Blood Ketone Research Articles

Serum concentrations of lipids, ketones and acylcarnitines during the postprandial and fasting state: the Postprandial Metabolism (PoMet) study in healthy young adults.

To improve the interpretation and utilisation of blood lipids, ketones and acylcarnitine concentrations as biomarkers in clinical assessments, more information is needed on their dynamic alterations in response to dietary intake and fasting. The aim of this intervention study was to characterise the changes in serum lipid, ketone and acylcarnitine concentrations 24 h after a standardised breakfast meal. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20-30 years were served a breakfast meal (∼500 kcal, 36 E% fat, 46 E% carbohydrates, 16 E% protein, 2E% fibre), after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Metabolite concentrations were plotted as a function of time since the completion of the breakfast meal. Results demonstrated that concentrations of HDL-cholesterol and LDL-cholesterol decreased until ∼2 h (-4 % for both), while TAG concentrations peaked at 3 h (+27 %). Acetoacetate and β-hydroxybutyrate were highest 24 h after the meal (+433 and +633 %, respectively). Acetylcarnitine, butyrylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine and dodecanoylcarnitine reached the lowest values at 60 min (decreases ranging from -47 to -70 %), before increasing and peaking at 24 h after the meal (increases ranging from +86 to +120 %). Our findings suggest that distinguishing between fasting and non-fasting blood samples falls short of capturing the dynamics in lipid, ketone, carnitine and acylcarnitine concentrations. To enhance the utility of serum acylcarnitine analyses, we strongly recommend accounting for the specific time since the last meal at the time of blood sampling.

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (<200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (>4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (>1000) and ketones (>40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

Effect of ketone monoester supplementation on elite operators' mountaineering training.

Special Operations Forces (SOF) often conduct operations in physiologically stressful environments such as severe heat, cold, or hypoxia, which can induce decreases in a variety of cognitive abilities. Given the promising empirical demonstration of the efficacy of exogenous ketone monoester (KME) supplementation in attenuating cognitive performance decrease during hypoxia at rest in a laboratory setting, we conducted a real-world, field experiment examining KME's efficacy during high-altitude mountaineering, an austere environment in which US SOF have conducted increasing numbers of operations over the past two decades. Specifically, 34 students and cadre at the US Army 10th Special Forces Group Special Operations Advanced Mountaineering School (SOAMS) participated in a randomized, double-blind, placebo (PLA)-controlled crossover trial (KME vs. PLA) over 2days of tactical mountain operations training. The participants ascended from 7,500 ft in altitude (basecamp) to 12,460 ft on 1 day and 13,627 ft the other day (in randomized order), while performing various training activities inducing high physical and cognitive loads over 8-12h, and consumed six doses of KME or PLA 2-3h apart throughout each training day. While KME increased blood ketone levels and decreased glucose levels, there were no clear indications that the elevated ketone level enhanced physical or cognitive performance. KME also produced a greater incidence of heartburn, nausea, and vomiting. In these elite operators, high-altitude mountaineering had a limited impact on cognitive performance, and KME supplementation did not demonstrate any benefit.

Examining capillary ketone testing in hospitalised patients: indications and outcomes.

Elevated blood ketone levels (ketosis) in inpatients with diabetes can herald diabetic ketoacidosis (DKA). However, ketosis can also occur in individuals without diabetes in certain settings. It is unclear what proportion of inpatients with ketosis are in DKA and which patients are at the highest risk of DKA. This study determined that many ketone tests are performed in individuals at low risk of DKA, and a β-hydroxybutyrate <1.0 mmol/L had a low incidence of DKA and less need for escalation in their management.

Feline acute patient physiologic and laboratory evaluation scores and other prognostic factors in cats with first-time diabetic ketoacidosis.

Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores have not been reported in cats with diabetic ketoacidosis (DKA). In cats with DKA, APPLE scores will be significantly higher in non-survivors compared with survivors and these scores will predict mortality. Sixty-eight cats with DKA. Retrospective study. The APPLE scores, blood glucose concentration (BG), venous pH, and ketone concentrations were compared between survivors and non-survivors. Simple logistic regression was used to determine if these variables predict the binary variable of survival or non-survival, and if they did, an empirical optimal cut point for mortality prediction was calculated. The APPLEfast and APPLEfull scores were significantly higher in non-survivors (30 cats; and , respectively) compared with survivors (38 cats; and ; P = .01 and P = .02, respectively). The APPLEfast (P = .03) but not the APPLEfull scores (P = .06) predicted mortality. For every 1 unit increase in the APPLEfast score, the odds of death increased by 1.08 (95% confidence interval [CI], 1.006-1.17; P = .03). Median BG was significantly higher in non-survivors (431 mg/dL; range, 260-832 mg/dL) compared with survivors (343 mg/dL; range, 256-738 mg/dL; P = .01) and BG predicted mortality (P = .02). For every 1 mg/dL increase in BG, the odds of death increased by 1.004 (95% CI, 1.0006-1.008). Empirical optimal cut points for APPLEfast and BG mortality prediction were 24.5 and 358 mg/dL, respectively. The APPLEfast score and BG predict mortality in cats with DKA and can be used to stratify populations by risk of mortality in clinical trials of DKA in cats.

Attenuation of brown adipocyte whitening in high-fat diet-induced obese rats: Effects of melatonin and β-hydroxybutyrate on Cidea, Fsp27 and MT1 expression.

To investigate the effects of β-hydroxybutyrate (BHB) and melatonin on brown adipose tissue (BAT) plasticity in rats fed a high-fat diet (HFD). We employed a 7-week experimental design for a study on 30 male Sprague-Dawley rats divided into five groups: (1) a control-diet fed group; (2) a high-fat diet (HFD)-fed group; (3) a group that received an HFD and a BHB solution in their drinking water; (4) a group that received an HFD with 10 mg/kg/day melatonin in their drinking water; and (5) a group that received an HFD and were also treated with the combination of BHB and melatonin. Following the treatment period, biochemical indices, gene expression levels of key thermogenic markers (including uncoupling protein 1 [UCP1], PR domain containing 16 [PRDM16], Cidea, fat-specific protein 27 [Fsp27], and metallothionein 1 [MT1]), and stereological assessments of BAT were evaluated. Treatment with BHB and melatonin significantly boosted blood ketone levels, improved lipid profiles, and reduced weight gain from an HFD. It also downregulated genes linked to WAT, namely, Cidea and Fsp27, and upregulated key BAT markers, including UCP1, PRDM16 and peroxisome proliferator-activated receptor-gamma coactivator-1-alpha. Additionally, the co-treatment increased MT1 receptor expression and enhanced the structural density of BAT. The combined oral administration of BHB and melatonin successfully prevented the whitening of BAT in obese rats fed an HFD, indicating its potential as a therapeutic strategy for obesity-related BAT dysfunction. The synergistic effects of this treatment underscore the potential of a combined approach to address BAT dysfunction in obesity.

Abstract Tu133: Cardiac Adaptations and Mitochondrial Protection Through Long Noncoding RNAs Regulation in Mice on a Ketogenic Diet

Background: Heart failure, characterized by a metabolic imbalance, leads to impaired mitochondrial ATP production. Ketone bodies not only serve as an alternate energy source but also mitigate heart failure by reducing cardiac remodeling and inflammation. The role of long noncoding RNAs (lncRNAs) in cardiac remodeling and mitochondrial metabolism is increasingly appreciated, and this study examines the effect of ketogenic diet on cardiac lncRNA regulation and mitochondrial protection. Methods and Results: In a six-month study, 10-week-old male and female C57BL/6J mice were assigned to either a control diet (10% fat, 20% protein, 70% carbohydrate) or a ketogenic diet (Keto; 80% fat, 15% protein, 5% carbohydrate). Data were analyzed using unpaired two-tailed t-tests (GraphPad Prism) and reported as mean ± SE. The keto diet significantly increased blood ketone bodies (n=36/group), indicating ketosis, and led to weight gain as well as a significant decrease in heart mass relative to body weight, suggesting cardiac metabolic adaptation (Fig 1A-B) . The cardiac expression analysis of lncRNAs Anril, Caren, Carmn, Gm15441, Malat1, Miat, and Oip5-as1 via qPCR (n=13/group) revealed significant upregulation of Anril and Malat1 in the Keto hearts ( Fig 1C-D ), indicating their potential regulatory roles under ketogenic conditions. Sex-specific differences were not observed in the lncRNA expressions. Key proteins involved in mitochondrial biogenesis, protection, and metabolic adaptation, including Nrf2 and PGC1α, were significantly increased at both mRNA and protein levels (n=6-10) in the hearts of mice on keto diet ( Fig 1E-H ). Conclusion: A six-month ketogenic diet in mice promotes cardiometabolic adaptations characterized by a reduction in relative heart mass and activation of key proteins involved in mitochondrial biogenesis and protection possibly through lncRNAs Anril and Malat1. These findings shed light on novel molecular targets and the potential of ketogenic diet/ketone bodies in treating heart failure.

Effects of angiotensin receptor-neprilysin inhibitor on ketone body metabolism in pre-heart failure/heart failure patients

Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] μmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients.

Effect of Oral Administration of Mytragina Speciosa on Blood Ketone Level and Glomerular Histology in Streptozotocin Induced Diabetic Mice

Effect of Oral Administration of Mytragina Speciosa on Blood Ketone Level and Glomerular Histology in Streptozotocin Induced Diabetic Mice

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes.MethodsA total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values.ResultsIn the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was − 1.07 (95% confidence interval [CI] − 1.29 to − 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight.ConclusionsIn patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo.Trial registration jRCTs031180120.

Euglycemic Ketoacidosis Induced by SGLT2 Inhibitor in Latent Autoimmune Diabetes in Adults: A Case Report

Background: Euglycemic ketoacidosis (EKA) is a medical condition characterized by the presence of ketoacidosis without significant hyperglycemia. It is particularly challenging to diagnose due to normal or near-normal blood glucose levels. SGLT2 inhibitors, used in managing type 2 diabetes mellitus, are known to cause EKA. This risk is increased in patients with latent autoimmune diabetes in adults (LADA), a type of Type 1diabetes presented in adult (Hybrid form of diabetes) Case Report: A 64-year-old male with a history of diabetes mellitus and hypothyroidism presented with shortness of breath, nausea, and dizziness. Despite taking Metformin, Glimepride, Thyroxin, and Empagliflozin, he had poor glycemic control (HbA1c 9%) Physical examination showed generalized vitiligo and tachycardia. Initial laboratory results revealed high anion gap metabolic acidosis with normal blood glucose, consistent with EKA. Extensive diagnostic workup confirmed the presence of LADA and SGLT2 inhibitor induced EKA. Result: The patient was diagnosed with type 1 diabetes mellitus (LADA) and EKA induced by SGLT2 inhibitors. Management included discontinuation of the SGLT2 inhibitor, initiation of insulin therapy, and monitoring of metabolic parameters. Conclusion: Euglycemic ketoacidosis induced by SGLT2 inhibitors in patients with LADA is a serious condition requiring prompt recognition and treatment. Clinicians should be vigilant in monitoring adult patients with diabetes and other autoimmune conditions who are on SGLT2 inhibitors for symptoms of ketoacidosis even when blood glucose levels are normal. Recommendations: Regular monitoring of blood ketone levels in patients on SGLT2 inhibitors. Consideration of alternative glucose-lowering therapies in patients with LADA. Education for patients and healthcare providers on the risks of EKA. Keywords: Euglycemic ketoacidosis, SGLT2 inhibitors, Latent autoimmune diabetes in adults, Diabetes management, Metabolic acidosis.

929-P: A Study to Evaluate Clinical and Metabolic Profile of Type 2 Diabetes Patients Receiving SGLT2 Inhibitors

Aim: The aim of the study was to determine the efficacy of SGLT2i and its impact on metabolic profile of type 2 diabetes (T2DM) patients with reference to serum glucagon and blood ketones. Methodology: The study was conducted in T2DM patients with inadequate glycemic control on a background therapy of either metformin and sulphonylurea (Group A) or metformin and DPP4 inhibitor(Group B) Blood samples were taken for estimation of fasting plasma glucose (FPG), post prandial plasma glucose (PPPG), HbA1c, beta-hydroxybutyrate (β-HB) and glucagon levels. Empagliflozin 10mg, was added to the existing anti-diabetic medication. The metabolic parameters were reassessed after 12 weeks. Results: At the end of 12 weeks glucagon levels increased significantly (28.8 ± 28.74 at baseline vs 108 ± 74 pg/ml; p&amp;lt;0.001). A significant increase in β-HB levels was also observed (0.1 ± 0.07 mmol/L at baseline versus 0.12 ± 0.07 mmol/L (p=0.03). FPG, PPPG and HbA1c decreased significantly by 30.33mg%, 53.16mg% and 1.05% respectively(p&amp;lt;0.01) In group A, FPG and PPPG decreased by 34.43 mg/dl and 51.71mg/dl respectively (p&amp;lt;0.001) with a mean HbA1c reduction of 1.09% (p&amp;lt;0.001) Serum glucagon and β-HB levels increased significantly [82.63 pg/ml (p&amp;lt;0.001) and 0.04 mmol/L (p&amp;lt;0.01) respectively]. In group B, there was decrease in FPG (mean difference 23.6mg %; p=0.003) and PPPG (mean difference 55.5mg%; p&amp;lt;0.001) at 12 weeks. HbA1c reduction of 0.99% was observed. (p=0.003) There was a significant increase in glucagon levels (mean difference +73.52 pg/ml; p&amp;lt;0.001). Conclusion: Addition of Empagliflozin to T2DM patients with inadequate glycemic control on either metformin and sulphonylurea or metformin and DPP4 inhibitors significantly improved efficacy. Plasma glucagon and β-HB levels increased with chronic empagliflozin treatment suggesting a change in substrate utilization towards fat. Disclosure S. Kandula: None. M.A. Meshram: None. A.C. Sonwane: None.

911-P: Effect of Dapagliflozin on Blood and Breath Ketones during Supervised Insulin Withdrawal in Adults with Type 1 Diabetes

911-P: Effect of Dapagliflozin on Blood and Breath Ketones during Supervised Insulin Withdrawal in Adults with Type 1 Diabetes

Effects of Different Carbohydrate Content Diet on Gut Microbiota and Aortic Calcification in Diabetic Mice.

Vascular calcification is a major cause of cardiovascular accidents in patients with type 2 diabetes mellitus. This study aimed to investigate the impact of carbohydrates on gut microbiota and aortic calcification in diabetic ApoE-/- mice. The diabetic ApoE-/- mice were randomly divided into 4 groups: ketogenic diet group, low carbohydrate diet group, medium carbohydrate diet group, and high carbohydrate diet group. The mice were fed continuously for 6 months, with blood glucose, blood ketone and body weight monitored monthly. Lipid metabolism indicators and inflammatory factors were detected using ELISA. The intestinal barrier, atherosclerotic lesion areas, and vascular calcifications were analyzed based on their morphology. Gut microbiota was analyzed using 16S rRNA genes. We found that ketogenic diet played some roles improving glucose, lipid metabolism, and inflammation. Ketogenic diet could improve the intestinal barrier to some extent and increase intestinal bacteria. Compared to the other three groups, the relative abundance of genus Allobaculum, species Blautia producta and Clostridium Ramosum in the ketogenic diet group was significantly increased (P <0.05), which has protective effects in diabetic ApoE-/- mice. Ketogenic diet could delay the onset of aortic atherosclerosis, aortic calcification and improve intestinal barrier function in diabetic ApoE-/- mice.

DIET2TREAT: A randomized, multi-center, phase 2 trial of a ketogenic diet vs standard dietary guidance in combination with standard-of-care treatment for patients with newly diagnosed glioblastoma.

TPS2103 Background: Presented with a dismal prognosis and limited treatment options, many glioblastoma (GBM) patients seek complementary interventions. Of particular interest is a high-fat / low-carbohydrate diet known as the ketogenic diet (KD). Preclinical models and results from early-phase trials suggest potential benefits with KD for patients with GBM receiving standard-of-care (SOC) treatment, but definitive evidence of clinical efficacy is still lacking. Methods: We are conducting a multicenter randomized controlled phase 2 clinical trial of KD vs standard dietary guidance (SD) for patients with newly diagnosed GBM. All patients will receive SOC chemoradiation. Patients with newly diagnosed GBM age ≥ 18 years with Karnofsky Performance Status ≥ 70 are eligible. Exclusion criteria include inability to wean steroids below 8 mg dexamethasone/day or equivalent, Body Mass Index &lt; 21 kg/m2, or food preferences incompatible with KD. Patients are randomized 1:1 to implement either KD (3:1 ratio between grams of fat to grams of carbohydrates + protein) or SD (based on guidelines from the American Cancer Society and American Institute of Cancer Research) for a study period of 18 weeks, starting the same time as chemoradiation. Post-randomization, all patients receive diet education, followed by in-person or virtual dietitian consultation every 2 weeks at minimum while on study. The primary objective is to assess overall survival for patients on the KD arm vs the SD arm. Secondary endpoints include assessments of progression-free survival, health-related quality-of-life (FACT-BR, FACIT-F), cognitive performance (HVLT-R, Trail-Making Test A/B), and physical activity (modified Godin leisure questionnaire, continuous activity monitoring (Fitbit)), as benefits in any of these domains would be impactful for patients. Patients randomized to the KD arm will be provided a fingerstick monitor (Keto-Mojo) to check blood ketone and glucose levels daily. Glucose and ketone levels are also periodically monitored for patients on the SD arm. Blood, tumor, and stool samples are being collected for high throughput profiling to assess the effects of KD on metabolic markers and immune response. While the primary analysis for this study is intent-to-treat, we will also perform secondary per protocol and as-treated analyses using food diaries plus glucose and ketone data. Target accrual is 170 patients over 5 years. Enrollment began in July 2023 and is ongoing. As of January 2024, the trial is open for enrollment at Cedars-Sinai Medical Center and will be opening at UCSF, Duke, Pacific Neuroscience Institute, and the Medical College of Wisconsin soon. Ten patients have been randomized so far. This trial is funded by NIH R01CA276919 and a grant from the Foundation for Metabolic Cancer Therapies and is registered as NCT05708352. Clinical trial information: NCT05708352 .

N-of-1 health optimization: Digital monitoring of biomarker dynamics to gamify adherence to metabolic switching.

The digital health field is experiencing substantial growth due to its potential for sustained and longitudinal deployment. In turn, this may drive improved monitoring and intervention as catalysts for behavioral change compared to traditional point-of-care practices. In particular, the increase in incidence of population health challenges such as diabetes, heart disease, fatty liver disease, and other disorders coupled with rising healthcare costs have emphasized the importance of exploring technical, economics, and implementation considerations, among others in the decentralization of health and healthcare innovations. Both healthy individuals and patients stand to benefit from continued technical advances and studies in these domains. To address these points, this study reports a N-of-1 study comprised of sustained regimens of intermittent fasting, fitness (strength and cardiovascular training), and high protein, low carbohydrate diet and parallel monitoring. These regimens were paired with serial blood ketone, blood glucose (wearable and finger stick) and blood pressure readings, as well as body weight measurements using a collection of devices. Collectively this suite of platforms and approaches were used to monitor metabolic switching from glucose to ketones as energy sources-a process associated with potential cardio- and neuroprotective functions. In addition to longitudinal biomarker dynamics, this work discusses user perspectives on the potential role of harnessing digital devices to these dynamics as potential gamification factors, as well as considerations for the role of biomarker monitoring in health regimen development, user stratification, and potentially informing downstream population-scale studies to address metabolic disease, healthy aging and longevity, among other indications.

Innovations and applications of ketone body monitoring in diabetes care.

Ketone bodies, comprising β-hydroxybutyric acid (BHB), acetoacetate (AcAc), and acetone, play a vital role as essential energy substrates. In individuals with diabetes, ketone bodies can be elevated under various conditions, including diabetic ketoacidosis, use of sodium-glucose transporter type 2 (SGLT2) inhibitors, and extreme carbohydrate restriction. There are three methods for measuring ketone bodies. Urine ketone analysis (AcAc) is a standard clinical test, whereas blood ketone testing (BHB+AcAc) is valuable in identifying or resolving diabetic ketoacidosis. Recently, technology for measuring breath acetone has been introduced, which provides an easy means of monitoring ketogenic diets in obese individuals. The basic breath alcohol detector also reacts with breath acetone. Therefore, it is important for professional drivers taking SGLT2 inhibitors to be cautious as workplace breath alcohol detectors may show false-positive results. Conversely, if a positive result is obtained, a detailed examination of ketosis is necessary. This review provides an overview of ketone body measurements in individuals with diabetes.

Application of an electronic nose for the diagnosis of ketosis in dairy cows

Ketosis in dairy cows is a nutritional and metabolic disease that severely affects the milk industry and dairy cow health. An electronic nose can identify volatile organic compounds (VOCs). This study applied the electronic nose to detect VOCs in dairy cow milk, feces, and blood. Blood ketone bodies (BHBA) were measured, and 10 ketosis cows, 71 subclinical ketosis cows, and 75 healthy cows were considered the research subjects. Cow milk, feces, and blood samples were collected for electronic nose testing. The measured VOC data were processed through multivariate analysis and machine learning algorithms. The electronic nose analysis results were validated through the GC-MS analysis of the milk samples. The results unveiled spatial differences in the electronic nose VOC values of milk, feces, and blood, and the cumulative contribution rates of both principal component variables (PC) 1 and PC2 reached more than 95%. The machine learning algorithm results revealed that the accuracy of the milk probabilistic neural network (PNN) was 87.5%, the stool support vector machine was 100%, and the blood PNN was 66.7%. This result revealed that electronic nose detection can effectively differentiate healthy, subclinical ketosis, and clinical ketosis cows. According to the milk GC-MS results, significant differences were noted in the VOC content of milk samples between the different groups.The aforementioned studies revealed that electronic nose can aid in the effective prediction and diagnosis of ketosis in dairy cows. This lays the foundation for establishing a new method for diagnosing ketosis in dairy cows.

The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2.

Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague-Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones.

Ketoacidosis and SGLT2 Inhibitors: A Narrative Review.

An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.