Intravenous Glucose Administration Research Articles

Impact of the Amount of Intravenous Glucose Administration on Hospitalization for Acute Gastroenteritis in a Pediatric Emergency Department.

In case of failure of oral rehydration, children with acute gastroenteritis can be hydrated using intravenous (IV) solution. The choice of the intravenous solution itself (solutions containing dextrose versus crystalloids alone) and the glucose quantities to administer are not well established. The main objective of this study was to evaluate the association between the amount of intravenous glucose provided and hospitalization for children with acute gastroenteritis. Another objective was to evaluate practice variation regarding the amount of glucose provided for IV rehydration in a pediatric emergency department (ED). We conducted a retrospective cohort study from 2019 to 2022 in a Canadian pediatric ED. We included children with acute gastroenteritis undergoing IV rehydration. Patient with hypoglycemia, metabolic disease, or diabetes were excluded. The IV glucose administered during the initial 4 hours of rehydration was quantified. The primary outcome was hospitalization, and return visit within the following week was a secondary outcome. Ten percent of the charts were evaluated in duplicate to assess interrater reliability. We examined glucose distribution at 1 and 4 hours and utilized multiple logistic regression to relate glucose amounts with hospitalization and second visit, accounting for age, weight, bicarbonate levels, ondansetron use, and amount of liquid infused. It was estimated that the evaluation of 250 cases would have at least 50 admissions. Among 6939 children evaluated for potential acute gastroenteritis, 250 met our inclusion/exclusion criteria. All variables included in the analysis had excellent interrater reliability. Notable variations existed in glucose quantities provided, both at 1 hour (first quartile, 87 mg/kg; third quartile, 294 mg/kg) and 4 hours (first quartile, 681 mg/kg; third quartile, 1174 mg/kg) of rehydration. Multiple logistic regression showed a negative association between hospitalization and glucose administration during the initial hour (OR for each 100 mg/kg increment, 0.60; 95% CI, 0.42-0.84) and 4 hours (OR, 0.76; 95% CI, 0.63-0.91) of rehydration. Moreover, children who received more dextrose during the first hour of rehydration were less likely of having a return visit (OR for each 100 mg/kg increment: 0.52; 95% CI, 0.35-0.78), as well as during the first 4 hours (OR for each 100 mg/kg increment, 0.83; 95% CI, 0.73-0.94). There was a wide practice variation in intravenous glucose provided to children with acute gastroenteritis. In this population, higher intravenous glucose amount was associated to a lower risk of hospitalization and lower risk of return visit.

Refractory hypoglycemia is sensitive to octreotide therapy: is it triggered by sorafenib or hepatocellular carcinoma?

Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient's sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient's requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.

31 Impact of the amount of intravenous glucose administration on hospitalization for acute gastroenteritis in a paediatric emergency department

Abstract Background In case of failure of oral rehydration, children with acute gastroenteritis can be hydrated using intravenous (IV) solution. The choice of the intravenous solution itself (solutions containing dextrose versus crystalloids alone) and the glucose quantities to administer are not well established. Objectives The main objective of this study was to evaluate the impact of the amount of intravenous glucose provided to children treated for acute gastroenteritis on hospitalizations. Other objectives were to evaluate practice variation regarding the amount of glucose and liquid provided for IV rehydration in a paediatric emergency department (ED). Design/Methods We conducted a retrospective cohort study from 2019-2022 in a Canadian paediatric ED. We included children with acute gastroenteritis undergoing IV rehydration. Patient with hypoglycemia, metabolic disease or diabetes were excluded. The IV glucose administered during the initial four hours of rehydration was quantified. The primary outcome was hospitalization and return visit in the following seven days was a secondary outcome. 10% of the charts were evaluated in duplicate to assess inter-rater reliability. We examined glucose distribution at one and four hours, and utilized multiple logistic regression to relate glucose amounts with hospitalization and second visit, accounting for age, weight, bicarbonate levels, ondansetron use, and amount of liquid infused. It was estimated that the evaluation of 250 cases would have at least 50 admissions. Results Among 6,939 children evaluated for potential acute gastroenteritis, 250 met our inclusion/exclusion criteria. All variables included in the analysis had excellent inter-rater reliability. Notable variations existed in glucose quantities provided, both at one hour (first quartile: 87 mg/Kg; third quartile: 294 mg/Kg) and four hours (first quartile: 681 mg/Kg; third quartile: 1174 mg/kg) of rehydration. Multiple logistic regression showed a greater hospitalization risk with smaller amount of glucose administered during the initial hour (OR for each 100mg/kg increment: 0.60; 95%CI: 0.42-0.84) and four hours (OR: 0.76; 95%CI: 0.63-0.91) of rehydration. Moreover, children who received more dextrose during the first hour of rehydration were at lower risk of return visit (OR for each 100mg/kg increment: 0.52; 95%CI: 0.35-0.78), as well as during the first four hours (OR for each 100 mg/kg increment: 0.83; 95%CI: 0.73-0.94). Conclusion There was a wide practice variation in intravenous glucose provided to children with acute gastroenteritis. In this population, higher intravenous glucose amount was associated to a lower risk of hospitalization and lower risk of return visit.

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.

Pancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells. Mice with β-cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance show an enhanced nutritional-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.

Whole‐brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism

Whole‐brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism

Incidence of encephalopathy and comorbidity in infants with perinatal asphyxia: a comparative prospective cohort study.

Programs that aim to improve the detection hypoxic-ischemic encephalopathy (HIE) should establish which neonates suffering from perinatal asphyxia need to be monitored within the first 6 h of life. An observational prospective cohort study of infants with gestational age ≥35 weeks, and above 1,800g, were included according to their arterial cord pH value (ApH): ≤7.00 vs. 7.01-7.10. Data was collected including obstetrical history, as well as neonatal comorbidities, including the presence of HIE, that happened within 6 h of life. A standardized neurological exam was performed at discharge. There were 9,537 births; 176 infants with ApH 7.01-7.10 and 117 infants with ApH ≤7.00. All 9 cases with moderate-to-severe HIE occurred among infants with ApH ≤7.00. The incidence of global and moderate-severe HIE was 3/1,000 and 1/1,000 births, respectively. Outcome at discharge (abnormal exam or death) showed an OR 12.03 (95% CI 1.53, 94.96) in infants with ApH ≤7.00 compared to ApH 7.01-7.10 cohort. Ventilation support was 5.1 times (95% CI 2.87, 9.03) more likely to be needed by those with cord ApH ≤7.00 compared to those with ApH 7.01-7.10, as well as hypoglycemia (37% vs. 25%; p = 0.026). In 55%, hypoglycemia occurred despite oral and/or intravenous glucose administration had been already initiated. Cord pH 7.00 might be a safe pH cut-off point when developing protocols to monitor infants born with acidemia in order to identify infants with moderate or severe HIE early on. There is non-negligible comorbidity in the ApH ≤7.00 cohort, but also in the 7.01-7.10 cohort.

Effects of Intravenous Glucose on Blood Potassium in Cattle

Abstract The aim of this study was to confirm whether a rapid intravenous glucose administration can lead to a significant drop in blood potassium levels in cattle. For this study, seven cattle were used according to internationally recognized guidelines for animal welfare. Glucose at a dose of 1 g.kg−1 body weight was administrated intravenously and then blood samples were taken before and 0.5, 1, 2, 4, and 6 hours after administration of glucose for measurement of potassium and glucose blood concentrations. For statistical analysis of glucose effects on both glucose and potassium levels one-way analysis of variance (ANOVA) for repeated measures was used. ANOVA showed a strong significant effect of the glucose administration on plasma glucose levels (P < 0.001). The glucose administration resulted in a mean plasma increase from 4.2 mmol.l−1 to 21.2 mmol.l−1 within the first minutes after the administration followed by a steady decrease back to the initial values. In contrast, ANOVA showed no significant effect of the glucose administration on plasma potassium levels. In conclusion, the glucose does not have a potassium-lowering effect when administered in a single large intravenous dose.

Ventricular fibrillation in a dog with refractory hyperkalaemia due to uroabdomen following extradural anaesthesia

AbstractA young adult, crossbreed dog was presented to a referral small animal veterinary hospital with uroabdomen causing a severe hyperkalaemia. Stabilisation of the condition consisted of abdominocentesis and intravenous administration of calcium gluconate, insulin, glucose and crystalloids. The patient was then anaesthetised for diagnostic and therapeutic procedures. An epidural was performed with levobupivacaine due to nociception and requirement for exploratory surgery. Marked bradycardia ensued and was treated with anticholinergics and terbutaline, among other repeated efforts to resolve a pharmaceutically resistant hyperkalaemia. However, cardiorespiratory arrest followed, characterised by ventricular fibrillation. Cardiopulmonary resuscitation utilised cardioversion to achieve return of spontaneous circulation within 16 minutes. After return of spontaneous circulation, serum potassium levels only decreased and remained below 7 mmol/L after repeat abdominocentesis, alongside continued medical therapy. Unfortunately, despite successful recovery from general anaesthesia, the patient later developed surgical wound dehiscence and was euthanased as a result.

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

BackgroundThe appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients. ObjectivesThe purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed. MethodsPlasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males. ResultsCompared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001). ConclusionsOur investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2.This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

Effect of Repeated Bolus and Continuous Glucose Infusion on DNA Damage and Oxidative Stress Biomarkers in Healthy Male Volunteers.

Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21-30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effect was found in the three DNA damage treatments as well as in PC and UCB possibly due to circadian changes on oxidative stress, but no intervention group effect was observed for any of the markers. In conclusion, bolus vs. continuous glucose administration had no significant acute effect on DNA damage and markers of oxidative stress in healthy men.

Butamirate citrate associated methemoglobinemia

Abstract Methemoglobinemia is a potentially life-threatening disease resulting from high blood levels of methemoglobin resulting in failure of binding and delivery of oxygen to tissues. The most common causes of methemoglobinemia are oxidizing toxins, such as butamirate citrate, which is a commonly used liquid antitussive, especially in pediatric patients. Herein, we present the case of a 3-year-old girl who accidentally ingested excessive amounts of butamirate citrate. She presented with mild lip cyanosis with high methemoglobin levels (6.5%) and normal oxygen saturation (98%), and was managed by prompt gut decontamination with activated charcoal, followed by monitoring and intravenous glucose administration. Therefore, methemoglobinemia should be considered a differential diagnosis in a patient presenting with cyanosis without any underlying lung or heart disease.

234-OR: Succinate Potentiates Insulin Secretion through SUCNR1

Here, we examined the role of succinate, a metabolite that acts by engaging the succinate receptor 1 (SUCNR1), in regulating insulin secretion by β-cells. We found that glucose increases SUCNR1 expression in β-cells and that activating SUCNR1 with either extracellular succinate or a synthetic agonist boosts glucose-stimulated insulin secretion through the Gq and PKC signaling pathways. Also, we identified that SUCNR1 is essential for preserving insulin secretion in a diet-induced insulin-resistance model. Mice with β-cell-specific SUCNR1 deficiency had impaired glucose tolerance and reduced insulin secretion when fed a high-fat diet, without changes in β-cell mass or insulin sensitivity. To investigate the physiological significance of succinate as a secretagogue in humans, we studied the potential connection between circulating succinate levels and β-cell function in response to oral and intravenous glucose challenges in a cohort of patients with impaired glucose tolerance (IGT). These patients were characterized by presenting hyperinsulinemia during both oral and intravenous glucose tests, compared to normal glucose tolerance (NGT) individuals. Moreover, succinate levels were elevated in IGT patients in response to these challenges compared to NGT patients, whereas circulating GLP-1 levels during the tests were not different between groups. Remarkably, we found that circulating succinate levels are positively correlated with insulin secretion potentiation during intravenous glucose administration, indicating that this system is activated by high glucose levels and partially regulated by the β-cell in an autocrine fashion. These findings suggest that succinate may act as a hormone, potentiating insulin secretion in humans through SUCNR1- a compensatory mechanism particularly relevant in the hyperinsulinemia elicited by insulin resistance. Our work sheds new light on the role of the succinate-SUCNR1 axis as a potential therapeutic target for improving insulin secretion in metabolic disorders. Disclosure J.Sabadell-basallote: None. J.J.Vendrell: None. S.Fernandez-veledo: None. B.D.Astiarraga: None. M.Ejarque: None. M.Repollés-de-dalmau: None. F.X.Sureda: None. D.F.De jesus: None. C.Núñez roa: None. A.Mari: Consultant; Eli Lilly and Company. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding Spanish Ministry of Science and Innovation (SAF2015-65019-R, RTI2018-093919-B-100); Instituto de Salud Carlos III (FI18/00151, CP10/00438, CPII16/00008); Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CB07708/0012); Catalan Association of Diabetes (PV21039S)

高度の尿糖排泄が遷延したSGLT2阻害薬関連正常血糖ケトアシドーシスの1例(A case of SGLT2 inhibitor–associated euglycemic diabetic ketoacidosis with prolonged high urinary glucose excretion)

40歳代の女性，10年来の糖尿病に対して，sodium–glucose cotransporter 2阻害薬（SGLT2i），dipeptidyl peptidase–4阻害薬，メトホルミンを服用していた。前医に交通外傷による上腕骨骨折で入院し，受傷後8日目に全身麻酔下に手術が行われた。術当日はすべての内服が中止された。術後より嘔気，多尿を認め，術後2日目には頻呼吸が出現した。精査加療目的に同日，救命救急センターに転院となった。血液検査にて，乳酸値が正常であるanion gap開大性の代謝性アシドーシスを認めた。血糖値159mg/dL，尿検査で尿糖3+（1,854mg/dL），ケトン体3+であった。SGLT2iの内服歴，尿中ケトン体陽性，代謝性アシドーシスから正常血糖ケトアシドーシス（euglycemic diabetic ketoacidosis: EDKA）と診断した。脱水の補正，インスリン，グルコースの経静脈的投与により，アシドーシスは改善したが，尿中の高度な糖排泄，多尿は持続した。全身状態は改善し，術後4日目に前医に転院となった。500mg/dL以上の尿中への糖排泄は，SGLT2i中止後も10日間以上持続した。SGLT2i中止後も長期にわたり高度の尿糖排泄が遷延する症例では，多尿，脱水に対して適切な水分管理が必要と考えられる。 A woman in her 40s with diabetes mellitus for 10 years was treated with sodium–glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase–4 inhibitor and metformin. Surgery to repair a humerus fracture caused by a car accident was performed on day 8 after the accident at her previous hospital. All medications were stopped on the day of surgery. Nausea and polyuria occurred following surgery. Tachypnea appeared on postoperative day (POD) 2, and she was transferred to our hospital for further treatment. Blood gas analysis showed metabolic acidosis with an open anion gap and normal blood glucose level of 159mg/dL. However, urinalysis showed 3+ glucose (urinary glucose level 1,854mg/dL) and 3+ ketones. She was diagnosed as having euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors. Correction of dehydration and intravenous administration of insulin and glucose tended to improve the acidosis, but her urinary glucose excretion and polyuria persisted. The patient was transferred back to her previous hospital on POD4. Urinary glucose excretion above 500mg/dL persisted for more than 10 days after discontinuation of SGLT2i. Urinary glucose excretion may persist for quite some time after discontinuation of SGLT2i and may require appropriate fluid management to prevent polyuria and dehydration. 糖尿病性ケトアシドーシス（diabetic ketoacidosis: DKA）は代謝性アシドーシス，高血糖，および尿中，もしくは血中のケトン体上昇を認める。DKA患者のうち，血糖値が正常であるものを正常血糖ケトアシドーシス（euglycemic diabetic ketoacidosis: EDKA）として1971年に報告された 1。 Sodium–glucose cotransporter 2阻害薬（SGLT2i）は，近年糖尿病だけでなく，慢性心不全，慢性腎臓病にも適応が拡大された。SGLT2iの重大な副作用にEDKAがある 2。EDKAの急性期の経過に関する報告は多数みとめるが，亜急性期の治療経過に関する報告は少ない。 今回我々は，整形外科術後にEDKAを発症し，SGLT2i中止後も10日以上にわたり尿中に500mg/dL以上の糖排泄が持続した症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされており，患者またはその家族より論文の出版に関する同意を得ている。 患 者：40歳代の女性 既往歴：高血圧，糖尿病 内服薬：カナグリフロジン（SGLT2i），テネリグリプチン，メトホルミン，ビソプロロール 現病歴：交通外傷により，左上腕骨近位端骨折，左第1趾基節骨骨折を受傷し前医に入院となった。入院時の身長は160cm，体重は80kg，BMIは31.25であった。SGLT2iを含むすべての内服薬を術当日に中止したうえで，左上腕骨骨折に対して観血的骨整復術を施行された。術後より，嘔気を訴えたため，術後悪心嘔吐として補液，制吐剤の投与がなされた。 術後1日目，SGLT2iを含むすべての内服薬を再開し，食事も再開となった。しかし嘔気が強く服薬はできたものの，食事摂取はできなかった。輸液量500mL/日に対して，6,850mL/日の多尿を認めた。 術後2日目には，嘔気の増悪があり，服薬もできなかった。多尿に加え，頻呼吸が出現し，尿定性検査で尿糖3+，ケトン体3+であった。外部機関による，動脈血液ガス分析（室内気）で，pH 7.131，PCO2 16.3mmHg，HCO3− 5.4mmol/L，anion gapは23.6と高値を示し，anion gap開大性の代謝性アシドーシスを認めた。乳酸値が不明であったことから，メトホルミンによる乳酸アシドーシスも鑑別にあがり，精査加療目的に当救命救急センターへ転院となった。頻呼吸が顕著であり，前医にて重炭酸ナトリウム7% 100mLを投与がなされた。 救命救急センター転院時の意識レベルはGlasgow coma scale E3V5M6であった。経皮的酸素飽和度100%（室内気），脈拍106/分，血圧136/78mmHg，体温37.4度，呼吸数25/分と著明な頻呼吸であり，口腔粘膜の乾燥，ケトン臭を認めた。動脈血液ガス分析（室内気）ではpH 7.146，PCO2 13.2mmHg，HCO3− 4.6mmol/L，BE −22.0mmol/L，乳酸9mg/dLであり，anion gapは15と開大しており，乳酸値は正常であった。血糖値は159mg/dLと正常であり，HbA1cは8.5%であった。その他の血液検査所見をTable 1に示す。尿の定性検査では尿糖3+，ケトン体3+，随時尿のグルコース濃度は1,854mg/dLと高値であった。頭部・胸腹部CT検査では感染巣含め，特記すべき異常所見は認めなかった。 乳酸値が正常であることから，メトホルミンによる乳酸アシドーシスは否定的と考えられた。EDKAの診断基準は除外診断 3，もしくは血糖値の上昇に乏しい（血糖値250mg/dL以下），アシドーシス（pH<7.30，HCO3− <18mEq/L），ケトーシス（血中βヒドロキシ酪酸3mmol/L以上，血中アセト酢酸の上昇，尿ケトン陽性でも代用可）の3つを満たすことであると記載されている 2。本症例では他の代謝性アシドーシスの原因となる疾患を指摘しえないこと，血糖値の上昇に乏しく，pH7.146，HCO3− 4.6mmol/Lと著明な代謝性アシドーシス，尿中ケトン陽性であり，ケトーシスを認めたことから，SGLT2iに伴うEDKAと診断した。同日血中ケトン体の測定を行ったところ，アセト酢酸3,397mmol/L，βヒドロキシ酪酸5,961mmol/Lと著明な上昇を認めた。 術後からの水分バランス，体重の推移をFig. 1に示す。術後1日目の水分バランスはマイナス6,350mL，2日目はマイナス2,700mLであり，食事摂取や水分摂取ができていなかったこともあり，救命救急センター転院時の体重は術前と比較して9kg減少していた。 Water balance and change in body weight over time. 救命救急センター入院後（術後2日目），脱水の補正目的に300mL/時間による輸液を開始した。また，救命救急センター入院3時間後より，ヒューマリン1単位/時間，グルコース7.5g/時間の経静脈的投与を開始した。救命救急センター入院13時間後の動脈血液ガス分析（室内気）では，pH 7.277，PCO2 22.3mmHg，HCO3− 10.4mmol/L，BS 172mg/dLとアシドーシスは残存するもanion gapは11.6と正常値を示した。脱水の補正のため，術後2日目には6L/日，3日目には10L/日を超える輸液がなされた（Fig. 1）。 術後4日目の動脈血液ガス分析ではpH 7.481，PCO2 35.7mmHg，HCO3− 26.7mmol/L，BS 150mg/dLとpHも正常化し，血液検査でアセト酢酸967mmol/L，βヒドロキシ酪酸1,894mmol/Lと救命センター入院時と比較して改善を認めたため，同日前医に帰院となった。 帰院後も輸液，ヒューマリンの持続投与と糖質の補充を継続した。救命救急センターでは絶食管理としていたが，前医に帰院した術後4日目から経口摂取が再開され摂取可能であった。その後も，2,000mL/日以上の多尿が持続したことから，輸液は漸減しながらも術後13日目まで継続した。 術後の血糖値，尿糖の推移をFig. 2に示す。術後2日目（カナグリフロジン最終服用から1日後）には尿中の糖排泄は1,854mg/dLであり，術後3日目（カナグリフロジン最終服用から2日後）には尿中の糖排泄は2,477mg/dLと高値を示した。術後8日目（カナグリフロジン最終服用から7日後）でも651mg/dLの糖排泄であった。術後9日目にヒューマリンの持続投与を終了し，術後10日目より，テネグリプチン，メトホルミンを再開した。カナグリフロジン最終服用から11日間にわたり尿糖3+（500mg/dL以上）の尿中への糖排泄がみられた（Fig. 2）。 Changes in the levels of blood and urine glucose over time. 術後17日目に自宅退院となった。前医退院日には入院時と比較して体重は8kg減少していた（Fig. 1）。 SGLT2iは新しい血糖降下作用機序を有する2型糖尿病治療薬として2014年4月17日に本邦で発売され，1型糖尿病，慢性心不全，慢性腎臓病などに適応が拡大し，SGLT2iの処方量は年々増加している 4。SGLT2iの作用機序は，腎臓の近位尿細管にあるナトリウム/グルコール共輸送体に作用し，尿中グルコース排出を促進することで，血糖降下作用を示す。SGLT2iの有害な合併症として，EDKAが知られており，SGLT2iの適応が拡大し使用が増加することで，救急医がEDKAに関わる頻度が増加することが予想される。 SGLT2iによるEDKAの発症には以下の機序が知られている 5。SGLT2iの内服により，尿からのグルコース再吸収が抑制されることで相対的な糖質不足となり，糖代謝から脂質代謝にシフトすることに伴い，血中ケトン体濃度が上昇する。血中のケトン体の増加に加え，尿中グルコース排出の促進に伴う浸透圧利尿による脱水，尿中グルコース排出による血糖降下作用により，EDKAを発症する。SGLT2iに関連したEDKAは嘔吐，脱水，インスリンの中止・減量，インスリン分泌促進薬の中止，手術，感染，絶食・または摂取カロリーの減量，大量飲酒などによって引き起こされる 6。手術によりEDKAを発症する可能性があるため，術前3日前からの休薬が推奨されている 7。本症例ではSGLT2iの休薬が術当日のみになり，術当日の絶食による糖質不足に手術侵襲などが加わりEDKAを発症した可能性が考えられた。 EDKAの症状は一般的なDKAと同様であり，悪心，嘔吐，腹痛が最も多く報告される 2。一方で，血糖値が正常であることから，診断が難しく50%以上の症例で診断が遅れることが報告されている 2。本症例でも，頻呼吸，尿中ケトン体が陽性であったことから前医でもDKAを強く疑ったが，血糖値が159mg/dLであったため確定診断には至らなかった。また，血液ガス分析にてanion gap開大性の代謝性アシドーシスを認めたため，メトホルミンによる乳酸アシドーシスも鑑別に挙がり，前医では十分な評価ができず診断が遅れた。 EDKAの初期治療は通常のDKAと同様に輸液による脱水の補正である。脱水の補正に続いて，0.02～0.05単位/kg/時間でインスリンの持続静脈投与を開始する 2。通常のDKA管理と異なり，低血糖を回避するために，インスリン注入と同時期より，10%のブドウ糖を125mL/時間で開始し 8，血糖値の目標は150～200mg/dLとする 6。その後，カリウムを中心とした電解質補正を行い，重炭酸，アニオンギャップ，pHの正常化をもって治療を終了する。本症例では，低血糖にならないように十分なモニタリングを行ったうえで，インスリンを0.014単位/kg/時間，ブドウ糖を7.5g/時間で投与した。集中治療室で治療された31例のDKA患者の報告 9ではアニオンギャップの正常化に要した時間は中央値で10.4時間とされている。本症例ではアニオンギャップの正常化（12以下）には13時間を要した。本症例では低血糖を懸念したため，文献に記載されているよりも少量のインスリン投与を行ったことで，細胞内への十分な糖質の補充ができず，ケトアシドーシスが遷延した可能性がある。正常血糖ケトアシドーシスにおいても，十分な糖質補充とインスリンの投与が有効であるか，今後の検討が必要である。 カナグリフロジンの代謝動態を調べた研究 10によると，カナグリフロジンを2週間服用した場合，血中薬物濃度の半減期は11.81時間とされている。本症例と同様にカナグリフロジン100mgを服用した場合，おおよその尿中グルコース排泄量はカナグリフロジン服用前と比較して服用当日でプラス100g/日，翌日でプラス60g/日，翌々日でプラス20g/日であった。本症例では，カナグリフロジンの最終服用から2日後の尿中グルコース濃度は2,477mg/dL，尿量は9,240mL/日であったことから，約170g/日の糖が尿中から排泄されたと考えられた。同様に最終服用から3日後は130g/日，7日後で70g/日の尿糖排泄を認めた。また，カナグロフロジン中止後，血糖値は100〜200mg/dLにも関わらず，中止後11日間にわたり尿糖は3+であった。カナグリフロジンの血中薬物濃度が低下して以降も，持続的な薬理学的反応としての尿中グルコース排泄は過去にも報告されている 11, 12。これらの原因として，SGLT2iは内服後，血液中より腎臓に多く分布しており，局所的な薬物濃度が維持されている可能性，代謝酵素の多型，腎機能障害による半減期の延長，薬物の親油性が高く脂肪組織への分布などが挙げられている。本症例では，尿糖排泄が持続した原因として，腎局所でSGLT2iの薬物濃度が維持されている可能性があること，BMI 30以上の肥満であり脂肪組織へSGLT2iが分布していた可能性が考えられた。尿糖陽性である期間は浸透圧利尿により多尿となり，脱水になりやすいことが考えられる。本症例のように，SGLT2i中止後も長期にわたり高度の尿糖排泄が遷延する症例では，多尿，脱水に対して適切な水分管理が必要と考えられる。 整形外科術後にSGLT2iに関連したEDKAの症例を経験した。SGLT2i中止後も長期にわたり高度の尿糖排泄が持続する可能性があり，多尿，脱水に対して適切な水分管理が必要と考えられる。 本論文の投稿にあたり，開示すべき利益相反はない。

Hypothalamic Reactivity and Connectivity following Intravenous Glucose Administration.

Dysfunctional glucose sensing in homeostatic brain regions such as the hypothalamus is interlinked with the pathogenesis of obesity and type 2 diabetes mellitus. However, the physiology and pathophysiology of glucose sensing and neuronal homeostatic regulation remain insufficiently understood. To provide a better understanding of glucose signaling to the brain, we assessed the responsivity of the hypothalamus (i.e., the core region of homeostatic control) and its interaction with mesocorticolimbic brain regions in 31 normal-weight, healthy participants. We employed a single-blind, randomized, crossover design of the intravenous infusion of glucose and saline during fMRI. This approach allows to investigate glucose signaling independent of digestive processes. Hypothalamic reactivity and connectivity were assessed using a pseudo-pharmacological design and a glycemia-dependent functional connectivity analysis, respectively. In line with previous studies, we observed a hypothalamic response to glucose infusion which was negatively related to fasting insulin levels. The observed effect size was smaller than in previous studies employing oral or intragastric administration of glucose, demonstrating the important role of the digestive process in homeostatic signaling. Finally, we were able to observe hypothalamic connectivity with reward-related brain regions. Given the small amount of glucose employed, this points toward a high responsiveness of these regions to even a small energy stimulus in healthy individuals. Our study highlights the intricate relationship between homeostatic and reward-related systems and their pronounced sensitivity to subtle changes in glycemia.

Hyperkalaemia in a greyhound under general anaesthesia

AbstractCases of intraoperative hyperkalaemia in healthy greyhound dogs under general anaesthesia have previously been reported in veterinary literature. This case report describes the identification and treatment of hyperkalaemia in an otherwise healthy greyhound undergoing general anaesthesia for a fracture repair. The clinical signs were sudden bradycardia and loss of P waves on the electrocardiogram waveform. Treatment consisted of intravenous 10% calcium gluconate, rapid recovery from anaesthesia, intravenous glucose administration and continued serum potassium monitoring postoperatively. Potential aetiologies of the hyperkalaemia are discussed.

Insulinoma - The Approach to the Diagnosis, Based on a Case Report

Insulinoma is the most common cause of endogenous hyperinsulinism. Most are benign and solitary. Hereby the authors present a 36-year-old woman who was admitted for confusion, aggressive behaviour, and visual hallucinations. Initial investigation revealed hypoglycaemia, and the patient recovered after the administration of intravenous glucose. The 72-hour fasting test was compatible with hyperinsulinism. Endoscopic ultrasound detected a nodule in the tail of the pancreas. Surgical resection of the nodule was performed, and histological examination revealed a pancreatic neuroendocrine tumour. The patient had a favourable outcome with resolution of the symptoms.

PSAT277 Glucocorticoid Therapy for Management of Hypoglycemia in the context of Non-Islet Cell Tumor-Induced Hypoglycemia

Abstract Background Non-islet cell tumor-induced hypoglycemia (NICTH) is a rare paraneoplastic syndrome which can cause recurrent hypoglycemia. There is no clear standard of care for management of hypoglycemia. Often, these patients have high morbidity and therefore surgical tumor resection is not always possible. Clinical case: This is the case of a 69 year-old male presenting with altered mental status in the context of hypoglycemia without clear etiology with an initial serum glucose level of 32 mg/dL (normal range 60-100 mg/dL) which quickly corrected after administration of intravenous glucose. He was found to have a large bowel obstruction with CT abdomen revealing an underlying neoplasm. Biopsy of suspected lesion on colonoscopy revealed colorectal adenocarcinoma. Repeated episodes of hypoglycemia complicated by seizures required inpatient management. Workup included serum insulin level which resulted in suppressed level (&amp;lt;1. 0 uU/mL, normal range 1.9-23. 0 uU/mL), low c-peptide level (0.1 ng/mL, normal range 1.1-4.4 ng/mL), low beta hydroxybutyrate level (0. 07 mmol/L, normal level &amp;lt;0.3 mmol/L), cortisol level of 43.7 mcg/dL, undetectable insulin like growth factor-1 (IGF-1) level (&amp;lt;10 ng/mL, normal range 59-230 ng/mL) and low insulin like growth factor-2 (IGF-2) level (66 ng/mL, normal range 333 - 967 ng/mL). IGF2: IGF1 ratio was 66 (ratio &amp;gt;10 is indicative for diagnosis of non-islet cell tumor hypoglycemia). Due to extremely poor oral intake and recurrent episodes of hypoglycemia despite continuous dextrose infusion, the patient was started on 20 mg prednisone daily. Eventually, 40 mg of intravenous methylprednisolone in addition to dextrose infusion was needed as maintenance therapy effectively preventing hypoglycemia. Given his poor functional status, the surgical and oncology team decided he was no longer a surgical or chemotherapy candidate. Eventually, palliative medicine was consulted and the patient was transitioned to comfort care with a plan for outpatient hospice. Conclusion NICTH should be suspected in any patient with hypoglycemia without clear etiology, especially if there are suggestions to NICTH such as known malignancy or newly diagnosed mass. Once NICTH is identified and a primary tumor is found, complete tumor resection represents ideal management, however, not always attainable. In such cases, dextrose infusion might be insufficient to prevent hypoglycemia and is not always the preferred option given the required long-term venous access. In these circumstances, early high dose glucocorticoids are safe and appear to successfully prevent hypoglycemic events. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

S3055 Late Manifestation of Heterozygous H63D Mutation as Hereditary Hemochromatosis in 89-Year-Old Man

Introduction: Hereditary hemochromatosis (HH) is an autosomal recessive that usually affects middle-aged people [1]. In most patients, homozygous C282Y mutations in the HFE gene express the disease. But in some occurrences, compound heterozygous, including C282Y and H63D mutations, were also witnessed. We present an atypical case where heterozygous H63D manifested as HH in an 89-year-old man. Case Description/Methods: An 89-year-old Caucasian man of Italian descent presented with confusion, left-sided facial droop, and slurring of speech. Past medical history included end-stage renal disease on hemodialysis and atrial fibrillation. For the past few months before presentation, the patient has been complaining of increasingly tired with intermittent episodes of slurring speech, mainly after he receives dialysis. During the initial physical examination, the patient had confusion but was alert & oriented to self and time. There was mild abdominal distension and positive for asterixis, and the skin was bronze in color. Initial labs showed in table 1. The patient had persistent hypoglycemia and required intravenous glucose administration. Brain imaging was normal. CT scan of the abdomen, pelvis, and chest showed severe cardiomegaly and a moderate amount of ascites. Iron studies were abnormal. Ascites fluid analysis was consistent with cirrhosis. Although, an ultrasound right upper quadrant was negative for any cirrhotic morphology. MRI showed hemosiderosis. 2D Echo showed a severely dilated right ventricle. The patient empirically underwent two sessions of phlebotomy. Genetic testing confirmed heterozygous H63D mutation. The patient followed up for the phlebotomy sessions and demonstrated significant improvement. Discussion: This case highlights the consideration of HH in differential regardless of age if a patient presents with symptoms suspected of HH. Standard genetic testing includes testing C282Y and H63D mutations in the HFE gene on chromosome 6. Less frequently tested S65C, HFE4, TFR2-HHC, and FTH1 gene mutations also have the expression of HH in sporadic cases [2-3]. Previously, heterozygous C282Y carriers with iron overload are assumed to have other genetic changes or influence by environmental factors, such as alcohol or liver disease, that increase disease expression [2]. However, no such literature is available for heterozygous H63D carriers. Given the unusual age for phenotype expression and atypical disease, the presentation makes this unique case for learning the pathophysiology and genetics of HH.Figure 1.: A: MRI of liver showing decreased signal of the liver and spleen on in phase imaging is likely due to hemosiderosis. B: Two-dimensional transthoracic echocardiography showing severely dilated right ventricle and both atria. Moderate pulmonary hypertension was also noticed. Table 1. - Day 1 Day 2 Day 3 Day 4 Day 15 Day 42 Hemoglobin (g/dL) 15.6 14.8 15.1 13.8 13.6 12.2 AST (U/L) 85 102 135 125 109 71 ALT (U/L) 56 57 70 74 72 46 Bilirubin (mg/dL) 3.0 2.9 2.6 2.9 2.6 2.1 INR 1.3 1.4 1.4 1.4 1.2 1.2 Ammonia (µmol/L) 99 45 46 42 31 Platelets (10ˆ3/µL) 103 86 82 63 59 91 Ferritin (ng/ml) 1283 725 Iron (µg/dL) 187 130 Transferrin Saturation (%) 94 74 Total Iron-binding Capacity (µg/dL) 200 276

Isseki nichō (one stone, two birds): a dual incretin receptor agonist for type 2 diabetes

The fact that stimulation of insulin is much greater after an oral or enteral rather than isoglycaemic intravenous administration of glucose has been known for more than 60 years—this incretin effect is mediated by two gut hormones—GLP-1 and GIP. Management of people with type 2 diabetes and obesity is being revolutionised with the emergence of increasingly effective therapies based on GLP-1.1 Tirzepatide, which acts on GLP-1 and GIP receptors, is the first dual agonist for the management of type 2 diabetes to gain regulatory approval by the US Food and Drug Administration (on May 13, 2022).

Standard-Dose Oral Dextrose Gel for Neonatal Hypoglycemia

Standard-Dose Oral Dextrose Gel for Neonatal Hypoglycemia