Ketone Levels Research Articles

530-P: Capillary Blood Ketone Level and the Prediction of Future Diabetic Ketoacidosis Risk in Type 1 Diabetes

Identification of those at risk of diabetic ketoacidosis (DKA) in T1D is challenging. Rather than during illness while DKA is developing, we aimed to determine if levels of routine point-of-care capillary blood ketones could predict DKA months prior to the event. In exploratory analysis, we examined 484 participants randomly assigned to placebo in an adjunct-to-insulin medication trial program (NCT02414958 and NCT02580591). Participants provided morning fasted capillary blood ketone levels twice per week via electronic logbook, and we calculated the maximum and mean level for each individual during a 2-month baseline period. Outcome was the 6 to 12-month occurrence of trial-adjudicated DKA. Area under the Curve (AUC) for the Receiver Operator Characteristic curves were generated. In sensitivity analysis we applied supervised machine learning methods (gradient-boosted trees). Participants had median age 43 [IQR 33, 54], mean HbA1c 8.2±0.6 percent, and provided 2 [1, 4] ketone measurements per week. Twelve DKA events occurred at median 105 [43, 199] days. Maximum and mean ketone levels were higher at baseline for the 12 cases compared to controls (for example, maximum ketone level 0.8 [0.6, 1.2] compared to 0.3 [0.2, 0.7] mmol/L, p=0.002). Maximum ketone level had AUC of 0.769 (95% CI 0.655-0.883). Maximum ketone ≥0.8 mmol/L had sensitivity 64%, specificity 78%, and likelihood ratios positive and negative of 2.9 and 0.5. Machine learning methods outperformed the single-metric analyses. Results provide proof-of-concept that routine capillary ketone surveillance can identify individuals at high-risk of future DKA. Simple or complex machine learning algorithms could be implemented in ketone meters or in future continuous ketone measurement technology. Disclosure C.Song: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. D.Mumford: None. G.Tomlinson: None. L.Lovblom: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). S.Dhaliwal: None. P.Bapat: None. A.M.K.Bakhsh: None. D.R.Budhram: None. D.Scarr: None. A.Weisman: None. M.Fralick: None. N.Ivers: Consultant; Novo Nordisk Canada Inc., IQVIA Inc. Funding Diabetes Canada (OG-3-21-5572-BP)

878-P: Absolute Amount of Urinary Glucose Excretion, Not the Change, Is the Measure Determinant for the Effects of SGLT2 inhibitors

SGLT2 inhibitors exhibit hypoglycemic effect via increased urinary glucose excretion (UGE) by inhibiting glucose reabsorption in the kidney. Although the effects of SGLT2 inhibitors are theoretically dependent on UGE, clinical trials have shown renoprotective effect even in severely impaired kidney function. Thus, we aimed to investigate the relationship between UGE and various parameters before and after the administration of SGLT2 inhibitors. The patients newly administered SGLT2 inhibitors and measured 24-hour UGE before and after the administration during hospitalization for diabetes education were included. Body weight (BW), blood ketone levels, hematocrit (Ht), eGFR, and 7-point SMBG (DBG) were measured, and the correlations between the parameters before(b-), after (a-) and the change (Δ-) were analyzed by simple linear regression. A total of 32 patients (age 59.3±10.9 years, 19 males) were included (empagliflozin 5, tohogliflozin 6, dapagliflozin 2, canagliflozin 4, luseogliflozin 15). The mean A1C and BW were 8.8±1.2% and 77.7±11.5kg, and mean UGE, average of DBG at baseline were 15.4 ± 27.5g/day and 10.3±2.0mM/L, respectively. As shown in table, ΔDBG showed correlation only with UGE before and after administration but not with ΔUGE. In conclusion, hypoglycemic effect of SGLT2 inhibitors is dependent on absolute amount of UGE but not on ΔUGE after administration. Disclosure Y.Hamamoto: None. Y.Yamada: Speaker's Bureau; Novo Nordisk Pharma Ltd., Teijin Pharma Limited, Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd. Y.Seino: Research Support; Terumo Corporation, Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Merck & Co., Inc., Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd.

99-LB: Myocardial Blood Flow in Association with Baseline Ejection Fraction after Elevation in Plasma Ketones in Patients with T2DM and Heart Failure

Background: SGLT2 inhibitors have been shown to provide CV benefits in HFpEF and HFrEF patients with and without diabetes. The underlying mechanisms continue being explored. Objective: To examine the effect of hyperketonemia on myocardial blood flow (MBF) in patients with HF and T2DM. Methods: Subjects with T2DM and HF (EF <50%) received a 6-hr BOHB infusion or a HCO3 infusion (control). A cardiac MRI and a PET study with 18FDG and 15O water were performed before and after the infusion. Results: Twelve Subjects were studied (Age=60; BMI=32 kg/m2; A1c = 7.7%). Plasma ketone levels reached 1.6±0.2mmol/L. MBF significantly increased in six subjects (“responders” 1.05±0.13 to 1.38±0.17, p = 0.003) and decrease in six subjects (“non-responders” 1.44±0.07 to 0.95±0.08, p = 0.007). With multivariable analysis, only baseline EF was shown to significantly correlate with the increase in MBF. Conclusion: These findings suggest that patients with a higher baseline EF might be more responsive to ketones and be able to increase MBF as an additional mechanism of CV improvement. These novel results shed new light on the potential effect of ketones in different populations of patients with HF and needs to be further explored. Disclosure C. Solis-Herrera: None. Y. Qin: None. H. Honka: None. F. M. Acosta: None. A. Moody: None. A. Chavez: None. C. L. Triplitt: Speaker's Bureau; Novo Nordisk. G. D. Clarke: None. E. Cersosimo: None. R. A. DeFronzo: Speaker's Bureau; AstraZeneca. Advisory Panel; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Novo Nordisk. Research Support; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc. Funding Max and Minnie Tomerlin Voelcker Fund; Merck & Co., Inc.

100-LB: Dapagliflozin for Inpatient Hyperglycemia in Cardiac Surgery Patients with Type 2 Diabetes—Randomized Controlled Trial

Sodium/glucose cotransporter-2 (SGLT2) inhibitors have not been assessed extensively for the treatment of hyperglycemia in noncritically ill, hospitalized patients with type 2 diabetes (T2D). In this investigator-initiated, treat-to-target, randomized trial, 250 cardiac surgery patients with T2D were randomly assigned (1:1) to receive dapagliflozin 10 mg daily plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean differences between groups in their daily blood glucose (BG) concentrations. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within the target BG of 70-180 mg/dL (82.7% vs. 82.5%), daily total insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. Mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but none developed DKA. There were no differences in the proportion of patients with BG <70 mg/dL (9.6% vs. 7.2%) between the treatment groups. Numerically fewer patients in the DAPA group developed acute kidney injury (7.2%) than in the insulin group (12.8%). These findings indicate that dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus in hospitalized cardiac surgery patients with T2D. However, dapagliflozin is safe and does not increase the incidence of DKA or other complications during the hospital stay. Disclosure M. S. Kuchay: Other Relationship; Boehringer-Ingelheim, Novartis India, Sanofi, Novo Nordisk, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd., USV Private Limited, MSD Life Science Foundation. C. Kohli: None. G. Bakshi: None. V. Radhika: None. S. Saheer: None. M. K. Singh: None. S. Mishra: Other Relationship; Abbott, Novo Nordisk, Sanofi, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd., Merck Sharp & Dohme Corp., Cipla Inc. P. Khatana: None. M. Mishra: None. P. S: None. P. Kaur: Other Relationship; Abbott, AstraZeneca, Boehringer Ingelheim Inc., Eris Lifesciences Ltd., Novartis India, Sanofi. J. S. Wasir: Other Relationship; Abbott, AstraZeneca, Novartis. H. Kaur: Other Relationship; AstraZeneca, Novo Nordisk, Sanofi, Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd. A. Singh: None. R. Jain: Other Relationship; Abbott, AstraZeneca, Lilly Diabetes. Funding Diabetes and Endocrinology Foundation of India

The effect of Lactobacillus plantarum LP-115 strain on improving the savor and aroma of milk containing grape sap through fermentation

Nowadays, maintaining the health of the body and choosing food and drinks with high nutritional value has become a general concern. Milk-containing grape sap (MGS) is a novel and emerging drink in countries of the world, especially Iran. Consumption of raw milk mixed with grape sap may not have a pleasant taste for some consumers. To solve this problem, mild fermentation of MGS with Lactobacillus plantarum LP-115 was proposed, which improves the drink's initial unpleasant taste and preserves the milk's enzyme balance due to heat. Gas chromatography - amino acid analyzer and mass spectrometry were used to evaluate the effect of LP-115 strain on free fatty acids (FAA) and aromatic ingredients. After 16 h of fermentation by LP-115, the MGS exhibited high levels of antioxidants (543.56 mg/L), sweet amino acids (293.47 mg/L), essential amino acids (49.66 mg/L), and unsaturated fatty acids (UFA: 2774.51 mg/L), according to the results obtained. The results indicate that increased levels of umami and sweet compounds, as well as UFAs, enhanced the aroma and functional properties of the fermented MGS. Additionally, the study found that reduced aldehyde levels and increased ketone, ester, acid, and alcohol levels contributed to the improved flavor quality of MGS. This study establishes a theoretical foundation for the industrial-scale production of fermented MGS.

#3873 UTILITY OF BLOOD KETONE MONITORING IN HAEMODIALYSIS PATIENTS UNDER INPATIENT NEPHROLOGY CARE

Abstract Background and Aims There is a lack of evidence regarding the relationship between capillary blood glucose (CBG) >15 mmol/L and blood ketones in maintenance haemodialysis dialysis patients meaning the utility of ketone measurement in this group is uncertain. Despite this, guidance published by the Joint British Diabetes Society for Inpatient Care (JBDS-IP) in 2022 states that blood ketones should be measured in patients on maintenance haemodialysis with diabetes mellitus (DM) who have pre- or post-dialysis CBG >15mmol/L and symptoms consistent with diabetic ketoacidosis (DKA), acknowledging that these can be non-specific [1]. We sought to identify if there is a relationship between elevated CBG and blood ketone levels in haemodialysis patients, and if haemodialysis affects blood ketone levels. Method Maintenance haemodialysis patients with DM admitted to a single ward over 2 separate 2 month periods were included. Nursing staff recorded CBG and blood ketone levels pre- and post-dialysis using a FreeStyle PrecisionPro ketone meter. For each patient, further demographic data were collected from the electronic patient record. Results 79 measures were collected from 30 patients, with between 1 and 7 measures for each patient. 57% patients (n = 17) were male, 37% (n = 11) had T1DM, and 80% (n = 24) were on insulin therapy. The median pre-HD CBG for all measures was 10.5mmol/L (IQR 8.15-15.05), median post-HD CBG was 9.1mmol/L (IQR 6.8-12.95), median pre-HD ketones were 0.1mmol/L (IQR 0.1-0.2) and median post-HD ketones were 0.1mmol/L (IQR 0.1-0.3). There was no significant difference in blood ketones pre-and post-HD for all measures (p = 0.09) (Figure 1). For measures where pre-HD CBG was >15mmol/L (n = 21) median pre-HD and post-HD ketones were 0.1 (IQR 0.1-0.2) and 0.2mmol/L (IQR 0.1-0.2) respectively (p = 0.45). For measures where pre-HD CBG was >20mmol/L (n = 6) median pre-HD and post-HD ketones were 0.1 mmol/L (IQR 0.1-0.13) and 0.2 mmol/L (IQR 0.1-0.2) respectively (p = 0.13). For measures where pre-HD CBG was <15mmol/L, median pre-HD ketones were 0.1 (IQR 0.1-0.2). There was no significant difference in blood ketones pre-HD between those with a pre-HD CBG >15mmol/L and those with a pre-HD CBG <15mmol/L (p = 0.69). Conclusion These results demonstrate no significant relationship between elevated CBG measures (>15mmol/L) and blood ketone levels in haemodialysis patients, nor do they demonstrate a significant change in blood ketone levels post haemodialysis. Unwell haemodialysis patients with elevated CBG clearly warrant medical assessment, but there is a lack of evidence that blood ketones are useful to aid assessment and guide management of these patients.

The epidemiology of ketosis and low bicarbonate concentration in inpatients treated with sodium-glucose linked cotransporter inhibitors or dipeptidyl peptidase-4 inhibitors

AimsTo compare the level of ketones and bicarbonate in inpatients treated with sodium-glucose linked cotransporter 2 inhibitors (SGLT2i) and those treated with dipeptidyl peptidase-4 inhibitors (DPP4i). MethodsWe conducted an electronic medical records-based cohort study. We identified patients with type 2 diabetes, with ketone measurements available, who received SGLT2i (n = 82) or DPP4i (n = 308) during admission. We compared ketone levels between those who received SGLT2i or DPP4i using mixed ordinal logistic regression. The primary outcome was level of ketosis (<0.6, 0.6–1.5, 1.6–3.0, >3 mmol/L). Secondary outcomes included bicarbonate levels, hospital complications, ICU admission, and death. ResultsSGLT2i use was not associated with greater ketosis than DPP4i use, after adjusting for age, weight, Charlson Comorbidity Index, HbA1c, estimated glomerular filtration rate, principal diagnosis category, admission type and insulin administration (OR 4.52 95 % CI (0.33, 61.82)). After adjustment, there was no difference in complications (p = 0.14), ICU admissions (p = 0.64), mortality (p = 0.30), or bicarbonate levels (p = 0.97). ConclusionKetone levels were not greater in patients who received SGLT2i than those who received DPP4i. There were no differences in bicarbonate levels, complications, ICU admissions, or mortality, implying that, in inpatients, SGLT2i use is neither associated with ketosis nor adverse clinical outcomes.

Defining Physiological Ketosis Following Very-Low-Calorie Diets

IntroductionVery low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance. Materials and methodsTwenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005. ClinicalTrials.gov ID: NCT05442918. ResultsPatients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1. ConclusionsPreoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.

The ketogenic diet plus standard of care for adults with recently diagnosed glioblastoma: Results from a phase 1 trial.

2076 Background: Facing limited treatment options, brain tumor patients are often highly motivated to use complementary therapies, including diet, to help themselves. There is now an abundance of preclinical evidence suggesting possible benefit with a ketogenic diet (KD) for brain tumor patients, but clinical evidence is still limited. Thus, we conducted a single-arm, phase 1 safety and feasibility trial of a KD among patients with recently diagnosed glioblastoma (GBM) during standard- of-care (SOC) treatment. Methods: Adults with GBM within 3 months of diagnosis followed a supervised 16-week diet intervention of a standard 3:1 KD (Fat(g):Carbohydrate+Protein(g)) plus SOC chemoradiation. Primary outcome was safety, evaluated by weekly assessments of weight and body mass index (BMI). Secondary outcomes included feasibility (pre-specified as &gt; 50% of patients maintaining blood ketone levels &gt; 0.3 mM over 50% of study days), progression-free survival (PFS), overall survival (OS), health-related quality-of-life (QOL), and cognitive function. Twice daily blood glucose and ketone levels, weight/BMI, physical activity, and sleep were assessed by remote monitoring. Results: Seventeen patients were evaluable: 53% women, median age 55, median Karnofsky Performance Status 85. All participants met the primary safety objective with no instances of excessive weight loss or related serious adverse events. Adherence to KD was high: all 17 patients maintained nutritional ketosis (≥0.3 mM/dL) &gt;50% of study days, where 14 patients maintained nutritional ketosis &gt;85% of study days. Median time to ketosis from diet initiation was 3 days. Diet-related AEs were mild and manageable; no patients came off study due to inability to tolerate KD. Median progression-free survival (PFS) and overall survival (OS) were 12.5 months and 28.6 months from KD initiation respectively. QOL, symptom control, and cognitive function remained stable or improved, although these did not reach statistical significance. Conclusions: This phase 1 trial demonstrates that KD is safe and feasible for GBM patients receiving SOC, may improve outcomes, and provides a foundation for future randomized trials to assess efficacy. Clinical trial information: NCT03451799 .

A KETOGENIC DIET REDUCES TISSUE SODIUM CONTENT: AN EXPLORATORY STUDY

Objective: Hypertension and diabetes are a substantial global public health problem. The prevalence of these diseases will further increase in the near future, leading to increased health and socioeconomic costs. Hence efficient therapeutic approaches are urgently needed. It has been previously shown that nutritional approaches including a very-low carbohydrate, or a ketogenic diet potentially decrease body weight, blood pressure and glucose levels in patients with type 2 diabetes along with an overall significant reduction in their pill burden. However, the detailed physiological mechanisms underlying the observed induction and maintenance of diabetes remission remain largely unknown. Previous studies have shown that the skin could be a buffer system for sodium and that skin sodium content could be both a pathogenic cause and a marker of hypertension and salt sensitivity. Since a nutritionally created metabolic milieu such as nutritional ketosis can lower blood pressure, we hypothesize that this dietary approach also reduces tissue sodium content. Design and method: By using 7-T 23Na MRI technique, we performed an exploratory study and analyzed skin and muscle sodium concentration before, and after a 6-week ketogenic diet in three healthy probands. Nutritional ketosis was verified by frequent check of blood ketone (beta-hydroxybutyrate; BOHB) levels greater than 0.3 mmol/L. Results: Preliminary data of our planned exploratory study (in patients with chronic kidney disease and type 2 diabetes mellitus and healthy probands) demonstrated that compared to baseline 6 weeks of ketogenic diet decreased tissue sodium content in the skin (16.6 ± 2.1 vs. 12.6 ± 2.1 mmol/L), in the medial gastrocnemius muscle (20.5 ± 0.9 vs. 16.7 ± 0.7 mmol/L), in the lateral gastrocnemius muscle (19.7 ± 1.0 vs. 16.0 ± 1.0 mmol/L) and in the soleus muscle (13.1 ± 0.8 vs. 11.5 ± 0.5 mmol/L). Conclusions: Our results indicate a massive reduction of tissue sodium concentration in healthy volunteers in response to a ketogenic diet which might be associated with the observed clinical benefits and be implicated in the anti-hypertensive effects of this powerful dietary intervention. Findings of this study could have an impact on future treatment strategies of various chronic diseases.

Utility of serum ketone levels for assessment of myocardial glucose suppression for 18F-fluorodeoxyglucose PET in patients referred for evaluation of endocarditis

Background18F-FDG PET/CT is used to diagnose cardiac sarcoidosis and endocarditis. It requires myocardial glucose utilization (MGU) suppression to avoid false positives, which occur in up to 20% of patients. Serum beta-hydroxybutyrate (BHB) levels may help identify incomplete suppression of MGU. We determined the optimal timing and diagnostic thresholds to identify incomplete suppression of MGU. Methods and resultsWe retrospectively identified 114 patients referred for 18F-FDG PET/CT for endocarditis, wherein myocardial uptake outside of paravalvular regions is not related to pathology and can be confidently ascribed as being due to inadequate suppression of MGU. Patients followed a high-fat, low-carbohydrate diet and received heparin. Serum BHB, insulin, glucose and hemoglobin A1c were measured. Maximum standardized uptake value (SUVmax) of left ventricle (LV) and mean SUV (SUVmean) in LV blood pool (LVBP) was measured. Logistic regression and area under the receiver-operating characteristic analyses were used to quantify the relationship between biomarkers and MGU suppression. A threshold of BHB ≥ 0.35 mmol·L−1 to detect suppression resulted in sensitivity of 88% and specificity of 61%. A threshold of BHB ≥ 0.95 mmol·L−1 resulted in sensitivity of 45% and specificity of 100%. AUC was 0.87. BHB measured ~ 4 hours prior to 18F-FDG injection performed similarly to or better than later timepoints. ConclusionsSerum BHB levels are useful for assessing suppression of MGU and could simplify interpretation of 18F-FDG PET/CT inflammation studies.

The Effect of IMS on Cognitive and Behavioral Abilities of mutant Drosophila, causing Neuroplasticity

The goal of this experiment was to determine the effect of the Intermediate Metabolic Switching (IMS) diet on the short and long-term memory of mutant Drosophila due to neuroplasticity. Neuroplasticity creates new neural networks and can be measured in ketone count. The IMS diet includes two components: fasting and a low-carbohydrate, high-fat diet. The Phenol-Sulfuric Acid Test and the Hanus Iodine Solution Test were both used to quantify two ratios, a 2:2 ratio carbs to fats, and the 4:1 ratio fats to carbs. It was hypothesized that if fruit flies are fed the IMS diet, leading to plasticity, then their overall memory and behavioral health will increase because of the amount of ketones released, increasing memory formation. Mutant Drosophila tested, which lacked the Amyloid-Precursor Protein-like gene (APPL), exhibited similarities to early-stage Alzheimer's patients. Assays include the Aversive Phototaxic Suppression Assay to measure short term memory, the Aversive Pavlovian Olfactory Assay to measure long-term memory, the Drosophila Activity Monitor software to track movement of Drosophila, the Drosophila Stress Odorent (dSO) Assay to measure mood changes, and the ß-Hydroxybutyrate Ketone Quantification assay to measure ketone levels and ensure the IMS diet worked. Results were all conclusive, establishing that the flies in the 4:1 diet were more sensitive but retain short and long term memory, showing IMS could be used as a preventative mechanism for Alzheimer’s.

Ketogenic diet acutely improves gas exchange and sleep apnoea in obesity hypoventilation syndrome: A non-randomized crossover study.

Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention. We conducted a single-arm crossover clinical trial to examine the impact of a ketogenic diet on CO2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models. A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L (p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO2 by 3.0 mm Hg (p = 0.008), bicarbonate by 1.8 mmol/L (p = 0.001), and weight by 3.4 kg (p < 0.001). Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin-like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated. This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.

Supplementing sodium butyrate to limit-fed heifers: Effects on growth, coccidiosis, urinary purine derivatives, and apparent total-tract nutrient digestibility

The objective of this study was to assess the growth, apparent total-tract digestibility of nutrients, the prevalence of coccidia, and purine derivatives (PD) in post-weaned heifers when limit-fed a diet supplemented with sodium butyrate (SB). A 12 wk randomized complete block experiment was conducted using 24 Holstein heifers [92.8 d ± 1.9 d of age and initial body weight (BW) of 99.6 ± 15.2 kg (mean ± SD)]. Treatments were 100 g soybean meal (control; CON) and 0.75 g of SB/kg of BW + 100g soybean meal (SB). Diets were formulated to contain 16.4% crude protein (CP), 2.27 Mcal/kg metabolizable energy (ME), and fed at a feed out rate of 2.15% of BW on a dry matter basis. Intakes were recorded daily while growth measurements and BW were recorded weekly. Urine and fecal samples were taken biweekly. On d 42 through d 49 an apparent total-tract digestibility phase took place using acid detergent insoluble ash as a marker. Growth measurements were similar among treatments except CON heifers grew longer and tended to be taller at the withers. A trend was observed for CON animals to have lower levels of coccidian oocytes by week. Heifers fed SB had lower blood glucose levels and higher levels of ketones in their blood. Urinary volume was greater for heifers fed SB throughout the 12 wk study. Total purine derivatives (PD) were greater in CON heifers. Dry matter, organic matter and acid detergent fiber digestibilities were greater for heifers fed SB compared with CON heifers. Crude protein, neutral detergent fiber, and ash digestibilities tended to be greater in heifers fed SB than in CON heifers. These results suggested no growth benefit of supplementing SB to limit-fed heifers, however apparent total-tract fiber, ash and crude protein digestibilities were improved in the SB fed heifers likely due to improved ruminal and intestinal development.

The impact of sport-specific physical fitness change patterns on lower limb non-contact injury risk in youth female basketball players: a pilot study based on field testing and machine learning.

Background: In recent years, identifying players with injury risk through physical fitness assessment has become a hot topic in sports science research. Although practitioners have conducted many studies on the relationship between physical fitness and the likelihood of injury, the relationship between the two remains indeterminate. Consequently, this study utilized machine learning to preliminary investigate the relationship between individual physical fitness tests and injury risk, aiming to identify whether patterns of physical fitness change have an impact on injury risk. Methods: This study conducted a retrospective analysis by extracting the records of 17 young female basketball players from the sport-specific physical fitness monitoring and injury registration database in Fujian Province. Sports-specific physical fitness tests included physical performance, physiological, biochemical, and subjective perceived responses. The data for each player was standardized individually using Z-scores. Synthetic minority over-sampling techniques and edited nearest neighbor algorithms were used to sample the training set to address the negative impact of class imbalance on model performance. Feature extraction was performed on the dataset using linear discriminant analysis, and the prediction model was constructed using the cost-sensitive neural network. Results: The 10 replicate 5-fold stratified cross-validation showed that the lower limb non-contact injury prediction model based on the cost-sensitive neural network had achieved good discrimination and calibration (average Precision: 0.6360; average Recall: 0.8700; average F2-Score: 0.7980; average AUC: 0.8590; average Brier-score: 0.1020), which could be well applied in training practice. According to the attribution analysis, agility and speed were important physical attributes that affect youth female basketball players' non-contact lower limb injury risk. Specifically, there was enhance in the performance of the 1-min double under, accompanied by an increase in urinary ketone and urinary blood levels following the agility test. The 3/4 basketball court sprint performance improved, while urinary protein and RPE levels decreased after the speed test. Conclusion: The sport-specific physical fitness change pattern can impact the lower limb non-contact injury risk of young female basketball players in Fujian Province, specifically in terms of agility and speed. These findings will provide valuable insights for planning athletes' physical training programs, managing fatigue, and preventing injuries.

Effects of a Preoperative Carbohydrate Load on Postoperative Recovery in Children: A Randomised, Double-Blind, Placebo-Controlled Trial

BackgroundNausea and vomiting are common causes for prolonged postoperative length of hospital stay (LOS) in children. A preoperative carbohydrate load may reduce postoperative nausea and vomiting by improving the perioperative metabolic state. The aim of this study was to determine if a preoperative carbohydrate-containing drink would lead to an improvement in the perioperative metabolic state and consequently reduce the incidence of postoperative nausea, vomiting and LOS in children undergoing day-case surgical procedures. MethodRandomised, double-blind, placebo-controlled trial involving children aged 4 to 16-years undergoing day-case surgical procedures. Patients were randomised to receive a carbohydrate-containing drink or a placebo. During the induction of anaesthesia, a venous blood gas, and blood glucose and ketone levels were measured. Postoperatively, the incidence of nausea, vomiting, and LOS were documented. Results120 patients were randomised with 119/120 (99.2%) undergoing analysis. Blood glucose level was higher in the carbohydrate group; 5.4 mmol/L [3.3–9.4] versus 4.9 mmol/L [3.6–6.5] (p = 0.01). Blood ketone level was lower in the carbohydrate group; 0.2 mmol/L versus 0.3 mmol/L (p = 0.003). The incidence of nausea and vomiting was not different (p > 0.9 and p = 0.8, respectively). LOS in the carbohydrate group was 26 min shorter than the placebo group (p = 0.02). ConclusionAlthough a preoperative carbohydrate load may provide a more stable metabolic state at the induction of anaesthesia, we did not find a reduction in postoperative nausea and vomiting. A preoperative carbohydrate load has also minimal effects on the postoperative LOS. Type of studyRandomised clinical trial. Level of evidenceI.

Fasting ketone levels vary by age: implications for differentiating physiologic from pathologic ketotic hypoglycemia.

Ketone production is a physiological phenomenon that occurs during beta-oxidation of free fatty acids. Distinguishing physiologic ketosis from pathologic over-production/underutilization of ketones is critical aspart of the diagnostic evaluation of disorders of carbohydrate metabolism, but there is limited literature on normal ketone production with fasting. Our aim is tomeasure fasting serum beta-hydroxybutyrate (BHB) concentrations in healthy children after an overnight fast. Children≤18 years of age were 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. Serum glucose, cortisol, and BHB were assessed after an overnight fast. Data from 94 participants (mean 8.3±5.7 years, 54 % male, 46 % female, were analyzed. Children≤3 years of age (19) have significantly higher mean (0.40±0.06 mmol/L) and median (0.4, IQR 0.2-0.6 mmol/L) BHB concentrations compared to children >3 years of age (75) with mean (0.21±0.02 mmol/L) and median BHB (0.1, IQR 0.1-0.2 mmol/L) (p<0.0001). Fasting BHB levels of >1.0 mmol/L was rare (2 %, N=2) and 74 % (N=70) of participants had BHB levels <0.3 mmol/L. BHB concentrations are significantly higher in young children (≤3 years of age) compared to older children. Fasting BHB levels >1.0 mmol/L are rare within our population and therefore may identify a value above which there may a greater concern for pathologic ketotic hypoglycemia. It is imperative to establish the normative range in children to differentiate physiological from pathological ketotic hypoglycemia.

A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes

Ketogenic diets (KDs) affect the circadian rhythms of behavior and clock gene expression in experimental animals. However, these diets were designed to simulate a fasting state; thus, whether these effects are caused by diet-induced ketogenesis or persistent starvation is difficult to distinguish. The present study aimed to define the effects of a KD containing medium-chain triglycerides (MCT-KD) that increase blood ketone levels without inducing carbohydrate starvation, on circadian rhythms and sleep regulation. Mice were fed with a normal diet (CTRL) or MCT-KD for 2 weeks. Blood β-hydroxybutyrate levels were significantly increased up to 2 mM by the MCT-KD, whereas body weight gain and blood glucose levels were identical between the groups, suggesting that ketosis accumulated without carbohydrate starvation in the MCT-KD mice. Circadian rhythms of wheel-running activity and core body temperature were almost identical, although wheel-running was slightly reduced in the MCT-KD mice. The circadian expression of the core clock genes, Per1, Per2, Bmal1, and Dbp in the hypothalamus, heart, liver, epididymal adipose tissues, and skeletal muscle were almost identical between the CTRL and MCT-KD mice, whereas the amplitude of hepatic Per2 and adipose Per1 expression was increased in MCT-KD mice. The MCT-KD reduced the duration of rapid-eye-movement (REM) sleep without affecting the duration of non-REM sleep and the duration of wakefulness. These findings suggested that the impact of ketone bodies on circadian systems are limited, although they might reduce locomotor activity and REM sleep duration.

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants

Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as β-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception. Eight healthy young adults (4 women, 4 men, age 24±3 years, BMI 24.3±3.1kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured. Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p>0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110±54kcal/d vs. ISO, p<0.05) and SEE (+201±90kcal/d vs. ISO, p<0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48±27g/d, p<0.05) resulting in a positive CHO balance (p<0.05). No differences between the interventions were found for subjective appetite ratings (all p>0.05). A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance. NCT04490226 https://clinicaltrials.gov/.

Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study.

In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. MATERIALSANDMETHODS: Patients with 7.5%-9.0% glycated haemoglobin treated with metformin and sulphonylurea were randomly assigned to ipragliflozin (50 mg, n = 70) or sitagliptin (100 mg, n = 70) therapy for 24 weeks. Measures of glycaemic control, fatty liver indices, other metabolic parameters and subclinical atherosclerosis were compared by a paired t-test before and after 24 weeks of treatment. Mean glycated haemoglobin levels decreased from 8.5% to 7.5% in the ipragliflozin group and from 8.5% to 7.8% in the sitagliptin group, resulting in a 0.34% between-group difference (95% confidence interval, 0.10%-0.43%, p = .088). Fasting and postprandial 2-h glucose levels also showed a similar trend, with a greater reduction with ipragliflozin therapy. An increase of over 70% in ketone levels and a decrease in whole body and abdominal fat masses were observed with ipragliflozin treatment. Fatty liver indices also improved with ipragliflozin treatment. Despite no difference in carotid intima-media thickness and ankle-brachial index, ipragliflozin therapy improved flow-mediated vasodilation, reflecting endothelial function, while sitagliptin did not. The safety profile did not differ between the two groups. Ipragliflozin add-on therapy can be a viable option for better glycaemic control with multiple vascular and metabolic benefits in patients with type 2 diabetes who are inadequately controlled with metformin and sulphonylurea.