Epilepsy ; diet therapy ; metabolism ; Food-Drug Interactions ; Humans ; Ketone Bodies ; biosynthesis

In this study, the Autokit Total Ketone Bodies kit (Wako Pure Chemical, Japan), a total ketone measurement assay using an enzymatic method, was evaluated using a Roche Cobas e702 instrument (Roche Diagnostics, Germany). Precision, linearity, carryover, and reference range verification were evaluated with reference to Clinical Laboratory Standards Institute guidelines. Standard materials provided by the manufacturer and patient samples were used for the evaluation. The precision and carryover of the evaluation result satisfied the acceptance criteria. Linearity was also acceptable at more than 0.99. The quantitative Autokit Total Ketone Bodies kit is precise, and can be widely used in clinical laboratories.
3-Hydroxybutyric Acid ; Evaluation Studies as Topic ; Humans ; Ketone Bodies* ; Methods ; Reference Values

BACKGROUND: Urine ketone test is commonly used to screen for diabetic ketoacidosis (DKA). Ketonuria also develops in patients with disease conditions other than DKA. However, the prevalence of DKA in patients with ketonuria is not known. We investigated the prevalence of ketonuria and characteristics of patients with ketonuria and estimated the prevalence of DKA among them to study the clinical significance of ketonuria as an indicator of DKA. METHODS: We studied 1,314 adult and 1,027 pediatric patients who underwent urinalysis. The prevalence of ketonuria in the different groups of patients, classified according to the types of their visits to the institution, was investigated, and the relationships between ketonuria and albuminuria, glycosuria, and bilirubinuria were evaluated. RESULTS: The overall prevalence of ketonuria was 9.1%. The prevalences of ketonuria in adult and pediatric patients were 4.3% and 15.2%, respectively. The prevalences of ketonuria were the highest in the adult (9.7%) and pediatric (28%) patients in the group that had visited the emergency department. Among patients with ketonuria, 7% adult and 3.8% pediatric patients showed glycosuria. CONCLUSIONS: This study showed that the prevalence of DKA in patients with ketonuria, defined as the simultaneous presence of ketone bodies and glucose in urine, was only 7%. Therefore, we concluded that ketonuria might be clinically significant as an indicator of acute or severe disease status rather than of DKA.
Adult ; Albuminuria ; Diabetic Ketoacidosis ; Emergencies ; Glucose ; Glycosuria ; Humans ; Ketone Bodies ; Ketosis ; Prevalence ; Urinalysis

Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.
Humans ; Heart Failure/metabolism* ; Myocardium/metabolism* ; Ketone Bodies/metabolism* ; Cardiovascular Diseases ; Fatty Acids/metabolism* ; Energy Metabolism

Sodium-glucose cotransporter 2 inhibitors are antidiabetic drugs that increase urinary glucose excretion by inhibiting proximal tubular reabsorption of glucose in the kidney. Some sodium-glucose cotransporter 2 inhibitors have been shown to afford effective glycemic control and to decrease the risks of major adverse cardiovascular events. However, these drugs may increase the risk of diabetic ketoacidosis. This is a rare complication that occurs in less than 0.1% of treated patients with type 2 diabetes. The condition may be euglycemic, and is triggered by controllable precipitating factors such as surgery, infection, and insulin reduction or omission. It is important to understand individual patient profiles and to prevent diabetic ketoacidosis by appropriate prescribing, by withholding sodium-glucose cotransporter 2 inhibitors when indicated, and by counseling patients on sick day management.
Counseling ; Diabetic Ketoacidosis ; Glucose ; Humans ; Hypoglycemic Agents ; Insulin ; Ketone Bodies ; Ketosis* ; Kidney ; Precipitating Factors ; Sick Leave ; Sodium-Glucose Transporter 2

Sodium glucose cotransporter 2 (SGLT2) inhibitor has been recently reported of diabetic ketoacidosis due to accumulation of ketone bodies in patients with severe dehydration caused from such like diarrhea even though the patient had normal glucose level. This is a case of ketoacidosis in normal glucose level as production of ketone bodies is stimulated in liver with increased secretion of glucagon by stimulation of α cells in pancreas due to increase of lipolysis caused from reducing insulin and by SGLT2 inhibitor among patients who are under concurrent insulin and SGLT2 inhibitor. Thus, insulin dosage reduction requires caution in order to control blood glucose level on combined treatment of SGLT2 inhibitor in a patient who is administering insulin because the patient may be caused ketoacidosis in normal blood glucose level.
Blood Glucose ; Dehydration ; Diabetic Ketoacidosis* ; Diarrhea ; Glucagon ; Glucose* ; Humans ; Insulin* ; Ketone Bodies ; Ketosis ; Lipolysis ; Liver ; Pancreas ; Sodium*

During hemorrhagic shock, liver is susceptible to ischemia and decreased hepatic energy charge results in decreasing arterial ketone body ratio(AKBR). Reperfusion after hemorrhagic shock can greatly amplify the generation of toxic oxygen metabolites. As a result, the fluxes of these highly toxic metabolites can overwhelm the endogenous antioxident defense mechanisms and lead to tissue injury. In order to observe the effect of glutathione(GSH) on the AKBR in hemorrhagic shock, dogs(n=16) were anesthetized with 1% enflurane in 02. We pretreated glutathione (100 mg/kg) intravenously before hemorrhagic shock in glutathione (GSH) group (n=8). Shock was induced with bleeding and mean arterial pressure was maintained 50 mmHg for 30 minutes. Recovery from shock was done with transfusion of preserved blood and maintained for 30 minutes. We measured arterial ketone bodies and ketone body ratio before, during and after shock, and compared them to control group (n=8) which was not pretreated with glutathione. AKBR during and after hemorrhagic shock in GSH group (0.8 and 1.0) were higher than those in control group (0.5 and 0.8). Light microscopic examination of liver biopsy revealed less portal degeneration during and after hemorrhagic shock in GSH group than control group. Pharmacologic modulation of hepatocytic function with glutathione before hemorrhagic shock has shown some beneficial effect with protection of decreased AKBR and histological change during and after hemorrhagic shock.
Animals ; Arterial Pressure ; Biopsy ; Defense Mechanisms ; Dogs* ; Enflurane ; Glutathione* ; Hemorrhage ; Ischemia ; Ketone Bodies ; Liver ; Oxygen ; Reperfusion ; Shock ; Shock, Hemorrhagic*

PURPOSE: Ketogenic diet(KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable epilepsy. The mechanisms underlying its anticonvulsant action remain poorly understood. Furthermore, its possible side effects have not been investigated systematically. The present study was designed to investigate untoward side effects of KD on liver in rats. METHODS: A KD([fat]:[protein+carbohydrate] ratio of 4.3:1) was administered to male Sprague-Dawley rats, while control animals were fed a standard rodent chow for treatment period of either 3(KD n=5 vs. control n=4) or 5(KD n= 4 vs. control n=5) weeks. Dietary treatment was initiated at postnatal 3 weeks. At the end of treatment, blood beta-hydroxybutyrate(BHB) was assayed and then the animals were sacrificed for liver and blood sampling. Their livers were examined to evaluate fatty changes using oil red O technique. Serum levels of AST, ALT, alkaline phosphatase, and total bilirubin were assayed. RESULTS: The mean(+/-SEM) blood BHB levels in the KD group were significantly higher than those of the control group in animals treated for 3(5.9+/-0.1 vs. 0.6+/-0.1 mM, P<0.001) or 5(4.1+/-0.3 vs. 0.4+/-0.1 mM, P<0.001) weeks. Very distinct fatty changes were noticed microscopically in liver specimens of all rats treated with KD for either 3 or 5 weeks. Serum ALT levels were also significantly higher in the KD group than in the control in both 3(87.6+/-12.1 vs. 37.0+/-3.7 IU/L, P<0.01) and 5(118.5+/-2.9 vs. 31.6+/-2.6 IU/L, P<0.001) weeks treatment periods. In animals treated for 5 weeks, serum AST levels were also significantly(P<0.01) higher in the KD group(205.0+/-29.5 IU/L) than in the control(99.2+/-5.4 IU/L), whereas in animals treated for 3 weeks, no significant differences were noticed in AST levels between the two groups(133.2+/-11.7 vs. 122.8+/-13.1 IU/L, P>0.5). Other biochemical assay results showed no significant differences. CONCLUSION: This study demonstrates that KD causes some significant changes in the hepatic function and morphology at least in rats. It is well known that KD produces ketosis, i.e. elevated blood levels of ketone bodies, which are generated mainly in the liver. Thus, some changes in the liver, either harmful or beneficial, may easily be suspected. Further basic and/or clinical studies on this issue should be performed in a near future.
Alkaline Phosphatase ; Animals ; Bilirubin ; Epilepsy ; Humans ; Ketogenic Diet* ; Ketone Bodies ; Ketosis ; Liver* ; Male ; Rats* ; Rats, Sprague-Dawley ; Rodentia

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

BACKGROUND: Diabetes mellitus and alcohol consumption are the most common causes of ketoacidosis in adults. Recently, beta-hydroxybutyric acid (betaHBA) was reported to be a potential serum biomarker in the diagnosis and monitoring of ketoacidosis. We evaluated the performance of T-KB-H and 3-HB kits for the measurement of ketone bodies [acetoacetate (AcAc)+betaHBA] and betaHBA, respectively. METHODS: Quantitative enzymatic assays were performed using the T-KB-H and 3-HB kits (Nittobo Medical Co., Japan) and the Architect ci16200 Integrated System (Abbott Laboratories, USA). Simultaneously, the ketone body levels in these serum samples were determined by gas chromatography-mas spectrometry (GC-MS). We evaluated precision and linearity of these kits and correlation with GC-MS, and established reference intervals in children and adults. RESULTS: The coefficients of variation for the T-KB-H and 3-HB kits were less than 4.0% at analyte levels of 50, 100, and 400 micromol/L. Linearity was observed for AcAc and betaHBA over a 0-1,000 micromol/L range (R2<0.99). Results from the T-KB-H and 3-HB kits were in good agreement with those from the GC-MS analysis, with correlation coefficients of 0.94 for AcAc and 0.96 for betaHBA. Reference intervals determined for the T-KB-H kit were 9.8-270.1 micromol/L and 18.5-531.8 micromol/L in children and adults, respectively. For the 3-HB kit, the reference intervals were 6.4-234.0 micromol/L and 16.0-437.2 micromol/L in children and adults, respectively. CONCLUSIONS: The T-KB-H and 3-HB kits displayed good precision, clinically acceptable linearity, and reliable correlation with an established assay. This indicates that the kits can be used clinically for measuring serum ketone bodies.
3-Hydroxybutyric Acid* ; Adult ; Alcohol Drinking ; Child ; Diabetes Mellitus ; Diabetic Ketoacidosis ; Diagnosis ; Enzyme Assays ; Gas Chromatography-Mass Spectrometry ; Humans ; Ketone Bodies ; Ketosis ; Spectrum Analysis