Ketone Body Formation Research Articles

Short-term reduction in feed intake by dairy cows in the postpartum period leads to subclinical ketosis development

Subclinical ketosis is widespread in highly productive dairy cows after calving and often remains undiagnosed, leading to reduced productivity. Physiologically controlled feeding in the first weeks after calving and during the intensive lactation period can reduce the incidence of ketosis. The study aimed to determine how a short-term reduction of feed after calving affects the formation of ketone bodies in blood, urine and milk of dairy cows. The group of ten Ukrainian black-spotted dairy breed cows after calving aged from 4 to 6 years was involved in the experiment lasted for 72 h. In 24 h the amount of compound feed, haylage, and silage received by cows was gradually reduced until complete exclusion in the diet. Blood, urine, and milk samples were collected three times a day. The content of ketone bodies, β-hydroxybutyrate and glucose was estimated with the corresponding sets of indicator strips. The content of total bilirubin, cholesterol, albumin and enzymes activity in the blood serum were determined on biochemical analyzer. It was found that in 24 h after the beginning of feed reduction the level of blood glucose decreased, persistent hypoglycemia within 48 and 72 h was developed, the concentration of β-hydroxybutyrate in blood and milk and of ketone bodies in urine was elevated. The increase in total bilirubin concentration and liver enzymes activity in the blood serum with a simultaneous decrease in albumin level and delayed sodium propionate conversion into glucose were observed. Thus, short-term reduction in feed intake by dairy cows after calving causes ketosis development and violation of liver functions. Keywords: dairy сows, feeding level, glucose, ketosis, liver damage, β-hydroxybutyrate

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

GLP-1 mimetics and diabetic ketoacidosis: possible interactions and clinical consequences.

Diabetic ketoacidosis is a serious diabetes-related consequence that occurs in type 1 diabetes and less commonly in type 2 diabetes and is a major cause of death. It results from the metabolic consequences due to a lack of insulin secretion or impaired insulin activity in diabetes leading to dysregulated pathophysiologic pathways resulting in excessive ketone body formation. While ketone bodies are physiologic molecules, their high levels reduce the physiological pH of the blood and induce ketoacidosis, leading to increasing metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) mimetics are a class of recently developed diabetes therapy that do not lead to hypoglycemic, but some reports have suggested a relationship between GLP-1 mimetics and ketogenesis. To clarify the possible interactions between GLP-1 mimetics and ketogenesis in diabetes, this review was undertaken to collate and interpret the literature.

Relevance of plasma lipoproteins and small metabolites in assessment of nutritional status among patients with severe injuries

BackgroundThis study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries. MethodsThis observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression. ResultsOverall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value >1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value >1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value >1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (P <0.05); however, the association did not persist after correcting the false discovery rate (P=0.35 for all). ConclusionIncreased triglyceride in several lipoprotein subfractions and decreased levels of other lipoprotein subfraction lipids and several small metabolites (involved in the homocysteine cycle, ketone body formation, and muscle metabolism) may be indicative of malnutrition risk. Following validation in larger cohorts, these indicators may guide institution of preventive nutritional measures in patients admitted to the ICU with severe injuries.

How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system?

What mechanisms can link the inhibition of sodium-glucose cotransporter 2 (SGLT2) in the early proximal tubule to kidney and heart protection in patients with and without type 2 diabetes? Due to physical and functional coupling of SGLT2 to other sodium and metabolite transporters in the early proximal tubule (including NHE3, URAT1), inhibitors of SGLT2 (SGLT2i) reduce reabsorption not only of glucose, inducing osmotic diuresis, but of other metabolites plus of a larger amount of sodium than expected based on SGLT2 inhibition alone, thereby reducing volume retention, hypertension and hyperuricemia. Metabolic adaptations to SGLT2i include a fasting-like response, with enhanced lipolysis and formation of ketone bodies that serve as additional fuel for kidneys and heart. Making use of the physiology of tubulo-glomerular communication, SGLT2i functionally lower glomerular capillary pressure and filtration rate, thereby reducing physical stress on the glomerular filtration barrier, tubular exposure to albumin and nephrotoxic compounds, and the oxygen demand for reabsorbing the filtered load. Together with reduced gluco-toxicity in the early proximal tubule and better distribution of transport work along the nephron, SGLT2i can preserve tubular integrity and transport function and, thereby, glomerular filtration rate in the long-term. By shifting transport downstream, SGLT2i may simulate systemic hypoxia at the oxygen sensors in the deep cortex/outer medulla, which stimulates erythropoiesis and, together with osmotic diuresis, enhances hematocrit and thereby improves oxygen delivery to all organs. The described SGLT2-dependent effects may be complemented by off-target effects of SGLT2i on the heart itself and on the microbiome formation of cardiovascular-effective uremic toxins.

Effects of long-term dehydration on stress markers, blood parameters, and tissue morphology in the dromedary camel (Camelus dromedarius).

Dromedary camels robustly withstand dehydration, and the rough desert environment but the adaptation mechanisms are not well understood. One of these mechanisms is that the dromedary camel increases its body temperature to reduce the process of evaporative cooling during the hot weather. Stress in general, has deleterious effects in the body. In this study, we sought to determine the effects of dehydration and rehydration on stress parameters in the dromedary camels and how it pacifies these effects. Nineteen male camels were randomly divided into control, dehydrated and rehydrated groups, and fed alfalfa hay ad-libitum. The dehydrated and rehydrated groups were water-restricted for 20 days after which the rehydrated camels were provided with water for 72 h. The control and dehydrated camels were slaughtered at day 20 from the start of experiment whereas the rehydrated group was killed 72 h later. Many biochemical, hematological histopathological parameters and gene analysis were performed in relevant tissues collected including blood, plasma, and tissues. It was observed that severely dehydrated camels lost body weight, passed very hard feces, few drops of concentrated urine, and were slightly stressed as reflected behaviorally by loss of appetite. Physiologically, the stress of dehydration elicited modulation of plasma stress hormones for water preservation and energy supply. Our results showed significant increase in cortisol, norepinephrine and dopamine, and significant decrease in epinephrine and serotonin. The significant increase in malondialdehyde was accompanied with significant increase in antioxidants (glutathione, retinol, thiamin, tocopherol) to provide tissue protection from oxidative stress. The physiological blood changes observed during dehydration serve different purposes and were quickly restored to normality by rehydration. The dehydrated/rehydrated camels showed reduced hump size and serous atrophy of perirenal and epicardial fat. The latter changes were accompanied by significantly increased expression of genes encoding proteins for energy production (ANGPTL4, ACSBG1) from fat and significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure. This process is vital for camel survival in the desert. Dehydration induced no major effects in the vital organs. Only minor degenerative changes were observed in hepatic and renal cells, physiological cardiomyocyte hypertrophy in heart and follicular hyperplasia in splenic but lipidosis was not depicted in liver hepatocytes. Ketone bodies were not smelled in urine, sweat and breathing of dehydrated animals supporting the previous finding that the ß hydroxybutyrate dehydrogenase, a key enzyme in ketone body formation, is low in the camel liver and rumen. Rehydration restored most of blood and tissues to normal or near normal. In conclusion, camels are adapted to combat dehydration stress and anorexia by increasing anti-stressors and modulating genes involved in fat metabolism.

PERIOPERATIVE DIABETIC KETOACIDOSIS ASSOCIATED WITH SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS : A SYSTEMATIC REVIEW

DKA or diabetic ketoacidosis is an emergency condition caused by hyperglycemia in which excessive acid is produced in the blood. Patients with type 1 and type 2 diabetes who undergo surgery, have an infection, or are under extreme stress can also develop DKA. The body generates the hormone adrenaline to combat infection and stress, but this can have a negative effect on blood glucose levels (adrenaline is counterinsulin). This can worsen if the patient refuses to take diabetes medication or inject insulin during stressful or infectious situations. The fundamental components of the pathophysiological mechanisms at play in diabetic ketoacidosis (DKA) include shifts in hormone levels and the ensuing inflammatory response. Alterations in the concentration of hormones lead to shifts in the production and consumption of glucose, as well as an increase in lipolysis and the formation of ketone bodies. Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are agents approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus (DM) in adults. Acting on proteins, the four agents are SGLT2 inhibitor class agents. SGLT-2 is expressed in the kidney's proximal tubule. This may result in a decrease in filtered glucose reabsorption, a decrease in the renal threshold for glucose (RTG), and an increase in glucose excretion via urine. Diabetes patients treated with sodium–glucose transport protein 2 (SGLT2) inhibitors have also been reported to experience DKA. The results of a study indicate that DKA is uncommon among T2DM patients treated with SGLT2 inhibitors.

Denture Base Polymer Biodegradation: In Vitro Study

Abstract Introduction Acrylic resins are the most frequently used materials for the bases of prostheses, and are also used in the re-optimization and the repair of prostheses. The aim of our study was to investigate whether direct contact with the resin causes decomposition of methyl methacrylate and formation of ketone bodies in the oral cavity. Material and methods The in vitro study included 12 samples of autopolymerized polymethyl methacrylate and 8 samples of thermopolymerized polymethyl methacrylate. Some of the resin samples were intentionally prepared incorrectly, with modified powder to liquid ratios or thermal regime, to be able to compare them with samples prepared according to the manufacturer’s instructions. Some of the samples were immersed in gastric juice or alcohol for 48 h at 37 °C in a thermostatic bath to simulate the environment and temperature of the oral cavity, while others were kept at room temperature. The Legal reaction was used to identify the presence of ketone bodies in the solutions. Results The samples that were prepared incorrectly and were kept at 37 °C were the most affected. The presence of ketone bodies was demonstrated by the formation of a precipitate on the bottom of the test tube and the color change of the solution. Samples that were kept at room temperature were less affected, both from a spectrophotometric and biochemical point of view. Conclusion The quality of polymethyl methacrylate can be improved by respecting the manufacturer’s instructions and work protocols, and by avoiding substances that are considered aggressive, such as gastric juice, alcohol, and local factors in the oral cavity.

Ketone Bodies and Brain Metabolism: New Insights and Perspectives for Neurological Diseases.

Ketone Bodies and Brain Metabolism: New Insights and Perspectives for Neurological Diseases.

The blockade of Artsakh causing long-term food, nutrition shortage and starvation: How functional food education can help resolve health related conditions

Throughout history, regimes have utilized starvation as a form of genocide. Genocide is defined by Rafael Lempkin as an intentional effort to annihilate a national group. The purpose of this research is to analyze the physiological immediate and lasting effects of starvation in the human body. In the current conflict in Artsakh (Nagorno-Karabakh), ecologists from Azerbaijan are preventing fuel, medicine, and food from entering the Armenian border at the Berdzor (Lachin) Corridor since December 12, 2022. Russian peacekeepers are simultaneously stationed at the Berdzor Corridor, which connects Artsakh and Armenia. In this article, observations are presented on the effects of starvation and recovery on the human body as they relate to historical genocides. Short and long-term effects of starvation can be severe, especially in minority populations and small territories. Although prolonged starvation has more profound impacts on the body, metabolic processes and increased stress levels can cause serious harm to someone who hasn’t consumed food for even only a few days. The predominant physiological shift during a short period of starvation is the transition from gluconeogenesis as a form of fuel production to lipid oxidation as fuel production, resulting in formation of ketone bodies. This switch ultimately leads to metabolic acidosis and the beginning of further complications if trends continue.A prolonged lack of food can lead to an altered mental state, cardiac dysrhythmia, loss of bone density and various other abnormal physiological processes. Many of these findings are potentially reversible via proposed treatments for recovery, although some are not. The blockade of Artsakh has the potential to cause both severe short and long-term physical and psychological damage as discussed below. The blockade began more than 80 days ago, thus certain damage has already occurred.We strongly urge the international community to act against this blockade and help prevent a future genocide.Keywords: food shortage, Starvation, genocide,Artsakh (Nagorno-Karabakh), blockade, Berdzor (Lachin) corridor, bioactive compounds, functional foods

INFLUENCE OF KETOSIS AND GLYCEMIA LEVELS ON CRAVING FOR ETHANOL IN ALCOHOLIZED RATS

Relevance. In case of developed alcoholic disease, under conditions of alcoholic hypoglycemia, ketone bodies act as an energy substrate for the brain. However, the role of ketone hunger for maintaining the craving for alcohol has not been established. The assumption of such a connection has a right to exist, since it is alcohol that stimulates the formation of ketone bodies. Therefore, with developed alcoholism, the desire to consume alcohol (and, in fact, "saturate" the brain with ketone bodies) can be considered as a consequence of hypoketonemia. Accordingly, the hunger of the alcoholic is the result of hypoketonemia, but not hypoglycemia. Therefore, it is relevant to conduct a study in which the given variables (controlled by us) were the level of glycemia and the level of ketonemia, and the amount of alcohol consumed voluntarily (under conditions of free choice) was a derivative and dependent value.&#x0D; Objective: to study the relationship between craving for alcohol, and levels of glycemia and ketonemia in alcoholized rats.&#x0D; Materials and methods. Male white rats (n = 40) were forcibly alcoholized with 10% ethanol in 16 weeks. After that, for 30 days, they had a free choice of three types of drinking: clean water, 5% glucose, and 10% ethanol. The volume of consumed liquids was recorded. The criterion for the developed alcohol dependence was the preference of ethanol. At this stage, the animals were divided into 4 groups. Rats were injected per os with 0.8-1.5 ml of: 1.4% unitiol (3.5 mg / kg) to suppress ketonemia – group 1 (n = 10); 40% starch (1.0 g / kg) to eliminate hypoglycemia – group 2 (n = 10); 2.8% unitiol and 80% starch to suppress ketonemia and eliminate hypoglycemia – group 3 (n = 10); 0.9% NaCl as a control – group 4 (n = 10). Blood glucose (from the tail vein) and urine ketone bodies were monitored. The glucose level was determined with a glucometer. Test strips were used to detect ketone bodies in urine. The results were processed with MedStat software. To measure the strength of the correlation between the indicators, Spearman and Pearson tests were used.&#x0D; Results. No ketone bodies were found in the urine of healthy animals; however, after the end of forced alcoholization, varying levels of ketonuria were recorded in all rats: from 0.5 to 10 mmol / L (Spearman's rank correlation test was 0.8). Glycemia in healthy rats was 7.0 ± 1.4 mmol / L. After alcoholization, it decreased (p &lt;0.001) to 3.0 ± 0.7 mmol / l. Ethanol consumption during first 10 days of forced alcoholization was 3.2 ± 0.7 ml per 100 g of animal weight; by the end of the third week - 4.9 ± 1.1 ml; by the end of the sixth week - 6.4 ± 1.4 ml (this was a climax of consumption, since consumption did not increase up to the 16th week).&#x0D; After a 30-day correction, the level of glycemia (mmol / L) was as follows: animals of the 1st group (unitiol) - 4.0 ± 0.8; animals of the 2nd group (enhanced carbohydrate diet) - 7.1 ± 1.2; animals of the 3rd group (unitiol + enhanced carbohydrate diet) - 7.1 ± 1.1; animals of the 4th group (0.9% NaCl) - 3.5 ± 0.8.&#x0D; Alcohol consumption (ml per 100 g of animal weight) after 30-day correction was as follows: in group 1 (unitiol) - 5.1 ± 0.9; in group 2 (enhanced carbohydrate diet) - 2.7 ± 1; in group 3 (unitiol + enhanced carbohydrate diet) - 3.5 ± 1.5; in group 4 (0.9% NaCl) - 4.5 ± 1.2.&#x0D; A positive strong correlation was found between ethanol consumption and a decrease in glycemia (Pearson's test – 0.8).&#x0D; Conclusion. In alcoholized animals with severe hypoglycemia and ketosis, drug suppression of ketosis does not reduce the craving for ethanol. Metabolic correction, aimed at eliminating hypoglycemia, helps to reduce alcohol consumption and reduce the severity of ketosis. The reason for maintaining a stable craving for alcohol is the metabolic demand of the brain for ketone bodies, as alternative food sources in conditions of alcoholic hypoglycemia, and the synthesis of which is stimulated by alcohol intake.

PSUN261 Diabetic Ketoacidosis Complicating Gestational Diabetes Mellitus: A Case Report

Abstract Diabetic ketoacidosis (DKA) in pregnancy is a rare but serious medical emergency. Its incidence ranges between 0.2%-9% and carries a fetal mortality rate up to 90%. DKA remains to be an extremely rare complication of gestational diabetes (GDM). Early diagnosis and management may be delayed due to its atypical presentation. We present a case of DKA in GDM with no pre-existing diagnosis of type 1 diabetes (T1DM) or type 2 diabetes (T2DM). A 33-year-old African American woman G2P0010 with GDM on insulin diagnosed in current pregnancy, presented at 30-weeks of gestation with a 3-day history of general malaise, altered mentation, and emesis. Severe DKA (blood glucose 920 mg/dL, pH 7.02, anion gap 38, bicarbonate 5.0 mEq/L, and positive serum ketones), systemic inflammatory response syndrome (tachycardia, WBC of 24,000/mcL), and intrauterine fetal demise via ultrasound were determined upon presentation. MICU admission for prompt and vigorous medical management with intravenous fluid resuscitation, insulin and bicarbonate infusions, and broad-spectrum antibiotic therapy was required. Clinical course was complicated by worsening hypokalemia. Spontaneous vaginal delivery of a non-viable fetus occurred at the MICU. After delivery, resolution of DKA was achieved. Once the patient's mentation was back to her baseline, she admitted complete cessation of insulin 1-week prior to admission. Workup revealed negative glutamic acid decarboxylase, islet cell, and zinc transporter-8 autoantibodies in addition to normal C-peptide levels. A new HbA1C of 9% compared to HbA1C of 5.5% at 6 weeks of gestation, made pre-existing T2DM unlikely. Eventually, the patient was downgraded to the medicine wards for continuity of care. DKA in pregnancy is a rare complication typically associated with T1DM. It may occur at near-normal blood glucose levels, known as euglycemic DKA, causing a delay in diagnosis. Physiologic changes during the last trimester of gestation explain the higher incidence of DKA at this stage. These include the relative state of insulin resistance, which in addition to insulin-antagonistic hormones such as human placental lactogen, prolactin, cortisol, and progesterone contribute to this state. Furthermore, a relative accelerated state of starvation with an increase in maternal ketone body formation, and a reduction in the buffering capacity when exposed to ketonemia places gravida women with impaired glucose tolerance at higher risk to develop DKA. Fetal loss may result from reduced uteroplacental perfusion and fetal hypokalemia leading to fatal arrhythmia. The most common precipitating factors of DKA in pregnancy are infection, including COVID-19, insulin therapy non-adherence, steroid use, dehydration, and unrecognized new-onset diabetes which accounts for up to 30% of cases. It has been described that a genetic polymorphism in SLC26A6 gene may increase the susceptibility to develop DKA in GDM. Prevention, early diagnosis, and vigorous medical management of DKA in pregnancy may possibly reduce maternal and fetal mortality. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PREVENTION OF METABOLIC DISTURBANCES OF NEWLY CALVED COWS

Newly calved cows that do not receive a ration corresponding to their lactation performance before calving and during milking period become susceptible to ketosis with its adverse consequences. This disease is usually detected within the first 10-40 days after calving: cows lose weight very quickly and reduce milk productivity; they have many problems during calving and milking. Cows with high milk productivity are more prone to ketosis than cows of low productivity. Inclusion of propionates in the rations of cows helps to reduce formation of ketone bodies. The research was carried out atOOO Krasnoe Sormovo, Krasnoarmeiskiy district of the Chuvash Republic. The duration of the production experiment was 60 days before calving and 100 days afterwards. The results obtained during the research showed that the cows of the experimental group, whose ration included 150 g of propylene glycol per head per day two weeks before and 250 g within four weeks after calving, were healthy, their daily milk yield was 2.6 kg more than that of the control group of cows, milk productivity during the milking period was 4.42%. It allowedto obtain 4.2 tons more milk from the cows of the experimental group than from the cows of the control group. As far as the control group is concerned, 10% of the cows of this group had ketone bodies in milk,consequently, the same number of cows had a low fatness index, which indicated a lack of energy in the body in the period after calving.

Changes of biochemical indexes of blood of high-performance cows are at subclinical ketosisand its effect on milk productivity

The article provides data on changes in biochemical indicators of blood serum of high-yielding cows under conditions of subclinical ketosis and its effect on milk's physical and chemical composition. The decrease in glucose and insulin concentrations mediates the main metabolic changes necessary to stabilize blood glucose levels, which include an increase in the rate of gluconeogenesis, a decrease in lipogenesis and an increase in the release of nonesterified fatty acids from fat, an increase in the uptake and metabolism of fatty acids in hepatocyte mitochondria, and excessive formation of ketone bodies. Fatty acids and ketone bodies are used as an alternative source of energy in the heart, kidney, skeletal muscle, and mammary glands to conserve glucose further and restore energy balance. However, cows that do not undergo the necessary metabolic adaptations are susceptible to hyperketonemia. Hypoglycemia, increased activity of enzymes, and increased activity of alanine and aspartate aminotransferases were detected in sick animals by two and three times, respectively, compared to healthy animals. The total bilirubin content in sick cows' blood serum increased three times compared to the indicators of healthy animals. An increase in milk fat (up to 5 %), 1.3 times more than in healthy animals, and a decrease in total protein (up to 3.11 %). The number of somatic cells in the average milk sample of sick animals was 349 thousand/cm3 and 90 thousand/cm3 in healthy ones, which significantly worsens milk quality. The increase in the number of somatic cells in the milk of animals suffering from subclinical ketosis is due to a decrease in both the general resistance of the body and the ability of macrophages to phagocytosis; with ketonemia, a significant amount of histamine is formed, which leads to inflammatory processes of the mammary gland; the ability of leukocytes to migrate to the foci of inflammation decreases, which determines the protracted course of the disease.

EFFECT OF PROPYLENE GLYCOL ON BLOOD METABOLITES, RUMINAL AND PRODUCTIVE PARAMETERS OF GROWING-FINISHING LAMBS

&lt;p class="Default"&gt;&lt;strong&gt;Background. &lt;/strong&gt;Propylene glycol has been used successfully since the 1950’s for him acute and prophylactic treatment of ketosis in dairy cows however; its use has been poorly evaluated in beef cattle and meat sheep.&lt;strong&gt; Objective&lt;/strong&gt;. Evaluate the effects of different doses of propylene glycol on the productive parameters, blood metabolites and ruminal parameters in fattening lambs. &lt;strong&gt;Methodology&lt;/strong&gt;. Twenty lambs 14.70 ±0.57 kg of weigh, 2 months old, males and Katahdin-Black Belly breed, were randomly assigned to one of four treatments, a control mixed ration and an experimental diet with three different levels of propylene glycol: 1.0, 1.5 and 2.0 g/20 kg live weight/day. The effects of propylene glycol on blood metabolites, ruminal and productive parameters were assessed. &lt;strong&gt;Results&lt;/strong&gt;. Propylene glycol supplementation did not affect (P&amp;gt;0.05) glucose, total lipids, triglycerides and cholesterol concentration as well as increased (P&amp;lt;0.05) the concentration of beta hydroxybutyrate. In addition, its inclusion resulted in an increase in pH and protozoa population and in a decrease of reductive activity (P&amp;lt;0.05). No effect was observed (P&amp;gt;0.05) on feed intake, weight gain and feed conversion ratio of lambs but carcass yield was improved without increasing the feeding cost of production. &lt;strong&gt;Implications&lt;/strong&gt;. Propylene glycol is a viable option as an energy source in fattening lambs. &lt;strong&gt;Conclusion&lt;/strong&gt;. Inclusion of PPG increased the pH and the population of ruminal protozoa, reduced the formation of ketone bodies and improved the carcass yield of lambs without increasing the meat production cost.&lt;/p&gt;

The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice

Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver’s response to nutrient deprivation, such as fatty acid oxidation and ketone body formation. However, it is unknown whether SIRT3 also regulates gluconeogenesis. Our study revealed that palmitoleic acid reduced hepatic gluconeogenesis and the expression of SIRT3 under high-fat diet conditions. Overexpression of SIRT3 in the liver and hepatocytes enhanced gluconeogenesis. Further study revealed that SIRT3 played a role in enhancing the activities of gluconeogenic enzymes, such as PEPCK, PC, and MDH2. Therefore, our study indicated that under a high-fat diet, palmitoleic acid decreased gluconeogenesis by reducing enzymatic activities of PEPCK, PC, and MDH2 by down-regulating the expression of SIRT3.

Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals

Background and aimsIncreased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression. MethodsCross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression. ResultsOf 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84–1.06) and 0.82 (0.71–0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965–0.995). ConclusionsWe found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

Ketogenic HMG-CoA lyase and its product β-hydroxybutyrate promote pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDA) tumor cells are deprived of oxygen and nutrients and therefore must adapt their metabolism to ensure proliferation. In some physiological states, cells rely on ketone bodies to satisfy their metabolic needs, especially during nutrient stress. Here, we show that PDA cells can activate ketone body metabolism and that β-hydroxybutyrate (βOHB) is an alternative cell-intrinsic or systemic fuel that can promote PDA growth and progression. PDA cells activate enzymes required for ketogenesis, utilizing various nutrients as carbon sources for ketone body formation. By assessing metabolic gene expression from spontaneously arising PDA tumors in mice, we find HMG-CoA lyase (HMGCL), involved in ketogenesis, to be among the most deregulated metabolic enzymes in PDA compared to normal pancreas. In vitro depletion of HMGCL impedes migration, tumor cell invasiveness, and anchorage-independent tumor sphere compaction. Moreover, disrupting HMGCL drastically decreases PDA tumor growth in vivo, while βOHB stimulates metastatic dissemination to the liver. These findings suggest that βOHB increases PDA aggressiveness and identify HMGCL and ketogenesis as metabolic targets for limiting PDA progression.

61-Year-Old Man With Nausea and Vomiting

61-Year-Old Man With Nausea and Vomiting

Effects of intermittently scanned continuous glucose monitoring on blood glucose control and the production of urinary ketone bodies in pregestational diabetes mellitus

ObjectiveTo investigate the effects of intermittently scanned continuous glucose monitoring (isCGM) on blood glucose control, clinical value of blood glucose monitoring and production of urinary ketone bodies in pregestational diabetes mellitus. MethodA total of 124 patients with pregestational diabetes mellitus at 12–14 weeks of gestation admitted to the gestational diabetes clinic of our hospital from December 2016 to December 2018 were selected and randomly divided into two groups. Sixty patients adopted self-monitoring of blood glucose (SMBG) were taken as the control group, and the other 64 patients adopted isCGM system by wearing the device for 14 days. Blood sugar control, glycosylated albumin level, ketone production in urine, the maximum and minimum of blood sugar value measured by different monitoring methods and their occurrence time were observed in the two groups.Result(1) No statistically significant differences were found between the groups in terms of maternal age, gestational age at first visit, family history, duration of diabetes, education level, total insulin dose, chronic hypertension, abortion history, nulliparity, assisted reproductive technology, history of macrosomia childbirth, pre-pregnancy BMI, and overweight (%) at the first visit and hypoglycemia, (2) the value of Glycated Albumin was lower in the CGM group compared to the control group at 2ed weeks (14.6 ± 2.2 vs. 16.8 ± 2.7, p < 0.001). The women in the CGM group spent increased time in the recommended glucose control target range of 3.5–7.8 mmol/L (69 ± 10% vs. 62 ± 11%, p < 0.001) and reduced time above target compared with those in the control group at 2 weeks (25 ± 7% vs. 31 ± 8%, p < 0.001). In the second week of the study, the positive rate of urinary ketone body in isCGM group was lower than that in the control group (42 ± 5 vs. 54 ± 5, p < 0.001), and (3) the minimum blood glucose of 31.2% (20/64) cases in isCGM group appeared during 0:00–2:59 at night, and 26.6% (17/64) cases appeared during 3:00–5:59 at night. The minimum values of 40.0% (24/60) cases in the control group appeared within the 30 min before lunch, 23.3% (14/60) within the 30 min before breakfast, and 11.7% (7/60) within the 30 min before dinner. The cases of minimum of blood sugar before meals accounted for 75% of all the minimum values, and the cases of minimum at night only accounted for 8.3%.ConclusionIntermittently scanned continuous glucose monitoring can reduce hyperglycemia exposure and ketone body formation in pregestational diabetes mellitus. In addition, isCGM is better than SMBG in detecting nocturnal hypoglycemia.