Non-diabetic ketoacidosis: A case of alcoholic ketoacidosis accompanied by hyperglycemia.

Alcoholic ketoacidosis (AKA) lacks specific clinical presentation. The results of blood testing commonly show hemoconcentration, elevated ß-hydroxybutyrate levels, and acidosis in patients with AKA. Herein, we report a case of AKA accompanied by hyperglycemia and review the related literature. Case report: AKA associated with hyperglycemia is rare, and its pathogenesis is similar to that of diabetic ketoacidosis, thereby making differentiation challenging. Accordingly, AKA is easily misdiagnosed by endocrinologists. The main symptoms of a 37-year-old female included hyperglycemia, elevated ß-hydroxybutyrate levels, and metabolic acidosis. Primary clinical presentations were severe nausea and vomiting. The patient initially diagnosed with DKA were eventually confirmed as AKA, who recovered after active therapy with rehydration and correction of hyperglycemia, electrolyte imbalance, and ketosis. This study provides a reference for clinicians to reduce missed diagnosis and the misdiagnosis rates of AKA.

Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?

Induced ketosis (or ketone body ingestion) can ameliorate several changes associated with neuroprogressive disorders, including schizophrenia, bipolar disorder, and major depressive disorder. Thus, the effects of glucose hypometabolism can be bypassed through the entry of beta-hydroxybutyrate, providing an alternative source of energy to glucose. The weight of evidence suggests that induced ketosis reduces levels of oxidative stress, mitochondrial dysfunction, and inflammation-core features of the above disorders. There are also data to suggest that induced ketosis may be able to target other molecules and signaling pathways whose levels and/or activity are also known to be abnormal in at least some patients suffering from these illnesses such as peroxisome proliferator-activated receptors, increased activity of the Kelch-like ECH-associated protein/nuclear factor erythroid 2-related factor 2, Sirtuin-1 nuclear factor-κB p65, and nicotinamide adenine dinucleotide (NAD). This review explains the mechanisms by which induced ketosis might reduce mitochondrial dysfunction, inflammation, and oxidative stress in neuropsychiatric disorders and ameliorate abnormal levels of molecules and signaling pathways that also appear to contribute to the pathophysiology of these illnesses. This review also examines safety data relating to induced ketosis over the long term and discusses the design of future studies.

Inhibition of adenosine A1 receptors abolished the nutritional ketosis-evoked delay in the onset of isoflurane-induced anesthesia in Wistar Albino Glaxo Rijswijk rats.

BACKGROUND: It has been demonstrated that administration of exogenous ketone supplement ketone salt (KS) and ketone ester (KE) increased blood ketone level and delayed the onset of isoflurane-induced anesthesia in different rodent models, such as Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. The modulatory effect of adenosinergic system may have a role in the ketone supplementation-evoked effects on isoflurane-generated anesthesia. Thus, we investigated whether adenosine receptor antagonists can modulate the effect of exogenous ketone supplements on the onset of akinesia induced by isoflurane. METHODS: To investigate the effect of exogenous ketone supplements on anesthetic induction we used ketone supplement KE, KS, KEKS (1:1 mix of KE and KS), KSMCT and KEMCT (1:1 mix of KS and KE with medium chain triglyceride/MCT oil, respectively) in WAG/Rij rats. Animals were fed with standard diet (SD), which was supplemented by oral gavage of different ketone supplements (2.5 g/kg/day) for 1 week. After 7 days, isoflurane (3%) was administered for 5 min and the time until onset of isoflurane-induced anesthesia (time until immobility; light phase of anesthesia: loss of consciousness without movement) was measured. Changes in levels of blood ß-hydroxybutyrate (ßHB), blood glucose and body weight of animals were also recorded. To investigate the putative effects of adenosine receptors on ketone supplements-evoked influence on isoflurane-induced anesthesia we used a specific adenosine A1 receptor antagonist DPCPX (intraperitoneally/i.p. 0.2 mg/kg) and a selective adenosine A2A receptor antagonist SCH 58261 (i.p. 0.5 mg/kg) alone as well as in combination with KEKS. RESULTS: Significant increases were demonstrated in both blood ßHB levels and the number of seconds required before isoflurane-induced anesthesia (immobility) after the final treatment by all exogenous ketone supplements. Moreover, this effect of exogenous ketone supplements positively correlated with blood ßHB levels. It was also demonstrated that DPCPX completely abolished the effect of KEKS on isoflurane-induced anesthesia (time until immobility), but not SCH 58261. CONCLUSIONS: These findings strengthen our previous suggestion that exogenous ketone supplements may modulate the isoflurane-induced onset of anesthesia (immobility), likely through A1Rs.

Carbohydrate intake and ketosis in self-sufficient multi-stage ultramarathon runners.

Ultra-endurance athletes accumulate an energy deficit throughout their events and those competing in self-sufficient multi-stage races are particularly vulnerable due to load carriage considerations. Whilst urinary ketones have previously been noted in ultra-endurance exercise and attributed to insufficient carbohydrate (CHO) availability, not all studies have reported concomitant CHO intake. Our aim was to determine changes in blood glucose and ß-hydroxybutyrate concentrations over five days (240 km) of a self-sufficient multi-stage ultramarathon in combination with quantification of energy and macronutrient intakes, estimated energy expenditure and evaluation of energy balance. Thirteen runners (8 male, 5 female, mean age 40 ± 8 years) participated in the study. Glucose and ß-hydroxybutyrate were measured every day immediately post-running, and food diaries completed daily. CHO intakes of 301 ± 106 g·day-1 (4.3 ± 1.8 g·kg-1·day-1) were not sufficient to avoid ketosis (5-day mean ß-hydroxybutyrate: 1.1 ± 0.6 mmol.L-1). Furthermore, ketosis was not attenuated even when CHO intake was high (9 g·kg-1·day-1). This suggests that competing in a state of ketosis may be inevitable during multi-stage events where load reduction is prioritised over energy provisions. Attenuating negative impacts associated with such a metabolic shift in athletes unaccustomed to CHO and energy restriction requires further exploration.

Associations of pre- and postpartum lying time with metabolic, inflammation, and health status of lactating dairy cows.

The objective was to evaluate the associations of pre- and postpartum lying time (LT) with serum total calcium (Ca), nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), and haptoglobin concentrations, hemogram, and health status of dairy cows. A total of 1,052 Holstein cattle (401 nulliparous heifers and 651 parous cows) from 3 commercial dairy farms were fitted with electronic data loggers (IceQube, IceRobotics, Edinburgh, UK) on a hind leg 14 ± 3 d before parturition (dpp) and removed at 14 ± 3 d in milk (DIM) to assess their LT. Lying time data were summarized and reported daily (min/d or h/d). Serum concentrations of NEFA (at 14 ± 3 and 7 ± 3 dpp), total serum calcium within 48 h after calving, and BHB (at 7 ± 3 and 14 ± 3 DIM) were determined. Serum concentration of haptoglobin was determined and a hemogram was performed on a subsample of 577 cows (237 primiparous and 340 multiparous) at 7 ± 3 DIM. Cases of milk fever, retained placenta, metritis, mastitis, pneumonia, and digestive disorders within 30 DIM were recorded and cows were categorized into 1 of 4 groups: (1) nondiseased (ND, n = 613; cows without ketosis and any other health conditions); (2) cows with only ketosis (KET, n = 152); (3) sick cows experiencing ≥1 health conditions, but without ketosis (SICK, n = 198); or (4) cows with ketosis plus at least one other health condition (KET+, n = 61). Data were analyzed using mixed linear regression models or logistic regression (MIXED or GLIMMIX procedures). Lying time within 14 dpp had a significant positive quadratic association with serum NEFA concentrations at 14 ± 3 and 7 ± 3 dpp but was not significantly associated with serum Ca concentration within 48 h after calving. Lying time during the first 14 DIM after parturition had a significant linear association with the risk of ketosis within 14 DIM. For every 1-h increment in mean LT (from 8 to 15 h/d) within the first 14 DIM after calving, the risk of diagnosis with ketosis within 14 DIM increased by 3.7 percentage points. Regardless of parity, a greater proportion of KET and KET+ groups had increased serum prepartum NEFA concentration (≥400 µEq/L) and increased body condition loss from 14 dpp to 28 DIM compared with SICK and ND cows. A greater proportion of multiparous KET and KET+ cows had hypocalcemia within 48 h after calving compared with ND and SICK cows, but we did not detect a significant association between hypocalcemia and health status on primiparous cows. Multiparous KET+ cows had significantly reduced neutrophils and white blood cell count compared with ND cows, but lymphocytes did not differ. Regardless of parity, KET+ and SICK cows had significantly higher concentrations of serum haptoglobin compared with ND cows. These results suggest that LT along with energy and Ca balance are critical for transition cow health.

Prediction of blood ß-hydroxybutyrate content and occurrence of hyperketonemia in early-lactation, pasture-grazed dairy cows using milk infrared spectra.

The objective of this study was to evaluate the ability of milk infrared spectra to predict blood ß-hydroxybutyrate (BHB) concentration for use as a management tool for cow metabolic health on pasture-grazed dairy farms and for large-scale phenotyping for genetic evaluation purposes. The study involved 542 cows (Holstein-Friesian and Holstein-Friesian × Jersey crossbreds), from 2 farms located in the Waikato and Taranaki regions of New Zealand that operated under a seasonal-calving, pasture-based dairy system. Milk infrared spectra were collected once a week during the first 5 wk of lactation. A blood "prick" sample was taken from the ventral labial vein of each cow 3 times a week for the first 5 wk of lactation. The content of BHB in blood was measured immediately using a handheld device. After outlier elimination, 1,910 spectra records and corresponding BHB measures were used for prediction model development. Partial least square regression and partial least squares discriminant analysis were used to develop prediction models for quantitative determination of blood BHB content and for identifying cows with hyperketonemia (HYK). Both quantitative and discriminant predictions were developed using the phenotypes and infrared spectra from two-thirds of the cows (randomly assigned to the calibration set) and tested using the remaining one-third (validation set). A moderate accuracy was obtained for prediction of blood BHB. The coefficient of determination (R2) of the prediction model in calibration was 0.56, with a root mean squared error of prediction of 0.28 mmol/L and a ratio of performance to deviation, calculated as the ratio of the standard deviation of the partial least squares model calibration set to the standard error of prediction, of 1.50. In the validation set, the R2 was 0.50, with root mean squared error of prediction values of 0.32 mmol/L, which resulted in a ratio of performance to deviation of 1.39. When the reference test for HYK was defined as blood concentration of BHB ≥1.2 mmol/L, discriminant models indicated that milk infrared spectra correctly classified 76% of the HYK-positive cows and 82% of the HYK-negative cows. The quantitative models were not able to provide accurate estimates, but they could differentiate between high and low BHB concentrations. Furthermore, the discriminant models allowed the classification of cows with reasonable accuracy. This study indicates that the prediction of blood BHB content or occurrence of HYK from milk spectra is possible with moderate accuracy in pasture-grazed cows and could be used during routine milk testing. Applicability of infrared spectroscopy is not likely suited for obtaining accurate BHB measurements at an individual cow level, but discriminant models might be used in the future as herd-level management tools for classification of cows that are at risk of HYK, whereas quantitative models might provide large-scale phenotypes to be used as an indicator trait for breeding cows with improved metabolic health.

Effect of heat-shock protein B7 on oxidative stress in adipocytes from preruminant calves.

Dairy cows with ketosis display excessive lipolysis in adipose tissue. Heat-shock protein B7 (HSPB7), a small heat-shock protein, plays important roles in mediating cytoprotective responses to oxidative stress in rodent adipose tissue. Accordingly, it is assumed that HSPB7 may also play important roles in the antioxidant response in adipose tissue of ketotic cows. Therefore, the aim of this study is to investigate (1) the redox state of adipose tissue in ketotic cows and (2) the role and mechanism of HSPB7 on the regulation of oxidative stress in adipocytes from preruminant calves. An in vivo study consisting of 15 healthy and 15 clinically ketotic cows was performed to harvest subcutaneous adipose tissue and blood samples. In addition, adipocytes isolated from calves were treated with different concentrations of H2O2 (0, 12.5, 25, 50, 100, or 200 µM) for 2 h, transfected with adenovirus-mediated overexpression of HSPB7 for 48 h, or transfected with small interfering RNA of HSPB7 for 48 h followed by exposure to H2O2 (200 µM) for 2 h. Serum concentrations of nonesterified fatty acids and ß-hydroxybutyrate were greater in cows with clinical ketosis, whereas serum concentration of glucose was lower. Compared with healthy cows, the malondialdehyde content was greater but the activity of glutathione peroxidase and superoxide dismutase was lower in adipose tissue of clinically ketotic cows. The abundance of HSPB7 and nuclear factor, erythroid 2 like 2 (NFE2L2) was greater in adipose tissue of clinically ketotic cows. In vitro, H2O2 treatment induced the overproduction of reactive oxygen species and malondialdehyde, and inhibited the activity of antioxidant enzymes glutathione peroxidase and superoxide dismutase in adipocytes from preruminant calves. The low concentration of H2O2 (12.5, 25, and 50 µM) increased the abundance of HSPB7 and NFE2L2, but high concentrations of H2O2 (100 or 200 µM) reduced the abundance of HSPB7 and NFE2L2. The overexpression of HSPB7 improved the H2O2-induced oxidative stress in adipocytes via increasing the abundance of NFE2L2 and its downstream target genes heme oxygenase-1 (HMOX1) and NADH quinone oxidoreductase 1 (NQO1). Knockdown of HSPB7 markedly inhibited the expression of NFE2L2, HMOX1, and NQO1 and further exacerbated H2O2-induced oxidative stress. Overall, these results indicate that activation of the HSPB7-NFE2L2 pathway increases cellular antioxidant capacity, thereby alleviating oxidative stress in bovine adipocytes.

Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle II: Postpartum uterine health, ketosis, and milk production.

To evaluate the effect of recombinant bovine interleukin-8 (rbIL-8) on uterine health and milk production, 2 separate studies were conducted. For study 1, postpartum Holstein cows (n = 213) were randomly allocated into 1 of 3 intrauterine treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 11.25 µg of rbIL-8 diluted in 250 mL of saline solution), and high dose (H-IL8, 1,125 µg of rbIL-8 diluted in 250 mL of saline solution). Intrauterine delivery of treatments was performed within 12 h of parturition. Cows were evaluated for retained fetal membranes, puerperal metritis, and clinical endometritis. Blood samples were collected immediately before treatment and 1, 2, and 3 d in milk for assessment of IL-8, haptoglobin, fatty acids, and ß-hydroxybutyrate concentrations. Treatment with rbIL-8 reduced the incidence of puerperal metritis in multiparous cows (CTR = 34.3, L-IL8 = 8.11, and H-IL8 = 6.35%). Both the L-IL8 and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with placebo-treated controls. A second study was performed to confirm the effect of rbIL-8 on milk production. In study 2, 164 primiparous cows were randomly allocated into 1 of 4 treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 0.14 µg of rbIL-8), medium dose (M-IL8, 14 µg of rbIL-8), and high dose (H-IL8, 1,400 µg of rbIL-8). Treatments were prepared and administered as described for study 1. Cows in the L-IL8, M-IL8, and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with control cows. In conclusion, treatment with rbIL-8 decreased the incidence of puerperal metritis in multiparous cows. The administration of rbIL-8 was repeatedly associated with a dramatic and long-lasting improvement of lactation performance.

High concentrations of fatty acids and ß-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows.

The hepatic growth hormone (GH)-insulin-like growth factor (IGF)-I axis is essential for regulating intrahepatic lipid metabolism. Ketotic cows are characterized by high blood concentrations of fatty acids and ß-hydroxybutyrate (BHB), which display lipotoxicity. The aim of this study was to investigate changes in the hepatic GH-IGF-I axis in ketotic cows and to determine the effects of fatty acids and BHB on the GH-IGF-I axis in calf hepatocytes. Liver and blood samples were collected from healthy (n = 15) and clinically ketotic (n = 15) cows. Hepatocytes were isolated from calves and treated with various concentrations of GH, fatty acids, and BHB. The results showed that clinically ketotic cows displayed a high blood concentration of GH, a low blood concentration of IGF-I, and decreased hepatic GHR1A expression as well as impaired hepatic Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling. In vitro, GH treatment induced activation of the JAK2-STAT5 pathway to increase the mRNA expression and secretion of IGF-I in calf hepatocytes. More importantly, treatment with fatty acids or BHB significantly inhibited GHR1A mRNA and JAK2 protein expression, as well as the STAT5 phosphorylation level and phospho-STAT5 nuclear translocation; these effects markedly reduced IGF1 mRNA expression and secretion in calf hepatocytes. In summary, these results indicate that high blood concentrations of fatty acids or BHB can impair the intrahepatic GH-mediated JAK2-STAT5 pathway and downregulate IGF-I expression and secretion in ketotic cows.

Short communication: The association of adiponectin and leptin concentrations with prepartum dietary energy supply, parity, body condition, and postpartum hyperketonemia in transition dairy cows.

Adipokines-hormones produced by adipose tissue-have important regulatory functions, and their concentrations can change around the time of calving when energy balance rapidly decreases. Hence, energy balance may be an important factor in determining the circulating concentrations of adipokines, particularly adiponectin and leptin. The objective of our study was to investigate the association between the level of energy fed to prepartum Holstein cows and circulating concentrations of adiponectin and leptin before and after calving. Holstein dairy cows entering second or greater lactation were fed either a controlled-energy diet formulated to supply approximately 100% of energy requirements (n = 28) or a high-energy diet formulated to supply approximately 150% of energy requirements throughout the entire dry period (n = 28). Serum samples were analyzed for adiponectin and leptin concentrations at 56, 28, 10, and 1 d prepartum as well as on d 1, 10, 21, and 42 postpartum using ELISA. Parity was dichotomized into cows entering second versus higher parity. Average peripartum body condition score (BCS) was computed from weekly measurements and dichotomized into animals with an average BCS of ≤3.25 and >3.25. In addition, cows were classified according to the occurrence of hyperketonemia (ß-hydroxybutyrate concentrations ≥1.2 mmol/L at any time between 3 and 21 d in milk). Data were analyzed using repeated-measures ANOVA. Serum leptin but not adiponectin concentrations were associated with prepartum feeding level such that leptin concentrations increased transiently during the dry period in cows overfed energy, but concentrations were not different postpartum. Cows entering second parity had higher adiponectin and lower leptin concentrations compared with cows in higher parities. Cows that developed hyperketonemia postpartum had consistently lower adiponectin concentrations during the study period. Cows with average BCS >3.25 had higher leptin concentrations during the dry period only, but adiponectin concentrations were not associated with BCS. In conclusion, prepartum energy level had only transient effects on leptin concentrations and did not lead to changes in adiponectin concentrations.

Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia.

Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.Trp96Cys] and c.643C>T [p.Leu215Phe]) in CYC1, encoding the cytochrome c1 subunit of complex III, in two unrelated children presenting with recurrent episodes of ketoacidosis and insulin-responsive hyperglycemia. Cytochrome c1, the heme-containing component of complex III, mediates the transfer of electrons from the Rieske iron-sulfur protein to cytochrome c. Cytochrome c1 is present at reduced levels in the skeletal muscle and skin fibroblasts of affected individuals. Moreover, studies on yeast mutants and affected individuals' fibroblasts have shown that exogenous expression of wild-type CYC1 rescues complex III activity, demonstrating the deleterious effect of each mutation on cytochrome c1 stability and complex III activity.

Short communication: Association of milk fatty acids with early lactation hyperketonemia and elevated concentration of nonesterified fatty acids.

The objective of our study was to extend the limited research available on the association between concentrations of milk fatty acids and elevated nonesterified fatty acids (NEFA) and ß-hydroxybutyrate (BHB) concentrations in early lactation dairy cattle. Measurement of milk fatty acids for detection of cows in excessive negative energy balance has the potential to be incorporated in routine in-line monitoring systems. Blood samples were taken from 84 cows in second or greater lactation 3 times per week between 3 to 14 d in milk. Cows were characterized as hyperketonemic (HYK) if blood BHB concentration was ≥1.2mmol/L at least once and characterized as having elevated concentrations of NEFA (NEFAH) if serum NEFA concentration was ≥1mmol/L at least once. Composition of colostrum and milk fatty acids at wk 2 postpartum was used to investigate the potential diagnostic value of individual fatty acids and fatty acid ratios for the correct classification of cows with NEFA and BHB concentrations above these thresholds, respectively. Receiver operating characteristic (ROC) curves were used to identify thresholds of fatty acid concentration and fatty acid ratios when ROC area under the curve was ≥0.70. Correct classification rate (CCR, %) was calculated as {[(number of true positives + number of true negatives)/total number tested] × 100}. None of the colostrum fatty acids yielded a sufficiently high area under the curve in ROC analysis for the association with HYK and NEFAH. The following fatty acids and fatty acid ratios were identified for an association with NEFAH (threshold, CCR): C15:0 (≤0.65g/100g, 68.3%); cis-9 C16:1 (≥1.85g/100g, 70.7%); cis-9 C18:1 (≥26g/100g, 69.5%), cis-9 C18:1 to C15:0 ratio (≥45, 69.5%); cis-9 C16:1 to C15:0 (≥2.50, 73.2%). Several fatty acids were associated with HYK (threshold, CCR): C6:0 (≤1.68g/100g, 80.5%), C8:0 (≤0.80g/100g, 80.5%), C10:0 (≤1.6g/100g, 79.3%); C12:0 (≤1.42g/100g, 82.9%); C14:0 (≤6.10g/100g, 84.1%); C15:0 (≤0.50g/100g, 82.9%), cis-9 C18:1 (≥30g/100g, 81.7%). The use of fatty acid ratios did not improve CCR over using individual fatty acids for the classification of HYK. Colostrum fatty acid composition was not useful in predicting NEFAH or HYK between 3 to 14 d in milk. Accuracy of milk fatty acids and fatty acid ratios to correctly classify cows with elevated concentrations of NEFA and BHB between 3 to 14 d in milk was moderate and overall higher for HYK. Determining changes in the fatty acid composition of milk fat from milk samples at wk 2 postpartum for the detection of cows with elevated concentrations of BHB and NEFA can currently not be recommended to replace direct measurement. Future applications should target repeated milk sampling between 3 to 14 d in milk to identify the best sampling for determination of milk fatty acid composition within the first 2 wk postpartum.

Ketoacidosis in a non-diabetic woman who was fasting during lactation.

Ketoacidosis is a potential complication of type 1 diabetes. Severe ketoacidosis with a blood pH below 7.0 is only rarely seen in other diseases.Three weeks after delivery, a young woman was admitted because of tachypnoe and tachycardia. Blood gas analysis showed a severe metabolic acidosis with a high anion gap. Further workup revealed the presence of ketone bodies in the urine with normal blood glucose and no history of diabetes. The patient reported that she had not eaten for days because of abdominal pain. After initial treatment in the ICU and immediate re-feeding, the patient's condition rapidly improved.While under normal circumstances fasting causes at most only mild acidosis, it can be dangerous during lactation. Prolonged fasting in combination with different forms of stress puts breast feeding women at risk for starvation ketoacidosis and should therefore be avoided.

Ketonemia in dairy goats: effect of dry period length and effect on lying behavior.

In dairy animals, a successful transition from one lactation to the next includes minimizing negative energy balance. Cows experiencing excessive negative energy balance typically develop metabolic complications following parturition (e.g., ketosis); does are also susceptible before kidding (e.g., pregnancy toxemia). It is not known to what extent the provision and the length of the dry period affect these conditions in does. Furthermore, whereas clinical symptoms of these conditions include lethargy, behavioral changes resulting from ketosis and pregnancy toxemia have not been quantified in small ruminants. The aims of this study were to (1) describe the relationship between the dry period and negative energy balance, and (2) determine if lying behavior changes are indicative of the metabolic status of dairy goats. A total of 420 does on 10 commercial dairy goat farms in southern Ontario, Canada, were enrolled in the study (mean ± SD: 42±18 does/farm). Each doe was affixed with a data logger to measure lying behavior from 12 d before to 12 d after kidding. Blood samples were collected at least once before and at least once following kidding to determine blood ß-hydroxybutyrate (BHBA) concentration as an indicator of negative energy balance. Does were categorized as healthy (HLTH; both pre- and postkidding samples BHBA <0.9 mmol/L), PREGTOX (prekidding BHBA ≥1.7 mmol/L), or KET (postkidding BHBA ≥1.7 mmol/L). Behaviors were analyzed according to 5 periods: P-2 (d -12 to d -2 relative to kidding), P-1 (d -1 relative to kidding), P0 (d 0, kidding day), P1 (d 1 relative to kidding), and P2 (d 2 to 12 relative to kidding). Dry period length and milk production after kidding were recorded when available. Farms ranged from 0 to 15% and 0 to 50% in prekidding and postkidding ketonemia, respectively. The HLTH does had shorter dry periods compared with PREGTOX and KET does (43 vs. 55 d, SE of the differences of means=4 d). One farm kept some does milking, while drying off others; on this farm more PREGTOX and KET does (11/28) were found in the dry group versus the continuously milked group (1/16). Overall, does that had ketonemia before kidding (PREGTOX) spent more time lying down compared with healthy does (16.1 vs. 12.7 h/d, SE of the differences of means=0.9). Both PREGTOX and HLTH does had increased lying bouts in P-2 compared with the day before (P-1) kidding [(mean (95% CI): 16.8 (15.8-17.8) vs. 20.5 (19.4-21.8) bout/d]. Compared with HLTH does, animals that were ketonemic following kidding (KET) had higher mean lying times throughout the study (14.5 vs. 13.5 h/d, SE=0.4). Previous work has shown a relationship between shorter and skipped dry periods and improved energy balance in dairy cows; the current study is the first to indicate a similar relationship in dairy goats. Furthermore, goats that developed ketonemia, particularly before kidding, displayed decreased activity, including longer lying times and fewer lying bouts in the days around kidding.

Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

BACKGROUND: There is a population of children with epilepsy that is refractory to anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen, is one alternative treatment to decrease seizure activity. Special considerations are required for patients on the ketogenic diet undergoing cardiopulmonary bypass (CPB) to prevent exposure to glucose substrates that could alter ketosis, increasing the risk of recurrent seizures. CASE STUDY: A 2-year-old, 9 kilogram male with a history of infantile spasms with intractable epilepsy, trisomy 21 status post tetralogy of Fallot repair, presented to the cardiac operating room for closure of a residual atrial septal defect. All disciplines of the surgical case minimized the use of carbohydrate-containing and contraindicated medications. Changes to the standard protocol and metabolic monitoring ensured the patient maintained ketosis. DISCUSSION: All disciplines within cardiac surgery need to be cognizant of patients on the ketogenic diet and prepare a modified protocol. Future monitoring considerations include thromboelastography, electroencephalography and continuous glucose measurement. Key areas of focus with this patient population in the cardiac surgical theater are to maintain a multidisciplinary approach, alter the required CPB prime components, address cardiac pharmacological concerns and limit any abnormal hematological occurrences.

Evaluation of 2 electronic handheld devices for diagnosis of ketonemia and glycemia in dairy goats.

The objective of this study was to evaluate the suitability of the electronic handheld devices FreeStyle Precision (FSP; Abbott Germany, Wiesbaden, Germany) and GlucoMen LX Plus (GML; A. Menarini GmbH, Vienna, Austria) for the measurement of ß-hydroxybutyrate (BHBA) in whole blood in dairy goats. Additionally, glucose concentration was analyzed with the FSP device. For method comparison, the samples were also analyzed in the laboratory by standard methods, which served as the gold standard in our study. A further objective was to evaluate the agreement between samples obtained by minimal invasive venipuncture of an ear vein and measurements of whole blood samples from the jugular vein (vena jugularis). In total, 173 blood sample pairs collected from 28 goats were obtained from an ear vein and from the jugular vein. The Spearman correlation coefficients (rsp) for BHBA concentrations determined with the FSP or GML and the gold standard were 0.95 and 0.85 for the ear vein and 0.98 and 0.88 for the jugular vein, respectively. Bland-Altman plots of differences showed a positive bias of 0.12 (ear vein) and 0.21 (jugular vein) when determination was performed with the FSP and a negative bias of 0.21 (ear vein) and 0.24 (jugular vein) when using the GML. For the FSP, applying the adjusted thresholds determined by ROC analysis of 0.9 (ear vein) and 1.0 mmol/L (jugular vein) allowed to distinguish between healthy goats and animals with hyperketonemia with sensitivities (Se) and specificities (Sp) for samples from the ear vein of 0.98 and 0.85, and from the jugular vein of 0.99 and 0.94, respectively. For the GML, adjusted thresholds were 0.5 mmol/L for the ear vein (Se=0.94, Sp=0.75) and 0.6 mmol/L for the jugular vein (Se=0.88, Sp=0.91). Repeated analyses of defined whole blood samples showed average inter- and intraassay coefficients of variation of 6.6 and 7.3% for FSP, and of 35.6 and 35.4% for GML, respectively. Test characteristics for determining glucose concentration with the FSP compared with the gold standard were poor (ear vein: rsp=0.41; jugular vein: rsp=0.51), with low validity to distinguish between hypo- and normoglycemia (Se=0.71, Sp=0.66). The present study showed good test characteristics for the FSP and moderate for the GML device for determining BHBA concentrations in whole blood. Additionally the results demonstrate the suitability of testing BHBA concentration in a blood drop obtained from an ear vein. Based on the results of this study, the FSP device is not suitable to differentiate normo- from hypoglycemia in goats.

Diseases, reproductive performance, and changes in milk production associated with subclinical ketosis in dairy cows: a meta-analysis and review.

Many studies have shown that subclinical ketosis (SCK) is associated with an increased risk of developing various diseases, reproductive disorders, and changes in milk production. The present work aims at producing an overview between this disorder and theses outcomes. A meta-analysis of the literature, including 131 different models from 23 papers, or a review when the literature was scarce was conducted. For each outcome, the odds ratio (OR), relative risk, or hazard ratio was presented for various moderators to reduce heterogeneity among the studies. The raw change in milk production associated with SCK was estimated and adjusted, taking into consideration the outcomes known to interact with milk production during the peripartum period. The results showed that 2 main categories of moderators had a significant effect on the adjusted risk. First, the adjustment made by defining SCK as (1) ß-hydroxybutyrate concentration >1.4 mM, (2) nonesterified fatty acid (NEFA) concentration >0.4 mM prepartum, or (3) NEFA concentration >1.0 mM postpartum corrected the underestimated risk (despite low significance). This is because several trials reported the relevant risks using lower thresholds for the ß-hydroxybutyrate or NEFA values. Using a low threshold leads to lower risk of disease compared with using a high threshold. Second, the correction produced using the polyfactorial terms corrected the overestimation of risk because many trials reported only univariable models. The relative risk or OR (95% confidence interval) related to abomasal displacement, clinical ketosis, early culling and death, metritis, placental retention, clinical mastitis, lameness, and a doubling of the SCC in cases with SCK were 3.33 (2.60-4.25), 5.38 (3.27-8.83), 1.92 (1.60-2.30), 1.75 (1.54-2.01), 1.52 (1.20-1.93), 1.61 (1.24-2.09), 2.01(1.64-2.44), and 1.42 (1.26-1.60), respectively. The precision level of the estimate depended on the outcome. The direct mean ± standard deviation of the 305-d milk losses associated with SCK were 251 ± 73 kg after adjusting for abomasal displacement, clinical ketosis, metritis, and placental retention. The OR (95% confidence interval) for first service calving risk in cases of SCK was 0.67 (0.53-0.83). The calving-to-first-service interval was 8 d longer and the calving-to-conception interval was 16 to 22 d longer in cows with SCK. The relationships among the different reproductive indicators were quantified in only 1 or 2 trials. The present work highlights the need to conduct further studies on the associations between SCK and the risks of diseases, changes in milk production, and reproductive parameters.

Effects of prepartal body condition score and peripartal energy supply of dairy cows on postpartal lipolysis, energy balance and ketogenesis: an animal model to investigate subclinical ketosis.

Subclinical ketosis is a metabolic disorder which often goes undiagnosed and leads to constricted performance and an impairment of general condition. In the current study subclinical ketosis was characterised by a ß-hydroxybutyrate (BHB) concentration of >1·2 mmol/l in blood serum. To generate this metabolic situation, an animal model was created. The model, based on group-specific interaction of dietary energy supply and body condition, is appropriate for testing the medical effectiveness of treating this kind of ketosis and its concomitants. During the trial, 18 dairy cows (primiparous and pluriparous) were assigned, according to their body condition score (BCS) 6 weeks before expected parturition, to a normal [6.78 MJ net energy for lactation (NEL)/kg dry matter; 20% concentrate] or to a high-energy feeding group (7·71 MJ NEL/kg dry matter; 60% concentrate). Therefore cows with the highest BCS were allocated to the high-energy group to enhance the contrast with the control group. Statistical analysis was done using the MIXED procedure of SAS. Effects were declared significant when P-values were ⩽0.05. Owing to the higher energy concentration and dry matter intake, the energy intake and balance was significantly higher in the high-energy feeding group, with strong effects on lipid metabolism and health in blood and liver post partum. Within the first 2 weeks after calving, 8 out of 9 cows (89%) of the high-energy group had BHB values indicative of subclinical ketosis. These cows also had significantly higher values of non-esterified fatty acids (NEFA), aspartate transaminase (AST) and glutamate dehydrogenase (GLDH) post partum, as well as a raised total lipid content of the liver. RQUICKI, a calculated parameter which is based on serum concentrations of glucose, insulin and NEFA to assess the insulin sensitivity, was not affected by treatment. Therefore, RQUICKI does not seem to be the right parameter for diagnosing decreased insulin sensitivity in cows affected by subclinical ketosis. The milk fat and the fat:protein ratio of the high-energy group was also higher, even though there was no decrease in milk yield for cows with subclinical BHB values.