BHB over time, which on average remained well below the clinically important level of 0.6 mmol/L. Although the DKA incidence was &amp;lt;4% overall on SOTA, the proportions of patients with ≥1 BHB measurement ≥0.6 mmol/L (∼45-47%) or ≥1.5 mmol/L (∼6-8%) suggest many BHB elevations were recognized and managed without progression to DKA. Disclosure A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. S. Sawhney: None. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.

720-P: Prurigo Pigmentosa: An Acute Complication of Ketogenic Diet

A 22-year old female with type 1 diabetes (T1DM) presented with generalized rash. She was diagnosed at the age of 9 years and is treated with insulin pump and CGMS (continues glucose monitoring sensors), her recent HbA1c was 7.4%. Four weeks prior to her rash presentation she started a low carbohydrate diet (50 gr of carbs per day) in order to improve her glycemic control. Pruritic erythematous papules, papulovesicular, and vesicles appeared on her axillary region, upper back and groins. Lesions were associated with severe pruritus and negatively affected her quality of life. Various therapies were initiated by dermatologist as: antifungal agent, Itraconazole, and Betamethasone Esters, without any improvement. Her serum beta-hydroxybutyrate levels were between 1.1-1.2 mmol/l. Prurigo pigmentosa, a rare pruritic inflammatory dermatosis secondary to her high ketones levels was diagnosed. Her condition resolved after she increased her carbohydrate intake to 75 gr per day. Beta-hydroxybutyrate level decreased concomitantly to 0.1-0.2 mmol/l. When carbohydrate restriction was rechallenged, she again entered ketosis, followed by recurrence of the pruritic lesions. Carbohydrate intake was increased and subsequently all lesions resolved with remaining reticular hyperpigmentation. During the last few years low carb diets have gained popularity among patients with T1DM. This case illustrates the rare side effect of high ketones body levels. Health care providers should be familiar with this side effect. Disclosure N. levran: None. K. Mazor-Aronovitch: None. S. Grenberger: None. N. Levek: None. B. Sher: None. E. Mauda: None. Z. Landau: None. E. Monsonego-Ornan: None. O. Pinhas-Hamiel: None.

SAT-251 New Diagnosis of Acromegaly with DKA as Initial Presentation

Background: While diabetes mellitus from growth hormone related insulin resistance is not uncommon in GH secreting tumors, initial presentation with diabetic ketoacidosis is rare. Clinical Case: 31 YO male with no significant past medical history presented with c/o fatigue, 40 lb weight loss, polyuria, polydipsia. Clinical features of acromegaly with frontal bossing, protruding jaw, large hands and feet, thick spade like fingers, hammer toes, high arches and thickened fat pads on both feet were noted. Initial labs were consistent with DKA with anion of 31 mmol/L (0-20), blood glucose 241 mg/dl, bicarb 12 mmol/L (22-29), serum betahydroxy butyrate > 8 mmol/L (0-0.29), urine positive for glucose, ketones, protein. Patient was initially treated with IV insulin per DKA protocol, transitioned to subcutaneous insulin.MRI brain showed 2.1x1.3x2.1 cm pituitary macro adenoma. Labs showed elevated IGF1 LC/MS, S 1094 ng/ml (54-310), IGFBP3 14 mcg/ml (3.5-7), Z score IGF MS Mayo > 3 (-2 to +2), normal FSH 7.1 m unit/ml (1.5-12.4), normal LH 3.4 m unit/ml (1.7-8.6), normal prolactin 6 ng/ml (4-15), normal ACTH 10 pg/ml, cortisol 13.4 mcg/dl, low total testosterone 48.2 ng/dl (193-836), normal free testosterone 7.92 ng/dl (4.85-19), normal TSH 1.55 mc unit/ml (0.27-4.2) and free T4 1.17 ng/dl (0.93-1.7). The patient was discharged home on 120+ units of total daily dose of insulin, after initial hospital admission.He underwent trans sphenoidal resection of pituitary macro adenoma one month after his initial presentation. Surgical pathology confirmed growth hormone producing adenoma. He was successfully weaned off from insulin in one month following surgery. Conclusion: DKA is an unusual initial presentation of growth hormone producing tumors. As more cases are being reported it is important to be vigilant to look for DKA presentation in these patients and adjust/wean patients insulin once the growth hormone producing tumor is treated either with surgery or medications.

SUN-901 A Case of Coexisting Insulinoma and Islet Cell Hyperplasia

IntroductionInsulinoma is the most common neuroendocrine tumour of the pancreas and cause of endogenous hyperinsulinemia hypoglycaemia. Islet cell hyperplasia is a rare cause of hypoglycaemia in adults.Clinical CaseA 42-year-old lady presented with hyperphagia, giddiness, decreased concentration and weight gain of 10 kg over one year. Her symptoms occurred both during fasting and postprandial. She did not have any medical conditions and did not take alcohol.A 72-hour fast confirmed the presence of endogenous hyperinsulinemia; serum glucose of 2.4 mmol/L paired with insulin 8.14 mU/L and C -peptide 0.71 nmol/L occurring after 16 hours of fasting. Screening for sulphonylureas and meglitinides was negative. Serum beta-hydroxybutyrate was 0.1 mmol/L with a 1.6 mmol/L rise in serum glucose post 1 mg glucagon administration. Computed tomography (CT) of the abdomen showed a 13 X 11 X 15 mm exophytic lesion at the superior aspect of the pancreatic body and another exophytic projection measuring 9 X 8 X 6 mm arising from the tail. In view of possible multifocal insulinoma, a 68Ga-DOTATATE scan was performed and it showed an intensely DOTATATE-avid exophytic nodule arising from the pancreatic body and a second indeterminate DOTATATE-avid nodule close to the pancreatic tail. In addition, there was diffuse DOTATATE uptake in the tail of pancreas.She underwent enucleation of pancreatic body nodule and spleen-saving distal pancreatectomy as the pancreatic tail nodule was not seen intra-operatively. Histology showed an insulinoma; a well-differentiated neuroendocrine tumour (Grade 1, pT1 N0 Mx) that was positively stained for synaptophysin, CD56, insulin, SSTR2 and SSTR5. The pancreatic tail nodule and distal pancreatectomy specimen showed islet cell hyperplasia; the pancreatic parenchyma showed multiple foci of well-circumscribed nests of bland islet cells with similar morphology to those seen in the insulinoma. She did not have further hypoglycaemia episodes post-operatively.Concomitant presence of fasting and postprandial hypoglycaemia may suggest underlying dual pathology. Clinical and biochemical differentiation between insulinoma and islet cell hyperplasia is difficult. Therefore, imaging for diagnosis and precise preoperative localisation is important for successful resection of suspected lesions. 68Ga-DOTATATE scan can be as useful as 68Ga-DOTANOC and 68Ga-DOTATOC scan and is better than CT scan in localising not only insulinoma but also islet cell hyperplasia. In this case, islet cell hyperplasia-induced hyperinsulinemic hypoglycaemia may have persisted if distal pancreatectomy was not performed.ConclusionAdult-onset endogenous hyperinsulinemia hypoglycaemia can be caused by concurrent insulinoma and islet cell hyperplasia. 68Ga-DOTATATE scan may be a useful, non-invasive investigation, especially in cases where CT imaging suggests multifocal disease.

Brain adaptations of insulin signaling kinases, GLUT 3, p-BADser155 and nitrotyrosine expression in various hypoglycemic models of mice

Aim and objectiveInsulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. ResultsInsulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. ConclusionDuring hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.