The concentration of free amino acids in blood serum of dairy cows with primary ketosis.

PubMed

Marczuk, J; Brodzki, P; Brodzki, A; Kurek, Ł

2018-03-01

Ketosis is a common condition found in the initial stages of lactation in high-yielding dairy cows. The major cause of ketosis is a negative energy balance. During the energy deficiency, proteolysis processes develop parallel to lipolysis. During proteolysis, muscle tissue can be used as a source of amino acid. To date, the participation of amino acids in gluconeogenesis (glucogenic amino acids) and ketogenesis (ketogenic amino acids) has not been determined in detail. This paper presents the study on determination of the parameters of protein and free amino acid metabolism in blood serum of dairy cows with primary ketosis compared to healthy cows. This study contributes to better understanding of the role of amino acids in pathogenesis of ketosis. A total of 30 cows, divided into two groups: experimental (15 cows with ketosis) and control (15 healthy cows), were included in the study. The concentrations of glucose, β-hydroxybutyrate, total protein, albumin, urea, and free amino acids were determined in peripheral blood. Statistically significantly higher concentrations of glutamine, glutamic acid, isoleucine (p≤0.001), and tyrosine (p≤0.05) were found in cows with primary ketosis compared to healthy cows. Significant decrease in the concentrations of asparagine, histidine, methionine, and serine (p≤0.001), alanine, leucine, lysine and proline (p≤0.05) was observed. Significant increase of total ketogenic and glucogenic amino acids (p≤0.05), and an increased ratio of total ketogenic and glucogenic amino acids to total amino acids (p≤0.001) were noted in cows with ketosis. In our study, the changes, in particular observed in amino acid concentration in cows with primary ketosis, indicate its intensive use in both ketogenesis and gluconeogenesis processes. Therefore, a detailed understanding of the role that amino acids play in gluconeogenesis and ketogenesis will improve ketosis diagnostics and monitoring the course of a ketosis episode. Perhaps, the

Alcoholic Ketosis: Prevalence, Determinants, and Ketohepatitis in Japanese Alcoholic Men.

PubMed

Yokoyama, Akira; Yokoyama, Tetsuji; Mizukami, Takeshi; Matsui, Toshifumi; Shiraishi, Koichi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

2014-11-01

Alcoholic ketosis and ketoacidosis are metabolic abnormalities often diagnosed in alcoholics in emergency departments. We attempted to identify determinants or factors associated with alcoholic ketosis. The subjects of this cross-sectional survey were 1588 Japanese alcoholic men (≥40 years) who came to an addiction center within 14 days of their last drink. The results of the dipstick urinalyses revealed a prevalence of ketosis of 34.0% (±, 21.5%; +, 8.9%; and 2+/3+; 3.6%) in the alcoholics. Higher urine ketone levels were associated with higher serum total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyl transpeptidase levels. A multivariate analysis by the proportional odds model showed that the odds ratio (95% confidence interval) for an increase in ketosis by one category was 0.94 (0.84-1.06) per 10-year increase in age, 0.93 (0.89-0.97) per 1-day increase in interval since the last drink, 1.78 (1.41-2.26) in the presence of slow-metabolizing alcohol dehydrogenase-1B (ADH1B*1/*1), 1.61 (1.10-2.36) and 1.30 (1.03-1.65) when the beverage of choice was whiskey and shochu, respectively (distilled no-carbohydrate beverages vs. the other beverages), 2.05 (1.27-3.32) in the presence of hypoglycemia <80 mg/dl, 0.91 (0.88-0.94) per 1-kg/m(2) increase in body mass index (BMI), 1.09 (1.00-1.18) per +10 cigarettes smoked, and 2.78 (2.05-3.75) when the serum total bilirubin level was ≥2.0 mg/dl, and 1.97 (1.47-2.66) when the serum AST level was ≥200 IU/l. Ketosis was a very common complication and frequently accompanied by alcoholic liver injury in our Japanese male alcoholic population, in which ADH1B*1/*1 genotype, consumption of whiskey or shochu, hypoglycemia, lower BMI and smoking were significant determinants of the development of ketosis. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

FGF-21: promising biomarker for detecting ketosis in dairy cows.

PubMed

Xu, Chuang; Xu, Qiushi; Chen, Yuanyuan; Yang, Wei; Xia, Cheng; Yu, Hongjiang; Zhu, Kuilin; Shen, Taiyu; Zhang, Ziyang

2016-03-01

The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein-Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits. In a combined population of all 90 cows, we found that serum FGF-21 level was lower (P < 0.001) in cows suffering from ketosis. When the β-hydroxybutyric acid (BHBA) level increased over 1.2 mmol/L, the FGF-21 level tended to decline below 300.85 pg/ml. The area under the receiver operating characteristic curve (AUC-ROC) for serum FGF-21 for diagnosis of fatty liver was 0.952-0.025 [95% confidence interval (CI) 0.904, 1.000] which was higher than the AUC-ROC for glucose (Glc) and other tested parameters. We concluded that FGF-21 could be a diagnostic parameter in the evaluation and auxiliary diagnosis of changes in the energy metabolism state, and serum FGF-21 measurement would have a considerable clinical impact and lead to greater profitability in the dairy industry.

Clinical ketosis and standing behavior in transition cows.

PubMed

Itle, A J; Huzzey, J M; Weary, D M; von Keyserlingk, M A G

2015-01-01

Ketosis is a common disease in dairy cattle, especially in the days after calving, and it is often undiagnosed. The objective of this study was to compare the standing behavior of dairy cows with and without ketosis during the days around calving to determine if changes in this behavior could be useful in the early identification of sick cows. Serum β-hydroxybutyrate (BHBA) was measured in 184 cows on a commercial dairy farm twice weekly from 2 to 21d after calving. Standing behavior was measured from 7d before calving to 21d after calving using data loggers. Retrospectively, 15 cows with clinical ketosis (3 consecutive BHBA samples >1.2mmol/L and at least one sample of BHBA >2.9mmol/L) were matched with 15 nonketotic cows (BHBA <1.2mmol/L). Five periods were defined for the statistical analyses: wk -1 (d -7 to -1), d 0 (day of calving), wk +1 (d 1 to 7), wk +2 (d 8 to 14), and wk +3 (d 15 to 21). The first signs of clinical ketosis occurred 4.5±2.1d after calving. Total daily standing time was longer for clinically ketotic cows compared with nonketotic cows during wk -1 (14.3±0.6 vs. 12.0±0.7h/d) and on d 0 (17.2±0.9 vs. 12.7±0.9h/d) but did not differ during the other periods. Clinically ketotic cows exhibited fewer standing bouts compared with nonketotic cows on d 0 only (14.6±1.9 vs. 20.9±1.8bouts/d). Average standing bout duration was also longer for clinically ketotic cows on d 0 compared with nonketotic cows [71.3min/bout (CI: 59.3 to 85.5) vs. 35.8min/bout (CI: 29.8 to 42.9)] but was not different during the other periods. Differences in standing behavior in the week before and on the day of calving may be useful for the early detection of clinical ketosis in dairy cows. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry.

PubMed

Zhang, Hongyou; Wu, Ling; Xu, Chuang; Xia, Cheng; Sun, Lingwei; Shu, Shi

2013-09-26

Ketosis is an important problem for dairy cows` production performance. However, it is still little known about plasma metabolomics details of dairy ketosis. A gas chromatography/mass spectrometry (GC/MS) technique was used to investigate plasma metabolic differences in cows that had clinical ketosis (CK, n=22), subclinical ketosis (SK, n=32), or were clinically normal controls (NC, n=22). The endogenous plasma metabolome was measured by chemical derivatization followed by GC/MS, which led to the detection of 267 variables. A two-sample t-test of 30, 32, and 13 metabolites showed statistically significant differences between SK and NC, CK and NC, and CK and SK, respectively. Orthogonal signal correction-partial least-square discriminant analysis (OPLS-DA) revealed that the metabolic patterns of both CK and SK were mostly similar, with the exception of a few differences. The development of CK and SK involved disturbances in many metabolic pathways, mainly including fatty acid metabolism, amino acid metabolism, glycolysis, gluconeogenesis, and the pentose phosphate pathway. A diagnostic model arbitrary two groups was constructed using OPLS-DA and receiver-operator characteristic curves (ROC). Multivariate statistical diagnostics yielded the 19 potential biomarkers for SK and NC, 31 for CK and NC, and 8 for CK and SK with area under the curve (AUC) values. Our results showed the potential biomarkers from CK, SK, and NC, including carbohydrates, fatty acids, amino acids, even sitosterol and vitamin E isomers, etc. 2-piperidinecarboxylic acid and cis-9-hexadecenoic acid were closely associated with metabolic perturbations in ketosis as Glc, BHBA and NEFA for dealing with metabolic disturbances of ketosis in clinical practice. However, further research is needed to explain changes of 2,3,4-trihydroxybutyric acid, 3,4-dihydroxybutyric acid, α-aminobutyric acid, methylmalonic acid, sitosterol and α-tocopherol in CK and SK, and to reveal differences between CK and SK. Our

Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

PubMed

Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

2017-01-01

Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

Peripartum back fat thickness of multiparous Holstein-Friesian cows with displacement of the abomasum or ketosis.

PubMed

Yamakawa, Kazuhiro; Aoki, Takahiro; Matsui, Motozumi; Yamada, Kazutaka; Ishii, Mitsuo

2012-05-01

To establish a method to predict postpartum diseases using prepartum back fat thickness (BFT), the peripartum BFTs of 54 healthy multiparous cows before calving, which were diagnosed with postpartum displacement of the abomasum (DA), clinical ketosis or subclinical ketosis were compared with those of healthy cows from 8 weeks before the expected calving date to 8 weeks after calving. The peripartum BFTs of the cows with DA or clinical ketosis were significantly higher than those of healthy cows. The peripartum BFTs of the cows with subclinical ketosis were not significantly higher than those of the healthy cows.

Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

PubMed Central

Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

2014-01-01

Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

Hyperglycaemia and ketosis in a non-diabetic patient--an unusual cause of delayed recovery.

PubMed

Pawar, Sundeep T; Nath, Soumya S; Ansari, Farrukh

2014-01-01

We report a case of hyperglycaemia and ketosis developing in a non-diabetic patient who underwent a neurosurgical procedure under general anaesthesia. A 52-year-old non-diabetic female patient underwent excision of acoustic neuroma under general anaesthesia. Pancreatic function was not disturbed and she received a single dose of dexamethasone (8 mg) and paracetamol (1 g). Delayed recovery from anaesthesia occurred. On investigation, she was found to have hyperglycaemia and ketosis. She was further managed on the line of diabetic ketoacidosis. After 24 hours, when blood glucose had normalised and ketosis abated, she could be weaned from mechanical ventilation and extubated. The patient did not receive any drugs known to cause such a condition. To the best of our knowledge, hyperglycaemia and ketosis developing in a non-diabetic patient causing delayed recovery and extubation is here reported for the first time.

HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

PubMed Central

Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

2016-01-01

Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

Pathogenesis of A-beta+ ketosis-prone diabetes

USDA-ARS?s Scientific Manuscript database

A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnit...

Relationship between ketosis and dairy cows' blood metabolites in intensive production farms of the periurban area of Dakar.

PubMed

Yameogo, Nongasida; Ouedraogo, Georges Anicet; Kanyandekwe, Christine; Sawadogo, Germain Jerome

2008-10-01

This study which involved 140 Holstein and Montbeliard was carried out in the periurban area of Dakar with the aim to establish the relationship between ketosis, milk production and biochemical blood metabolites. The results showed that ketosis is a real problem in periurban farms around the city of Dakar with high proportions of 33.57% for subclinical ketosis and 6.43% for clinical ketosis. In their second month of milking, cows with subclinical ketosis had a decrease of 12.4 and 15.,6% in milk yield respectively for Montbeliard and Holstein, whereas cows with clinical ketosis had a decrease of 18.6 and 26%. Ketogenic cows (subclinical and clinical) have significantly lower average levels of blood glucose (p<0.05) and significantly higher average levels of blood urea (p<0.05) than cows with normal blood beta-Hydroxy Butyrate (BbHB) levels. Also, from one farm to another, significant difference was recorded with concentration of total proteins and globulin, calcium and magnesium.

Prevalence of ketosis in dairy cows in milk shed areas of Odisha state, India.

PubMed

Biswal, Sangram; Nayak, Dhruba Charan; Sardar, Kautuk Kumar

2016-11-01

The present study was conducted to ascertain the prevalence of ketosis in dairy cows in dairy herds, milksheds, and mixed population of milk cows selected randomly in milkshed areas of Odisha state, India. The investigation was conducted in 280 private dairy herds with variable herd size of 10-15 cows comprising crossbred Jersey cows (CBJ), crossbred Holstein Friesian (CHF) cows, and indigenous local breeds. The analysis of urine (Rothera's test), milk (Ross test), and blood samples of 2760 test cows were conducted through qualitative assessment by Rothera's test and Ross test, respectively, for the presence of ketone bodies to screen the ketotic animals. Cut-points have been decided based on β-hydroxybutyric acid level (≥1.2-1.4 mmol/L) in milk. We noted positive cases of ketosis with a prevalence rate of 36.7% (1014/2760) entailing 27.2% in clinical ketosis and 9.6% in subclinical ketosis. The breed wise incident rate was recorded to be the highest (38.0%) in CBJs. The age-wise prevalence rate was found to be the highest (40.8%) in the age group of 5.5-6.5 years. The season wise prevalence rate in 5 th calver was recorded to be the highest (38.6%) in summer season as compared to other seasons. The prevalence of ketosis was observed to be the highest at 56.7% on the first stage of lactation at the 1 st month after 2 weeks. The incidence rates for clinical and subclinical ketosis were found to be 25.2%; 12.2%, 26.6%; 11.2% and 30.3%; 2.9% in CBJ, CHF and indigenous cows, respectively. The breed wise overall prevalence rate was recorded to be 38.0% in CBJ, 37.8% in CHF, and 33.2% in indigenous cows. Ketosis and subclinical ketosis is highly prevalent metabolic disorder and has severe effect on the production status of affected animal and needs to be prevented, rather than treated, by maintaining cows in good and healthy conditions. We have attempted to give great attention for diagnosis, management, and control of this disease during risk stage to prevent

Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry

PubMed Central

2013-01-01

Background Ketosis is an important problem for dairy cows` production performance. However, it is still little known about plasma metabolomics details of dairy ketosis. Results A gas chromatography/mass spectrometry (GC/MS) technique was used to investigate plasma metabolic differences in cows that had clinical ketosis (CK, n=22), subclinical ketosis (SK, n=32), or were clinically normal controls (NC, n=22). The endogenous plasma metabolome was measured by chemical derivatization followed by GC/MS, which led to the detection of 267 variables. A two-sample t-test of 30, 32, and 13 metabolites showed statistically significant differences between SK and NC, CK and NC, and CK and SK, respectively. Orthogonal signal correction-partial least-square discriminant analysis (OPLS-DA) revealed that the metabolic patterns of both CK and SK were mostly similar, with the exception of a few differences. The development of CK and SK involved disturbances in many metabolic pathways, mainly including fatty acid metabolism, amino acid metabolism, glycolysis, gluconeogenesis, and the pentose phosphate pathway. A diagnostic model arbitrary two groups was constructed using OPLS-DA and receiver–operator characteristic curves (ROC). Multivariate statistical diagnostics yielded the 19 potential biomarkers for SK and NC, 31 for CK and NC, and 8 for CK and SK with area under the curve (AUC) values. Our results showed the potential biomarkers from CK, SK, and NC, including carbohydrates, fatty acids, amino acids, even sitosterol and vitamin E isomers, etc. 2-piperidinecarboxylic acid and cis-9-hexadecenoic acid were closely associated with metabolic perturbations in ketosis as Glc, BHBA and NEFA for dealing with metabolic disturbances of ketosis in clinical practice. However, further research is needed to explain changes of 2,3,4-trihydroxybutyric acid, 3,4-dihydroxybutyric acid, α-aminobutyric acid, methylmalonic acid, sitosterol and α-tocopherol in CK and SK, and to reveal differences

Prevalence of ketosis in dairy cows in milk shed areas of Odisha state, India

PubMed Central

Biswal, Sangram; Nayak, Dhruba Charan; Sardar, Kautuk Kumar

2016-01-01

Aim: The present study was conducted to ascertain the prevalence of ketosis in dairy cows in dairy herds, milksheds, and mixed population of milk cows selected randomly in milkshed areas of Odisha state, India. Materials and Methods: The investigation was conducted in 280 private dairy herds with variable herd size of 10-15 cows comprising crossbred Jersey cows (CBJ), crossbred Holstein Friesian (CHF) cows, and indigenous local breeds. The analysis of urine (Rothera’s test), milk (Ross test), and blood samples of 2760 test cows were conducted through qualitative assessment by Rothera’s test and Ross test, respectively, for the presence of ketone bodies to screen the ketotic animals. Cut-points have been decided based on β-hydroxybutyric acid level (≥1.2-1.4 mmol/L) in milk. Results: We noted positive cases of ketosis with a prevalence rate of 36.7% (1014/2760) entailing 27.2% in clinical ketosis and 9.6% in subclinical ketosis. The breed wise incident rate was recorded to be the highest (38.0%) in CBJs. The age-wise prevalence rate was found to be the highest (40.8%) in the age group of 5.5-6.5 years. The season wise prevalence rate in 5th calver was recorded to be the highest (38.6%) in summer season as compared to other seasons. The prevalence of ketosis was observed to be the highest at 56.7% on the first stage of lactation at the 1st month after 2 weeks. The incidence rates for clinical and subclinical ketosis were found to be 25.2%; 12.2%, 26.6%; 11.2% and 30.3%; 2.9% in CBJ, CHF and indigenous cows, respectively. The breed wise overall prevalence rate was recorded to be 38.0% in CBJ, 37.8% in CHF, and 33.2% in indigenous cows. Conclusion: Ketosis and subclinical ketosis is highly prevalent metabolic disorder and has severe effect on the production status of affected animal and needs to be prevented, rather than treated, by maintaining cows in good and healthy conditions. We have attempted to give great attention for diagnosis, management, and control

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

PubMed Central

Villamena, Frederick A.

2018-01-01

Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations. PMID:29607218

Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.

PubMed

Kang, Dong Young; S P, Nipin; Darvin, Pramod; Joung, Youn Hee; Byun, Hyo Joo; Do, Chang Hee; Park, Kyung Do; Park, Mi Na; Cho, Kwang Hyun; Yang, Young Mok

2017-07-03

Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.

Beta-hydroxybutyrate in milk as screening test for subclinical ketosis in dairy cows.

PubMed

Ježek, J; Cincović, M R; Nemec, M; Belić, B; Djoković, R; Klinkon, M; Starič, J

2017-09-26

Ketosis is a very frequent metabolic disease in dairy cows, resulting in lower milk production, impaired fertility and increased frequency of other diseases. The course of the disease is often subclinical, so early detection is very important. The aim of the study was to investigate the relation between the concentration of beta-hydroxybutyrate in blood and milk and to determine the cut-off value in milk for detection of subclinical ketosis. The study included 94 cows, which were in the first third of lactation. Beta-hydroxybutyrate (BHB) concentrations were measured in blood and milk serum using a biochemical analyser. The average concentration of BHB in the blood serum samples was 1.14 mmol/L while in the milk it was about ten times lower at 0.117 mmol/L. A statistically significant positive correlation between the concentration of BHB in blood and milk (r=0.705, p<0.001) was found. In cows with BHB in blood below 2.0 mmol/L a stronger correlation between blood and milk BHB was established (r=0.658, p<0.001) than in cows with blood BHB above 2.0 mmol/L (r=-0.292, p=0.206). Therefore, BHB in milk is a very suitable indicator in the diagnosis of subclinical ketosis as there is a good correlation between BHB in the blood and milk of cows with subclinical ketosis. The cut-off concentration of BHB in milk set at ≥0.080 mmol/L (AUC=0.91±0.03; p<0.001) is a significant indicator for subclinical ketosis in dairy cows. The sensitivity of the test was 94% and specificity 74%. Beta-hydroxybutyrate in milk is a good indicator of subclinical ketosis in dairy cows and can be measured accurately with a biochemical analyser.

Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

PubMed Central

Lu, Hongyun; Hu, Fang; Zeng, Yingjuan; Zou, Lingling; Luo, Shunkui; Sun, Ying; Liu, Hong; Sun, Liao

2014-01-01

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P < 0.05). Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P < 0.05). From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM. PMID:24829925

A field study to determine the prevalence, dairy herd management systems, and fresh cow clinical conditions associated with ketosis in western European dairy herds.

PubMed

Berge, Anna C; Vertenten, Geert

2014-01-01

The aim of this study was to determine the prevalence, major management systems, and fresh cow clinical conditions associated with ketosis in western European dairy herds. A total of 131 dairies were enrolled in Germany, France, Italy, the Netherlands, and the United Kingdom during 2011 to 2012. A milk-based test for ketones (Keto-Test; Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan; distributed by Elanco Animal Health, Antwerp, Belgium) was used for screening cows between d 7 and 21 after calving and ketosis was defined as a Keto-Test ≥100µmol/L. Study cows were observed for clinical disease up to 35d postcalving. Multivariate analysis (generalized estimating equation logistic regression) was performed to determine country, farm, management, feed, and cow factors associated with ketosis and to determine associations between ketosis and fresh cow diseases. Thirty-nine percent of the cows were classified as having ketosis. The herd average of ketosis was 43% in Germany, 53% in France, 31% in Italy, 46% in the Netherlands, and 31% in the United Kingdom. Of the 131 farms, 112 (85%) had 25% or more of their fresh cows resulting as positive for ketosis. Clinical ketosis was not reported in most farms and the highest level of clinical ketosis reported was 23%. The risks of ketosis were significantly lower in Italy and the United Kingdom compared with France, the Netherlands, and Germany. Larger herd size was associated with a decreased risk of ketosis. The farms that fed partially mixed rations had 1.5 times higher odds of ketosis than those that fed total mixed rations. Cows that calved in April to June had the highest odds of ketosis, with about twice as high odds compared with cows that calved in July to September. The cows that calved in January to March tended to have 1.5 times higher risk of ketosis compared with cows that calved in July to September. The odds of ketosis in parity 2 and parity 3 to 7 was significantly higher (1.5 and 2.8 times higher

A field trial on the effect of propylene glycol on milk yield and resolution of ketosis in fresh cows diagnosed with subclinical ketosis.

PubMed

McArt, J A A; Nydam, D V; Ospina, P A; Oetzel, G R

2011-12-01

The purpose of this study was to determine the effect of oral propylene glycol (PG) administration on ketosis resolution and milk yield in cows diagnosed with subclinical ketosis (SCK). Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 d in milk on Mondays, Wednesdays, and Fridays. Subclinical ketosis was defined as a β-hydroxybutyrate (BHBA) concentration of 1.2 to 2.9 mmol/L, [corrected] and clinical ketosis was defined as ≥ 3.0 mmol/L. [corrected]. Cows with SCK were randomized to the treatment group (oral PG) or control group (no PG); treatment cows were drenched with 300 mL of PG once daily from the day they tested 1.2 to 2.9 mmol/L [corrected] until the day they tested <1.2 mmol/L. [corrected]. Outcomes evaluated for all farms included time from SCK until BHBA test <1.2 mmol/L [corrected] or until BHBA test ≥ 3.0 mmol/L. [corrected]. Individual milk weights for the first 30 d of lactation were evaluated for the 3 farms monitoring daily milk. Semiparametric proportional hazards models were used to evaluate time to event outcomes; repeated-measures ANOVA was used to assess milk weights. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least one BHBA test of 1.2 to 2.9 mmol/L. [corrected]. Of these, 372 were assigned to the treatment group and 369 to the control group. Based on hazard ratios, PG-treated cows were 1.50 times more likely (95% confidence interval=1.26 to 1.79) to resolve their SCK and 0.54 times less likely (95% confidence interval=0.34 to 0.86) to develop clinical ketosis than control cows. Across the 3 herds measuring individual milk weights, treated cows produced 0.23 kg more milk per milking in the first 30 d of lactation than control cows, for a total difference of 0.69 kg/cow per day. After identification of a treatment by herd interaction, stratification by herd showed that treated cows produced more milk per milking on farm A (0.44 kg) and farm B (0.53 kg) in

1,3,5,8-tetrahydroxyxanthone regulates ANGPTL3-LPL pathway to lessen the ketosis in mice.

PubMed

Xiao, Hong-Bo; Sun, Zhi-Liang; Zhou, Nan

2012-05-12

Ketosis is a metabolic disorder closely associated with both lipid and carbohydrate metabolism. Recent studies show that angiopoietin-like protein 3 (ANGPTL3) contributes to the development of metabolic disorder. The objective of this study was to explore the inhibitory effect of 1,3,5,8-tetrahydroxyxanthone (Xan), a naturally occurring flavonoid compound, on ketosis and the mechanisms involved in this regulation. After 4weeks, Xan (10 or 30mg/kg, intragastrically) treatment decreased plasma total ketone bodies, malondialdehyde, 8-isoprostane, triglyceride, total cholesterol levels, and hepatic ANGPTL3 expression concomitantly with increased plasma glucose concentration and adipose lipoprotein lipase (LPL) expression in ketosis murine. The present results suggest that Xan regulates ANGPTL3-LPL pathway to lessen the ketosis in mice. Copyright © 2012 Elsevier B.V. All rights reserved.

Epilepsy and the ketogenic diet: assessment of ketosis in children using breath acetone.

PubMed

Musa-Veloso, Kathy; Rarama, Exequiel; Comeau, Felix; Curtis, Rosalind; Cunnane, Stephen

2002-09-01

High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p < 0.05), but not in children on a ketogenic diet. Children who were on the ketogenic diet for longer periods of time had a significantly lower fasting breath acetone (R(2) = 0.55, p = 0.014). In one child on the ketogenic diet, breath acetone was determined hourly over a 9-h period, both by gas chromatography and by a prototype hand-held breath acetone analyzer. Preliminary results using this hand-held breath acetone analyzer are encouraging. Breath acetone may be a useful tool in examining the relationship between ketosis and seizure control and enhancing our understanding of the mechanism of the ketogenic diet.

Ketosis in buffalo (Bubalus bubalis): clinical findings and the associated oxidative stress level.

PubMed

Youssef, Mohamed A; El-Khodery, Sabry Ahmed; El-deeb, Wael M; Abou El-Amaiem, Waleed E E

2010-12-01

As little is known about the oxidant/antioxidant status in buffalo with ketosis, the present study was delineated to assess the oxidative stress level associated with clinical ketosis in water buffalo. A total of 91 parturient buffalo at smallholder farms were studied (61 suspected to be ketotic and 30 healthy). Clinical and biochemical investigations were carried out for each buffalo. Based on clinical findings and the level of beta-hydroxybutyrate (BHB), buffalo were allocated into ketotic (42), subclinical cases (19). Clinically, there was an association between clinical ketosis and anorexia (p<0.001), constipation (p<0.001), decreased milk yield (p<0.001), ruminal stasis (p<0.001), and loss of body condition (p<0.01). Biochemically, in clinical ketosis compared with subclinical and control cases, there was a significant increase (p<0.05) of BHB, malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase (AST), L-alanine aminotransferase (ALT). However, there was a significant decrease of glucose, phosphorus, magnesium,total cholesterol and HDL-cholesterol. There was a positive correlation between BHB and MDA (r=0.433), BHB and NO (r=0.37), MDA and NO (r=0.515), and Glucose and phosphorus(r=0.521). However, there was a negative correlation between BHB and glucose (r= -0.341) and HDL and NO (r= -0.379). The result of the present study indicates that hyperketonemia in buffalo is associated with an increase of oxidative stress levels. Further studies need to be done on the efficacy of antioxidants as an ancillary treatment to relief the oxidative stress caused by ketosis.

The effect of storage temperature on the accuracy of a cow-side test for ketosis

PubMed Central

Hubbard, Jennifer; LeBlanc, Stephen; Duffield, Todd; Bagg, Randal; Dubuc, Jocelyn

2010-01-01

The objective of this study was to assess the effect of storage conditions on the accuracy of a milk test strip for ketosis. Storage at 21°C for up to 18 wk had little effect on accuracy for diagnosis and classification of subclinical ketosis. PMID:20676298

Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows.

PubMed

Suthar, V S; Canelas-Raposo, J; Deniz, A; Heuwieser, W

2013-05-01

Subclinical ketosis (SCK) is defined as concentrations of β-hydroxybutyrate (BHBA) ≥ 1.2 to 1.4 mmol/L and it is considered a gateway condition for other metabolic and infectious disorders such as metritis, mastitis, clinical ketosis, and displaced abomasum. Reported prevalence rates range from 6.9 to 43% in the first 2 mo of lactation. However, there is a dearth of information on prevalence rates considering the diversity of European dairy farms. The objectives of this study were to (1) determine prevalence of SCK, (2) identify thresholds of BHBA, and (3) study their relationships with postpartum metritis, clinical ketosis, displaced abomasum, lameness, and mastitis in European dairy farms. From May to October 2011, a convenience sample of 528 dairy herds from Croatia, Germany, Hungary, Italy, Poland, Portugal, Serbia, Slovenia, Spain, and Turkey was studied. β-Hydroxybutyrate levels were measured in 5,884 cows with a handheld meter within 2 to 15 d in milk (DIM). On average, 11 cows were enrolled per farm and relevant information (e.g., DIM, postpartum diseases, herd size) was recorded. Using receiver operator characteristic curve analyses, blood BHBA thresholds were determined for the occurrence of metritis, mastitis, clinical ketosis, displaced abomasum, and lameness. Multivariate binary logistic regression models were built for each disease, considering cow as the experimental unit and herd as a random effect. Overall prevalence of SCK (i.e., blood BHBA ≥ 1.2 mmol/L) within 10 countries was 21.8%, ranging from 11.2 to 36.6%. Cows with SCK had 1.5, 9.5, and 5.0 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively. Multivariate binary logistic regression models demonstrated that cows with blood BHBA levels of ≥ 1.4, ≥ 1.1 and ≥ 1.7 mmol/L during 2 to 15 DIM had 1.7, 10.5, and 6.9 times greater odds of developing metritis, clinical ketosis, and displaced abomasum, respectively, compared with cows with lower

Prevalence and clinical characteristics of non-alcoholic fatty liver disease in newly diagnosed patients with ketosis-onset diabetes.

PubMed

Li, T-T; Wang, A-P; Lu, J-X; Chen, M-Y; Zhao, C-C; Tang, Z-H; Li, L-X; Jia, W-P

2018-03-21

As the prevalence and clinical characteristics of non-alcoholic fatty liver disease (NAFLD) are still unknown in ketosis-onset diabetes, the present study compared the characteristics of NAFLD in type 1 diabetes (T1D), ketosis-onset and non-ketotic type 2 diabetes (T2D) patients. This cross-sectional study was performed with newly diagnosed Chinese patients with diabetes, including 39 T1D, 165 ketosis-onset and 173 non-ketotic T2D, with 30 non-diabetics included as controls. NAFLD was determined by hepatic ultrasonography, then its clinical features were analyzed and its associated risk factors evaluated. NAFLD prevalence in patients with ketosis-onset diabetes (61.8%) was significantly higher than in controls (23.3%; P=0.003) and in T1D patients (15.4%; P<0.001). However, there was no difference in prevalence between ketosis-onset and non-ketotic T2D patients (52.6%; P=0.229), although BMI and alanine aminotransferase (ALT) proved to be independent risk factors for the presence of NAFLD in both these groups whereas, in T1D patients, serum uric acid levels were independent risk factors. NAFLD prevalence and risk factors in ketosis-onset diabetes were similar to those in non-ketotic T2D, but different from those in T1D. These data provide further evidence that ketosis-onset diabetes should be classified as a subtype of T2D rather than idiopathic T1D. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Critical thresholds of liver function parameters for ketosis prediction in dairy cows using receiver operating characteristic (ROC) analysis.

PubMed

Sun, Yuhang; Wang, Bo; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Wu, Ling; Xia, Cheng

2015-01-01

Fatty liver syndrome and ketosis are important metabolic disorders in high-producing cows during early lactation with fatty liver usually preceding ketosis. To date, parameters for early prediction of the risk of ketosis have not been investigated in China. To determine the predictive value of some parameters on the risk of ketosis in China. In a descriptive study, 48 control and 32 ketotic Holstein Friesian cows were randomly selected from one farm with a serum β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as cutoff point. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) analysis. In line with a high BHBA concentration, blood glucose concentration was significantly lower in ketotic cows compared to control animals (2.77 ± 0.24 versus 3.34 ± 0.03 mmol/L; P = 0.02). Thresholds were more than 0.76 mmol/L for nonesterified fatty acids (NEFA, with 65% sensitivity and 92% specificity), more than 104 U/L for aspartate aminotransferase (AST, 74% and 85%, respectively), less than 140 U/L for cholinesterase (CHE, 75% and 59%, respectively), and more than 3.3 µmol/L for total bilirubin (TBIL, 58% and 83%, respectively). There were significant correlations between BHBA and glucose (R = -4.74), or CHE (R = -0.262), BHBA and NEFA (R = 0.520), or AST (R = 0.525), or TBIL (R = 0.278), or direct bilirubin (DBIL, R = 0.348). AST, CHE, TBIL and NEFA may be useful parameters for risk prediction of ketosis. This study might be of value in addressing novel directions for future research on the connection between ketosis and liver dysfunction.

Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

PubMed

Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

2016-08-01

The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

PubMed Central

2013-01-01

Background The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. Methods In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. Results The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, p<0.001), but no significant difference was found compared with the non-ketotic type 2 diabetics (0.73±0.19 mm, p=0.582) after controlling for differences in age and sex. In both the ketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both p<0.001) after controlling for sex, but no sex difference was observed (p=0.479 and p=0.707, respectively) after controlling for age. In the ketosis-onset diabetics, the presence of

Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China

PubMed Central

Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

2016-01-01

Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China. PMID:26966435

Healthcare Resource Utilization and Costs Associated with Ketosis Events in Pediatric and Adult Patients with Type 1 Diabetes Mellitus in the UK.

PubMed

Thalange, Nandu; Aldhouse, Natalie Valerie Jane; Kitchen, Helen; Howard, Daniel; Tutkunkardas, Deniz; Håkan-Bloch, Jonas

2017-10-01

Ketosis is a metabolic state associated with insulin deficiency. Untreated, it develops into diabetic ketoacidosis, a significant contributor to mortality and morbidity in people with type 1 diabetes mellitus (T1DM). Little is understood about how patients utilize healthcare resources during ketosis events. This study aimed to identify and quantify healthcare resource utilization and provide estimates of associated costs of ketosis events in T1DM, treated unaided or with healthcare professional (HCP) assistance in the UK. Qualitative interviews with adult patients, pediatric carers, and HCPs identified resources used by patients/carers during ketosis events. An online quantitative survey was then used to quantify patients/carers resource use during their/their child's most recent ketosis event, and HCPs estimated patient resource uptake to corroborate the findings. Associated costs estimated from UK data sources were applied to the survey results to calculate the cost of ketosis events in adults and children. Quantitative survey responses from 93 adults, 76 carers, and 52 HCPs were analyzed. Patients and carers monitored ketosis during and following the event with ketone strips and additional glucose strips, and administered treatment comprising insulin and pump set changes where appropriate. Additionally, patients/carers accessed phone services and many received follow-up medical appointments. In total, 70% (n = 65) of adult and 66% (n = 50) of pediatric ketosis events were managed at home, for which resource use costs per event were £23.87 and £38.00 respectively. Remaining events were treated in NHS facilities costing £217.57 per adult and £352.92 per child. Weighted averages identified that ketosis events cost £81.98 per adult and £142.97 per child. Indirect costs from work productivity loss increase these figures to £225.11 per adult and £256.88 per child. Healthcare resource use for ketosis events is high in adults and children with T1DM and

(1)H-Nuclear magnetic resonance-based plasma metabolic profiling of dairy cows with clinical and subclinical ketosis.

PubMed

Sun, L W; Zhang, H Y; Wu, L; Shu, S; Xia, C; Xu, C; Zheng, J S

2014-03-01

The purpose of this study was to assess the metabolic profile of plasma samples from cows with clinical and subclinical ketosis. According to clinical signs and 3-hydroxybutyrate plasma levels, 81 multiparous Holstein cows were selected from a dairy farm 7 to 21 d after calving. The cows were divided into 3 groups: cows with clinical ketosis, cows with subclinical ketosis, and healthy control cows. (1)H-Nuclear magnetic resonance-based metabolomics was used to assess the plasma metabolic profiles of the 3 groups. The data were analyzed by principal component analysis, partial least squares discriminant analysis, and orthogonal partial least-squares discriminant analysis. The differences in metabolites among the 3 groups were assessed. The orthogonal partial least-squares discriminant analysis model differentiated the 3 groups of plasma samples. The model predicted clinical ketosis with a sensitivity of 100% and a specificity of 100%. In the case of subclinical ketosis, the model had a sensitivity of 97.0% and specificity of 95.7%. Twenty-five metabolites, including acetoacetate, acetone, lactate, glucose, choline, glutamic acid, and glutamine, were different among the 3 groups. Among the 25 metabolites, 4 were upregulated, 7 were downregulated, and 14 were both upregulated and downregulated. The results indicated that plasma (1)H-nuclear magnetic resonance-based metabolomics, coupled with pattern recognition analytical methods, not only has the sensitivity and specificity to distinguish cows with clinical and subclinical ketosis from healthy controls, but also has the potential to be developed into a clinically useful diagnostic tool that could contribute to a further understanding of the disease mechanisms. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus.

PubMed

Kruljac, Ivan; Ćaćić, Miroslav; Ćaćić, Petra; Ostojić, Vedran; Štefanović, Mario; Šikić, Aljoša; Vrkljan, Milan

2017-01-01

Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.

Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

PubMed Central

Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

2010-01-01

Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

Low cortisol levels in blood from dairy cows with ketosis: a field study

PubMed Central

2010-01-01

Background An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Methods Cortisol, insulin, β-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. Results No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). Conclusions The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research. PMID:20487518

Screening for ketosis using multiple logistic regression based on milk yield and composition

PubMed Central

KAYANO, Mitsunori; KATAOKA, Tomoko

2015-01-01

Multiple logistic regression was applied to milk yield and composition data for 632 records of healthy cows and 61 records of ketotic cows in Hokkaido, Japan. The purpose was to diagnose ketosis based on milk yield and composition, simultaneously. The cows were divided into two groups: (1) multiparous, including 314 healthy cows and 45 ketotic cows and (2) primiparous, including 318 healthy cows and 16 ketotic cows, since nutritional status, milk yield and composition are affected by parity. Multiple logistic regression was applied to these groups separately. For multiparous cows, milk yield (kg/day/cow) and protein-to-fat (P/F) ratio in milk were significant factors (P<0.05) for the diagnosis of ketosis. For primiparous cows, lactose content (%), solid not fat (SNF) content (%) and milk urea nitrogen (MUN) content (mg/dl) were significantly associated with ketosis (P<0.01). A diagnostic rule was constructed for each group of cows: (1) 9.978 × P/F ratio + 0.085 × milk yield <10 and (2) 2.327 × SNF − 2.703 × lactose + 0.225 × MUN <10. The sensitivity, specificity and the area under the curve (AUC) of the diagnostic rules were (1) 0.800, 0.729 and 0.811; (2) 0.813, 0.730 and 0.787, respectively. The P/F ratio, which is a widely used measure of ketosis, provided the sensitivity, specificity and AUC values of (1) 0.711, 0.726 and 0.781; and (2) 0.678, 0.767 and 0.738, respectively. PMID:26074408

Low cortisol levels in blood from dairy cows with ketosis: a field study.

PubMed

Forslund, Kristina B; Ljungvall, Orjan A; Jones, Bernt V

2010-05-20

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Cortisol, insulin, beta-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

Screening for ketosis using multiple logistic regression based on milk yield and composition.

PubMed

Kayano, Mitsunori; Kataoka, Tomoko

2015-11-01

Multiple logistic regression was applied to milk yield and composition data for 632 records of healthy cows and 61 records of ketotic cows in Hokkaido, Japan. The purpose was to diagnose ketosis based on milk yield and composition, simultaneously. The cows were divided into two groups: (1) multiparous, including 314 healthy cows and 45 ketotic cows and (2) primiparous, including 318 healthy cows and 16 ketotic cows, since nutritional status, milk yield and composition are affected by parity. Multiple logistic regression was applied to these groups separately. For multiparous cows, milk yield (kg/day/cow) and protein-to-fat (P/F) ratio in milk were significant factors (P<0.05) for the diagnosis of ketosis. For primiparous cows, lactose content (%), solid not fat (SNF) content (%) and milk urea nitrogen (MUN) content (mg/dl) were significantly associated with ketosis (P<0.01). A diagnostic rule was constructed for each group of cows: (1) 9.978 × P/F ratio + 0.085 × milk yield <10 and (2) 2.327 × SNF - 2.703 × lactose + 0.225 × MUN <10. The sensitivity, specificity and the area under the curve (AUC) of the diagnostic rules were (1) 0.800, 0.729 and 0.811; (2) 0.813, 0.730 and 0.787, respectively. The P/F ratio, which is a widely used measure of ketosis, provided the sensitivity, specificity and AUC values of (1) 0.711, 0.726 and 0.781; and (2) 0.678, 0.767 and 0.738, respectively.

Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production.

PubMed

Gordon, J L; Duffield, T F; Herdt, T H; Kelton, D F; Neuder, L; LeBlanc, S J

2017-04-01

The objective of this study was to determine the effects of butaphosphan-cyanocobalamin (B+C), glargine insulin, and propylene glycol on resolution of ketosis and average daily milk yield after treatment. Cows from 16 herds in Ontario, Canada, and 1 herd in Michigan were tested at weekly intervals between 3 and 16 DIM. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. All ketotic cows were given a baseline treatment of 3 d of 300 g of propylene glycol orally. Animals were then randomly assigned to treatment with 3 doses of either 25 mL of B+C or 25 mL of saline placebo and 1 dose of either 2 mL (200 IU) of glargine insulin or 2 mL of saline placebo in a 2 × 2 factorial arrangement. Outcomes of interest on all farms were ketosis cure (blood BHB <1.2 mmol/L 1 wk postenrollment), maintenance of ketosis cure (blood BHB <1.2 mmol/L 1 and 2 wk postenrollment), and blood BHB concentrations at 1 and 2 wk postenrollment. Milk weights were collected daily in 1 large freestall herd. Repeated measures ANOVA was used to evaluate blood BHB concentrations 2 wk after treatment and milk production for 30 d after treatment. Poisson regression was used to examine the effect of treatment on cure and maintenance of cure. Due to a regulatory delay causing temporary unavailability of B+C in Canada, data were analyzed in 2 sets of models: one for insulin and the corresponding placebo (n = 620) and one for the full trial (n = 380). Animals with blood glucose concentrations ≤2.2 mmol/L at the time of ketosis diagnosis were 2.1 times more likely (95% CI = 1.2 to 3.7) to be cured if treated with B+C. Animals in lactation 3 or higher that had blood glucose concentrations <2.2 mmol/L at enrollment produced 4.2 kg/d (95% CI = 1.4 to 7.1) more milk if treated with insulin versus placebo and 2.8 kg/d (95% CI = 0.9 to 4.7) more milk if treated with B+C versus placebo. Animals in lactation 3 or higher with blood glucose ≥2.2 mmol/L that were treated with insulin produced 2

Concentrations of sodium, potassium, magnesium, and iron in the serum of dairy cows with subclinical ketosis.

PubMed

Zhang, Zhigang; Li, Xiaobing; Wang, Hongbin; Guo, Changming; Gao, Li; Liu, Lei; Gao, Ruifeng; Zhang, Yi; Li, Peng; Wang, Zhe; Li, Yanfei; Liu, Guowen

2011-12-01

Serum concentrations of sodium, potassium, magnesium, and iron were measured in dairy cows with subclinical ketosis. Compared with healthy cows, the subclinically ketotic cows had significantly higher levels of non-esterified fatty acids and β-hydroxybutirate in serum and significantly lower levels of blood glucose (p < 0.01). No significant differences were observed, suggesting that the mineral elements measured are not involved in the pathogenesis of subclinical ketosis.

Effects of elevated parameters of subclinical ketosis on the immune system of dairy cows: in vivo and in vitro results.

PubMed

Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

Using an established model in which subclinical ketosis is induced, the response of differential blood counts and levels of various haematological variables, including the inflammatory marker haptoglobin (Hp), were tested over the last six weeks of parturition until the 56th day post-partum in cows with lower or higher body condition scores (LBC and HBC, respectively; n = 9/group). Animals in the HBC group evidenced subclinical ketosis whereas LBC animals were metabolically healthy. For in vitro examination with ß-hydroxybutyrate (BHB) as a further stimulus, peripheral blood mononuclear cell (PBMC) counts of cows with and without subclinical ketosis (n = 5/group) were observed. Counts of leucocytes, granulocytes and lymphocytes (LY) peaked at day 1 post-partum in HBC cows, with a more marked increase in heifers. In subclinical ketosis LY count increased again, with significantly higher values in the HBC group. The red blood cell (RBC) profile was affected by parity (counts were higher in heifers). Hp showed a positive linear correlation with BHB and non-esterified fatty acids (NEFA; R(2) = 0.41). PBMC from cows that were not pre-stressed with subclinical ketosis were more sensitive to increasing levels of BHB in vitro, as evidenced by both their higher proliferative capability and increased release of nitric oxide (NO). In summary, cows with subclinical ketosis showed a heightened immune response compared with metabolically healthy individuals, based on increased LY counts, increasing stimulative properties of PBMC and a relationship between Hp and typically increased values of BHB and NEFA. Concentrations of BHB in vivo during subclinical ketosis did not alter the proliferative capability of bovine PBMC in vitro, which was first significantly decreased at a dosage of 5 mM BHB.

Risk factors for displaced abomasum or ketosis in Swedish dairy herds.

PubMed

Stengärde, L; Hultgren, J; Tråvén, M; Holtenius, K; Emanuelson, U

2012-03-01

Risk factors associated with high or low long-term incidence of displaced abomasum (DA) or clinical ketosis were studied in 60 Swedish dairy herds, using multivariable logistic regression modelling. Forty high-incidence herds were included as cases and 20 low-incidence herds as controls. Incidence rates were calculated based on veterinary records of clinical diagnoses. During the 3-year period preceding the herd classification, herds with a high incidence had a disease incidence of DA or clinical ketosis above the 3rd quartile in a national database for disease recordings. Control herds had no cows with DA or clinical ketosis. All herds were visited during the housing period and herdsmen were interviewed about management routines, housing, feeding, milk yield, and herd health. Target groups were heifers in late gestation, dry cows, and cows in early lactation. Univariable logistic regression was used to screen for factors associated with being a high-incidence herd. A multivariable logistic regression model was built using stepwise regression. A higher maximum daily milk yield in multiparous cows and a large herd size (p=0.054 and p=0.066, respectively) tended to be associated with being a high-incidence herd. Not cleaning the heifer feeding platform daily increased the odds of having a high-incidence herd twelvefold (p<0.01). Keeping cows in only one group in the dry period increased the odds of having a high incidence herd eightfold (p=0.03). Herd size was confounded with housing system. Housing system was therefore added to the final logistic regression model. In conclusion, a large herd size, a high maximum daily milk yield, keeping dry cows in one group, and not cleaning the feeding platform daily appear to be important risk factors for a high incidence of DA or clinical ketosis in Swedish dairy herds. These results confirm the importance of housing, management and feeding in the prevention of metabolic disorders in dairy cows around parturition and in early

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

PubMed Central

2014-01-01

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

PubMed Central

Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

2010-01-01

Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

PubMed Central

Brownlow, Milene L.; Jung, Seung H.; Moore, Raquel J.; Bechmann, Naomi; Jankord, Ryan

2017-01-01

Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group

Post-exercise ketosis.

PubMed Central

Koeslag, J H; Noakes, T D; Sloan, A W

1980-01-01

1. The effect of exercise on blood ketone body concentrations was studied in trained athletes and in sedentary subjects pedalling a bicycle ergometer. 2. Although the untrained subjects had higher heart rates and blood lactate concentrations at the same work load as the athletes, neither group developed ketonaemia even after intense or prolonged exercise. 3. Older subjects developed post-exercise ketonaemia, reaching maximum about 3 hr after exercise. 4. A high-carbohydrate diet before the exercise could prevent the onset of post-exercise ketonaemia and a low-carbohydrate diet enhanced it. The highest post-exercise blood ketone levels were recorded in marathon runners after a "glycogen-stripping' regimen. 5. Concentrations of free fatty acids, glucose, growth hormone and insulin in blood after exercise followed different patterns from that of ketones. 6. Post-exercise ketosis, when it occurs in untrained subjects, may be due to a lower carbohydrate intake than that of athletes. PMID:6997456

Ketosis After Cardiopulmonary Bypass in Children Is Associated With an Inadequate Balance Between Oxygen Transport and Consumption.

PubMed

Klee, Philippe; Arni, Delphine; Saudan, Sonja; Schwitzgebel, Valérie M; Sharma, Ruchika; Karam, Oliver; Rimensberger, Peter C

2016-09-01

Hyperglycemia after cardiac surgery and cardiopulmonary bypass in children has been associated with worse outcome; however, causality has never been proven. Furthermore, the benefit of tight glycemic control is inconsistent. The purpose of this study was to describe the metabolic constellation of children before, during, and after cardiopulmonary bypass, in order to identify a subset of patients that might benefit from insulin treatment. Prospective observational study, in which insulin treatment was initiated when postoperative blood glucose levels were more than 12 mmol/L (216 mg/dL). Tertiary PICU. Ninety-six patients 6 months to 16 years old undergoing cardiac surgery with cardiopulmonary bypass. None. Metabolic tests were performed before anesthesia, at the end of cardiopulmonary bypass, at PICU admission, and 4 and 12 hours after PICU admission, as well as 4 hours after initiation of insulin treatment. Ketosis was present in 17.9% patients at the end of cardiopulmonary bypass and in 31.2% at PICU admission. Young age was an independent risk factor for this condition. Ketosis at PICU admission was an independent risk factor for an increased difference between arterial and venous oxygen saturation. Four hours after admission (p = 0.05). Insulin corrected ketosis within 4 hours. In this study, we found a high prevalence of ketosis at PICU admission, especially in young children. This was independently associated with an imbalance between oxygen transport and consumption and was corrected by insulin. These results set the basis for future randomized controlled trials, to test whether this subgroup of patients might benefit from increased glucose intake and insulin during surgery to avoid ketosis, as improving oxygen transport and consumption might improve patient outcome.

Microfluidic biosensor for β-Hydroxybutyrate (βHBA) determination of subclinical ketosis diagnosis.

PubMed

Weng, Xuan; Zhao, Wenting; Neethirajan, Suresh; Duffield, Todd

2015-02-12

Determination of β-hydroxybutyrate (βHBA) is a gold standard for diagnosis of Subclinical Ketosis (SCK), a common disease in dairy cows that causes significant economic loss. Early detection of SCK can help reduce the risk of the disease progressing into clinical stage, thus minimizing economic losses on dairy cattle. Conventional laboratory methods are time consuming and labor-intensive, requiring expensive and bulky equipment. Development of portable and robust devices for rapid on-site SCK diagnosis is an effective way to prevent and control ketosis and can significantly aid in the management of dairy animal health. Microfluidic technology provides a rapid, cost-effective way to develop handheld devices for on-farm detection of sub-clinical ketosis. In this study, a highly sensitive microfluidics-based biosensor for on-site SCK diagnosis has been developed. A rapid, low-cost microfluidic biosensor with high sensitivity and specificity was developed for SCK diagnosis. Determination of βHBA was employed as the indicator in the diagnosis of SCK. On-chip detection using miniaturized and cost-effective optical sensor can be finished in 1 minute with a detection limit of 0.05 mM concentration. Developed microfluidic biosensor was successfully tested with the serum samples from dairy cows affected by SCK. The results of the developed biosensor agreed well with two other laboratory methods. The biosensor was characterized by high sensitivity and specificity towards βHBA with a detection limit of 0.05 mM. The developed microfluidic biosensor provides a promising prototype for a cost-effective handheld meter for on-site SCK diagnosis. By using microfluidic method, the detection time is significantly decreased compared to other laboratory methods. Here, we demonstrate a field-deployable device to precisely identify and measure subclinical ketosis by specific labeling and quantification of β-hydroxybutyate in cow blood samples. A real-time on-site detection system will

Antepartal insulin-like growth factor 1 and insulin-like growth factor binding protein 2 concentrations are indicative of ketosis in dairy cows.

PubMed

Piechotta, M; Mysegades, W; Ligges, U; Lilienthal, J; Hoeflich, A; Miyamoto, A; Bollwein, H

2015-05-01

A study involving a small number of cows found that the concentrations of insulin-like growth hormone 1 (IGF1) may be a useful predictor of metabolic disease. Further, IGF1 may provide also a pathophysiological link to metabolic diseases such as ketosis. The objective of the current study was to test whether the low antepartal total IGF1 or IGF1 binding protein (IGFBP) concentrations might predict ketosis under field conditions. Clinical examinations and blood sampling were performed antepartum (262-270 d after artificial insemination) on 377 pluriparous pregnant Holstein Friesian cows. The presence of postpartum diseases were recorded (ketosis, fatty liver, displacement of the abomasum, hypocalcemia, mastitis, retention of fetal membranes, and clinical metritis or endometritis), and the concentrations of IGF1, IGFBP2, IGFBP3, and nonesterified fatty acids were measured. Cows with postpartum clinical ketosis had lower IGF1 concentrations antepartum than healthy cows. The sensitivity of antepartal IGF1 as a marker for postpartum ketosis was 0.87, and the specificity was 0.43; a positive predictive value of 0.91 and a negative predictive value of 0.35 were calculated. The cows with ketosis and retained fetal membranes had lower IGFBP2 concentrations compared with the healthy cows. It can be speculated that lower IGF1 production in the liver during late pregnancy may increase growth hormone secretions and lipolysis, thereby increasing the risk of ketosis. Lower IGFBP2 concentrations may reflect the suppression of IGFBP2 levels through higher growth hormone secretion. In conclusion, compared with nonesterified fatty acids as a predictive parameter, IGF1 and IGFBP2 may represent earlier biomarkers of inadequate metabolic adaptation to the high energy demand required postpartum. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Incidence and clinical vital parameters in primary ketosis of Murrah buffaloes

PubMed Central

Kumar, Ankit; Sindhu, Neelesh; Kumar, Parmod; Kumar, Tarun; Charaya, Gaurav; Surbhi; Jain, V. K.; Sridhar

2015-01-01

Aim: The present study was undertaken to ascertain the incidence and clinical vital parameters in cases of primary ketosis in Murrah buffaloes brought to teaching veterinary clinical complex, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar and from adjoining villages of the district Hisar, Haryana, India. Materials and Methods: The investigation was conducted on 24 clinical cases (out of total 145 screened) of primary ketosis. The diagnosis was confirmed on the basis of clinical signs and significantly positive two tests for ketone bodies in urine (Rothera’s and Keto-Diastix strip test). Data collected were statistically analyzed using independent Student’s t-test. Results: Overall incidence of disease in these areas was found to be 16.55% and all the animals were recently parturited (mean: 1.42±0.14 month), on an average in their third lactation (mean: 2.38±0.30) and exhibited clinical signs such as selective anorexia (refusal to feed on concentrate diet), drastic reduction in milk yield (mean: 64.4±5.35%), ketotic odor from urine, breath, and milk and rapid loss of body condition. All the clinical vital parameters in ketotic buffaloes (body temperature, heart rate, respiration rate, and rumen movements) were within normal range. Conclusion: Primary ketosis in Murrah buffaloes was the most common seen in the third lactation, within the first 2 months after parturition with characteristics clinical signs and no variability in vital parameters. The disease has severe effect on the production status of affected animal. PMID:27047203

Evaluation of the change of serum copper and zinc concentrations of dairy cows with subclinical ketosis.

PubMed

Zhang, Zhigang; Liu, Guowen; Li, Xiaobing; Gao, Li; Guo, Changming; Wang, Hongbin; Wang, Zhe

2010-12-01

Ketosis in dairy cows can lead to poor reproductive success and decreased milk production. Since the serum concentrations of copper (Cu) and zinc (Zn) are closely associated with the health status of cows, we investigated whether serum concentrations of Cu and Zn differed in dairy cows with subclinical ketosis and healthy dairy cows. Blood samples of 19 healthy dairy cows and 15 subclinically ketotic dairy cows were collected from three farms, and the concentrations of β-hydroxybutyrate (BHBA), glucose, non-esterified fatty acids (NEFA), Cu, and Zn were determined. Subclinically ketotic dairy cows had significantly higher BHBA and NEFA levels (p < 0.01) and lower glucose (p < 0.01) than healthy dairy cows. Likewise, serum concentrations of Zn were significantly decreased (p < 0.05) in dairy cows with subclinical ketosis. There was no significant difference observed for serum Cu concentration between healthy and subclinically ketotic dairy cows. This study suggests that a decreased serum Zn concentration could be a cause of decreased reproductive performance in subclinically ketotic dairy cows.

Use of test day milk fat and milk protein to detect subclinical ketosis in dairy cattle in Ontario.

PubMed Central

Duffield, T F; Kelton, D F; Leslie, K E; Lissemore, K D; Lumsden, J H

1997-01-01

Serum beta-hydroxybutyrate (BHB) levels were determined for 1333 dairy cows in various stages of lactation and parity on 93 dairy farms in Ontario. The data were collected in a cross-sectional manner, as part of the 1992 Ontario Dairy Monitoring and Analysis Program. The median serum BHB was 536 mumol/L for all cows, with a range of 0 to 5801 mumol/L. When subclinical ketosis was defined as a serum BHB level of 1200 mumol/L or higher, the prevalence of ketosis for cows in early lactation (< 65 days in milk (DIM)) was 14.1%. Prevalences for mid lactation (65-149 DIM), late lactation (> 149 DIM), and dry cows were 5.3%, 3.2%, and 1.6%, respectively. The mean serum BHB was significantly higher in the early group compared with each of the other 3 groups (P < 0.05). There was a trend of increasing prevalence with increasing parity across all stages of lactation. Only the difference between the parity-1 group and the parity-4 and greater group was statistically significant (P < 0.05). Both test-day fat percent and test-day protein percent were significantly associated with subclinical ketosis. However, test-day fat percent and test-day protein percent, used alone or in combination, were not useful screening tests for identifying cows with subclinical ketosis. PMID:9360791

NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis.

PubMed

Klein, Matthias S; Buttchereit, Nina; Miemczyk, Sebastian P; Immervoll, Ann-Kathrin; Louis, Caridad; Wiedemann, Steffi; Junge, Wolfgang; Thaller, Georg; Oefner, Peter J; Gronwald, Wolfram

2012-02-03

Ketosis is a common metabolic disease in dairy cows. Diagnostic markers for ketosis such as acetone and beta-hydroxybutyric acid (BHBA) are known, but disease prediction remains an unsolved challenge. Milk is a steadily available biofluid and routinely collected on a daily basis. This high availability makes milk superior to blood or urine samples for diagnostic purposes. In this contribution, we show that high milk glycerophosphocholine (GPC) levels and high ratios of GPC to phosphocholine (PC) allow for the reliable selection of healthy and metabolically stable cows for breeding purposes. Throughout lactation, high GPC values are connected with a low ketosis incidence. During the first month of lactation, molar GPC/PC ratios equal or greater than 2.5 indicate a very low risk for developing ketosis. This threshold was validated for different breeds (Holstein-Friesian, Brown Swiss, and Simmental Fleckvieh) and for animals in different lactations, with observed odds ratios between 1.5 and 2.38. In contrast to acetone and BHBA, these measures are independent of the acute disease status. A possible explanation for the predictive effect is that GPC and PC are measures for the ability to break down phospholipids as a fatty acid source to meet the enhanced energy requirements of early lactation.

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

PubMed

Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

2000-04-01

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Determination of single nucleotide polymorphisms associated with subclinical ketosis in Jersey cattle

USDA-ARS?s Scientific Manuscript database

Subclinical ketosis is a fresh cow disorder that is costly in terms of lost milk production and treatment cost. Although treatment and prevention strategies are available, prevention requires targeting animals that are likely to develop the disease. Whole-herd genotyping is becoming more common with...

Arginine metabolism is altered in adults with A-B + ketosis-prone diabetes

USDA-ARS?s Scientific Manuscript database

A-B + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible B cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. The objective of this study was to determine the relation be...

The role of exogenous insulin in the complex of hepatic lipidosis and ketosis associated with insulin resistance phenomenon in postpartum dairy cattle.

PubMed

Hayirli, A

2006-10-01

As a result of a marked decline in dry matter intake (DMI) prior to parturition and a slow rate of increase in DMI relative to milk production after parturition, dairy cattle experience a negative energy balance. Changes in nutritional and metabolic status during the periparturient period predispose dairy cattle to develop hepatic lipidosis and ketosis. The metabolic profile during early lactation includes low concentrations of serum insulin, plasma glucose, and liver glycogen and high concentrations of serum glucagon, adrenaline, growth hormone, plasma beta-hydroxybutyrate and non-esterified fatty acids, and liver triglyceride. Moreover, during late gestation and early lactation, flow of nutrients to fetus and mammary tissues are accorded a high degree of metabolic priority. This priority coincides with lowered responsiveness and sensitivity of extrahepatic tissues to insulin, which presumably plays a key role in development of hepatic lipidosis and ketosis. Hepatic lipidosis and ketosis compromise production, immune function, and fertility. Cows with hepatic lipidosis and ketosis have low tissue responsiveness to insulin owing to ketoacidosis. Insulin has numerous roles in metabolism of carbohydrates, lipids and proteins. Insulin is an anabolic hormone and acts to preserve nutrients as well as being a potent feed intake regulator. In addition to the major replacement therapy to alleviate severity of negative energy balance, administration of insulin with concomitant delivery of dextrose increases efficiency of treatment for hepatic lipidosis and ketosis. However, data on use of insulin to prevent these lipid-related metabolic disorders are limited and it should be investigated.

Risk factors for subclinical and clinical ketosis and association with production parameters in dairy cows in the Netherlands.

PubMed

Vanholder, T; Papen, J; Bemers, R; Vertenten, G; Berge, A C B

2015-02-01

Ketosis is associated with many transition cow diseases and the subclinical form has been found to be a common condition in high-producing dairy cows. The objectives of this field study in the Netherlands were (1) to determine risk factors for subclinical ketosis [SCK; 1.2-2.9mmol of β-hydroxybutyrate (BHBA)/L of serum] and clinical ketosis (CK: ≥3.0mmol of BHBA/L of serum) at 7 to 14 d in milk and (2) to assess the association of SCK and CK with production parameters at the first dairy herd improvement (DHI) testing. Twenty-three dairies were enrolled by a local veterinary practice from 2009 to 2010, and 1,715 cows were screened for ketosis by measuring serum BHBA concentrations at 7 to 14 d in milk. Overall, 47.2% of cows had SCK and 11.6% had CK. Mixed generalized logit models with a random effect of herd were used to evaluate cow level factors associated with SCK and CK. The associations of SCK and CK with milk production parameters were tested using mixed linear models with a random effect of herd. Cows at a moderate (3.25-3.75) or fat (≥4) body condition score before calving were more likely to develop SCK and CK than thin (body condition score≤3.0) cows. The risk for developing SCK was higher in parity 2 and older cows compared with heifers, whereas for CK only, parity ≥3 cows had a higher risk. The quarter of the year in which a cow calved was associated with the risk for SCK and CK. For SCK quarter 1 (January-March) and quarter 2 (April-June), and for CK quarter 1, quarter 2, and quarter 3 (July-September) all increased the risk of development of the condition compared with quarter 4 (October-December). An increased yield of colostrum at first milking was associated with increasing risk for SCK and CK. Prolonged previous lactation length and dry period length were both associated with increased odds for SCK and CK. Subclinical ketosis and CK were associated with a higher milk yield, a higher milk fat percentage, and a lower milk protein percentage

Correlation between composition of the bacterial community and concentration of volatile fatty acids in the rumen during the transition period and ketosis in dairy cows.

PubMed

Wang, Xiaoxu; Li, Xiaobing; Zhao, Chenxu; Hu, Pan; Chen, Hui; Liu, Zhaoxi; Liu, Guowen; Wang, Zhe

2012-04-01

The transition period is a severe challenge to dairy cows. Glucose supply cannot meet demand and body fat is mobilized, potentially leading to negative energy balance (NEB), ketosis, or fatty liver. Propionate produces glucose by gluconeogenesis, which depends heavily on the number and species of microbes. In the present study, we analyzed the rumen microbiome composition of cows in the transition period, cows with ketosis, and nonperinatal cows by terminal restriction fragment length polymorphism (TRFLP) analysis of 16S rRNA genes and quantitative PCR. TRFLP analysis indicated that the quantity of Veillonellaceae organisms was reduced and that of Streptococcaceae organisms was increased in rumen samples from the transition period and ketosis groups, with the number of Lactobacillaceae organisms increased after calving. Quantitative PCR data suggested that the numbers of the main propionate-producing microbes, Megasphaera elsdenii and Selenomonas ruminantium, were decreased, while numbers of the main lactate-producing bacterium, Streptococcus bovis, were increased in the rumen of cows from the transition period and ketosis groups, with the number of Lactobacillus sp. organisms increased after calving. Volatile fatty acid (VFA) and glucose concentrations were decreased, but the lactic acid concentration was increased, in rumen samples from the transition period and ketosis groups. Our results indicate that the VFA concentration is significantly related to the numbers of Selenomonas ruminantium and Megasphaera elsdenii organisms in the rumen.

Correlation between Composition of the Bacterial Community and Concentration of Volatile Fatty Acids in the Rumen during the Transition Period and Ketosis in Dairy Cows

PubMed Central

Wang, Xiaoxu; Li, Xiaobing; Zhao, Chenxu; Hu, Pan; Chen, Hui; Liu, Zhaoxi

2012-01-01

The transition period is a severe challenge to dairy cows. Glucose supply cannot meet demand and body fat is mobilized, potentially leading to negative energy balance (NEB), ketosis, or fatty liver. Propionate produces glucose by gluconeogenesis, which depends heavily on the number and species of microbes. In the present study, we analyzed the rumen microbiome composition of cows in the transition period, cows with ketosis, and nonperinatal cows by terminal restriction fragment length polymorphism (TRFLP) analysis of 16S rRNA genes and quantitative PCR. TRFLP analysis indicated that the quantity of Veillonellaceae organisms was reduced and that of Streptococcaceae organisms was increased in rumen samples from the transition period and ketosis groups, with the number of Lactobacillaceae organisms increased after calving. Quantitative PCR data suggested that the numbers of the main propionate-producing microbes, Megasphaera elsdenii and Selenomonas ruminantium, were decreased, while numbers of the main lactate-producing bacterium, Streptococcus bovis, were increased in the rumen of cows from the transition period and ketosis groups, with the number of Lactobacillus sp. organisms increased after calving. Volatile fatty acid (VFA) and glucose concentrations were decreased, but the lactic acid concentration was increased, in rumen samples from the transition period and ketosis groups. Our results indicate that the VFA concentration is significantly related to the numbers of Selenomonas ruminantium and Megasphaera elsdenii organisms in the rumen. PMID:22267666

Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.

PubMed

Cartwright, Martina M; Hajja, Waddah; Al-Khatib, Sofian; Hazeghazam, Maryam; Sreedhar, Dharmashree; Li, Rebecca Na; Wong-McKinstry, Edna; Carlson, Richard W

2012-10-01

Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute nutritional ketosis: implications for exercise performance and metabolism

PubMed Central

2014-01-01

Ketone bodies acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB) may provide an alternative carbon source to fuel exercise when delivered acutely in nutritional form. The metabolic actions of ketone bodies are based on sound evolutionary principles to prolong survival during caloric deprivation. By harnessing the potential of these metabolic actions during exercise, athletic performance could be influenced, providing a useful model for the application of ketosis in therapeutic conditions. This article examines the energetic implications of ketone body utilisation with particular reference to exercise metabolism and substrate energetics. PMID:25379174

Association between Serum Albumin Concentration and Ketosis Risk in Hospitalized Individuals with Type 2 Diabetes Mellitus.

PubMed

Cheng, Po-Chung; Hsu, Shang-Ren; Cheng, Yun-Chung

2016-01-01

Objective. This study examined the association between serum albumin concentration and ketosis risk in hospitalized individuals with type 2 diabetes mellitus (T2DM). Methods. A retrospective cross-sectional study was conducted at a medical center in Taiwan. Inclusion criteria were endocrinology ward inpatients exceeding 21 years of age, with preexisting diagnosis of T2DM, and blood glucose above 13.9 millimoles per liter (mmol/L) at admission. Individuals without measurement of serum albumin, urine ketone, or hemoglobin A1C, or harboring active infection, myocardial infarction, cerebrovascular event, cirrhosis, malignancy, or overt proteinuria were excluded. Using serum albumin concentration below 3.0 grams per deciliter to define hypoalbuminemia, 151 hypoalbuminemic cases and 104 normoalbuminemic controls were enrolled. The presence of ketones in urine established ketosis. Results. The prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in normoalbuminemic controls (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.26-3.57; P = 0.004). Moreover, among the 156 subjects with serum beta-hydroxybutyrate measurement in addition to urine ketone, 33% of the hypoalbuminemic individuals had ketonemia exceeding 3 mmol/L compared to 19% of those with normoalbuminemia (OR: 2.12, 95% CI: 0.99-4.48, P = 0.051). Conclusions. Serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with T2DM.

Association between Serum Albumin Concentration and Ketosis Risk in Hospitalized Individuals with Type 2 Diabetes Mellitus

PubMed Central

2016-01-01

Objective. This study examined the association between serum albumin concentration and ketosis risk in hospitalized individuals with type 2 diabetes mellitus (T2DM). Methods. A retrospective cross-sectional study was conducted at a medical center in Taiwan. Inclusion criteria were endocrinology ward inpatients exceeding 21 years of age, with preexisting diagnosis of T2DM, and blood glucose above 13.9 millimoles per liter (mmol/L) at admission. Individuals without measurement of serum albumin, urine ketone, or hemoglobin A1C, or harboring active infection, myocardial infarction, cerebrovascular event, cirrhosis, malignancy, or overt proteinuria were excluded. Using serum albumin concentration below 3.0 grams per deciliter to define hypoalbuminemia, 151 hypoalbuminemic cases and 104 normoalbuminemic controls were enrolled. The presence of ketones in urine established ketosis. Results. The prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in normoalbuminemic controls (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.26–3.57; P = 0.004). Moreover, among the 156 subjects with serum beta-hydroxybutyrate measurement in addition to urine ketone, 33% of the hypoalbuminemic individuals had ketonemia exceeding 3 mmol/L compared to 19% of those with normoalbuminemia (OR: 2.12, 95% CI: 0.99–4.48, P = 0.051). Conclusions. Serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with T2DM. PMID:27504458

Genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins.

PubMed

Koeck, A; Miglior, F; Jamrozik, J; Kelton, D F; Schenkel, F S

2013-07-01

The aim of this study was to investigate the genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins. Health data recorded by producers were available from the national dairy cattle health system in Canada. Test-day records of milk, fat, and protein yields were obtained from the routine milk recoding scheme. Ketosis and displaced abomasum were defined as binary traits (0 = healthy; 1 = sick) based on whether or not the cow had at least 1 case of the respective disease in the period from calving to 100 d after calving. Mean frequencies of ketosis and displaced abomasum were 4.1 and 2.7%, respectively. The following milk production traits were considered: milk yield, fat percentage (Fat%), protein percentage (Prot%), fat-to-protein (F:P) ratio, and F:P ratio >1.5. The trait F:P ratio >1.5 was scored as 1 or 0, based on whether or not the cow had an F:P ratio >1.5. For milk production traits, the first (5-30 d in milk) and the second (31-60 d in milk) test days were considered. Data were analyzed using bivariate linear animal models. Average heritabilities of 0.02 and 0.04 were obtained for ketosis and displaced abomasum, respectively. For milk production traits, the lowest heritabilities were obtained for F:P >1.5 (0.04 to 0.08), whereas the highest estimates were found for Prot% (0.27 to 0.38). Ketosis and displaced abomasum were genetically uncorrelated with milk yield in early lactation. Moderate favorable correlations were found between metabolic diseases and milk composition traits. Ketosis was significantly correlated with Fat% (0.33), F:P ratio (0.30), and F:P ratio >1.5 (0.35) at the first test day, whereas all genetic correlations with milk composition traits at the second test day were not significant and close to zero. Significant favorable genetic correlations were also found between displaced abomasum and F:P ratio (0.26), F:P ratio >1.5 (0.25) and Prot% (-0.19) at the first test

Effects of β-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis.

PubMed

van der Drift, S G A; Everts, R R; Houweling, M; van Leengoed, L A M G; Stegeman, J A; Tielens, A G M; Jorritsma, R

2013-06-01

An in vitro model was used to investigate effects of β-hydroxybutyrate and isoproterenol (β-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n=5) and cows with clinical ketosis (n=3). Incubation with 3.0 mmol/L β-hydroxybutyrate reduced lipolysis in isolated adipocytes. This inhibitory effect was lower in the first lactation week (47%±16%) compared with late pregnancy (71%±6.5%). Incubation with 0.3 μmol/L isoproterenol stimulated lipolysis in isolated adipocytes from periparturient dairy cows. Basal lipolysis resulted in non-esterified fatty acid to glycerol ratios in the incubation media of 2.0±0.23 in prepartum samples, 2.1±0.23 in the first lactation week and 2.2±0.09 in cows with clinical ketosis. β-Hydroxybutyrate reduced lipolysis by 45%±9.6% in isolated adipocytes from cows with clinical ketosis, indicating that impaired feedback of β-hydroxybutyrate may not play a role in the disease etiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Changes of serum 3-methylhistidine concentration and energy-associated metabolites in dairy cows with ketosis.

PubMed

Akamatsu, Hirohisa; Saitoh, Yoshihide; Serizawa, Masahumi; Miyake, Koji; Ohba, Yoshikazu; Nakashima, Kazuki

2007-10-01

The present study examined the Serum 3-methylhistidine concentrations and energy-associated variables of 5 healthy Holstein cows and 5 Holstein cows with ketosis. The serum total cholesterol and apolipoprotein B-100 concentrations and lecithin-cholesterol acyltransferase (LCAT) activity of the ketotic cows were lower than those of the healthy cows 14 days before parturition. The serum non-esterified fatty acid (NEFA) concentration on the day of parturition and 3-methylhistidine concentration 14 days after parturition were higher in the ketotic cows. The serum 3-methylhistidine concentration 14 days after parturition was negatively correlated with the serum LCAT activity 14 days before parturition and was positively correlated with the serum NEFA concentration on the day of parturition. Insufficiency of cholesterol metabolism and acceleration of body fat degradation occur before parturition in cows with ketosis, and these characteristics are correlated with acceleration of protein degradation after parturition.

Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows.

PubMed

Abuajamieh, Mohannad; Kvidera, Sara K; Fernandez, Maria V Sanz; Nayeri, Amir; Upah, Nathan C; Nolan, Erin A; Lei, Sam M; DeFrain, Jeffery M; Green, Howard B; Schoenberg, Katie M; Trout, William E; Baumgard, Lance H

2016-12-01

Ketosis is a prevalent periparturient metabolic disorder and we hypothesize that lipopolysaccharide (LPS) infiltration may play a key role in its etiology. Study objectives were to characterize biomarkers of inflammation during the transition period in healthy and clinically diagnosed ketotic cows. Cows were retrospectively categorized into one of two groups: healthy and clinically diagnosed ketotic. Two data sets were utilized; the first dataset (Study A) was obtained as a subset of cows (n=16) enrolled in a larger experiment conducted at the Iowa State University Dairy utilizing Holstein cows (8 healthy; 8 ketotic), and the second dataset (Study B; 22 healthy; 22 ketotic) was obtained from a commercial farm. For both experiments, blood samples were collected prior to and following calving. Ketotic cows in both studies had reduced milk production compared to healthy cows (P<0.01). Post-calving, ketotic cows had increased serum amyloid A (4.2 and 1.8 fold in studies A and B, respectively; P=0.03 and P=0.04), haptoglobin (>6 fold and ~4 fold; P=0.04 and P=0.03), and lipopolysaccharide binding protein (66 and 45%; P<0.01 and P=0.02) compared with their healthy counterparts. Antepartum circulating LPS in ketotic cows was increased (2.3 fold; P=0.01) compared to healthy cows in Study B. In summary, increased biomarkers of inflammation appear to be closely associated with ketosis in transition dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis

PubMed Central

Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Rehage, Jürgen; Piechotta, Marion; Meyerholz, Maria; Breves, Gerhard; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis.

PubMed

Schulz, Kirsten; Frahm, Jana; Kersten, Susanne; Meyer, Ulrich; Rehage, Jürgen; Piechotta, Marion; Meyerholz, Maria; Breves, Gerhard; Reiche, Dania; Sauerwein, Helga; Dänicke, Sven

2015-01-01

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like

Effect of two treatment protocols for ketosis on the resolution, postpartum health, milk yield, and reproductive outcomes of dairy cows.

PubMed

Jeong, Jae-Kwan; Choi, In-Soo; Moon, Sung-Ho; Lee, Soo-Chan; Kang, Hyun-Gu; Jung, Young-Hun; Park, Soo-Bong; Kim, Ill-Hwa

2018-01-15

We determined the effect of ketosis treatment with propylene glycol (PG) or PG plus l-carnitine and methionine (Metabolase ® , Fatro, Bologna, Italy) on the resolution, postpartum health, milk yield, and reproductive performances of dairy cows. Blood from 475 Holstein cows was collected weekly until 4 weeks after calving to measure blood β-hydroxybutyrate (BHBA) concentrations. Cows with blood BHBA concentration ≥1.2 mmol/L were diagnosed with ketosis and were enrolled. One hundred and fifty cows diagnosed with ketosis were randomly assigned to three treatment groups (Day 0): (1) PG (300 g, PO) for 3 days (PG group, n = 50), (2) PG (300 g, PO) plus l-carnitine (1.25 g) plus methionine (5 g, IV) for 3 days (PG + CM group, n = 50), and (3) no treatment (control group, n = 50). On Day 3, blood was collected to evaluate whether the ketosis had resolved. Cows in the PG and PG + CM groups with blood BHBA ≥1.2 mmol/L were retreated for an additional 2 days, and then blood BHBA concentration was evaluated on Days 5 and 10. Blood glucose and haptoglobin concentrations, rumen fill score (RFS), and body condition score (BCS) were measured on Days 0, 3, 5, and 10. Postpartum complications, milk yield during the first 2 months, and reproductive outcomes were evaluated. The probability of resolution from ketosis was higher (P < 0.05) in the PG + CM group than in the control group on Days 3, 5, and 10 (odds ratio: 2.6-6.3). Blood BHBA in the PG + CM group was lower (P < 0.05) than that of the control group on Days 3 and 5, whereas blood glucose in the PG + CM group was higher (P < 0.05) than that of the control group on Days 3 and 5. RFS in the PG and PG + CM groups was higher than that of the control group on Day 10 (P < 0.01), while BCS loss from Day 0-10 in the control group was higher than those of the PG and PG + CM groups (P < 0.05). Milk yields on the 30th and 60th days postpartum were higher in the PG + CM group than the control

Economic value of ionophores and propylene glycol to prevent disease and treat ketosis in Canada.

PubMed

Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

A partial budget model was developed to evaluate the economic value of Rumensin Controlled Release Capsule (CRC) boluses when administered before calving to reduce disease and increase milk production. After accounting for disease incidences in a herd and the percentage by which Rumensin CRC can reduce them, and the increase in milk production attributable to administration of Rumensin CRC, the return on investment (ROI) per lactation was 4:1. Another partial budget model was developed to estimate the economic value of propylene glycol (PG) to treat ketosis when diagnosed by 3 different cow-side tests or when administered to all cows without using any cow-side testing. After accounting for the sensitivity and specificity of each test, ROI per lactation ranged from 2:1 to 4:1. The ROI was 2:1 when no cow-side testing was used. In conclusion, prevention of diseases that occur in the postpartum period and treatment of ketosis after calving yielded a positive ROI that varies based on disease incidence and method of diagnosis.

Economic value of ionophores and propylene glycol to prevent disease and treat ketosis in Canada

PubMed Central

Gohary, Khaled; Overton, Michael W.; Von Massow, Michael; LeBlanc, Stephen J.; Lissemore, Kerry D.; Duffield, Todd F.

2016-01-01

A partial budget model was developed to evaluate the economic value of Rumensin Controlled Release Capsule (CRC) boluses when administered before calving to reduce disease and increase milk production. After accounting for disease incidences in a herd and the percentage by which Rumensin CRC can reduce them, and the increase in milk production attributable to administration of Rumensin CRC, the return on investment (ROI) per lactation was 4:1. Another partial budget model was developed to estimate the economic value of propylene glycol (PG) to treat ketosis when diagnosed by 3 different cow-side tests or when administered to all cows without using any cow-side testing. After accounting for the sensitivity and specificity of each test, ROI per lactation ranged from 2:1 to 4:1. The ROI was 2:1 when no cow-side testing was used. In conclusion, prevention of diseases that occur in the postpartum period and treatment of ketosis after calving yielded a positive ROI that varies based on disease incidence and method of diagnosis. PMID:27429461

Ketosis, ketogenic diet and food intake control: a complex relationship.

PubMed

Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M; Mangar, Devanand

2015-01-01

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

Ketosis, ketogenic diet and food intake control: a complex relationship

PubMed Central

Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

2015-01-01

Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis

PubMed Central

Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Duma, Danielle; Mason, Ronald P.; Kadiiska, Maria B.

2008-01-01

Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the α-(4-pyridyl-1-oxide)-N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression. PMID:18559982

Blood parameters in Swedish dairy herds with high or low incidence of displaced abomasum or ketosis.

PubMed

Stengärde, Lena; Holtenius, Kjell; Emanuelson, Ulf; Hultgren, Jan; Niskanen, Rauni; Tråvén, Madeleine

2011-10-01

Sixty dairy herds were studied to investigate the association between long-term incidence of displaced abomasum and clinical ketosis and body condition score and blood profiles, including parameters estimating energy metabolism and hepatic lipidosis in the periparturient period and early lactation. Blood samples were taken around parturition and in early lactation from cows without apparent clinical symptoms of metabolic disorders. A difference in metabolism between high and low incidence herds was shown post-partum by a lower metabolic index (the revised Quantitative Insulin Sensitivity Check Index, RQUICKI), and tendencies for higher concentrations of glucose, insulin and non-esterified fatty acids in the high incidence herds. High incidence herds had more cows and produced on average 1400kg energy-corrected milk per cow per year more than the low incidence herds. No differences were found in parameters reflecting liver cell damage. In the first 3weeks post-partum the RQUICKI was a more sensitive marker of herds with a high incidence of displaced abomasum and clinical ketosis than any of the individual parameters, but further research is needed before practical applications of the RQUICKI can be foreseen. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

PubMed

van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

2015-05-01

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized clinical field trial on the effects of butaphosphan-cyanocobalamin and propylene glycol on ketosis resolution and milk production.

PubMed

Gordon, J L; LeBlanc, S J; Kelton, D F; Herdt, T H; Neuder, L; Duffield, T F

2017-05-01

The purpose of this study was to determine the effects of a butaphosphan-cyanocobalamin combination product (B+C) and 2 durations of propylene glycol treatment (PG; 3 versus 5 d) on ketosis resolution and early lactation milk yield. Cows from 9 freestall herds (8 in Ontario and 1 in Michigan) were tested at weekly intervals between 3 and 16 d in milk. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. Ketotic cows were randomly assigned to treatment with 25 mL of B+C or 25 mL of saline placebo for 3 d and 3 or 5 d of 300 g of PG orally in a 2 × 2 factorial arrangement. Outcomes evaluated for all farms included ketosis cure (blood BHB <1.2 mmol/L at 1 wk after enrollment), maintenance of ketosis cure (blood BHB <1.2 mmol/L 1 and 2 wk after enrollment), and blood BHB concentrations at 1 and 2 wk after enrollment. Daily milk weights were collected in 3 herds. Poisson regression was used to evaluate cure and maintenance of cure, whereas repeated-measures ANOVA was used to evaluate blood BHB concentrations in the 2 wk after enrollment and average daily milk production in the 30 d after treatment. A total of 594 animals were enrolled in the study with 124 treated with B+C and 5 d of PG, 176 treated with B+C and 3 d of PG, 128 treated with saline and 5 d of PG, and 166 treated with saline and 3 d of PG. Animals with blood BHB >2.4 mmol/L at the time of enrollment were 1.7 times more likely [95% confidence interval (CI): 1.4 to 2.2] to cure and had a decrease of 0.25 ± 0.11 mmol/L blood BHB at 1 wk after enrollment if treated with 5 d of PG compared with 3 d, though this response was not seen in animals with BHB of 1.2 to 2.4 mmol/L at enrollment. Cows with blood glucose concentrations <2.2 mmol/L at enrollment produced 3.1 kg/d (95% CI: 1.3 to 5.0) more milk if treated with B+C and 3.4 kg/d (95% CI: 1.7 to 5.1) more milk if treated with 5 d of PG compared with their respective controls. This response was not seen in animals with blood glucose ≥2

Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

PubMed

Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O'Donnell, Martha

2012-07-01

Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.

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.

PubMed

Schulz, Kirsten; Frahm, Jana; Meyer, Ulrich; Kersten, Susanne; Reiche, Dania; Rehage, Jürgen; Dänicke, Sven

2014-08-01

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 β-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

Risk factors for clinical ketosis and association with milk production and reproduction variables in dairy cows in a hot environment.

PubMed

Mellado, M; Dávila, A; Gaytán, L; Macías-Cruz, U; Avendaño-Reyes, L; García, E

2018-05-02

The aims of the present study were to investigate (1) the risk factors that influence the occurrence of clinical ketosis (CK; blood β-hydroxybutyrate > 3.0 mmol/L) and (2) to determine the influence of subclinical ketosis (SCK; 1.2 ≤ β-hydroxybutyrate ≤ 2.9 mmol/L) and CK on reproductive performance and milk yield in high-yielding Holstein cows in a hot environment. Cows (n = 345) were blood sampled from 6 to 15 days postpartum for β-hydroxybutyrate (BHB) determination with a hand-held meter. Cows calving in spring had 3.7 increased odds of having CK (20.7% incidence) than cows calving in summer (3.9% incidence) and autumn (9.4% incidence). Temperature-humidity index < 83 was associated with 1.6 times higher risk for CK compared with cows calving in warmer days. First-service conception rate was 12 and 16 percentage point higher (P < 0.05) in nonketotic cows compared with cows with SCK and CK, respectively. Actual 305-day milk yields for healthy, SCK, and CK cows were 9991 ± 1411, 10,123 ± 1442, and 10,386 ± 1435 kg (mean ± SD), respectively, with no difference (P > 0.05) between groups. In conclusion, this study documented that ketosis was seasonal with lower incidence of this metabolic disease during hot seasons and with increased ambient temperature at calving. Also, 305-day milk yield of Holstein cows was not related to blood BHB content early in lactation in this hot environment. However, elevated circulating BHB was negatively associated with conception rate at first service and fetal losses.

Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

PubMed

Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

2018-01-01

In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

Subclinical Ketosis on Dairy Cows in Transition Period in Farms with Contrasting Butyric Acid Contents in Silages

PubMed Central

Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

2014-01-01

This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r 2 = 0.56; P < 0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake). PMID:25525616

Subclinical ketosis on dairy cows in transition period in farms with contrasting butyric acid contents in silages.

PubMed

Vicente, Fernando; Rodríguez, María Luisa; Martínez-Fernández, Adela; Soldado, Ana; Argamentería, Alejandro; Peláez, Mario; de la Roza-Delgado, Begoña

2014-01-01

This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review.

PubMed

Harvey, Cliff J D C; Schofield, Grant M; Williden, Micalla

2018-01-01

Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms "ketogenic diet", "ketogenic", "ketosis" and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Evidence, from one mouse study, suggests that leucine doesn't significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn't reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a ketogenic diet during the induction phase. Those that

Economic and Managerial Analysis of Effective Managerial Strategies on Prevention from Ketosis in Transition Period in Shahroud Commercial Dairy Farms

PubMed Central

Kashfi, H.; Yazdani, A. R.; Latifi, M.; Shirani Bidabadi, F.

2011-01-01

The purpose of this research is to study any effects of managerial strategies on prevention of ketosis metabolic disorder in transition period in Shahroud commercial dairy farms. For this purpose, a questionnaire was prepared in order to obtain required information about the performance of these managerial strategies, performance costs, involvement situation with disorders relying upon clinical signs and treatment and health records, producing and economic situation, and fertility rate and its costs. The considered managerial guidelines include body condition score management or type evaluation in transition period, increase in dry matter intake close to parturition, using propylene glycol, using niacin, and high-quality feeding (the importance of feed quality) in transition period. Finally and upon arrangement of data, it was possible to study any effects of mentioned managerial strategies on related variants through multiple linear regressions. Furthermore, in order to study any relation among variables, we considered Pearson correlation coefficients as well. Finally, it was revealed that any application of managerial strategies for prevention from Ketosis in transition period has a significant effect in betterment of managerial and economic parameters. PMID:23738102

The cost of a case of subclinical ketosis in Canadian dairy herds.

PubMed

Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation.

Risk factors for clinical mastitis, ketosis, and pneumonia in dairy cattle on organic and small conventional farms in the United States.

PubMed

Richert, R M; Cicconi, K M; Gamroth, M J; Schukken, Y H; Stiglbauer, K E; Ruegg, P L

2013-07-01

The US regulations for production of organic milk include a strict prohibition against the use of antimicrobials and other synthetic substances. The effect of these regulations on dairy animal health has not been previously reported. The objective of this study was to characterize disease detection and identify risk factors for selected diseases on organic (ORG) and similarly sized conventional (CON) farms. Dairy herds (n=292) were enrolled across 3 states (New York, Oregon, Wisconsin) with CON herds matched to ORG herds based on location and herd size. During a single herd visit, information was collected about herd management practices and animal disease occurring in the previous 60 d, and paperwork was left for recording disease occurrences during 60 d after the visit. For analysis, CON herds were further divided into grazing and nongrazing. Poisson regression models were used to assess risk factors for rate of farmer-identified and recorded cases of clinical mastitis, ketosis, and pneumonia. An increased rate of farmer-identified and recorded cases of clinical mastitis was associated with use of CON management, use of forestripping, presence of contagious pathogens in the bulk tank culture, proactive detection of mastitis in postpartum cows, and stall barn housing. An increased rate of farmer-identified and recorded cases of ketosis was associated with having a more sensitive definition of ketosis, using stall barn housing, and feeding a greater amount of concentrates. An increased rate of farmer-identified and recorded cases of pneumonia was associated with a lack of grazing, small or medium herd size, and Jersey as the predominant breed. Overall, disease definitions and perceptions were similar among grazing systems and were associated with the rate of farmer-identified and recorded cases of disease. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The cost of a case of subclinical ketosis in Canadian dairy herds

PubMed Central

Gohary, Khaled; Overton, Michael W.; Von Massow, Michael; LeBlanc, Stephen J.; Lissemore, Kerry D.; Duffield, Todd F.

2016-01-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation. PMID:27429460

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis.

PubMed

Du, Xiliang; Chen, Liang; Huang, Dan; Peng, Zhicheng; Zhao, Chenxu; Zhang, Yuming; Zhu, Yiwei; Wang, Zhe; Li, Xinwei; Liu, Guowen

2017-01-01

Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

PubMed

Jenkins, Nicholas T; Peña, Gustavo; Risco, Carlos; Barbosa, Carolina C; Vieira-Neto, Achilles; Galvão, Klibs N

2015-08-01

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows

PubMed Central

Jenkins, Nicholas T.; Peña, Gustavo; Risco, Carlos; Barbosa, Carolina C.; Vieira-Neto, Achilles; Galvão, Klibs N.

2015-01-01

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening. PMID:26246632

Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets.

PubMed

Prabhakar, Amlendu; Quach, Ashley; Zhang, Haojiong; Terrera, Mirna; Jackemeyer, David; Xian, Xiaojun; Tsow, Francis; Tao, Nongjian; Forzani, Erica S

2015-04-22

Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy. A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured. A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p < 0.0058. Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.

Epidemiology of subclinical ketosis in early lactation dairy cattle.

PubMed

McArt, J A A; Nydam, D V; Oetzel, G R

2012-09-01

The purpose of this study was to describe the epidemiology of subclinical ketosis (SCK) in dairy cows in early lactation and determine the association of (1) days in milk (DIM) at onset of SCK, and (2) blood β-hydroxybutyrate (BHBA) concentration at onset of SCK with development of displaced abomasum (DA) and removal from herd in the first 30 DIM, conception to first service, days to conception within 150 DIM, and early lactation milk yield. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a BHBA concentration of 1.2 to 2.9 mmol/L. Mixed-effects multivariable Poisson regression was used to assess DA, removal from herd, and conception to first service. Semiparametric proportional hazards models were used to evaluate days to conception, and repeated-measures ANOVA was used to evaluate milk yield in the first 30 DIM. A total of 741 of 1,717 (43.2%) eligible cows had a least one BHBA test of 1.2 to 2.9 mmol/L. Peak incidence of SCK occurred at 5 DIM, when 22.3% of cows had their first SCK-positive test. Peak prevalence of SCK occurred at 5 DIM, when 28.9% of cows had a SCK-positive test. Median time from first positive SCK test until BHBA test <1.2 mmol/L was 5d. Cows first testing SCK positive from 3 to 5 DIM were 6.1 times more likely [95% confidence interval (CI) = 2.3 to 16.0] to develop a DA than cows first testing SCK positive at 6 DIM or later. Cows first testing SCK positive from 3 to 7 DIM were 4.5 times more likely (95% CI = 1.7 to 11.7) to be removed from the herd, were 0.7 times as likely (95% CI = 0.6 to 0.8) to conceive to first service, and produced 2.2 kg less milk per day for the first 30 DIM than cows first testing positive at 8 DIM or later. Each 0.1 mmol/L increase in BHBA at first SCK-positive test increased the risk of developing a DA by a factor of 1.1 (95% CI = 1.0 to 1

Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia

PubMed Central

Meek, Thomas H.; Dorfman, Mauricio D.; Matsen, Miles E.; Fischer, Jonathan D.; Cubelo, Alexis; Kumar, Monica R.; Taborsky, Gerald J.

2015-01-01

Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia. PMID:25633417

Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows.

PubMed

Tetens, Jens; Heuer, Claas; Heyer, Iris; Klein, Matthias S; Gronwald, Wolfram; Junge, Wolfgang; Oefner, Peter J; Thaller, Georg; Krattenmacher, Nina

2015-04-01

Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant. Copyright © 2015 the American Physiological Society.

Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

PubMed Central

Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

2008-01-01

Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

PubMed

Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

2016-05-15

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

PubMed

Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

2002-02-01

This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P < 0.0001) and beta-hydroxybutyrate > 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein.

PubMed

Bielohuby, Maximilian; Menhofer, Dominik; Kirchner, Henriette; Stoehr, Barbara J M; Müller, Timo D; Stock, Peggy; Hempel, Madlen; Stemmer, Kerstin; Pfluger, Paul T; Kienzle, Ellen; Christ, Bruno; Tschöp, Matthias H; Bidlingmaier, Martin

2011-01-01

Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P < 0.001). In contrast, rats fed with LC-55/30 were not ketotic. Serum fibroblast growth factor-21, hepatic mRNA expression of hydroxymethylglutaryl-CoA-lyase, peroxisome proliferator-activated receptor-γ coactivator-1α, and peroxisome proliferator-activated receptor-γ coactivator-1β were increased with LC-75/10 only. Expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was downregulated by 50-70% in LC-HF groups. Furthermore, EE and LA were significantly decreased in all groups fed with LC-HFDs after 3 wk on the diets. In rats, the absence of dietary carbohydrates per se does not induce ketosis. LC-HFDs must be high in fat

Towards practical application of sensors for monitoring animal health; design and validation of a model to detect ketosis.

PubMed

Steensels, Machteld; Maltz, Ephraim; Bahr, Claudia; Berckmans, Daniel; Antler, Aharon; Halachmi, Ilan

2017-05-01

The objective of this study was to design and validate a mathematical model to detect post-calving ketosis. The validation was conducted in four commercial dairy farms in Israel, on a total of 706 multiparous Holstein dairy cows: 203 cows clinically diagnosed with ketosis and 503 healthy cows. A logistic binary regression model was developed, where the dependent variable is categorical (healthy/diseased) and a set of explanatory variables were measured with existing commercial sensors: rumination duration, activity and milk yield of each individual cow. In a first validation step (within-farm), the model was calibrated on the database of each farm separately. Two thirds of the sick cows and an equal number of healthy cows were randomly selected for model validation. The remaining one third of the cows, which did not participate in the model validation, were used for model calibration. In order to overcome the random selection effect, this procedure was repeated 100 times. In a second (between-farms) validation step, the model was calibrated on one farm and validated on another farm. Within-farm accuracy, ranging from 74 to 79%, was higher than between-farm accuracy, ranging from 49 to 72%, in all farms. The within-farm sensitivities ranged from 78 to 90%, and specificities ranged from 71 to 74%. The between-farms sensitivities ranged from 65 to 95%. The developed model can be improved in future research, by employing other variables that can be added; or by exploring other models to achieve greater sensitivity and specificity.

Prevalence of subclinical ketosis in mainly pasture-grazed dairy cows in New Zealand in early lactation.

PubMed

Compton, C W R; McDougall, S; Young, L; Bryan, M A

2014-01-01

The main aim of this study was to describe the prevalence of primary subclinical ketosis (SCK) in mainly pasture-grazed dairy cows in three dairy-farming regions of New Zealand 7-12, and 35-40 days post-calving. A second aim was to investigate herd- and cow-level factors associated with the prevalence of SCK. A cross-sectional longitudinal prevalence survey was undertaken in 1,620 dairy cows from 57 herds. A random sample of cows without disease in the prior 30 days were enrolled at one farm visit within 5 days of calving, and blood samples were collected 7 and 28 days later (7-12 and 35-40 days post-calving) for measurement of beta-hydroxy butyrate (BHBA) concentrations using an electronic cow-side meter. SCK was defined as blood BHBA concentration ≥1.4 mmol/L. Mean cow-level prevalence of SCK varied with interval post-calving (16.8 and 3.2% at 7-12 days and 35-40 days post-calving, respectively) and age (13.0 and 13.1% of 2-year olds and ≥8-year olds, respectively, compared to 7.2% of 3-4-year-old cows). Mean herd-level prevalence of SCK was 14.3 (min 0, max 60.0)% and 2.6 (min 0, max 24.4)% at 7-12 days and 35-40 days post-calving, respectively, and was greater in Southland (13.3%) than Waikato and Canterbury herds (6.9 and 4.7%, respectively). This is the first population-based report of the prevalence of SCK in New Zealand dairy herds and demonstrates that age and interval post-calving are important risk factors determining prevalence; and that there is wide variation in prevalence between herds. Subclinical ketosis may be unrecognised but common in many New Zealand dairy cows in the first 2 weeks of lactation.

Relationships among ketosis, serum metabolites, body condition, and reproductive outcomes in dairy cows.

PubMed

Shin, Eun-Kyung; Jeong, Jae-Kwan; Choi, In-Soo; Kang, Hyun-Gu; Hur, Tai-Young; Jung, Young-Hun; Kim, Ill-Hwa

2015-07-15

We determined the relationships among ketosis, serum metabolites, body condition, and reproductive disorders and performance in dairy cows. Blood samples from 213 dairy cows were collected at 4 and 2 weeks prepartum, just after calving, and at 1, 2, 4, 6, and 8 weeks postpartum to measure serum β-hydroxybutyrate, nonesterified fatty acids (NEFAs), glucose, total cholesterol, urea nitrogen, aspartate aminotransferase, γ-glutamyltransferase, and progesterone concentrations. Cows were grouped on the basis of the β-hydroxybutyrate concentration at 1 and/or 2 weeks postpartum into two groups: the ketotic group (≥1200 μmol/L, n = 59) and the nonketotic group (<1200 μmol/L, n = 154). The body condition score (BCS) was assessed simultaneously with blood collection. Clinical endometritis was diagnosed by observation of vaginal discharges (>50% pus), and subclinical endometritis was diagnosed by evaluation of uterine cytology (>18% neutrophils) at 4 weeks postpartum. Ovarian cysts were diagnosed by ultrasonography, and resumption of postpartum cyclicity was evaluated by progesterone concentrations (≥1 ng/mL) at 4, 6, and 8 weeks postpartum. In the ketotic group, NEFA levels were higher (P ≤ 0.0005), whereas glucose (P < 0.05-0.0005) and urea nitrogen levels (P < 0.05-0.01) were lower than those in the nonketotic group during the postpartum period. Aspartate aminotransferase levels were higher (P < 0.01) in the ketotic group than those in the nonketotic group at 2 weeks postpartum. The BCS of the ketotic group was higher than the nonketotic group during the prepartum (P < 0.001) and postpartum (P < 0.05-0.001) periods. The probabilities of clinical endometritis (odds ratio = 2.55) and ovarian cysts (odds ratio = 2.80) were higher (P < 0.05) in the ketotic group than those in the nonketotic group. The hazards of resumption of postpartum cyclicity by 8 weeks postpartum (hazard ratio = 0.67) and pregnancy by 360 days postpartum (hazard ratio = 0.68) were lower (P < 0

A Cause of Permanent Ketosis: GLUT-1 Deficiency.

PubMed

Chenouard, Alexis; Vuillaumier-Barrot, Sandrine; Seta, Nathalie; Kuster, Alice

2015-01-01

GLUT-1-deficiency syndrome (GLUT1-DS; OMIM 606777) is a treatable metabolic disorder caused by a mutation of SLC2A1 gene. The functional deficiency of the GLUT1 protein leads to an impaired glucose transport into the brain, resulting in neurologic disorders.We report on a 6-month-old boy with preprandial malaises who was treated monthly by a sorcerer because of a permanent acetonemic odor. He subsequently developed pharmaco-resistant seizures with microcephaly and motor abnormalities. Metabolic explorations were unremarkable except for a fasting glucose test which revealed an abnormal increase of blood ketone bodies. At the age of 35 months, GLUT1-DS was diagnosed based on hypoglycorrhachia with a decreased CSF to blood glucose ratio, and subsequent direct sequencing of the SLC2A1 gene revealed a de novo heterozygous mutation, c.349A>T (p.Lys117X) on exon 4. It was noteworthy that the patient adapted to the deficient cerebral glucose transport by permanent ketone body production since early life. Excessive ketone body production in this patient provided an alternative energy substrate for his brain. We suggest a cerebral metabolic adaptation with upregulation of monocarboxylic acid transporter proteins (MCT1) at the blood-brain barrier provoked by neuroglycopenia and allowing ketone body utilization by the brain. This case illustrates that GLUT1-DS should be considered in the differential diagnosis of permanent ketosis.

Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

PubMed

Tani, Naoto; Michiue, Tomomi; Chen, Jian-Hua; Oritani, Shigeki; Ishikawa, Takaki

2016-09-01

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

PubMed

Buckingham, Bruce A; Raghinaru, Dan; Cameron, Fraser; Bequette, B Wayne; Chase, H Peter; Maahs, David M; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Ly, Trang; Aye, Tandy; Hramiak, Irene; Clarson, Cheril; Stein, Robert; Gallego, Patricia H; Lum, John; Sibayan, Judy; Kollman, Craig; Beck, Roy W

2015-07-01

Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia.

PubMed

Meek, Thomas H; Dorfman, Mauricio D; Matsen, Miles E; Fischer, Jonathan D; Cubelo, Alexis; Kumar, Monica R; Taborsky, Gerald J; Morton, Gregory J

2015-07-01

Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The Role of TCA Cycle Anaplerosis in Ketosis and Fatty Liver in Periparturient Dairy Cows

PubMed Central

White, Heather M.

2015-01-01

The transition to lactation period in dairy cattle is characterized by metabolic challenges, negative energy balance, and adipose tissue mobilization. Metabolism of mobilized adipose tissue is part of the adaptive response to negative energy balance in dairy cattle; however, the capacity of the liver to completely oxidize nonesterified fatty acids may be limited and is reflective of oxaloacetate pool, the carbon carrier of the tricarboxylic acid cycle. Alternative metabolic fates of acetyl-CoA from nonesterified fatty acids include esterification to triacylglycerides and ketogenesis, and when excessive, these pathways lead to fatty liver and ketosis. Examination of the anaplerotic and cataplerotic pull of oxaloacetate by the tricarboxylic acid cycle and gluconeogenesis may provide insight into the balance of oxidation and esterification of acetyl-CoA within the liver of periparturient dairy cows. PMID:26479386

The Role of TCA Cycle Anaplerosis in Ketosis and Fatty Liver in Periparturient Dairy Cows.

PubMed

White, Heather M

2015-08-18

The transition to lactation period in dairy cattle is characterized by metabolic challenges, negative energy balance, and adipose tissue mobilization. Metabolism of mobilized adipose tissue is part of the adaptive response to negative energy balance in dairy cattle; however, the capacity of the liver to completely oxidize nonesterified fatty acids may be limited and is reflective of oxaloacetate pool, the carbon carrier of the tricarboxylic acid cycle. Alternative metabolic fates of acetyl-CoA from nonesterified fatty acids include esterification to triacylglycerides and ketogenesis, and when excessive, these pathways lead to fatty liver and ketosis. Examination of the anaplerotic and cataplerotic pull of oxaloacetate by the tricarboxylic acid cycle and gluconeogenesis may provide insight into the balance of oxidation and esterification of acetyl-CoA within the liver of periparturient dairy cows.

Evaluation of a point-of-care electrochemical meter to detect subclinical ketosis and hypoglycaemia in lactating dairy cows.

PubMed

Zakian, A; Tehrani-Sharif, M; Mokhber-Dezfouli, M R; Nouri, M; Constable, P D

2017-04-01

To evaluate and validate a hand-held electrochemical meter (Precision Xtra®) as a screening test for subclinical ketosis and hypoglycaemia in lactating dairy cattle. Method comparison study using a convenience sample. Blood samples were collected into plain tubes from the coccygeal vessels of 181 Holstein cows at 2-4 weeks of lactation during summer in Iran. Blood β-hydroxybutyrate concentration (BHB) and glucose concentration were immediately measured by the electrochemical meter after applying 20 μL of blood to the reagent strip. Passing-Bablok regression and Bland-Altman plots were used to determine the accuracy of the meter against laboratory reference methods (BHB dehydrogenase and glucose oxidase). Serum BHB ranged from 0.1 to 7.3 mmol/L and serum glucose ranged from 0.9 to 5.1 mmol/L. Passing-Bablok regression analysis indicated that the electrochemical meter and reference methods were linearly related for BHB and glucose, with a slope estimate that was not significantly different from 1.00. Clinically minor, but statistically significant, differences were present for the intercept value for Passing-Bablok regression analysis for BHB and glucose, and bias estimates in the Bland-Altman plots for BHB and glucose. The electrochemical meter provided a clinically useful method to detect subclinical ketosis and hypoglycaemia in lactating dairy cows. Compared with other method validation studies using the meter, we attributed the improved performance of the electrochemical meter to application of a fixed volume of blood (20 μL) to the reagent strip, use of the meter in hot ambient conditions and use of glucose oxidase as the reference method for glucose analysis. © 2017 Australian Veterinary Association.

FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

PubMed

Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J

2015-10-01

Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

Estimating the economic impact of subclinical ketosis in dairy cattle using a dynamic stochastic simulation model.

PubMed

Mostert, P F; Bokkers, E A M; van Middelaar, C E; Hogeveen, H; de Boer, I J M

2018-01-01

The objective of this study was to estimate the economic impact of subclinical ketosis (SCK) in dairy cows. This metabolic disorder occurs in the period around calving and is associated with an increased risk of other diseases. Therefore, SCK affects farm productivity and profitability. Estimating the economic impact of SCK may make farmers more aware of this problem, and can improve their decision-making regarding interventions to reduce SCK. We developed a dynamic stochastic simulation model that enables estimating the economic impact of SCK and related diseases (i.e. mastitis, metritis, displaced abomasum, lameness and clinical ketosis) occurring during the first 30 days after calving. This model, which was applied to a typical Dutch dairy herd, groups cows according to their parity (1 to 5+), and simulates the dynamics of SCK and related diseases, and milk production per cow during one lactation. The economic impact of SCK and related diseases resulted from a reduced milk production, discarded milk, treatment costs, costs from a prolonged calving interval and removal (culling or dying) of cows. The total costs of SCK were €130 per case per year, with a range between €39 and €348 (5 to 95 percentiles). The total costs of SCK per case per year, moreover, increased from €83 per year in parity 1 to €175 in parity 3. Most cows with SCK, however, had SCK only (61%), and costs were €58 per case per year. Total costs of SCK per case per year resulted for 36% from a prolonged calving interval, 24% from reduced milk production, 19% from treatment, 14% from discarded milk and 6% from removal. Results of the sensitivity analysis showed that the disease incidence, removal risk, relations of SCK with other diseases and prices of milk resulted in a high variation of costs of SCK. The costs of SCK, therefore, might differ per farm because of farm-specific circumstances. Improving data collection on the incidence of SCK and related diseases, and on consequences of

Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients.

PubMed

Balti, Eric V; Ngo-Nemb, Marinette C; Lontchi-Yimagou, Eric; Atogho-Tiedeu, Barbara; Effoe, Valery S; Akwo, Elvis A; Dehayem, Mesmin Y; Mbanya, Jean-Claude; Gautier, Jean-François; Sobngwi, Eugene

2015-01-01

We investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A(-) KPD) in comparison to type 2 diabetes (T2D). A(-) KPD and T2D sub-Saharan African patients aged 19-63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. Among the 130 participants, 35 (27%) were women and 57 (44%) were A(-) KPD. DRB1 and DQB1 allele frequencies were similar for both A(-) KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A(-) KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17-1.85], P=0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79-7.42], P=0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39-1.95], P=0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55-3.96], P=0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P>0.05) in A(-) KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. Factors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A(-) KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A(-) KPD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in dairy cows by using 3 different electronic hand-held devices.

PubMed

Kanz, P; Drillich, M; Klein-Jöbstl, D; Mair, B; Borchardt, S; Meyer, L; Schwendenwein, I; Iwersen, M

2015-09-01

The objective of this study was to evaluate the suitability of capillary blood obtained by a minimally invasive lancet technique to detect subclinical ketosis in 49 prepartum and 191 postpartum Holstein-Friesian cows using 3 different electronic hand-held devices [FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini), NovaVet (NOV, Nova Biomedical)]. The β-hydroxybutyrate (BHBA) concentration in serum harvested from coccygeal blood samples was analyzed in a laboratory and used as a reference value. Capillary samples were obtained from the skin of the exterior vulva by using 1 of 3 different lancets. In all samples, the concentration of BHBA was immediately analyzed with all 3 hand-held devices used in random order. All lancets used in the study were eligible for capillary blood collection but differed in the total number of incisions needed. Spearman correlation coefficients between the BHBA concentrations in capillary blood and the reference test were highly significant with 83% for the FSP, 73% for the NOV, and 63% for the GLX. Using capillary blood, the FSP overestimated the mean BHBA concentration compared with the reference test (+0.08 mmol/L), whereas the GLX and NOV underestimated the mean concentration (-0.07 and -0.01 mmol/L). When a BHBA concentration of 1.2 mmol/L in serum was used to define subclinical ketosis, the corresponding analyses of receiver operating characteristics resulted in optimized thresholds for capillary blood of 1.1 mmol/L for the NOV and GLX devices, and of 1.0 mmol/L for the FSP. Based on these thresholds, sensitivities (Se) and specificities (Sp) were 89 and 84% for the NOV, 80 and 89% for the GLX, and 100 and 76% for the FSP. Based on a serum BHBA concentration of 1.4 mmol/L, analyses of receiver operating characteristics resulted in optimized cut-offs of 1.4 mmol/L for the FSP (Se 100%, Sp 92%), 1.3 mmol/L for the NOV (Se 80%, Sp 95%), and 1.1 mmol/L (Se 90%, Sp 85%) for the GLX. Using these optimized thresholds

Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

PubMed Central

Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

2016-01-01

AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

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

PubMed

Raboisson, D; Mounié, M; Maigné, E

2014-12-01

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) β-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 β-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

Short communication: Use of genomic and metabolic information as well as milk performance records for prediction of subclinical ketosis risk via artificial neural networks.

PubMed

Ehret, A; Hochstuhl, D; Krattenmacher, N; Tetens, J; Klein, M S; Gronwald, W; Thaller, G

2015-01-01

Subclinical ketosis is one of the most prevalent metabolic disorders in high-producing dairy cows during early lactation. This renders its early detection and prevention important for both economical and animal-welfare reasons. Construction of reliable predictive models is challenging, because traits like ketosis are commonly affected by multiple factors. In this context, machine learning methods offer great advantages because of their universal learning ability and flexibility in integrating various sorts of data. Here, an artificial-neural-network approach was applied to investigate the utility of metabolic, genetic, and milk performance data for the prediction of milk levels of β-hydroxybutyrate within and across consecutive weeks postpartum. Data were collected from 218 dairy cows during their first 5wk in milk. All animals were genotyped with a 50,000 SNP panel, and weekly information on the concentrations of the milk metabolites glycerophosphocholine and phosphocholine as well as milk composition data (milk yield, fat and protein percentage) was available. The concentration of β-hydroxybutyric acid in milk was used as target variable in all prediction models. Average correlations between observed and predicted target values up to 0.643 could be obtained, if milk metabolite and routine milk recording data were combined for prediction at the same day within weeks. Predictive performance of metabolic as well as milk performance-based models was higher than that of models based on genetic information. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of quantum dots-based biosensor towards on-farm detection of subclinical ketosis.

PubMed

Weng, Xuan; Chen, Longyan; Neethirajan, Suresh; Duffield, Todd

2015-10-15

Early detection of dairy animal health issues allows the producer or veterinarian to intervene before the animals' production levels, or even survival, is threatened. An increased concentration of β-hydroxybutyrate (βHBA) is a key biomarker for diagnosis of subclinical ketosis (SCK), and provides information on the health stress in cows well before any external symptoms are observable. In this study, quantum dots (QDs) modified with cofactor nicotinamide adenine dinucleotide (NAD(+)) were prepared for the sensing event, by which the βHBA concentration in the cow's blood and milk samples was determined via fluorescence analysis of the functionalized QDs. The detection was performed on a custom designed microfluidic platform combining with a low cost and miniaturized optical sensor. The sensing mechanism was first validated by a microplate reader method and then applied to the microfluidic platform. Standard βHBA solution, βHBA in blood and milk samples from cows were successfully measured by this novel technology with a detection limit at a level of 35 µM. Side by side comparison of the developed microfluidic biosensor with a commercial kit presented its good performance. Copyright © 2015 Elsevier B.V. All rights reserved.

Ketosis and appetite-mediating nutrients and hormones after weight loss.

PubMed

Sumithran, P; Prendergast, L A; Delbridge, E; Purcell, K; Shulkes, A; Kriketos, A; Proietto, J

2013-07-01

Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

Latent class evaluation of a milk test, a urine test, and the fat-to-protein percentage ratio in milk to diagnose ketosis in dairy cows.

PubMed

Krogh, M A; Toft, N; Enevoldsen, C

2011-05-01

In this study, 3 commonly used tests to diagnose ketosis were evaluated with a latent class model to avoid the assumption of an available perfect test. The 3 tests were the KetoLac BHB (Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan) test strip that tests milk for β-hydroxybutyrate, the KetoStix (Bayer Diagnostics Europe Ltd., Dublin, Ireland) test strip that tests urine for acetoacetate, and the fat-to-protein percentage ratio (FPR) in milk. A total of 8,902 cows were included in the analysis. The cows were considered to be a random sample from the population of Danish dairy cattle under intensive management, thus representing a natural spectrum of ketosis as a disease. All cows had a recorded FPR between 7 and 21 d postpartum. The KetoLac BHB recordings were available from 2,257 cows and 6,645 cows had a KetoStix recording. The recordings were analyzed with a modified Hui-Walter model, in a Bayesian framework. The specificity of the KetoLac BHB test and the KetoStix test were both high [0.99 (0.97-0.99)], whereas the specificity of FPR was somewhat lower [0.79 (0.77-0.81)]. The best sensitivity was for the KetoStix test [0.78 (0.55-0.98)], followed by the FPR [0.63 (0.58-0.71)] and KetoLac BHB test [0.58 (0.35-0.93)]. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic analysis of milk β-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in early first lactation of Canadian Holsteins.

PubMed

Koeck, A; Jamrozik, J; Schenkel, F S; Moore, R K; Lefebvre, D M; Kelton, D F; Miglior, F

2014-11-01

The aim of this study was to estimate genetic parameters for milk β-hydroxybutyrate (BHBA) in early first lactation of Canadian Holstein cows and to examine its genetic association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of early lactation were between 0.14 and 0.29. Genetic correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in early lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher genetic merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately genetically correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and

The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review

PubMed Central

Schofield, Grant M.; Williden, Micalla

2018-01-01

Background Adaptation to a ketogenic diet (keto-induction) can cause unpleasant symptoms, and this can reduce tolerability of the diet. Several methods have been suggested as useful for encouraging entry into nutritional ketosis (NK) and reducing symptoms of keto-induction. This paper reviews the scientific literature on the effects of these methods on time-to-NK and on symptoms during the keto-induction phase. Methods PubMed, Science Direct, CINAHL, MEDLINE, Alt Health Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences Collection electronic databases were searched online. Various purported ketogenic supplements were searched along with the terms “ketogenic diet”, “ketogenic”, “ketosis” and ketonaemia (/ ketonemia). Additionally, author names and reference lists were used for further search of the selected papers for related references. Results Evidence, from one mouse study, suggests that leucine doesn’t significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to a ketogenic diet in humans, while increasing the protein-to-fat ratio of the diet, doesn’t reduce ketosis. Animal studies indicate that the short chain fatty acids acetic acid and butyric acid, increase ketone body concentrations. However, only one study has been performed in humans. This demonstrated that butyric acid is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but may inhibit ketogenesis. Conclusions There is a clear ketogenic effect of supplemental MCTs; however, it is unclear whether they independently improve time to NK and reduce symptoms of keto-induction. There is limited research on the potential for other supplements to improve time to NK and reduce symptoms of keto-induction. Few studies have specifically evaluated symptoms and adverse effects of a

Use of a hand-held meter for detecting subclinical ketosis in dairy cows.

PubMed

Voyvoda, Huseyin; Erdogan, Hasan

2010-12-01

The Optium Xceed is a new hand-held meter for determining blood β-hydroxybutyrate (BHBA) and glucose in human medicine. The objective of this study was to compare BHBA and glucose results obtained using the hand-held meter with those results made with a laboratory method and to evaluate its usefulness as a cowside test in the diagnosis of subclinical ketosis (SCK) in dairy cows. Seventy-eight blood samples from clinically healthy Holstein cows between 5 and 60 days post-calving were analysed. BHBA and glucose values were significantly higher with the hand-held meter versus laboratory methods. Correlation coefficients (r) for BHBA and glucose with the Optium Xceed versus laboratory methods were 0.97 and 0.63, respectively. Based on Bland-Altman plot and Passing-Bablok regression, agreement between two methods was good for BHBA but the agreement for glucose was only fair. When SCK was defined as plasma BHBA levels ≥ 1200 μmol/L, the sensitivity and specificity of the hand-held meter ketone testing in determining SCK were 85% and 94%, respectively. Raising the threshold of the laboratory method to ≥ 1400 μmol/L, the sensitivity and specificity incremented to 0.90 and 0.98, respectively. In conclusion, the blood ketone-monitoring device can be used as a rapid and reliable diagnostic test to detect SCK under field conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations.

PubMed

Chearskul, Supornpim; Delbridge, Elizabeth; Shulkes, Arthur; Proietto, Joseph; Kriketos, Adamandia

2008-05-01

Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior. The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain. The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance. Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60). Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.

Recreational drug abuse in patients hospitalized for diabetic ketosis or diabetic ketoacidosis.

PubMed

Isidro, María L; Jorge, Segundo

2013-04-01

To evaluate the association between recreational drug use and diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in our area. Retrospective examination of records from a 1,450 bed urban teaching hospital in Spain. All adult admissions for DK or DKA from January 1, 2005, to December 31, 2009 in our hospital were included. Demographic, exploratory (blood pressure, heart rate, respiratory rate), and analytical data (glucose, urea, creatinine, corrected Na(+), K(+), pH, HCO3(-) and HbA1c) at admittance were recorded. In 152 patients, 253 episodes of DK or DKA occurred. Screening for drug use was performed in 40.3% of the events; 20.6% of the episodes (n = 52) were shown to be substance abuse. Cocaine, followed by cannabis and alcohol, was the most frequently involved drug. Poly-substance abuse occurred in 67.3% of them. Comorbidities were present in 11.5 and 39.8% of the cases shown and not shown to be related to drug use (P = 0.00). Seventy percent of the patients who were at least once shown to have consumed drugs, and 15.9% of those who were never shown to have done so, were admitted more than once (P = 0.00). The frequency of recent drug misuse in patients presenting with DK or DKA was high. Substance abuse screening was frequently neglected. Adverse profile, most significantly in readmission to hospital, was found in the patients with positive drug findings. History taking in this context should routinely include questions on substance abuse, and toxicology screening may be worthwhile, particularly in those with the history of frequent readmissions.

Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?

PubMed

Brown, Andrew J

2007-01-01

Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse.

Feeding a higher forage diet prepartum decreases incidences of subclinical ketosis in transition dairy cows.

PubMed

Vickers, L A; Weary, D M; Veira, D M; von Keyserlingk, M A G

2013-02-01

A common feeding practice during the dry period is to switch dairy cows to an energy-dense diet 3 wk prepartum, but this practice may lead to the overconsumption of energy and increase the risk of metabolic disease postpartum. The aim of this trial was to compare the metabolic status of transition Holstein dairy cows fed a 77% forage diet (77F; NEl = 1.46 Mcal/kg; NDF = 41%) vs. those fed an 87% forage diet (87F; NEl = 1.41 Mcal/kg; 48% NDF). Approximately 60 d before calving, cows were dried off, housed in a free stall barn, and fed the 87F diet. Three weeks before expected calving, cows were randomly assigned to either the 77F treatment and switched to this diet (n = 45) or assigned to the 87F treatment and stayed on the dry cow ration until parturition (n = 42). After parturition, all cows were fed a common lactation diet (NEl = 1.59 Mcal/kg; 36% NDF). Dry matter intake was measured daily from 2 wk before to 2 wk after calving. Blood was sampled daily for 10 d postpartum. Subclinical ketosis was diagnosed using a threshold of β-hydroxybutyrate (BHBA) ≥ 1.0 mmol/L after calving. The percentage of cows pregnant and odds of being pregnant for each treatment group were determined at 60, 90, and 120 d in milk through ultrasound by the herd veterinarian. Cows on the 87F diet consumed less DM prepartum than those on the 77F diet (12.7 ± 0.3 kg/d vs. 15.4 ± 0.3 kg/d, P < 0.001), but no difference in DMI was detected after calving (19.7 ± 5.5 kg/d; P = 0.87). Although the calculated prepartum required energy intake was the same for the 2 treatments (15.3 ± 1.2 Mcal/d; P = 0.16), cows on the 77F diet consumed 4.5 Mcal/d more than those on the 87F diet (22.5 ± 0.5 Mcal/d vs. 18.0 ± 0.5 Mcal/d; P < 0.001). Postpartum concentration of BHBA was less for cows fed the 87F diet prepartum (0.49 ± 0.02 mmol/L vs. 0.59 ± 0.02 mmol/L; P = 0.02), and fewer animals on this diet were diagnosed subclinical ketosis (SCK; 49% vs. 17%; P = 0.001). Milk production tended to be

Significance of insulin resistance and oxidative stress in dairy cattle with subclinical ketosis during the transition period.

PubMed

Youssef, Mohamed; El-Ashker, Maged

2017-02-01

Health problems occurring during the transition period in dairy cattle are of utmost importance as they can decrease the animal's reproductive performance and favor the development of various metabolic diseases with resultant significant reproductive disorders. Among the commonly reported metabolic diseases occurring during that time, hyperketonemia is the most prevalent and could provoke a significant economic impact. The failing of a dairy cow to transit optimally between pregnancy and lactation is economically very relevant and should be considered. Until now, the role of insulin resistance (IR) in the etiology of subclinical ketosis (SCK) in dairy cattle is not clearly understood. This review aims to shed some light on the role of IR and oxidative stress in dairy cows with SCK during the transition period. The data presented in this review demonstrates that dairy cows could be vulnerable to the development of negative energy balance during transition. Moreover, the transitional cows could succumb to both IR and oxidative stress; however, the exact role of IR in cows with SCK needs further investigations. It is imperative to elaborate a suitable nutritional strategy to facilitate an easy transit of cows through this critical period and to minimize health problems and improve productivity during lactation.

Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: Basic mechanisms and therapeutic perspectives.

PubMed

Qiu, Hongyu; Novikov, Aleksandra; Vallon, Volker

2017-07-01

Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of antihyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk. However, a potential side effect that has been reported with SGLT2 inhibitors in patients with T2DM and particularly during off-label use in patients with type 1 diabetes is diabetic ketoacidosis. The US Food and Drug Administration recently warned that SGLT2 inhibitors may result in euglycemic ketoacidosis. Here, we review the basic metabolism of ketone bodies, the triggers of diabetic ketoacidosis, and potential mechanisms by which SGLT2 inhibitors may facilitate the development of ketosis or ketoacidosis. This provides the rationale for measures to lower the risk. We discuss the role of the kidney and potential links to renal gluconeogenesis and uric acid handling. Moreover, we outline potential beneficial effects of modestly elevated ketone body levels on organ function that may have therapeutic relevance for the observed beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system. Copyright © 2017 John Wiley & Sons, Ltd.

Subclinical ketosis in dairy cows: prevalence and risk factors in grazing production system.

PubMed

Garro, C J; Mian, L; Cobos Roldán, M

2014-10-01

The purpose of this study was to estimate the prevalence of Subclinical ketosis (SCK) between 4 and 19 days in milk (DIM) in a grazing production system and investigate the importance of potential risk factors for SCK. This cross-sectional study was conducted in dairy cows (n = 107), which had more of two parities. The concentration of β-hydroxybutyric (BHB) in blood was quantified through a hand-held meter. Potential risk factors evaluated were calving interval (CI), milk yield in previous lactation, metritis, dystocia, calf sex (male), parity (≤3 vs. ≥4) and pre-partum body condition score (BCS ≤ 3.5 vs. ≥3.75). Prevalence of SCK was 10.3% (95% CI 4.7-15) between 4 and 19 DIM. Risk factors identified were the occurrence of both metritis and pre-partum BCS ≥ 3.75. Cows with metritis had 4.9 (95% CI 1.17-20.98) times more risk of developing SCK than cows without metritis. And the cows with pre-partum BCS ≥ 3.75 had 5.25 (95% CI 1.32-21.11) times more risk of developing SCK than cows with pre-partum BCS ≤ 3.5. Metritis could induce a lower feed intake and promote the development of SCK. High pre-partum BCS could induce a greater mobilization of body reserves altering liver function and aggravating post-partum NEB. The results are indicative of the expected prevalence of SCK in grazing production system. Factors associated could help to identify cattle at risk of SCK and improve the management of strategies to limit the effects. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows

PubMed Central

Akbar, Haji; Batistel, Fernanda; Drackley, James K.; Loor, Juan J.

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

PubMed

Akbar, Haji; Batistel, Fernanda; Drackley, James K; Loor, Juan J

2015-01-01

In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

The effect of subclinical ketosis on activity at estrus and reproductive performance in dairy cattle.

PubMed

Rutherford, Andrew J; Oikonomou, Georgios; Smith, Robert F

2016-06-01

Our aims were to investigate the influence of subclinical ketosis (SCK) on physical activity at estrus using a neck accelerometer device and on future reproductive performance. Two hundred three Holstein-Friesian cows were studied on 3dairy farms in Northwest England between September 2013 and March 2014. Seventeen percent (35 of 203) of the enrolled cows were affected with SCK between 7 and 21d in milk, defined as a blood β-hydroxybutyrate concentration of 1.2 to 2.9mmol/L. Time to event analyses and multivariable regression analyses were used to assess the effect of SCK on reproductive performance and activity at estrus. The SCK cows exhibited a lower peak activity (measured as the number of standard deviations above mean activity) and shorter duration in activity clusters associated with first estrus and first insemination postpartum, compared with non-SCK cows. Peak activity and cluster duration associated with the insemination that led to a pregnancy were not different between SCK and non-SCK cows. Calving to first estrus, calving to first insemination, and calving to pregnancy intervals were prolonged in SCK cows. First insemination was 4.3 times (95% confidence interval=1.6 to 15.0) less likely to be successful in SCK cows compared with non-SCK cows. Adjusted mean number of inseminations per pregnancy was 2.8 for SCK cows and 2.0 for non-SCK cows. The current study confirms the long-lasting effects of SCK on reproductive efficiency. Furthermore, it is indicated that physical activity around estrus is reduced by SCK in early lactation, but this negative effect appears to diminish as cows progress through lactation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An evaluation of beta-hydroxybutyrate in milk and blood for prediction of subclinical ketosis in dairy cows.

PubMed

Samiei, A; Liang, J B; Ghorbani, G R; Hirooka, H; Yaakub, H; Tabatabaei, M

2010-01-01

The first objective of this study was to investigate the relationship between concentrations of beta-hydroxybutyrate (BHBA) in milk and blood to assess the reliability of the BHBA concentrations in milk measured by a semi quantitative keto-test paper to detect subclinical ketosis (SCK) in 50 fresh high-producing Iranian Holstein cows in Golestan Province, Iran. The second objective was the effects of SCK on milk yield and components. Concentrations of nonesterified fatty acids (NEFA) and BHBA were analyzed quantitatively in blood plasma and commercial keto-test paper was used for semi quantitative determination of BHBA concentration in milk. Milk yield was measured until 60 d after calving but milk compositions were measured until 30 d after calving. The mean plasma BHBA, milk BHBA, plasma NEFA, milk yield, milk fat percentage and milk fat: protein ratio were 1,234 micromol/L, 145 micromol/L, 0.482 mEq/L, 29.5 kg, 3.9% and 1.4, respectively. Fifty eight percent of the cows had SCK during the first month of lactation. High correlation coefficients were observed between blood BHBA and blood NEFA, and between blood and milk BHBA. The milk yield of cattle with SCK decreased (P < 0.01) but the fat percentage and milk fat: protein ratio increased (P < 0.01). The commercial keto-test paper used had a low false positive result at a cut-off point of 200 fmol of BHBA/L of milk. The results showed that the best time to assess SCK using the commercial keto-test paper was d 10, 14 and 17 after calving.

Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes and Alcoholic Ketosis Are Associated with the Serum Uric Acid Level in Japanese Alcoholic Men.

PubMed

Yokoyama, Akira; Yokoyama, Tetsuji; Mizukami, Takeshi; Matsui, Toshifumi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

2016-05-01

To identify determinants of hyperuricemia in alcoholics. The serum uric acid (UA) levels of 1759 Japanese alcoholic men (≥40 years) were measured on their first visit or within 3 days after admission; ADH1B and ALDH2 genotyping on blood DNA samples were performed. Dipstick urinalyses for ketonuria and serum UA measurements were simultaneously performed for 621 men on their first visit. Serum UA levels of >416 μmol/l (7.0 mg/dl) and ≥535 μmol/l (9.0 mg/dl) were observed in 30.4 and 7.8% of the subjects, respectively. Ketonuria was positive in 35.9% of the subjects, and a multivariate analysis revealed that the ketosis level was positively associated with the UA level. The presence of the ADH1B*2 allele and the ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) among subjects with a high UA level of >416 μmol/l (vs. ≤416 μmol/l; 2.04 [1.58-2.65] and 1.48 [1.09-2.01], respectively) and those with a high UA level of ≥535 μmol/l (vs. ≤416 μmol/l; 2.29 [1.42-3.71] and 3.03 [1.51-6.08], respectively). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs (2.86 [1.61-5.10] and 6.21 [1.49-25.88] for a UA level of >416 μmol/l and ≥535 μmol/l, respectively), compared with the ADH1B*1/*1 plus ALDH2*1/*2 combination. The presence of diabetes and the consumption of Japanese sake rather than beer were negatively associated with the UA levels. The faster metabolism of ethanol and acetaldehyde by the ADH1B*2 allele and ALDH2*1/*1 genotype and higher ketosis levels were associated with higher UA levels in alcoholics, while diabetes and the consumption of sake were negative determinants. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

A Program for Clinical Care in Physical Trauma.

DTIC Science & Technology

1976-03-01

nitrogen balance in fasting man. Carbohydrate at all levels of infusion markedly improves the utilization of amino acids. Thus, ketosis does not seem...specific- .4 ally, nor ketosis as a whole, in any way favors nitrogen economy. The impression gained from the literature that ketosis is a favorable

[Management of the dry and transition periods of dairy cattle in free stall housing systems in Lower Saxony. - Part 2: Risk factores for subclinical ketosis, hypocalcaemia and increased lipomobilisation].

PubMed

Oetting-Neumann, Pamela; Rohn, Karl; Hoedemaker, Martina

2018-02-01

Determination of the frequency of subclinical hypocalcaemia, increased lipomobilisation and subclinical ketosis as problems in dairy herds and identification of possible risk factors. Information was obtained from 51 dairy farms on husbandry, feeding, management of the cows and heifers, animal health and prophylactic treatments using a questionnaire. Blood samples from 20% of the cows and 30% of the heifers of each farm (= herd sample) were collected in the week ante partum (a. p.) for determination of serum calcium (Ca), magnesium (Mg), phosphorus (P) and non-esterified fatty acids (NEFA) concentrations and in the week post partum (p. p.) for measurement of serum β-hydroxybutyrate (BHB) concentration. For evaluation of the herd sample results, the percentage of animals with a laboratory value above a determined threshold value for the various parameters was calculated. When the percentage exceeded a certain threshold (alert) level, a herd problem was assumed. Alert levels from the literature and adapted levels were used. For minerals, an adapted alert level of 10% was taken as a basis. In cows, the alert level for Ca, Mg, P (too low) and P (too high) was exceeded in 13.7%, 13.7%, 25.7% and 7.8% of the herd samples, respectively. NEFA (a. p.) and BHB (p. p.) had an adapted alert level of 30%. For NEFA, the alert level was exceeded by cows and heifers on 47.1 % and 51.0% of the farms, respectively. For BHB, the alert level was exceeded by cows and heifers on 33.3% and 13.7% of the farms, respectively. As risk factors, a too large group size for the transition cows (Ca, Mg), pasturing (Ca, BHB), one phasic feeding of dry cows (Mg, BHB) and a lack of a separated dry cow area (BHB) were identi fied. Risk factors for the heifers were no pasturing of the young stock (NEFA) and a low frequency of pushing up the diet in the feed bunk (BHB). Subclinical ketosis in cows and an increased lipomobilisation in heifers were frequent herd problems in the dairy herds studied and

Improved outcomes in indigent patients with ketosis-prone diabetes: effect of a dedicated diabetes treatment unit.

PubMed

Maldonado, Mario R; D'Amico, Susana; Rodriguez, Lucille; Iyer, Dinakar; Balasubramanyam, Ashok

2003-01-01

To investigate whether a specialized intervention program could improve diabetes-related health outcomes in indigent patients with type 1 diabetes who were prone to occurrence of diabetic ketoacidosis (DKA). Patients with type 1 diabetes mellitus admitted because of DKA during a 24-month period were invited to receive outpatient care in a diabetes treatment unit (DTU). We compared DKA-related readmission rates, change in hemoglobin A1c (HbA1c) values, and diabetes-related medical costs in patients who participated in the DTU program (+DTU) and in those who did not (-DTU). During the study period, 115 patients underwent assessment. Of this overall group, 57 patients (49.6%) consented to participate in the DTU program, and 58 (50.4%) did not. After the follow-up period (median duration, 657 days), the following significant improvements were observed in the +DTU group (in comparison with the -DTU group): lower frequency of readmission for DKA (16% versus 43%; P = 0.001), lower number of readmissions for DKA per patient (0.22 +/- 0.6 versus 1.17 +/- 2.2 [mean +/- standard deviation]; P = 0.003), lower HbA1c level (10.4 +/- 2.3% versus 13.5 +/- 2.3%; P<0.0001), and lower cost of diabetes-related medical care (3,427.20 US dollars +/- 6,275.60 versus 10,119.10 US dollars +/- 19,688.10; P = 0.01). Multivariate analysis revealed that participation in the DTU program was the only factor associated with a significantly decreased risk of DKA-related readmission. Low-cost intervention by a dedicated outpatient DTU resulted in significant decreases in DKA-associated readmissions, in HbA1c values, and in costs of diabetes care in a multiethnic, indigent, ketosis-prone patient population.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes.

PubMed

Choukem, S P; Sobngwi, E; Garnier, J P; Letellier, S; Mauvais-Jarvis, F; Calvo, F; Gautier, J-F

2015-09-01

Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=-0.085, P=0.38). Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Subclinical ketosis in post-partum dairy cows fed a predominantly pasture-based diet: defining cut-points for diagnosis using concentrations of beta-hydroxybutyrate in blood and determining prevalence.

PubMed

Compton, C W R; Young, L; McDougall, S

2015-09-01

Firstly, to define, in dairy cows in the first 5 weeks post-calving fed a predominantly pasture-based diet, cut-points of concentrations of beta-hydroxybutyrate (BHBA) in blood, above which there were associations with purulent vaginal discharge (PVD), reduced pregnancy rates (PR) and decreased milk production, in order to better define subclinical ketosis (SCK) in such cattle; and secondly, to determine the prevalence, incidence and risk factors for SCK. An observational field study was conducted in 565 cows from 15 spring-calving and predominantly pasture-fed dairy herds in two regions of New Zealand during the 2010- 2011 dairy season. Within each herd, a cohort of randomly selected cows (approximately 40 per herd) was blood sampled to determine concentrations of BHBA on six occasions at weekly intervals starting within 5 days of calving. The key outcome variables were the presence/absence of PVD at 5 weeks post-calving, PR after 6 weeks (6-week PR) and after the completion of the breeding season (final PR), and mean daily milk solids production. Two cut-points for defining SCK were identified: firstly concentration of BHBA in blood≥1.2 mmol/L within 5 days post-calving, which was associated with an increased diagnosis of PVD (24 vs. 8%); and secondly concentration of BHBA in blood≥1.2 mmol/L at any stage within 5 weeks post-calving, which was associated with decreased 6-week PR (78 vs. 85%). The mean herd-level incidence of SCK within 5 weeks post-calving was 68 (min 12; max 100)% and large variations existed between herds in peak prevalence of SCK and the interval post-calving at which such peaks occurred. Cows>8 years of age and cows losing body condition were at increased risk of SCK within 5 weeks of calving. Cows with concentration of BHBA in blood≥1.2 mmol/L in early lactation had a higher risk of PVD and lower 6-week PR. Cow and herd-level prevalence of SCK varied widely in early lactation. Subclinical ketosis is common and is significantly

Association of rumination time with subclinical ketosis in transition dairy cows.

PubMed

Kaufman, E I; LeBlanc, S J; McBride, B W; Duffield, T F; DeVries, T J

2016-07-01

The objective of this study was to characterize the relationship between rumination and subclinical ketosis (SCK) in transition dairy cows. A study was conducted on 4 commercial dairy farms in eastern Ontario, Canada. A total of 339 Holstein dairy cows (107 primiparous and 232 multiparous) were monitored for rumination activity and SCK from 14 d before calving until 28 d after calving. Rumination was recorded daily using an automated monitoring system. A blood sample was taken from the coccygeal vein of each cow for measurement of β-hydroxybutyrate (BHB) once weekly throughout the 6-wk observation period. Cows with BHB ≥1.2mmol/L in any of the 4 postpartum samples were considered to have SCK. Cases of retained placenta, metritis, milk fever, or mastitis during the study period were also recorded. Cows were categorized into 1 of 4 groups: healthy cows (HLT) that had no SCK or any other recorded health problem (n=139); cows treated for at least one health issue other than SCK (HLT+; n=50); cows with SCK (hyperketonemia; HYK) with no other health problems during transition (n=97); or cows (HYK+) that had SCK and one or more other health problems (n=53). Daily rumination time was summarized by week and comparisons were made between HLT and HYK and HYK+. From 2 wk before calving (wk -2) to 4 wk after calving (wk +4), there was no difference in rumination time (409±9.8min/d) among HLT, HYK, and HYK+ cows in their first lactation. Multiparous cows in HLT spent an average of 459±11.3min/d ruminating from wk -2 to wk +4. Multiparous HYK cows ruminated 25±12.8min/d less than HLT cows, whereas HYK+ cows ruminated 44±15.6min/d less than HLT cows. The largest differences in rumination time between HLT and HYK+ cows were seen during wk -1, +1, and +2, when HYK+ cows ruminated 48±17.2, 73±16.0, and 65±19.4min/d less than HLT cows, respectively. In multiparous cows, increased odds of HYK were associated with greater milk yield in the previous lactation, greater loss of

A field trial on the effect of propylene glycol on displaced abomasum, removal from herd, and reproduction in fresh cows diagnosed with subclinical ketosis.

PubMed

McArt, J A A; Nydam, D V; Oetzel, G R

2012-05-01

The purpose was to determine the effect of oral propylene glycol (PG) administration in fresh cows diagnosed with subclinical ketosis (SCK). Measured outcomes were development of displaced abomasum (DA) and removal from herd in the first 30 d in milk (DIM), conception to first service, and time to conception within 150 DIM. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM on Mondays, Wednesdays, and Fridays using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a blood β-hydroxybutyrate concentration of 1.2 to 2.9 mmol/L. Cows with SCK were randomized to treatment group (oral PG) or untreated control group (no PG); treatment cows were orally drenched with 300 mL of PG once daily from the day they tested 1.2 to 2.9 mmol/L until the day they tested <1.2 mmol/L. Mixed effects multivariable Poisson regression was used to assess the effect of PG on DA, removal from herd, and conception to first service; a semiparametric proportional hazards model was used to evaluate the days-to-conception outcome. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least 1 β-hydroxybutyrate test of 1.2 to 2.9 mmol/L. Of these, 372 were assigned to the PG treatment group and 369 to the control group. Thirty-nine cows (5.3%) developed a DA after testing positive for SCK and 30 cows (4.0%) died or were sold within the first 30 DIM. Based on risk ratios, control cows were 1.6 times more likely [95% confidence interval (CI)=1.3 to 2.0] to develop a DA and 2.1 times more likely (95% CI=1.2 to 3.6) to die or be sold than cows treated with PG. In addition, PG-treated cows were 1.3 times more likely (risk ratio 95% CI=1.1 to 1.5) to conceive at first insemination than control cows in 3 of the herds. No difference was observed in days to conception within 150 DIM between treatment groups (hazard ratio for PG cows=1.1, 95% CI=0.8 to 1.4), with a median time to

Short communication: Association of lying behavior and subclinical ketosis in transition dairy cows.

PubMed

Kaufman, E I; LeBlanc, S J; McBride, B W; Duffield, T F; DeVries, T J

2016-09-01

The objective of this study was to characterize the association of lying behavior and subclinical ketosis (SCK) in transition dairy cows. A total of 339 dairy cows (107 primiparous and 232 multiparous) on 4 commercial dairy farms were monitored for lying behavior and SCK from 14d before calving until 28 d after calving. Lying time, frequency of lying bouts, and average lying bout length were measured using automated data loggers 24h/d. Cows were tested for SCK 1×/wk by taking a blood sample and analyzing for β-hydroxybutyrate; cows with β-hydroxybutyrate ≥1.2mmol/L postpartum were considered to have SCK. Cases of retained placenta, metritis, milk fever, or mastitis during the study period were recorded and cows were categorized into 1 of 4 groups: healthy (HLT) cows had no SCK or any other health problem (n=139); cows treated for at least 1 health issue other than SCK (n=50); SCK (HYK) cows with no other health problems during transition (n=97); or subclinically ketotic plus (HYK+) cows that had SCK and 1 or more other health problems (n=53). Daily lying time was summarized by week and comparisons were made between HLT, HYK, and HYK+, respectively. We found no difference among health categories in lying time, bout frequency, or bout length fromwk -2 towk +4 relative to calving for first-lactation cows. Differences in lying time for multiparous cows were seen inwk +1, when HYK+ cows spent 92±24.0 min/d more time lying down than HLT cows, and duringwk +3 and +4 when HYK cows spent 44±16.7 and 41±18.9 min/d, respectively, more time lying down than HLT cows. Increased odds of HYK+ were found to be associated with higher parity, longer dry period, and greater stall stocking density inwk -1 and longer lying time duringwk +1. When comparing HYK to HLT cows, the same variables were associated with odds of SCK; however, lying time was not retained in the final model. These results suggest that monitoring lying time may contribute to identifying multiparous cows

Ketones and Human Performance.

PubMed

Scott, Jonathan M; Deuster, Patricia A

Everyone is seeking nutritional strategies that might benefit performance. One approach receiving much attention is ketones, or ketosis. Ketones are very simple compounds made of hydrogen, carbon, and oxygen, and ketosis is a metabolic state whereby the body uses predominantly ketones. Ketosis can be achieved by fasting for longer than 72 hours or by following a very lowcarbohydrate, high-fat diet (ketogenic diet) for several days to weeks. Alternatively, ketone supplements purportedly induce ketosis rapidly and do not require strict adherence to any specific type of diet; however, much of the touted benefits are anecdotal. A potential role for ketosis as a performance enhancer was first introduced in 1983 with the idea that chronic ketosis without caloric restriction could preserve submaximal exercise capability by sparing glycogen or conserving the limited carbohydrate stores. Few human studies on the effects of a ketogenic diet on performance have yielded positive results, and most studies have yielded equivocal or null results, and a few negative results. Many questions about ketones relevant to Special Operations Forces (SOF) remain unanswered. At present, a ketogenic diet and/or a ketone supplement do not appear confer performance benefits for SOF. Instead, Operators should engage with their unit dietitian to develop individualized nutritional strategies based on unique mission requirements. The authors review the concept of a ketogenic diet, describe some potential benefits and risks of ketosis, review the performance literature and how to measure ketone status, and then summarize the landscape in 2017. 2017.

Investigating the within-herd prevalence and risk factors for ketosis in dairy cattle in Ontario as diagnosed by the test-day concentration of β-hydroxybutyrate in milk.

PubMed

Tatone, Elise H; Duffield, Todd F; LeBlanc, Stephen J; DeVries, Trevor J; Gordon, Jessica L

2017-02-01

An observational study of 790 to over 3,000 herds was conducted to estimate the within-herd prevalence and cow-level risk factors for ketosis in dairy cattle in herds that participate in a Dairy Herd Improvement Association (DHIA) program. Ketosis or hyperketolactia (KET) was diagnosed as milk β-hydroxybutyrate ≥0.15 mmol/L at first DHIA test when tested within the first 30 d in milk. Seven hundred ninety-five herds providing at least 61 first milk tests from June 2014 to December 2015 were used to estimate the provincial within-herd prevalence of KET. All herds on DHIA in Ontario (n = 3,042) were used to construct cow-level multilevel logistic regression models to investigate the association of DHIA collected variables with the odds of KET at first DHIA milk test. Primiparous and multiparous animals were modeled independently. The cow-level KET prevalence in Ontario was 21%, with an average within-herd prevalence of 21% (standard deviation = 10.6) for dairy herds enrolled in a DHIA program. The prevalence of KET had a distinct seasonality with the lowest prevalence occurring from July to November. Automatic milking systems (AMS) were associated with increased within-herd prevalence, as well as increased odds of KET in multiparous animals at first test (odds ratio: 1.45; 95% confidence interval: 1.30 to 1.63). Jersey cattle had over 1.46 times higher odds of KET than Holstein cattle. Milk fat yield ≥1.12 kg/d at the last test of the previous lactation was associated with decreased odds of KET in the current lactation (odds ratio: 0.56; 95% confidence interval: 0.53 to 0.59). Increased days dry and longer calving intervals, for multiparous animals, and older age at first calving for primiparous animals increased the odds of KET at first test. This study confirms previous findings that increased days dry, longer calving intervals, and increased age at first calving are associated with increased odds of KET and is the first report of increased KET in herds with

Genetic parameters of blood β-hydroxybutyrate predicted from milk infrared spectra and clinical ketosis, and their associations with milk production traits in Norwegian Red cows.

PubMed

Belay, T K; Svendsen, M; Kowalski, Z M; Ådnøy, T

2017-08-01

The aim of this study was to estimate genetic parameters for blood β-hydroxybutyrate (BHB) predicted from milk spectra and for clinical ketosis (KET), and to examine genetic association of blood BHB with KET and milk production traits (milk, fat, protein, and lactose yields, and milk fat, protein, and lactose contents). Data on milk traits, KET, and milk spectra were obtained from the Norwegian Dairy Herd Recording System with legal permission from TINE SA (Ås, Norway), the Norwegian Dairy Association that manages the central database. Data recorded up to 120 d after calving were considered. Blood BHB was predicted from milk spectra using a calibration model developed based on milk spectra and blood BHB measured in Polish dairy cows. The predicted blood BHB was grouped based on days in milk into 4 groups and each group was considered as a trait. The milk components for test-day milk samples were obtained by Fourier transform mid-infrared spectrometer with previously developed calibration equations from Foss (Hillerød, Denmark). Veterinarian-recorded KET data within 15 d before calving to 120 d after calving were used. Data were analyzed using univariate or bivariate linear animal models. Heritability estimates for predicted blood BHB at different stages of lactation were moderate, ranging from 0.250 to 0.365. Heritability estimate for KET from univariate analysis was 0.078, and the corresponding average estimate from bivariate analysis with BHB or milk production traits was 0.002. Genetic correlations between BHB traits were higher for adjacent lactation intervals and decreased as intervals were further apart. Predicted blood BHB at first test day was moderately genetically correlated with KET (0.469) and milk traits (ranged from -0.367 with protein content to 0.277 with milk yield), except for milk fat content from across lactation stages that had near zero genetic correlation with BHB (0.033). These genetic correlations indicate that a lower BHB is genetically

How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies.

PubMed

Mitchell, Rebecca; Thomas, Sunethra Devika; Langlois, Neil E I

2013-10-01

Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis.

A Program for Clinical Care in Physical Trauma.

DTIC Science & Technology

1981-08-01

of the leg. This model increases the release of skeletal muscle amino acids, fails to develop ketosis during starvation and injury/infection, and...develop ketosis following starvation during this stress. This model has great benefit to evaluate therapies that would reverse the marked catabolic...appears to be the lack of ketosis that occurs in the starved animals that are also infected (Table I). This response is also associated with a marked fall

Efficacy of controlled-release capsules containing monensin for the prevention of subclinical ketosis in pasture-fed dairy cows.

PubMed

Compton, C W R; Young, L; McDougall, S

2015-09-01

To determine the effectiveness of intra-rumenal controlled release capsules (CRC) containing 32 g of monensin administered pre-calving to reduce the cumulative incidence of subclinical ketosis (SCK) in mainly pasture-fed dairy cows. Cows (n=837) due to calve in the first 6 weeks of the spring calving period were enrolled from four commercial herds in the Waikato region of New Zealand in a blinded, randomised, negative-controlled field trial. Three weeks before the start of the calving period cows were randomly allocated to receive either no treatment (control) or a single CRC containing monensin and then blood sampled on two occasions, 7 days apart within 12 days following calving for measurement of concentrations of beta hydroxybutyrate (BHBA) in blood. Cows were diagnosed with SCK if the concentration of BHBA in blood in either of these samples was ≥1.2 mmol/L. Fewer treated cows were diagnosed with SCK within 12 days post-calving than control cows (144/340 (42.4%) vs. 192/336 (57.1%); p<0.001). There was no interaction between treatment group and age, breed or herd of origin. From the final multivariable model it was estimated that treatment with CRC containing monensin reduced the absolute cumulative incidence of SCK by 17.9 (95% CI=9.2-25.8)% compared to no treatment. Treatment with a CRC containing monensin>10 days prior to calving reduced the cumulative incidence of SCK of pasture-based dairy cows in commercial dairy herds within 12 days post-calving. Administration pre-calving of an intra-rumenal bolus containing monensin can be considered as one of a range of management options for the control of SCK in early lactation.

Ketone bodies as epigenetic modifiers.

PubMed

Ruan, Hai-Bin; Crawford, Peter A

2018-07-01

Ketone body metabolism is a dynamic and integrated metabolic node in human physiology, whose roles include but extend beyond alternative fuel provision during carbohydrate restriction. Here we discuss the most recent observations suggesting that ketosis coordinates cellular function via epigenomic regulation. Ketosis has been linked to covalent modifications, including lysine acetylation, methylation, and hydroxybutyrylation, to key histones that serve as dynamic regulators of chromatin architecture and gene transcription. Although it remains to be fully established whether these changes to the epigenome are attributable to ketone bodies themselves or other aspects of ketotic states, the regulated genes mediate classical responses to carbohydrate restriction. Direct regulation of gene expression may occur in-vivo via through ketone body-mediated histone modifications during adherence to low-carbohydrate diets, fasting ketosis, exogenous ketone body therapy, and diabetic ketoacidosis. Additional convergent functional genomics, metabolomics, and proteomics studies are required in both animal models and in humans to identify the molecular mechanisms through which ketosis regulates nuclear signaling events in a myriad of conditions relevant to disease, and the contexts in which the benefits of ketosis might outweigh the risks.

Mauna Kea III: Metabolic Effects of Dietary Carbohydrate Supplementation During Exercise at 4100 M Altitude.

DTIC Science & Technology

1987-05-01

not significantly altered by altitude or diet. B-hydroxybutyrate was measured in urine and serum as an index of ketosis . Uzine B-hydroxybutyrate in 24...h urine samples is shown in Table 6. In general, Urin B-ydrxybtyrae i 24h uine10 44~ -W the incidence of ketosis was markedly less in the EX + CHO...Ketone body metabolism in ketosis of starvation and alloxan diabetes. J. Biol. Chem. 245:4382-4390, 1970. 22. NORTON, A.C. Development and testing of a

Effects of butafosfan with or without cyanocobalamin on the metabolism of early lactating cows with subclinical ketosis.

PubMed

Nuber, U; van Dorland, H A; Bruckmaier, R M

2016-02-01

Fifty-one dairy cows with subclinical ketosis were used to investigate the effects of butafosfan alone or in combination with cyanocobalamin on metabolism. Treatments included i.v. injection of 10 ml/100 kg of body weight with butafosfan (BUT) or combined cyanocobalamin with butafosfan (BUTCO) at a similar concentration as in Catosal(®) . Control cows (CON) received a 0.9% saline solution. Cows were injected on days 1-3 at 22.3 ± 0.7 days post-partum. Milk production and composition were not affected by the treatments. In plasma, CON cows had a significantly higher plasma NEFA concentration (0.59 ± 0.03 mm) across the study period than BUTCO cows (p < 0.05; 0.42 ± 0.03 mm), whereas the plasma NEFA concentration of BUT was intermediate (0.52 ± 0.03 mm) but not significantly different from CON. Both BUTCO and BUT cows had lower (p < 0.05) plasma BHBA concentrations (1.02 ± 0.06 mm and 1.21 ± 0.06 mm, respectively) across the study period than CON (1.34 ± 0.06 mm). Plasma glucose was not different between treatments, but plasma glucagon concentrations were consistently high in BUT compared to BUTCO and CON. Lowest post-treatment glucagon levels were observed in BUTCO. Hepatic mRNA abundance of liver X receptor α, a nuclear receptor protein involved in lipid metabolism, was higher in BUTCO compared to BUT and CON (p < 0.05) on day 7. Furthermore, on day 7, the mRNA abundance of beta-hydroxybutyrate dehydrogenase 2 was higher in BUTCO compared to BUT and CON (p < 0.01). In conclusion, injections of combined cyanocobalamin with butafosfan post-partum in early lactation ketotic dairy cows act on lipid metabolism with effects on plasma metabolites, most likely mediated via modified activity of key factors in the liver. Results indicate that the application of butafosfan only in combination with cyanocobalamin exhibits the expected positive effects on metabolism. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Comparison of 2 electronic cowside tests to detect subclinical ketosis in dairy cows and the influence of the temperature and type of blood sample on the test results.

PubMed

Iwersen, M; Klein-Jöbstl, D; Pichler, M; Roland, L; Fidlschuster, B; Schwendenwein, I; Drillich, M

2013-01-01

The objective of this study was to determine the suitability of 2 electronic hand-held devices [FreeStyle Precision (FSP), Abbott GmbH & Co. KG, Wiesbaden, Germany and GlucoMen LX Plus (GLX), A. Menarini GmbH, Vienna, Austria] for measuring β-hydroxybutyrate (BHBA) in dairy cows. Three experiments were conducted to evaluate (1) the diagnostic performance of the devices, (2) the effect of the type of blood sample, and (3) the influence of the ambient temperature on the determined results. A total of 415 blood samples from lactating Holstein and Simmental cows were collected and analyzed with both devices (whole blood) and in a laboratory (serum). Correlation coefficients between whole-blood and serum BHBA concentrations were highly significant, with 94% for the FSP and 80% for the GLX device. Based on thresholds for subclinical ketosis of 1.2 and 1.4 mmol of BHBA/L, results obtained with the hand-held devices were evaluated by receiver operating characteristics analyses. This resulted in adjusted thresholds of 1.2 and 1.4 mmol/L for the FSP and 1.1 and 1.3 mmol/L for the GLX device. Applying these thresholds, sensitivities were 98 and 100% for the FSP and 80 and 86% for the GLX device, respectively. Corresponding specificities were 90 and 97% for the FSP and 87 and 96% for the GLX device, respectively. Additionally, concentrations of BHBA were tested with both devices in whole blood, EDTA-added whole blood, and in their resulting serum and plasma, collected from 65 animals. Determined BHBA concentrations were similar within each device for whole and EDTA-added blood, and in serum and plasma, but differed between whole blood and serum and between EDTA-added blood and plasma. Blood samples with low (0.4 mmol/L), medium (1.1 mmol/L), and high (1.6 mmol/L) BHBA concentrations were stored between +5 to +32°C and analyzed repeatedly at temperature levels differing by 4°C. Additionally, devices and test strips were stored at equal conditions and used for measurement

Exercise-Induced Changes in Metabolic Resposes to Infection in Trained Rats.

DTIC Science & Technology

1981-07-20

superimposed on fasting reduced it in sedentary rats (24). Swimming amplified fasting ketosis and diminished infection ketonemia and markedly decreased...Ketone body metabolism in the ketosis of starvation and alloxan diabetes. J. Biol. Chem. 245:4382-4390, 1970. 22. MOSES, L. E. Determination of oxygen

Biochemical Changes in Tissues during Infectious Illness: Metabolic Consequences of Interactions between Infectious Illness and Forced Exercise.

DTIC Science & Technology

1980-09-01

with the inoculation of S. typhimurium at 24 hrs post infection. Fasting ketosis was dramatically altered by the inoculation. Both plasma...as were both fasting and exercise associated ketosis . During fasting plasma Phydroxybutyrate increased 20-fold in the controls but only 13-fold in

The relationship between herd level disease incidence and a return over feed index in Ontario dairy herds.

PubMed

McLaren, Chris J; Lissemore, Kerry D; Duffield, Todd F; Leslie, Ken E; Kelton, David F; Grexton, Bill

2006-08-01

The objective of the current research was to examine the association of herd level disease incidence with the return over feed (ROF) (milk income minus feed cost) herd profit index offered through Canwest Dairy Herd Improvement. The lactational incidence risks (LIR) for displaced abomasum, retained placenta, clinical mastitis, milk fever, clinical ketosis, and lameness submitted by producers (n = 48) were similar to previous reports. However, there was no negative association of clinical disease LIR's with ROE Subclinical ketosis and subclinical mastitis cumulative incidence were determined during the early postpartum period by using a cow-side test for betahydroxybutyrate in milk and the California Mastitis Test, respectively. Subclinical mastitis was not associated with ROE However, a unit increase in the cumulative incidence of subclinical ketosis was associated with a decrease of dollars 0.015/cow/day in the ROE The results highlight the economic significance that subclinical ketosis may have in Ontario dairy herds.

Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.

PubMed

Courchesne-Loyer, Alexandre; Croteau, Etienne; Castellano, Christian-Alexandre; St-Pierre, Valérie; Hennebelle, Marie; Cunnane, Stephen C

2017-07-01

Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11 C-AcAc and 18 F-fluorodeoxyglucose ( 18 F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12-24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

Catecholamine, Corticosteroid and Ketone Excretion in Exercise and Hypoxia,

DTIC Science & Technology

OHCS excretion tended to be higher during the experimental period and subsequently lower overnight during the hypoxia week. Ketosis occurred in two...subjects. In one of these it could be readily related to previous extraneous stress. Excretion of unidentified ketones in overnight urines was sometimes suspected and occurred beyond doubt following gross ketosis . (Author)

Improving Warfighters’ Sustainment and Performance in Extreme Environmental Conditions

DTIC Science & Technology

2008-02-18

Physiol, 485 ( Pt 2) (1995) 525-530. 9. Puchowicz,M.A., Xu,K., Sun,X., Ivy,A., Emancipator,D., and LaManna,J.C., Diet-induced ketosis increases...2002) 1131-1139. 27. Puchowicz,M.A., Xu,K., Sun,X., Ivy,A., Emancipator,D., and LaManna,J.C., Diet-induced ketosis increases capillary density

Effect of Inflammatory and Noninflammatory Stress on Beta-Hydroxybutyrate and Free Fatty Acids in Rat Blood.

DTIC Science & Technology

fasting plus screen-restraint and fasting plus femoral fracture. Inflammatory stresses caused a marked inhibition of the normal fasting-induced ketosis ...and a reduction in the level of circulating free fatty acids. Noninflammatory stresses caused no inhibition of the normal fasting-induced ketosis but did cause a reduction in the level of circulating free fatty acids. (Author)

The economic impact of subclinical ketosis at the farm level: Tackling the challenge of over-estimation due to multiple interactions.

PubMed

Raboisson, D; Mounié, M; Khenifar, E; Maigné, E

2015-12-01

Subclinical ketosis (SCK) is a major metabolic disorder that affects dairy cows, and its lactational prevalence in Europe is estimated to be at 25%. Nonetheless, few data are available on the economics of SCK, although its management clearly must be improved. With this in mind, this study develops a double-step stochastic approach to evaluate the total cost of SCK to dairy farming. First, all the production and reproduction changes and all the health disorders associated with SCK were quantified using the meta-analysis from a previous study. Second, the total cost of SCK was determined with a stochastic model using distribution laws as input parameters. The mean total cost of SCK was estimated to be Є257 per calving cow with SCK (95% prediction interval (PI): Є72-442). The margin over feeding costs slightly influenced the results. When the parameters of the model are not modified to account for the conclusions from the meta-analysis and for the prevalence of health disorders in the population without SCK, the mean cost of SCK was overestimated by 68%, reaching Є434 per calving cow (95%PI: Є192-676). This result indicates that the total cost of complex health disorders is likely to be substantially overestimated when calculations use raw results from the literature or-even worse-punctual data. Excluding labour costs in the estimation reduced the SCK total cost by 12%, whereas excluding contributors with scarce data and imprecise calibrations (for lameness and udder health) reduced costs by another 18-20% (Є210, 95%PI=30-390). The proposed method accounted for uncertainty and variability in inputs by using distributions instead of point estimates. The mean value and associated prediction intervals (PIs) yielded good insight into the economic consequences of this complex disease and can be easily and practically used by decision makers in the field while simultaneously accounting for biological variability. Moreover, PIs can help prevent the blind use of economic

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

2015-04-01

A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

PubMed

Piantoni, P; Allen, M S

2015-08-01

To evaluate propylene glycol (PG) and glycerol (G) as potential treatments for ketosis, we conducted 2 experiments lasting 4 d each in which cows received one bolus infusion per day. Blood was collected before infusion, over 240min postinfusion, as well as 24 h postinfusion. Experiment 1 used 6 ruminally cannulated cows (26±7 d in milk) randomly assigned to 300-mL infusions of PG or G (both ≥99.5% pure) in a crossover design experiment with 2 periods. Within each period, cows were assigned randomly to infusion site sequence: abomasum (A)-cranial reticulorumen (R) or the reverse, R-A. Glucose precursors were infused into the R to simulate drenching and the A to prevent metabolism by ruminal microbes. Glycerol infused in the A increased plasma glucose concentration the most (15.8mg/dL), followed by PG infused in the R (12.6mg/dL), PG infused in the A (9.11mg/dL), and G infused in the R (7.3mg/dL). Infusion of PG into the R increased plasma insulin and insulin area under the curve (AUC) the most compared with all other treatments (7.88 vs. 2.13μIU/mL and 321 vs. 31.9min×μIU/mL, respectively). Overall, PG decreased plasma BHBA concentration after infusion (-6.46 vs. -4.55mg/dL) and increased BHBA AUC (-1,055 vs. -558min ×mg/dL) compared with G. Plasma NEFA responses were not different among treatments. Experiment 2 used 8 ruminally cannulated cows (22±5 d in milk) randomly assigned to treatment sequence in a Latin square design experiment balanced for carryover effects. Treatments were 300mL of PG, 300mL of G, 600mL of G (2G), and 300mL of PG + 300mL of G (GPG), all infused into the R. Treatment contrasts compared PG with each treatment containing glycerol (G, 2G, and GPG). Propylene glycol increased plasma glucose (14.0 vs. 5.35mg/dL) and insulin (7.59 vs. 1.11μIU/mL) concentrations compared with G, but only tended to increase glucose and insulin concentrations compared with 2G. Propylene glycol increased AUC for glucose (1,444 vs. 94.3mg/dL) and insulin (326

Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.

PubMed

Bhanpuri, Nasir H; Hallberg, Sarah J; Williams, Paul T; McKenzie, Amy L; Ballard, Kevin D; Campbell, Wayne W; McCarter, James P; Phinney, Stephen D; Volek, Jeff S

2018-05-01

Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m -2 ). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10 -12 ), LDL-P size (+ 1.1%, P = 6.0 × 10 -10 ), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10 -16 ), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10 -7 ), triglyceride/HDL-C ratio (- 29.1%, P < 10 -16 ), large VLDL-P (- 38.9%, P = 4.2 × 10 -15 ), and LDL-C (+ 9.9%, P = 4.9 × 10 -5 ). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10 -7 ) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10 -5 ). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P�

Significant changes in ITIH4, AHSG, ORM1, and CD46 content in milk fat globule membrane proteins of ketotic dairy cows.

PubMed

Gao, Sansi; Yang, Wei; Yu, Hongjiang; Liu, Runqi; Dong, Zhihao; Zhang, Hongyou; Xia, Cheng; Xu, Chuang

2017-11-01

High concentrations of non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHBA) in cows' blood caused by ketosis are associated with inflammatory states. We hypothesised that ketosis in postparturient dairy cows would result in altered levels on inflammation-related proteins not only in plasma but also in the milk fat globule membranes (MFGM). Thirty cows were selected from a dairy farm in Heilongjiang, China. Inflammatory milk fat globule membrane proteins were detected using ELISA kits, and a fully automatic biochemical analyser was used to measure the concentrations of BHBA, NEFA, glucose (GLU) and triglyceride (TG) in plasma. MFGM protein from milk of ketotic cows contained significantly different concentrations of acute-phase response proteins (complement C3 (C3), prothrombin (F2), alpha-1-acid glycoprotein (ORM1), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), alpha-2-HS-glycoprotein (AHSG), complement C9 (C9), complement regulatory protein variant 4 (CD46)) in comparison with milk from non-ketotic cows. Blood concentrations of C3, complement C9 (C9), tumour necrosis factor α (TNFα), MFGM C3, monocyte differentiation antigen CD14 (CD14) and ORM1 levels were correlated with energy balance. ITIH4 and CD46 increased, and AHSG and ORM1 decreased before the onset of ketosis. These biomarkers offer potential as predictors and monitors of ketosis in at-risk cows.

Decreased carbon shunting from glucose towards oxidative metabolism in diet-induced ketotic rat brain

PubMed Central

Zhang, Yifan; Zhang, Shenghui; Marin-Valencia, Isaac; Puchowicz, Michelle A.

2014-01-01

The mechanistic link of ketosis to neuroprotection under certain pathological conditions continues to be explored. We investigated whether chronic ketosis induced by ketogenic diet results in the partitioning of ketone bodies towards oxidative metabolism in brain. We hypothesized that diet-induced ketosis results in increased shunting of ketone bodies towards citric acid cycle (CAC) and amino acids with decreased carbon shunting from glucose. Rats were fed standard (STD) or ketogenic (KG) diets for 3.5 weeks and then infused with [U-13C]glucose or [U-13C]acetoacetate tracers. Concentrations and 13C-labeling pattern of CAC intermediates and amino acids were analyzed from brain homogenates using stable isotopomer mass spectrometry analysis. The contribution of [U-13C]glucose to acetyl-CoA and amino acids decreased by ~30% in the KG group vs STD, whereas [U-13C]acetoacetate contributions were more than 2-fold higher. The concentration of GABA remained constant across all groups; however, the 13C-labeling of GABA was markedly increased in the KG group infused with [U-13C]acetoacetate compared to STD. This study reveals that there is a significant contribution of ketone bodies to oxidative metabolism and GABA in diet-induced ketosis. We propose that this represents a fundamental mechanism of neuroprotection under pathological conditions. PMID:25314677

Economic Synergy between Dry Cow Diet Improvement and Monensin Bolus Use to Prevent Subclinical Ketosis: An Experimental Demonstration Based on Available Literature

PubMed Central

Raboisson, Didier; Barbier, Maxime

2017-01-01

The prevention of subclinical ketosis (SCK) is based on maintaining adequate nutrition in dairy cows during the dry period and close to calving. Recently, an oral-route monensin bolus to prevent SCK was approved in Europe. The present study aims to define the allocation of resources for SCK management at the herd level and evaluate the profitability of administering monensin boluses in cows at risk for SCK. A stochastic model was used to calculate the total cost of SCK for a population with a given prevalence of cows at risk for SCK. This model included the ability of the farmer to correctly target and preventatively treat these cows at risk for SCK. The results clearly demonstrated economic synergy between two management practices. First, reducing the prevalence of cows at risk for SCK dramatically reduces the total cost of SCK and seems profitable in most situations. Second, monensin bolus use to reduce the occurrence of SCK in cows already at risk for SCK is cost-effective. The results also highlighted three economic strategies to manage SCK in the dairy industry in Europe. First, monensin bolus use throughout an entire herd when the prevalence of cows at risk for SCK is high is only profitable in the short-term as a tool to correct acute deterioration at the herd level. Second, decreasing the prevalence of cows at risk for SCK through adequate feeding in the dry period is of financial interest as a baseline strategy when prevalence is high, assuming moderate additional cost linked to the new diet. Third, monensin bolus use when the prevalence of cows at risk for SCK is low is also profitable as a long-term strategy when only cows at high risk for SCK (such as cows that are over-conditioned, old, or have a previous history of SCK-related disorders) are targeted for preventative treatment. Authors suggest to use the present results considering that farmers have a correct, but not perfect, ability to target animals to be preventively targeted with the monensin

Economic Synergy between Dry Cow Diet Improvement and Monensin Bolus Use to Prevent Subclinical Ketosis: An Experimental Demonstration Based on Available Literature.

PubMed

Raboisson, Didier; Barbier, Maxime

2017-01-01

The prevention of subclinical ketosis (SCK) is based on maintaining adequate nutrition in dairy cows during the dry period and close to calving. Recently, an oral-route monensin bolus to prevent SCK was approved in Europe. The present study aims to define the allocation of resources for SCK management at the herd level and evaluate the profitability of administering monensin boluses in cows at risk for SCK. A stochastic model was used to calculate the total cost of SCK for a population with a given prevalence of cows at risk for SCK. This model included the ability of the farmer to correctly target and preventatively treat these cows at risk for SCK. The results clearly demonstrated economic synergy between two management practices. First, reducing the prevalence of cows at risk for SCK dramatically reduces the total cost of SCK and seems profitable in most situations. Second, monensin bolus use to reduce the occurrence of SCK in cows already at risk for SCK is cost-effective. The results also highlighted three economic strategies to manage SCK in the dairy industry in Europe. First, monensin bolus use throughout an entire herd when the prevalence of cows at risk for SCK is high is only profitable in the short-term as a tool to correct acute deterioration at the herd level. Second, decreasing the prevalence of cows at risk for SCK through adequate feeding in the dry period is of financial interest as a baseline strategy when prevalence is high, assuming moderate additional cost linked to the new diet. Third, monensin bolus use when the prevalence of cows at risk for SCK is low is also profitable as a long-term strategy when only cows at high risk for SCK (such as cows that are over-conditioned, old, or have a previous history of SCK-related disorders) are targeted for preventative treatment. Authors suggest to use the present results considering that farmers have a correct, but not perfect, ability to target animals to be preventively targeted with the monensin

Concentrations of plasma metabolites, hormones, and mRNA abundance of adipose leptin and hormone-sensitive lipase in ketotic and nonketotic dairy cows.

PubMed

Xia, C; Wang, Z; Xu, C; Zhang, H Y

2012-01-01

Ketosis is an important metabolic disorder of dairy cows during the transition period. There have been many reports on the etiology of ketosis in periparturient cows, but little is known about its molecular etiology. The objective of this study was to clarify the status of fat mobilization and mRNA abundance of leptin and hormone-sensitive lipase in cows with spontaneous clinical ketosis. Ten ketotic Holstein cows and 10 nonketotic Holstein cows were used as the experimental animals. Six blood biochemical parameters were evaluated by means of individual analysis method for 2 groups of cows. The mRNA abundance of leptin and hormone-sensitive lipase in tail fat tissue from 2 groups of cows was measured by real-time (RT)-PCR, with a fluorescent Taqman probe and a standard curve. The plasma concentrations of glucose (P = 0.01), and leptin (P = 0.03), insulin (P = 0.05), and the ratio of insulin to glucagon (P = 0.04) were lower in ketotic compared with nonketotic cows, whereas there were marked increases in the plasma concentrations of nonesterified fatty acid and β-hydroxybutyric acid (P = 0.005). The mRNA abundance of leptin (P = 0.04) and hormone-sensitive lipase (P = 0.02) in the fat tissue of ketotic cows was lower relative to that of nonketotic cows. The ketotic cows showed characteristics of type I ketosis and some adaptive changes to negative energy balance in the plasma leptin concentration and mRNA abundance of fat leptin and hormone-sensitive lipase. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Evaluation of the use of nonesterified fatty acids and β-hydroxybutyrate concentrations in pooled serum samples for herd-based detection of subclinical ketosis in dairy cows during the first week after parturition.

PubMed

Borchardt, Stefan; Staufenbiel, Rudolf

2012-04-15

To evaluate the use of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations in pooled serum samples for herd-based detection of subclinical ketosis (SCK) in dairy cows after calving. Cross-sectional study. 1,100 dairy cows from 110 herds. Blood samples were collected from 10 healthy cows/herd in the first week after parturition. Aliquots of serum were mixed to create a pooled sample. Concentrations of NEFA and BHBA were measured to estimate prevalence of SCK. Pooled sample test results were compared with those obtained for individual samples. Linear regression and receiver-operating characteristic curve analysis were performed; Bland-Altman plots were used to evaluate agreement between methods. Overall prevalence of SCK was 30.7%, 19.3%, and 13.6%, as determined by use of BHBA threshold concentrations of 1,000, 1,200, and 1,400 μmol/L, respectively. Pooled sample concentrations of NEFA and BHBA were significantly correlated (r = 0.98 and 0.97, respectively) with individual sample means and with the number of cows that had NEFA (R(2) range, 0.81 to 0.84) or BHBA (R(2) range, 0.65 to 0.76) concentrations above predefined thresholds. Pooled sample concentrations of NEFA and BHBA were very accurate to highly accurate for herd-based detection of SCK. Analysis of NEFA and BHBA concentrations in pooled serum samples was useful for herd-based detection of SCK. A sample size of 10 cows/herd was deemed adequate for monitoring dairy herds for SCK. Reference criteria specific to pooled samples should be used for this type of herd-based testing.

Acid-base safety during the course of a very low-calorie-ketogenic diet.

PubMed

Gomez-Arbelaez, Diego; Crujeiras, Ana B; Castro, Ana I; Goday, Albert; Mas-Lorenzo, Antonio; Bellon, Ana; Tejera, Cristina; Bellido, Diego; Galban, Cristobal; Sajoux, Ignacio; Lopez-Jaramillo, Patricio; Casanueva, Felipe F

2017-10-01

Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment. Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis. During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.

Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study

PubMed Central

2011-01-01

Background To examine the effect of genetic variation in APOE, IDE and IL1B on the response to induced ketosis in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in subjects with mild to moderate Alzheimer's disease (AD). Methods Genotype effects on ADAS-Cog scores from a randomized, double-blind, placebo-controlled study in mild to moderate AD were examined by an overall two way analysis of variance. In addition, interactions with the carriage status of the epsilon 4 allele of the APOE gene (APOE4) were examined. Results Significant differences in response to induced ketosis were found among non-carriers of putative gain-of-function polymorphisms in rs1143627 and rs16944 in the IL1B gene and among variants of the polymorphism rs2251101 in the IDE gene. Significant differences were found among non-carriers of the APOE4 gene, with notable improvement among the E3/E3 genotype group. Conclusions Variants in APOE, IL1B and IDE may influence the cognitive response to induced ketosis in patients with mild to moderate AD. Trial registration This trial was registered with ClinicalTrials.gov, registry number NCT00142805. PMID:21992747

A case of idiopathic type 1 diabetes with subsequent recovery of endogenous insulin secretion despite initial diagnosis of fulminant type 1 diabetes.

PubMed

Kaneko, Keizo; Satake, Chihiro; Yamamoto, Junpei; Takahashi, Hironori; Sawada, Shojiro; Imai, Junta; Yamada, Tetsuya; Katagiri, Hideki

2017-03-31

Fulminant type 1 diabetes is characterized by remarkably rapid and complete β-cell destruction. The established diagnostic criteria include the occurrence of diabetic ketosis soon after the onset of hyperglycemic symptoms, elevated plasma glucose with relatively low HbA1c at the first visit, and extremely low C-peptide. Serum C-peptide levels remain extremely low over a prolonged period. A 26-year-old-man with diabetic ketosis was admitted to our hospital. His relatively low HbA1c (7.6%), despite marked hyperglycemia (593 mg/dL) with marked ketosis, indicated abrupt onset. Islet-related autoantibodies were all negative. His data at onset, including extremely low serum C-peptide (0.11 ng/mL), fulfilled the diagnostic criteria for fulminant type 1 diabetes. However, his fasting serum C-peptide levels subsequently showed substantial recovery. While fasting C-peptide stayed below 0.30 ng/mL during the first two months post onset, the levels gradually increased and thereafter fluctuated between 0.60 ng/mL and 0.90 ng/mL until 24 months post onset. By means of multiple daily insulin injection therapy, his glycemic control has been well maintained (HbA1c approximately 6.0%), with relatively small glycemic fluctuations evaluated by continuous glucose monitoring. This clinical course suggests that, despite the abrupt diabetes onset with extremely low C-peptide levels, substantial numbers of β-cells had been spared destruction and their function later showed gradual recovery. Diabetes has come to be considered a much more heterogeneous disease than the present subdivisions suggest. This case does not fit into the existing concepts of either fulminant type 1 or ketosis-prone diabetes, thereby further highlighting the heterogeneity of idiopathic type 1 diabetes.

Nutritional and metabolic diseases involving the nervous system.

PubMed

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

PubMed

Gibson, A A; Seimon, R V; Lee, C M Y; Ayre, J; Franklin, J; Markovic, T P; Caterson, I D; Sainsbury, A

2015-01-01

Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet. © 2014 International Association for the Study of Obesity (IASO).

Hyperemesis Gravidarum (HG)

MedlinePlus

... of vomiting (e.g. gastric ulcers, esophageal bleeding, malnutrition, etc.) may also contribute to and worsen ongoing ... vomiting include debilitating fatigue, gastric irritation, ketosis, and malnutrition. Aggressive care early in pregnancy is very important ...

Nutrition and udder health in dairy cows: a review

PubMed Central

2009-01-01

Mastitis is still one of the three main diseases that affects the profitability of dairy farmers. Despite the implementation of the five-point mastitis control programme in the early 1970 s, the incidence in the UK has not reduced dramatically over the past 10 years. A review of the scientific literature indicates that there is a link between nutrition and mastitis in the dairy cow. The major impact of nutrition on udder health is via suppression of the immune system. Cows in negative energy balance are at a higher risk of ketosis and clinical ketosis is associated with a two-fold increase in the risk of clinical mastitis. Trace minerals and vitamins that can affect udder health are selenium and vitamin E, copper, zinc, and vitamin A and β-carotene. PMID:22082340

Genetics Home Reference: glycogen storage disease type VI

MedlinePlus

... glucose, a simple sugar that is the main energy source for most cells in the body. PYGL gene mutations prevent liver glycogen phosphorylase from breaking down glycogen ... energy, resulting in ketosis. Glycogen accumulates within liver cells, ...

Ketogenic Diet in Refractory Childhood Epilepsy

PubMed Central

Weijenberg, Amerins; van Rijn, Margreet; de Koning, Tom J.; Brouwer, Oebele F.

2018-01-01

Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis. PMID:29872664

Ketogenic Diet in Refractory Childhood Epilepsy: Starting With a Liquid Formulation in an Outpatient Setting.

PubMed

Weijenberg, Amerins; van Rijn, Margreet; Callenbach, Petra M C; de Koning, Tom J; Brouwer, Oebele F

2018-01-01

Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

Associations between subclinical hypocalcemia and postparturient diseases in dairy cows.

PubMed

Rodríguez, E M; Arís, A; Bach, A

2017-09-01

Dairy cows suffer blood Ca losses as lactation begins and might be affected by hypocalcemia in its clinical (total serum Ca concentration <1.50 mM) or subclinical form (total serum Ca concentration ≤2.14 mM). Several studies have suggested that hypocalcemia is associated with different health problems of the cow but results from different studies are not consistent. The objective of this study was to assess potential associations between subclinical hypocalcemia (SCHC) and displaced abomasum, intramammary infections, metritis, retained placenta, and ketosis. Also, the associations between SCHC and milk yield and reproductive function were evaluated. After discarding cows (32) with clinical hypocalcemia, a total of 764 cows from 6 different commercial farms were enrolled in this study. Blood samples were collected at 24 to 48 h postcalving and analyzed for total Ca concentration. Odds ratios of the different afflictions potentially associated with SCHC were calculated. Seventy-eight percent of the analyzed cows incurred SCHC. The occurrence of displaced abomasum, ketosis, retained placenta, and metritis was 3.7, 5.5, 3.4, and 4.3 times more likely, respectively, in cows that had SCHC than in cows with normocalcemia. Furthermore, the risk of incurring retained placenta or metritis increased in multiparous cows as serum Ca concentrations decreased compared with that in primiparous cows. Normocalcemic cows, independent of parity, were more likely to show their first estrus sooner after calving than SCHC cows, but no correlation was found between SCHC and other reproductive parameters. Different serum Ca concentration cutoffs were identified for several postpartum afflictions (≤1.93, ≤2.05, ≤2.05, and ≤2.10 mM for ketosis, retained placenta, metritis, and displaced abomasum, respectively). In conclusion, SCHC, defined as serum Ca ≤2.14 mM, is a frequent illness affecting the majority of the dairy cows with important repercussions on health. However, if SCHC

21 CFR 862.1435 - Ketones (nonquantitative) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... acidity of body fluids) or ketosis (a condition characterized by increased production of ketone bodies...

21 CFR 862.1435 - Ketones (nonquantitative) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... acidity of body fluids) or ketosis (a condition characterized by increased production of ketone bodies...

21 CFR 862.1435 - Ketones (nonquantitative) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... acidity of body fluids) or ketosis (a condition characterized by increased production of ketone bodies...

21 CFR 522.540 - Dexamethasone injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) For the treatment of primary bovine ketosis and as an anti-inflammatory agent in cattle and horses; (B... precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv... premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv) Not for use...

21 CFR 522.540 - Dexamethasone.

Code of Federal Regulations, 2013 CFR

2013-04-01

...: (A) For the treatment of primary bovine ketosis and as an anti-inflammatory agent in cattle and... precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv... followed by dystocia, fetal death, retained placenta, and metritis. (iv) Not for use in horses intended for...

21 CFR 522.540 - Dexamethasone injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) For the treatment of primary bovine ketosis and as an anti-inflammatory agent in cattle and horses; (B... precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv... premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv) Not for use...

21 CFR 522.540 - Dexamethasone injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) For the treatment of primary bovine ketosis and as an anti-inflammatory agent in cattle and horses; (B... precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv... premature parturition followed by dystocia, fetal death, retained placenta, and metritis. (iv) Not for use...

Case 22:Type II diabetes

USDA-ARS?s Scientific Manuscript database

Diabetes mellitus is characterized by elevated blood glucose levels. It is composed of two types depending on the pathogenesis. Type I diabetes is characterized by insulin deficiency and usually has its onset during childhood or teenage years. This is also called ketosis-prone diabetes. Type II diab...

Fulminant type 1 diabetes mellitus: a case report

NASA Astrophysics Data System (ADS)

Yunir, E.; Nenfiati

2018-03-01

Type 1 diabetes mellitus is a metabolic disease caused by insulin deficiency that results from destruction of β-cells in the pancreas. Based on American Diabetes Association, there are two types of type 1 diabetes mellitus: type 1A (autoimmune) and 1B (idiopathic). In this case, we are presenting a new archetype of type 1 diabetes named fulminant type 1 diabetes mellitus. This disease results from quick destruction of β-cells byanautoimmune mechanism. The manifestation of this disease consists of unspecific flu-like symptoms, abdominal symptoms, to specific hyperglycemia symptoms such as fatigue, malaise, change in mental status that are attributable to high blood glucose and ketosis. Laboratory examination reveals high blood glucose, normal glycosylated hemoglobin, ketosis or ketoacidosis, potassium depletion and elevation of liver function tests. Treatment consists of intravenous infusion followed by insulin injection for blood glucose control, followed by treatment of metabolic derangements such as acid-base and electrolyte disorder.

Accuracy of a cow-side test for the diagnosis of hyperketonemia and hypoglycemia in lactating dairy cows.

PubMed

Macmillan, K; López Helguera, I; Behrouzi, A; Gobikrushanth, M; Hoff, B; Colazo, M G

2017-12-01

The objective of this study was to evaluate the use of a cow-side device (FreeStyle Precision Neo™) to diagnose ketosis and hypoglycemia based on measures of blood β-hydroxybutyrate (BHBA) and glucose. Eleven commercial dairy farms were visited and blood samples were taken from Holstein cows between 2 and 14days in milk, yielding 441 samples for BHBA analysis and 308 samples for glucose analysis. Concentrations of BHBA and glucose were measured in two ways, 1) using the cow-side device with whole blood immediately after sampling and 2) serum samples analyzed with a standard laboratory assay (Animal Health Laboratory, University of Guelph, Canada). The accuracy of the device was determined by comparing the results to the laboratory method as well as the ability to diagnose ketosis (BHBA ≥1.2mmol/L) and hypoglycemia (glucose <2.5mmol/L). The concordance correlation coefficient (CCC), Bland-Altman plot and Kappa coefficient were calculated to evaluate agreement between the 2 methods using SAS (version 9.3). The CCC was 0.92 for BHBA and 0.56 for glucose measurements. The 95% confidence intervals of the Bland-Altman plot encompassed 97% and 95% of the mean difference between methods for BHBA and glucose measurements, respectively. The Kappa coefficients were 0.78 for BHBA and 0.23 for glucose measurements. These results indicate that the cow-side device is accurate for rapid measurement of blood BHBA and diagnosis of ketosis on farms but is not accurate for measurement of blood glucose concentrations and diagnosis of hypoglycemia. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Ketotic hyperglycemia with movement disorder

PubMed Central

Awasthi, Disha; Tiwari, Akhilesh Kumar; Upadhyaya, Abhinav; Singh, Balwinder; Tomar, Gaurav Singh

2012-01-01

Chorea, hemichorea-hemiballismus and severe partial seizures may be the presenting features of nonketotic hyperglycemia in older adults with type 2 diabetes, but cases in young adults with type 1 diabetes are rare. We hereby report a very rare case of diabetic ketosis with movement disorder in a young patient. PMID:22416165

Evaluation of the Nova Vet Meter for sheep-side monitoring of β-hydroxybutyric acid (BHBA) and description of ewe BHBA during late gestation in three flocks from the Northeastern U.S.

PubMed

Jones, Amanda K; Gately, Rachael E; Kellogg, Tasia D; Zinn, Steven A; Govoni, Kristen E; Reed, Sarah A

2018-05-07

Prevention of metabolic diseases in small ruminants may improve production efficiency and profitability, yet ewes carrying multiples or who are in poor body condition are at increased susceptibility to develop ketosis. This study evaluated the hand-held Nova Vet Meter to accurately detect β-hydroxybutyric acid (BHBA) concentrations in ewes and determined the percentage of ewes at moderate (0.8 to 1.5 mmol/L BHBA) and greatest (≥1.6 mmol/L BHBA) risk to develop ketosis during late gestation. To validate the Nova Vet Meter, BHBA concentrations of 104 paired blood samples were measured using the Nova Vet Meter and gold-standard laboratory analysis. Receiver operating characteristics were calculated. The accuracy and sensitivity of detecting BHBA concentrations at 0.8 to 1.5 mmol/L were 94.2% and 97.3%, respectively. The accuracy and sensitivity of detecting BHBA concentrations ≥ 1.6 mmol/L were 98.0% and 50.0%, respectively. Ewe body weight (BW), body condition score (BCS), and BHBA of 117 ewes from three flocks were determined weekly during the four weeks before parturition. During the last three weeks of gestation >20% of ewes were identified with moderate risk to develop ketosis. During the last four weeks of gestation, ewes carrying triplets had reduced BCS (P = 0.0002) and increased BHBA concentrations (P < 0.0001) compared with singleton and twin pregnancies. Ewe BHBA did not correlate with lamb birth weight (R 2  = 0.003; P = 0.41). In conclusion, the Nova Vet Meter is suitable for sheep-side BHBA monitoring between 0.8 and 1.5 mmol/L, but further testing is necessary to evaluate BHBA readings ≥1.6 mmol/L. Copyright © 2018 Elsevier Ltd. All rights reserved.

Energy balance in transition cows and its association with health, reproduction and milk production.

PubMed

Furken, C; Nakao, T; Hoedemaker, M

2015-01-01

It was the purpose of this study to determine the effects of non-esterified fatty acids (NEFA) concentrations at different time periods of the transition period as well as lactation number on metabolism, health, reproduction and milk production in dairy cows. This trial was conducted in a single dairy herd located in Northern Germany. Of the herd, which comprised 330 lactating Holstein cows housed in a free stall barn and fed a total mixed ration (TMR), 83 primiparous and multiparous cows were randomly selected. Animals were checked for body condition score (BCS), locomotion score, calving data, quality of colostrum, reproductive measures, daily rectal temperature of the first 10 days post-partum (p. p.), health data and culling rates up to 200 days in milk (DIM) as well as milk production until 305 DIM. Three different time periods were considered: 3 and 1 week ante partum (a. p.); partus and 1 week p. p.; 3 weeks p. p. Animals with NEFA concentrations ≥ 0.4 mmol/l ante partum had a higher risk of no ovarian activity in week 5 p. p. and of subclinical ketosis post partum than cows with lower NEFA concentrations (p < 0.05). Cows with NEFA concentrations ≥ 1.1 mmol/l in week 1 p. p., in comparison to those with lower NEFA concentrations, showed a higher prevalence of clinical ketosis (24.1% vs. 5.9%), subclinical ketosis (62.1% vs. 34.0%) and culling rate within 200 DIM (34.5% vs. 14.0%) (p    <   0.05). Cows with NEFA concentrations ≥ 0.3 mmol/l at week 3 p. p. had higher 100- and 305-day milk yields than cows with lower NEFA concentrations (p < 0.05). First lactating heifers were at higher risk to loose body condition ante partum, of dystocia, fever within the first 10 DIM, metritis, clinical and subclinical ketosis as well as to develop a disease within the first 30 DIM (p < 0.05). Multipara were more likely to loose body condition after calving, to a prolonged calving to first service interval and to higher

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

PubMed

Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

2017-02-01

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

PubMed

Melchior, R W; Dreher, M; Ramsey, E; Savoca, M; Rosenthal, T

2015-07-01

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. 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. 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. © The Author(s) 2014.

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows.

PubMed

González, Felix Diaz; Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

2011-09-01

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea.

Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

PubMed

Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

2016-03-01

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

Study of the exhaled acetone in type 1 diabetes using quantum cascade laser spectroscopy.

PubMed

Reyes-Reyes, Adonis; Horsten, Roland C; Urbach, H Paul; Bhattacharya, Nandini

2015-01-06

The acetone concentration exhaled in the breath of three type 1 diabetes patients (two minors and one adult) and one healthy volunteer is studied using a quantum cascade laser-based spectroscopic system. Using the acetone signature between 1150 and 1250 cm(-1) and a multiline fitting method, the concentration variations on the order of parts per billion by volume were measured. Blood glucose and ketone concentrations in blood measurements were performed simultaneously to study their relation with acetone in exhaled breath. We focus on personalized studies to better understand the role of acetone in diabetes. For each volunteer, we performed a series of measurements over a period of time, including overnight fastings of 11 ± 1 h and during ketosis-hyperglycemia events for the minors. Our results highlight the importance of performing personalized studies because the response of the minors to the presence of ketosis was consistent but unique for each individual. Also, our results emphasize the need for performing more studies with T1D minors, because the acetone concentration in the breath of the minors differs, with respect to those reported in the literature, which are based on adults.

The Use of Ketogenic Diet in Pediatric Patients with Epilepsy

PubMed Central

Misiewicz Runyon, Amanda; So, Tsz-Yin

2012-01-01

A ketogenic diet is a nonpharmacologic treatment strategy to control refractory epilepsy in children. Although this diet has been used successfully to reduce seizures since the 1920s, the anticonvulsant mechanism of ketosis remains unknown. The initiation of the diet requires an average four-day hospitalization to achieve ketosis in the patient as well as to provide thorough education on diet maintenance for both the patient and the caregivers. A ketogenic diet, consisting of low carbohydrate and high fat intake, leaves little room for additional carbohydrates supplied by medications. Patients on ketogenic diets who exceed their daily carbohydrate limit have the risk of seizure relapse, necessitating hospital readmission to repeat the diet initiation process. These patients are at a high risk for diversion from the diet. Patients admitted to the hospital setting are often initiated on multiple medications, and many hospital systems are not equipped with appropriate monitoring systems to prevent clinicians from introducing medications with high carbohydrate contents. Pharmacists have the resources and the expertise to help identify and prevent the initiation of medications with high carbohydrate content in patients on ketogenic diets. PMID:22970384

Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus.

PubMed

Arya, Ravindra; Peariso, Katrina; Gaínza-Lein, Marina; Harvey, Jessica; Bergin, Ann; Brenton, J Nicholas; Burrows, Brian T; Glauser, Tracy; Goodkin, Howard P; Lai, Yi-Chen; Mikati, Mohamad A; Fernández, Iván Sánchez; Tchapyjnikov, Dmitry; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2018-04-27

To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded. Fourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range [IQR] 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD. EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline. This series suggests efficacy and safety of KD for treatment of pediatric RSE. Copyright © 2018

Genetic Parameters of Milk β-Hydroxybutyric Acid and Acetone and Their Genetic Association with Milk Production Traits of Holstein Cattle

PubMed Central

Lee, SeokHyun; Cho, KwangHyun; Park, MiNa; Choi, TaeJung; Kim, SiDong; Do, ChangHee

2016-01-01

This study was conducted to estimate the genetic parameters of β-hydroxybutyrate (BHBA) and acetone concentration in milk by Fourier transform infrared spectroscopy along with test-day milk production traits including fat %, protein % and milk yield based on monthly samples of milk obtained as part of a routine milk recording program in Korea. Additionally, the feasibility of using such data in the official dairy cattle breeding system for selection of cows with low susceptibility of ketosis was evaluated. A total of 57,190 monthly test-day records for parities 1, 2, and 3 of 7,895 cows with pedigree information were collected from April 2012 to August 2014 from herds enrolled in the Korea Animal Improvement Association. Multi-trait random regression models were separately applied to estimate genetic parameters of test-day records for each parity. The model included fixed herd test-day effects, calving age and season effects, and random regressions for additive genetic and permanent environmental effects. Abundance of variation of acetone may provide a more sensitive indication of ketosis than many zero observations in concentration of milk BHBA. Heritabilities of milk BHBA levels ranged from 0.04 to 0.17 with a mean of 0.09 for the interval between 4 and 305 days in milk during three lactations. The average heritabilities for milk acetone concentration were 0.29, 0.29, and 0.22 for parities 1, 2, and 3, respectively. There was no clear genetic association of the concentration of two ketone bodies with three test-day milk production traits, even if some correlations among breeding values of the test-day records in this study were observed. These results suggest that genetic selection for low susceptibility of ketosis in early lactation is possible. Further, it is desirable for the breeding scheme of dairy cattle to include the records of milk acetone rather than the records of milk BHBA. PMID:27608643

Genetic Parameters of Milk β-Hydroxybutyric Acid and Acetone and Their Genetic Association with Milk Production Traits of Holstein Cattle.

PubMed

Lee, SeokHyun; Cho, KwangHyun; Park, MiNa; Choi, TaeJung; Kim, SiDong; Do, ChangHee

2016-11-01

This study was conducted to estimate the genetic parameters of β-hydroxybutyrate (BHBA) and acetone concentration in milk by Fourier transform infrared spectroscopy along with test-day milk production traits including fat %, protein % and milk yield based on monthly samples of milk obtained as part of a routine milk recording program in Korea. Additionally, the feasibility of using such data in the official dairy cattle breeding system for selection of cows with low susceptibility of ketosis was evaluated. A total of 57,190 monthly test-day records for parities 1, 2, and 3 of 7,895 cows with pedigree information were collected from April 2012 to August 2014 from herds enrolled in the Korea Animal Improvement Association. Multi-trait random regression models were separately applied to estimate genetic parameters of test-day records for each parity. The model included fixed herd test-day effects, calving age and season effects, and random regressions for additive genetic and permanent environmental effects. Abundance of variation of acetone may provide a more sensitive indication of ketosis than many zero observations in concentration of milk BHBA. Heritabilities of milk BHBA levels ranged from 0.04 to 0.17 with a mean of 0.09 for the interval between 4 and 305 days in milk during three lactations. The average heritabilities for milk acetone concentration were 0.29, 0.29, and 0.22 for parities 1, 2, and 3, respectively. There was no clear genetic association of the concentration of two ketone bodies with three test-day milk production traits, even if some correlations among breeding values of the test-day records in this study were observed. These results suggest that genetic selection for low susceptibility of ketosis in early lactation is possible. Further, it is desirable for the breeding scheme of dairy cattle to include the records of milk acetone rather than the records of milk BHBA.

Effects of a combination of plant bioactive lipid compounds and biotin compared with monensin on body condition, energy metabolism and milk performance in transition dairy cows

PubMed Central

Hausmann, Janis; Deiner, Carolin; Patra, Amlan K.; Immig, Irmgard; Starke, Alexander

2018-01-01

The aim of this study was to test whether a combination of plant bioactive lipid compounds (also termed ‘essential oils’) and biotin (PBLC+B) could decrease the mobilization of body reserves and ketosis incidence in postpartum dairy cows. We compared non-supplemented control (CON) cows with cows receiving monensin (MON) as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day (d) -21 before calving until calving (Phase 1) and further until d 37 after calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase 3). The PBLC+B cows had higher body weight and higher back fat thickness than CON cows and lesser body weight change than MON and CON cows in Phase 3. Body condition score was not different among groups. Milk protein concentration tended to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with significantly higher values in PBLC+B vs. MON cows on the second herd test day. Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows, respectively, with lower mean β-hydroxybutyrate values in MON than in PBLC+B cows in Phase 1 prepartum. The serum triglyceride concentration was higher in PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea, non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate transaminase and γ-glutamyltranspeptidase but not glutamate dehydrogenase activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We conclude that PBLC+B prevent body weight loss after parturition and are associated with similar ketosis incidence and partly higher yields of energy-corrected milk compared to MON supplementation of dairy cows. PMID:29584764

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows

PubMed Central

Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

2011-01-01

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea. PMID:21897097

Survey of ketolactia, determining the main predisposing management factors and consequences in Hungarian dairy herds by using a cow-side milk test

PubMed Central

Zechner, Gerhard; Csorba, Csaba; Könyves, László

2018-01-01

The aims of the survey were to determine the prevalence of ketosis in dairy herds by measuring the concentration of beta-hydroxybutyrate (BHBA) in milk by Keto-Test (Sanwa Kagaku Kenkyusho, Nagoya, Japan); risk factors and the relationship with postpartum diseases were investigated. 1667 early lactating (days in milk 0–75) cows were tested in 52 dairy herds in 2013 and 2014 years. In total, 29.3 per cent of samples were positive (BHBAMILK ≥100 µmol/l), including 3.7 per cent high positives (BHBAMILK ≥500 µmol/l). The prevalence was similar in herds with less than or more than 9000 kg milk yield (0.34 and 0.38, respectively, P=0.4); however, it was higher in the herds with more than 1000 cows than in smaller herds (<500 and 500–1000 cows) (0.46, P=0.03). The BHBA level in milk was in a non-linear positive relationship with parity (P=0.01), associated with retained placenta (P=0.0006), mastitis (P=0.02) and clinical ketosis (P<0.001). The results confirm the high prevalence of ketolactia in Hungarian dairy herds and its links to herd-related and cow-related risk factors and diseases occurring commonly in fresh cows. PMID:29868171

The effect of nutritional management of the dairy cow on reproductive efficiency.

PubMed

Roche, James F

2006-12-01

The cause of low fertility in dairy cows is multifactorial. Poor nutrition during the dry and early postpartum periods results in reduced glucose, insulin, insulin-like growth factor (IGF-I) and low LH pulse frequency with concomitant increases in beta-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol. Cows must mobilize large lipid, but also some protein reserves, with a consequent increased incidence of such metabolic disorders as hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and ketosis affects uterine contractions, delays calving and increases the risk of retained foetal membranes (RFM) and endometritis. The nutritional risk factors that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and deficiencies in Vitamin E and selenium. The risk factors for endometritis are hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders predispose cows to gynaecological disorders, thereby reducing reproductive efficiency. Cows that are overconditioned at calving or those that lose excess body weight are more likely to have a prolonged interval to first oestrus, thereby prolonging days open. Nutritionally induced postpartum anoestrus is characterized by turnover of dominant follicles incapable of producing sufficient oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition can also increase metabolic clearance rate of steroid hormones such as progesterone or oestradiol. Lower concentrations of oestradiol on the day of oestrus are highly correlated with the occurrence of suboestrus, thereby making the detection of oestrus in high yielding cows even more difficult. Nutrition also affects conception rate (CR) to AI. Cows that develop hypocalcaemia, ketosis, acidosis or displaced abomasums have lower CRs and take longer to become pregnant. Excessive loss of BCS and excess protein content of the ration can reduce CR while supplemental fats

Ketogenic diet for high partial pressure oxygen diving.

PubMed

Valadao, Jason M; Vigilante, John A; DiGeorge, Nicholas W; O'Connor, Sunila E; Bear, Alexandria; Kenyon, Jeffrey; Annis, Heather; Dituri, Joseph; Dituri, Amy E; Whelan, Harry T

2014-01-01

A ketogenic diet (KD) may decrease central nervous system oxygen toxicity symptoms in divers, and in view of this implication a feasibility/ toxicity pilot study was performed to demonstrate tolerance of KD while performing normal diving profiles. The exact mechanism of neuroprotection from the KD remains unknown; however, evidence to support the efficacy of the KD in reducing seizures is present in epilepsy and oxygen toxicity studies, and may provide valuable insight in diving activities. Three divers (two males and one female ages 32-45 with a history of deep diving and high pO2 exposure) on the KD made dives to varying depths in Hawaii using fully closed-circuit MK-15 and Inspiration rebreathers. These rebreathers have an electronically controlled set point, allowing the divers to monitor and control the oxygen level in the breathing loop, which can be varied manually by the divers. Oxygen level was varied during descent, bottom depth and ascent (decompression). Divers fasted for 12-18 hours before diet initiation. The ketosis level was verified by urinating on a Ketostix (reagent strips for urinalysis). Ketosis was achieved and was easily monitored with Ketostix in the simulated operational environment. The KD did not interfere with the diving mission; no seizure activity or signs or symptoms of CNS toxicity were observed, and there were no adverse effects noted by the divers while on the KD.

Towards practical application of sensors for monitoring animal health: the effect of post-calving health problems on rumination duration, activity and milk yield.

PubMed

Steensels, Machteld; Maltz, Ephraim; Bahr, Claudia; Berckmans, Daniel; Antler, Aharon; Halachmi, Ilan

2017-05-01

Three sources of sensory data: cow's individual rumination duration, activity and milk yield were evaluated as possible indicators for clinical diagnosis, focusing on post-calving health problems such as ketosis and metritis. Data were collected from a computerised dairy-management system on a commercial dairy farm with Israeli Holstein cows. In the analysis, 300 healthy and 403 sick multiparous cows were studied during the first 3 weeks after calving. A mixed model with repeated measurements was used to compare healthy cows with sick cows. In the period from 5 d before diagnosis and treatment to 2 d after it, rumination duration and activity were lower in the sick cows compared to healthy cows. The milk yield of sick cows was lower than that of the healthy cows during a period lasting from 5 d before until 5 d after the day of diagnosis and treatment. Differences in the milk yield of sick cows compared with healthy cows became greater from 5 to 1 d before diagnosis and treatment. The greatest significant differences occurred 3 d before diagnosis for rumination duration and 1 d before diagnosis for activity and milk yield. These results indicate that a model can be developed to automatically detect post-calving health problems including ketosis and metritis, based on rumination duration, activity and milk yield.

On the Metabolism of Exogenous Ketones in Humans

PubMed Central

Stubbs, Brianna J.; Cox, Pete J.; Evans, Rhys D.; Santer, Peter; Miller, Jack J.; Faull, Olivia K.; Magor-Elliott, Snapper; Hiyama, Satoshi; Stirling, Matthew; Clarke, Kieran

2017-01-01

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB. Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and

Insulin suppresses the AMPK signaling pathway to regulate lipid metabolism in primary cultured hepatocytes of dairy cows.

PubMed

Li, Xinwei; Li, Yu; Ding, Hongyan; Dong, Jihong; Zhang, Renhe; Huang, Dan; Lei, Lin; Wang, Zhe; Liu, Guowen; Li, Xiaobing

2018-05-01

Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis. Furthermore, AMPKα inactivation decreased the gene and protein expression levels of peroxisome proliferator-activated receptor-α (PPARα), which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation. In addition, insulin decreased the very low density lipoprotein (VLDL) assembly. Consequently, triglyceride content was significantly increased in insulin treated hepatocytes. Activation of AMPKα induced by AICAR could reverse the effect of insulin on PPARα, SREBP-1c, and ChREBP, thereby decreasing triglyceride content. These results indicate that insulin inhibits the AMPKα signaling pathway to increase lipid synthesis and decrease lipid oxidation and VLDL assembly in cow hepatocytes, thereby inducing TG accumulation. This mechanism could partly explain the causal relationship between hepatic fat accumulation and hyperinsulinemia in dairy cows with type II ketosis.

Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus.

PubMed

Durocher, Lawren L; Hinchcliff, Kenneth W; DiBartola, Stephen P; Johnson, Susan E

2008-05-01

To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus. Cross-sectional study. 48 dogs with diabetes mellitus and 17 healthy dogs. Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups. Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 micromol/L had a serum insulin concentration < 5 microU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum beta-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased. Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

The ketogenic diet: initiation at goal calories versus gradual caloric advancement.

PubMed

Bansal, Seema; Cramp, Laura; Blalock, Dan; Zelleke, Tesfaye; Carpenter, Jessica; Kao, Amy

2014-01-01

Inpatient initiation of the ketogenic diet has historically involved fasting followed by gradual advancement of calories and/or diet ratio. Complications during this initiation period are common. We sought to determine if the initiation of the diet at goal calories would reduce these complications while maintaining efficacy. Sixty patients were admitted to a tertiary care hospital for elective initiation of the ketogenic diet between October 2007 and January 2013. All patients were placed on a ketogenic diet initiation pathway. In 2010, the pathway was modified from gradual caloric advancement to initiation at goal calories. We selected 30 consecutive patients before and after the change for comparison. Each child's record was reviewed for the occurrence of hypoglycemia, number of days to reach full ketosis (defined as 4 + urine ketones), acidosis requiring commencement of sodium citrate, length of admission, and long-term efficacy. Both methods of initiation had similar rates of dehydration, vomiting, lethargy, and irritability. More patients initiated at goal received sodium citrate (P = 0.005); however, mean daily values of carbon dioxide were not significantly different. Onset of ketosis was slightly delayed (P = 0.009) in patients initiated at goal, but length of stay was not affected (P > 0.1). Hypoglycemia was uncommon and rates were similar between the groups. Efficacy at 3 months was better in patients initiated at full calories (P < 0.05). Initiation of the ketogenic diet full calories is a reasonable alternative to the current standard practice of gradual advancement of calories and/or diet ratio. Copyright © 2014 Elsevier Inc. All rights reserved.

Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

PubMed

Sanya, E O; Soladoye, A O; Desalu, O O; Kolo, P M; Olatunji, L A; Olarinoye, J K

2017-03-06

The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures

Development of Fourier transform mid-infrared calibrations to predict acetone, β-hydroxybutyrate, and citrate contents in bovine milk through a European dairy network.

PubMed

Grelet, C; Bastin, C; Gelé, M; Davière, J-B; Johan, M; Werner, A; Reding, R; Fernandez Pierna, J A; Colinet, F G; Dardenne, P; Gengler, N; Soyeurt, H; Dehareng, F

2016-06-01

To manage negative energy balance and ketosis in dairy farms, rapid and cost-effective detection is needed. Among the milk biomarkers that could be useful for this purpose, acetone and β-hydroxybutyrate (BHB) have been proved as molecules of interest regarding ketosis and citrate was recently identified as an early indicator of negative energy balance. Because Fourier transform mid-infrared spectrometry can provide rapid and cost-effective predictions of milk composition, the objective of this study was to evaluate the ability of this technology to predict these biomarkers in milk. Milk samples were collected in commercial and experimental farms in Luxembourg, France, and Germany. Acetone, BHB, and citrate contents were determined by flow injection analysis. Milk mid-infrared spectra were recorded and standardized for all samples. After edits, a total of 548 samples were used in the calibration and validation data sets for acetone, 558 for BHB, and 506 for citrate. Acetone content ranged from 0.020 to 3.355mmol/L with an average of 0.103mmol/L; BHB content ranged from 0.045 to 1.596mmol/L with an average of 0.215mmol/L; and citrate content ranged from 3.88 to 16.12mmol/L with an average of 9.04mmol/L. Acetone and BHB contents were log-transformed and a part of the samples with low values was randomly excluded to approach a normal distribution. The 3 edited data sets were then randomly divided into a calibration data set (3/4 of the samples) and a validation data set (1/4 of the samples). Prediction equations were developed using partial least square regression. The coefficient of determination (R(2)) of cross-validation was 0.73 for acetone, 0.71 for BHB, and 0.90 for citrate with root mean square error of 0.248, 0.109, and 0.70mmol/L, respectively. Finally, the external validation was performed and R(2) obtained were 0.67 for acetone, 0.63 for BHB, and 0.86 for citrate, with respective root mean square error of validation of 0.196, 0.083, and 0.76mmol/L. Although

Validation of genomic predictions for wellness traits in US Holstein cows.

PubMed

McNeel, Anthony K; Reiter, Brenda C; Weigel, Dan; Osterstock, Jason; Di Croce, Fernando A

2017-11-01

The objective of this study was to evaluate the efficacy of wellness trait genetic predictions in commercial herds of US Holstein cows from herds that do not contribute phenotypic information to the evaluation. Tissue samples for DNA extraction were collected from more than 3,400 randomly selected pregnant Holstein females in 11 herds and 2 age groups (69% nulliparous, 31% primiparous) approximately 30 to 60 d before their expected calving date. Lactation records from cows that calved between September 1, 2015, and December 31, 2015, were included in the analysis. Genomically enhanced predicted transmitting abilities for the wellness traits of retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness were estimated by the Zoetis genetic evaluation and converted into standardized transmitting abilities. Mean reliabilities of the animals in the study ranged between 45 and 47% for each of the 6 traits. Animals were ranked by their standardized transmitting abilities within herd and age group then assigned to 1 of 4 groups of percentile-based genetic groups of equal size. Adverse health events, including retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness, were collected from on-farm herd management software, and animal phenotype was coded as either healthy (0), diseased (1), or excluded for each of the 6 outcomes of interest. Statistical analysis was performed using a generalized linear mixed model with genetic group, age group, and lactation as fixed effects, whereas herd and animal nested within herd were set as random effects. Results of the analysis indicated that the wellness trait predictions were associated with differences in phenotypic disease incidence between the worst and best genetic groups. The difference between the worst and best genetic groups in recorded disease incidence was 2.9% for retained placenta, 10.8% for metritis, 1.1% for displaced abomasum, 1.7% for ketosis, 7.4% for mastitis, and 3

Thirty years of personal experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state.

PubMed

Kitabchi, Abbas E; Umpierrez, Guillermo E; Fisher, Joseph N; Murphy, Mary Beth; Stentz, Frankie B

2008-05-01

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) cause major morbidity and significant mortality in patients with diabetes mellitus. For more than 30 yr, our group, in a series of prospective, randomized clinical studies, has investigated the pathogenesis and evolving strategies of the treatment of hyperglycemic crises. This paper summarizes the results of these prospective studies on the management and pathophysiology of DKA. Our earliest studies evaluated the comparative efficacy of low-dose vs. pharmacological amounts of insulin and the use of low-dose therapy by various routes in adults and later in children. Subsequent studies evaluated phosphate and bicarbonate therapy, lipid metabolism, ketosis-prone type 2 patients, and use of rapid-acting insulin analogs as well as leptin status, cardiac risk factors, proinflammatory cytokines, and the mechanism of activation of T lymphocytes in hyperglycemic crises. The information garnered from these studies resulted in the creation of the 2001 American Diabetes Association (ADA) technical review on DKA and HHS as well as the ADA Position and Consensus Paper on the therapy for hyperglycemic crises. Areas of future research include prospective randomized studies to do the following: 1) establish the efficacy of bicarbonate therapy in DKA for a pH less than 6.9; 2) establish the need for a bolus insulin dose in the initial therapy of DKA; 3) determine the pathophysiological mechanisms for the absence of ketosis in HHS; 4) investigate the reasons for elevated proinflammatory cytokines and cardiovascular risk factors; and 5) evaluate the efficacy and cost benefit of using sc regular insulin vs. more expensive insulin analogs on the general ward for the treatment of DKA.

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

PubMed

Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

Safety and efficacy of blood glucose management practices at a diabetes camp.

PubMed

Gunasekera, Hasantha; Ambler, Geoffrey

2006-10-01

Camps are an important part of diabetic management in children yet data on the safety and efficacy of camps are limited. We assessed the safety and efficacy of blood glucose management guidelines at summer camps for diabetic children. Consistent management guidelines were implemented during 10 consecutive diabetes camps held in the same facility between 1998 and 2002. Using the entire sample of campers aged 9-13 years, we analysed insulin dosage alterations, the frequency of hypoglycaemia (<4 mmol/L), hyperglycaemia (>15 mmol/L) and ketosis and evaluated our overnight management guidelines. The effects of sex, year, age, insulin regimen and duration of diagnosis on hypoglycaemia frequency were determined. Mean insulin doses decreased 19.2% (95% confidence interval 16.9-21.6%) by the last day of camp (day 6) relative to the day prior to camp. Mean blood glucose levels were 11.4 mmol/L before breakfast and the main evening meal, 11.3 mmol/L before bed, 10.8 mmol/L at midnight and 9.4 mmol/L at 3 am. Of the 10 839 readings analysed, 984 (9.1%) were below 4 mmol/L (0.5 per camper/day) with no clinical grade 3 (seizure or coma) hypoglycaemia. Hypoglycaemia frequency was independent of sex, year, age, insulin regimen and duration of diagnosis (all P > 0.05). There were 2570 (23.7%) readings above 15 mmol/L (1.4 per camper/day) but only 42 (0.4%) were associated with significant ketosis. Children at diabetes camps experience considerable blood glucose variability; however, the careful application of monitoring and management guidelines can avoid serious adverse events.

A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

PubMed

Maahs, David M; Calhoun, Peter; Buckingham, Bruce A; Chase, H Peter; Hramiak, Irene; Lum, John; Cameron, Fraser; Bequette, B Wayne; Aye, Tandy; Paul, Terri; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Kollman, Craig; Beck, Roy W

2014-07-01

Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels. Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred. Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm. Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis. © 2014 by the American Diabetes Association.

Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows.

PubMed

Ceciliani, Fabrizio; Lecchi, Cristina; Urh, Christiane; Sauerwein, Helga

2018-04-30

The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as "production diseases", such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. For high-yielding dairy cows there are several "occupational diseases" that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

PubMed

Stangaferro, M L; Wijma, R; Caixeta, L S; Al-Abri, M A; Giordano, J O

2016-09-01

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

PubMed Central

RIEGER, JOHANNES; BÄHR, OLIVER; MAURER, GABRIELE D.; HATTINGEN, ELKE; FRANZ, KEA; BRUCKER, DANIEL; WALENTA, STEFAN; KÄMMERER, ULRIKE; COY, JOHANNES F.; WELLER, MICHAEL; STEINBACH, JOACHIM P.

2014-01-01

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet. PMID:24728273

The effect of injectable butaphosphan and cyanocobalamin on postpartum serum beta-hydroxybutyrate, calcium, and phosphorus concentrations in dairy cattle.

PubMed

Rollin, E; Berghaus, R D; Rapnicki, P; Godden, S M; Overton, M W

2010-03-01

The objective of this study was to determine the effect of an injection of 10% butaphosphan and cyanocobalamin (Catosal, Bayer, Shawnee Mission, KS) on the day of calving and 1 d later on the prevalence of subclinical ketosis in dairy cattle in the early postpartum period. Cows from 4 herds (n=1,122) were randomized to receive either 25mL of 10% butaphosphan and cyanocobalamin or 25mL of sterile water subcutaneously on both days. Each milliliter of Catosal contained 0.05mg of cyanocobalamin and 100mg of butaphosphan, which provided 17.3mg of P in the form of [1-(butylamino)-1-methylethyl]-phosphonic acid. Serum was sampled for beta-hydroxybutyrate (BHBA) concentration at calving (pretreatment) and again between 3 and 10 d in milk. A subset of samples from mature cows was also evaluated for serum Ca and P concentrations. When cows from all age groups were included in the analysis, there was no difference between the median serum BHBA concentrations of cows in the 2 treatment groups, and no difference in the proportion of hyperketonemic cows (serum BHBA >or=1,200micromol/L) during the first week postpartum. When the analysis was restricted to mature cows (lactation >or=3), both the median BHBA concentration and the proportion of hyperketonemic cows were significantly lower in the treatment group than in the placebo group. Serum Ca and P concentrations did not differ between treatment groups. Our results suggest that injection of butaphosphan and cyanocobalamin on the day of calving and 1 d later may decrease the prevalence of subclinical ketosis during the week after calving in mature dairy cows, but not in first- and second-lactation animals.

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

PubMed Central

Schugar, Rebecca C.; Huang, Xiaojing; Moll, Ashley R.; Brunt, Elizabeth M.; Crawford, Peter A.

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet – weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction – were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation. PMID:24009777

Accuracy of a continuous glucose monitoring system in dogs and cats with diabetic ketoacidosis.

PubMed

Reineke, Erica L; Fletcher, Daniel J; King, Lesley G; Drobatz, Kenneth J

2010-06-01

(1) To determine the ability of a continuous interstitial glucose monitoring system (CGMS) to accurately estimate blood glucose (BG) in dogs and cats with diabetic ketoacidosis. (2) To determine the effect of perfusion, hydration, body condition score, severity of ketosis, and frequency of calibration on the accuracy of the CGMS. Prospective study. University Teaching Hospital. Thirteen dogs and 11 cats diagnosed with diabetic ketoacidosis were enrolled in the study within 24 hours of presentation. Once BG dropped below 22.2 mmol/L (400 mg/dL), a sterile flexible glucose sensor was placed aseptically in the interstitial space and attached to the continuous glucose monitoring device for estimation of the interstitial glucose every 5 minutes. BG measurements were taken with a portable BG meter every 2-4 hours at the discretion of the primary clinician and compared with CGMS glucose measurements. The CGMS estimates of BG and BG measured on the glucometer were strongly associated regardless of calibration frequency (calibration every 8 h: r=0.86, P<0.001; calibration every 12 h: r=0.85, P<0.001). Evaluation of this data using both the Clarke and Consensus error grids showed that 96.7% and 99% of the CGMS readings, respectively, were deemed clinically acceptable (Zones A and B errors). Interpatient variability in the accuracy of the CGMS glucose measurements was found but was not associated with body condition, perfusion, or degree of ketosis. A weak association between hydration status of the patient as assessed with the visual analog scale and absolute percent error (Spearman's rank correlation, rho=-0.079, 95% CI=-0.15 to -0.01, P=0.03) was found, with the device being more accurate in the more hydrated patients. The CGMS provides clinically accurate estimates of BG in patients with diabetic ketoacidosis.

Carnitine status and lactate increase in patients with type I juvenile diabetes.

PubMed

Evangeliou, A; Gourgiotis, D; Karagianni, C; Markouri, M; Anogianaki, N; Mamoulakis, D; Maropoulos, G; Tsakalidis, C; Frentzayias, A; Nicolaidou, P

2010-12-01

In 32 juvenile patients suffering from insulin dependent diabetes we observed a carnitine imbalance (increase in acylcarnitine and reduction of free carnitine), which was higher in patients with the highest levels of glycosylated hemoglobin. Parallel to that, in patients with the most prominent carnitine imbalance, there was the highest increase in the postprandial lactic acid level and the highest increase in the lactate/pyruvate ratio, without relating to ketosis. In addition, we observed a decrease in free carnitine related to the length of time after appearance of diabetes. This was a prospective study of a cohort of 32 children and young adolescents with insulin dependent diabetes mellitus. All patients were on insulin treatment. Plasma concentrations of total, free and acyl-Carnitine were evaluated in 12 hours fasting blood samples and before the morning administration of insulin. Blood glucose, cholesterol, triglycerides, and lactate, pyruvate, beta-hydroxybutyrate and free fatty acid levels were measured. The postprandial highest increase of the lactate and lactate/pyruvate ratio observed in patients with the highest degree of carnitine imbalance, namely with poorliest regulated diabetes, raises the question of a coincidental mitochondrial dysfunction. On the ground of our own data, such a claim cannot be substantiated for our patients. In contrast we suggest that the role of other factors like increased gluconeogenesis, degree of ketosis need to be sought. In order to clarify the role of carnitine in the pathophysiology of disease we need also data from other tissues. Carnitine in the peripheral blood reflects only the 1% of the total body carnitine ; furthermore, patients with diabetes exhibit changes in carnitine status not only in the peripheral blood but also in other body tissues, mainly in muscles.

[Enterobiasis in pediatric subjects in north-western Italy: a study of home remedies].

PubMed

Dutto, M; Montù, D; Raineri, G

2012-01-01

The present study examines the most common home remedies in the Piedmont region of northwest Italy currently used in the treatment of pediatric enterobiasis, commonly known as pinworm infection. The remedies in question, typically based on popular beliefs and as such are nearly useless, were noted through interviews with subjects who had come to the local Hygiene and Public Health Services offices for information about pinworm prevention and treatment. Analysis of replies by the subjects clearly indicates that local families are ill-prepared to recognize the symptoms this parasitic infection; often it is confused with pediatric ketosis, therefore leading to inappropriate treatment which at times may be potentially harmful to the patient.

Phenformin in Insulin-Dependent Diabetics

PubMed Central

Bloom, Arnold; Kolbe, R. J.

1970-01-01

Forty-one diabetic patients on insulin were given 100mg. of phenformin daily for six weeks, either before or after a period of six weeks of inert capsules, in a double-blind cross-over trial. Eleven patients while on phenformin noticed hypoglycaemic effects and reduced their insulin on average by almost 20% without resultant rise in blood sugar levels. Twenty-eight patients felt no untoward effects and maintained their usual insulin dose. Phenformin led to improved control of the diabetes, with a significant decrease in blood sugar levels and a significant reduction in the variability of the weekly blood sugar readings. There was no increased ketosis, no change in cholesterol, and no significant loss of weight. PMID:4914612

A modified Girard derivatizing reagent for universal profiling and trace analysis of aldehydes and ketones by electrospray ionization tandem mass spectrometry.

PubMed

Johnson, David W

2007-01-01

4-Hydrazino-N,N,N-trimethyl-4-oxobutanaminium iodide (HTMOB) is a modified Girard derivatizing reagent synthesized to improve the sensitivity of analysis of aldehydes and ketones with electrospray ionization tandem mass spectrometry. Compared with Girard T reagent the measured signal intensity increase is between 3.3 times (succinylacetone) and 7.0 times (17-hydroxyprogesterone). HTMOB is a universal profiling reagent for aldehydes and ketones. A neutral loss of 59 Da scan detects all aldehydes and ketones from acetone to corticosteroids. Applications described include the profiling of ketones, ketoacids and ketodiacids in the urine of children with ketosis and the profiling of long-chain aldehydes incorporated in plasma plasmalogens. Copyright (c) 2007 John Wiley & Sons, Ltd.

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

PubMed Central

Kanikarla-Marie, Preeti; Jain, Sushil K.

2016-01-01

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body’s energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increasing the risk of morbidity and mortality in patients. PMID:27036365

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.

PubMed

Kanikarla-Marie, Preeti; Jain, Sushil K

2016-06-01

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

The inverse problem of brain energetics: ketone bodies as alternative substrates

NASA Astrophysics Data System (ADS)

Calvetti, D.; Occhipinti, R.; Somersalo, E.

2008-07-01

Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

Acute starvation ketoacidosis in pregnancy with severe hypertriglyceridemia: A case report.

PubMed

Hui, Li; Shuying, Li

2018-05-01

Pregnant women are more prone to ketosis due to the relative insulin resistance, accelerated lipolysis and increased free fatty acids. We report a pregnant woman with hyperlipidemia, who experienced severe metabolic acidosis after a short period of starvation. Based on her clinical symptoms, exclusion diagnosis and therapeutic diagnosis, her condition was diagnosed as starvation ketoacidosis. An emergency caesarean section under general anesthesia was implemented 2 hours after her admission. The metabolic acidosis was treated with fluid resuscitation using compound sodium lactate, bicarbonate, and 5% dextrose together with insulin 6U. Both mother and baby were discharged clinically well. Starvation ketoacidosis may happen in special patient who was in pregnancy and with severe hypertriglyceridemia, after just one day fasting and vomiting.

Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress.

PubMed

Ringseis, R; Gessner, D K; Eder, K

2015-08-01

The transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liver-associated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor α, interleukin-1β, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows

Transition diseases in grazing dairy cows are related to serum cholesterol and other analytes.

PubMed

Sepúlveda-Varas, Pilar; Weary, Daniel M; Noro, Mirela; von Keyserlingk, Marina A G

2015-01-01

The objectives of this study were to describe the incidence of postpartum disease and to evaluate the association with serum cholesterol concentrations during the first 3 weeks after calving in grazing dairy cows. The association between non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), calcium and postpartum diseases was also evaluated. A total of 307 Holstein dairy cows from 6 commercial grazing herds in Osorno, Chile, were monitored from calving until 21 days in milk. Cases of retained placenta, clinical hypocalcemia and clinical mastitis were recorded by the farmer using established definitions. Twice weekly, cows were evaluated for metritis by the same veterinarian based on vaginal discharge and body temperature. Postpartum blood samples were collected weekly and analyzed for serum concentrations of cholesterol, NEFA, BHBA and calcium. Cows were considered as having subclinical ketosis if BHBA >1.2 mmol/L, and subclinical hypocalcemia if calcium <2.0 mmol/L in any of the 3 weekly samples. Overall, 56% of the cows studied developed at least one clinical or subclinical disease after calving. Incidence of individual diseases was 8.8% for retained placenta, 4.2% for clinical hypocalcemia, 11.7% for clinical mastitis, 41.1% for metritis, 19.9% for subclinical hypocalcemia and 16.6% for subclinical ketosis. Lower postpartum cholesterol in cows was associated with developing severe metritis or having more than one clinical disease after calving. For every 0.4 mmol/L decrease in serum cholesterol cows were nearly twice as likely to be diagnosed with multiple clinical diseases after calving. Higher BHBA concentrations and lower calcium concentrations during week 1 were associated with severe cases of metritis. Low serum calcium concentration during week 1 was also associated with developing more than one clinical disorder after calving. In conclusion, the incidence of postpartum diseases can be high even in grazing herds and lower serum cholesterol

Transition Diseases in Grazing Dairy Cows Are Related to Serum Cholesterol and Other Analytes

PubMed Central

2015-01-01

The objectives of this study were to describe the incidence of postpartum disease and to evaluate the association with serum cholesterol concentrations during the first 3 weeks after calving in grazing dairy cows. The association between non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), calcium and postpartum diseases was also evaluated. A total of 307 Holstein dairy cows from 6 commercial grazing herds in Osorno, Chile, were monitored from calving until 21 days in milk. Cases of retained placenta, clinical hypocalcemia and clinical mastitis were recorded by the farmer using established definitions. Twice weekly, cows were evaluated for metritis by the same veterinarian based on vaginal discharge and body temperature. Postpartum blood samples were collected weekly and analyzed for serum concentrations of cholesterol, NEFA, BHBA and calcium. Cows were considered as having subclinical ketosis if BHBA >1.2 mmol/L, and subclinical hypocalcemia if calcium <2.0 mmol/L in any of the 3 weekly samples. Overall, 56% of the cows studied developed at least one clinical or subclinical disease after calving. Incidence of individual diseases was 8.8% for retained placenta, 4.2% for clinical hypocalcemia, 11.7% for clinical mastitis, 41.1% for metritis, 19.9% for subclinical hypocalcemia and 16.6% for subclinical ketosis. Lower postpartum cholesterol in cows was associated with developing severe metritis or having more than one clinical disease after calving. For every 0.4 mmol/L decrease in serum cholesterol cows were nearly twice as likely to be diagnosed with multiple clinical diseases after calving. Higher BHBA concentrations and lower calcium concentrations during week 1 were associated with severe cases of metritis. Low serum calcium concentration during week 1 was also associated with developing more than one clinical disorder after calving. In conclusion, the incidence of postpartum diseases can be high even in grazing herds and lower serum cholesterol

Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

PubMed Central

Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew P.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

2016-01-01

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a

Chorea as a rare manifestation of hyperglycaemia.

PubMed

Patil, Rajesh; Sangoi, Parin; Wasekar, Nilesh; Vishwanathan, Deepti; Jadhav, S G; Joglekar, V K

2013-09-01

We present a case of chorea presenting as a clinical manifestation of hyperglycaemia.The purpose of presenting this case is to highlight the fact that movement disorder may be the clinical presentation of hyperglycaemia and it reverts on treatment of hyperglycaemia. A 66-year-old female known case of type 2 diabetes mellitus and on oral hypoglycaemic drugs presented with abnormal and involuntary movements of the whole body and face since 7 days and high plasma glucose (446 mg/dl) and without ketosis. On controlling the blood sugar, there has been significant decrease in choreiform movements within 48 hrs and complete resolution of involuntary movements found at discharge at 1 week. Movement disorder like chorea may be the clinical presentation of the hyperglycaemia which could completely recover on rapid detection and correction of hyperglycaemia.

Ketogenic diet in endocrine disorders: Current perspectives

PubMed Central

Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

2017-01-01

Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.” PMID:29022562

Was Maria de' Medici a diabetic patient?

PubMed

de Leeuw, I

2009-06-01

Queen Maria de' Medici (1573-1642) died in a miserable, marasmic state. Infections, gangrene, weight loss, fatigue and respiratory problems suggest a progressive decompensation of a previously existing Type 2 diabetes. The lack of biochemical data, however, permits only circumstantial evidence of this hypothesis. The author proposes that the queen developed subclinical diabetes after the age of 45, when she became obese due to excessive eating and lack of exercise. With a clear familial predisposition, she could have become insulin resistant and chronically hyperglycaemic. The presence of an internal deviation of the left eye, visible on several late portraits, suggests a mononeuropathy of cranial nerve VI. Repeated skin infections and gangrene of the lower limbs during the last month of her life complete the clinical diagnosis. Hyperglycaemic ketosis with Kussmaul respiration without adequate treatment may have caused her death.

Providing Oral Nutrition to Women in Labor: American College of Nurse-Midwives.

PubMed

2016-07-01

Historically, oral intake for women during labor has been limited to nothing by mouth or clear liquids only. These restrictions are based on the risk of aspiration during or after the administration of general anesthesia. While aspiration can be life threatening, older methods of anesthesia are rarely used in current intrapartum care, and evidence is inconclusive that withholding oral nutrition reduces the risk of gastric aspiration. Additionally, withholding oral nutrition may result in the development of ketosis and may potentially contribute to a woman's stress and dissatisfaction with the birth experience. The purpose of this Clinical Bulletin is to review the evidence related to this practice and provide recommendations to promote informed, shared decision making regarding oral intake during labor with women at low risk for gastric aspiration. © 2016 by the American College of Nurse-Midwives.

Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats.

PubMed

Iwata, Kinuyo; Kinoshita, Mika; Yamada, Shunji; Imamura, Takuya; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Maeda, Kei-Ichiro

2011-03-01

Uncontrolled type 1 diabetes leads to hyperphagia and severe ketosis. This study was conducted to test the hypothesis that ketone bodies act on the hindbrain as a starvation signal to induce diabetic hyperphagia. Injection of an inhibitor of monocarboxylate transporter 1, a ketone body transporter, into the fourth ventricle normalized the increase in food intake in streptozotocin (STZ)-induced diabetic rats. Blockade of catecholamine synthesis in the hypothalamic paraventricular nucleus (PVN) also restored food intake to normal levels in diabetic animals. On the other hand, hindbrain injection of the ketone body induced feeding, hyperglycemia, and fatty acid mobilization via increased sympathetic activity and also norepinephrine release in the PVN. This result provides evidence that hyperphagia in STZ-induced type 1 diabetes is signaled by a ketone body sensed in the hindbrain, and mediated by noradrenergic inputs to the PVN.

Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1.

PubMed

McCarty, Mark F; DiNicolantonio, James J; O'Keefe, James H

2015-11-01

Ketogenic diets are markedly neuroprotective, but the basis of this effect is still poorly understood. Recent studies demonstrate that ketone bodies increase neuronal levels of hypoxia-inducible factor-1α (HIF-1α), possibly owing to succinate-mediated inhibition of prolyl hydroxylase activity. Moreover, there is reason to suspect that ketones can activate Sirt1 in neurons, in part by increasing cytoplasmic and nuclear levels of Sirt1's obligate cofactor NAD(+). Another recent study has observed reduced activity of mTORC1 in the hippocampus of rats fed a ketogenic diet - an effect plausibly attributable to Sirt1 activation. Increased activities of HIF-1 and Sirt1, and a decrease in mTORC1 activity, could be expected to collaborate in the induction of neuronal macroautophagy. Considerable evidence points to moderate up-regulation of neuronal autophagy as a rational strategy for prevention of neurodegenerative disorders; elimination of damaged mitochondria that overproduce superoxide, as well as clearance of protein aggregates that mediate neurodegeneration, presumably contribute to this protection. Hence, autophagy may mediate some of the neuroprotective benefits of ketogenic diets. Brain-permeable agents which activate AMP-activated kinase, such as metformin and berberine, as well as the Sirt1 activator nicotinamide riboside, can also boost neuronal autophagy, and may have potential for amplifying the impact of ketogenesis on this process. Since it might not be practical for most people to adhere to ketogenic diets continuously, alternative strategies are needed to harness the brain-protective potential of ketone bodies. These may include ingestion of medium-chain triglycerides or coconut oil, intermittent ketogenic dieting, and possibly the use of supplements that promote hepatic ketogenesis - notably carnitine and hydroxycitrate - in conjunction with dietary regimens characterized by long daily episodes of fasting or carbohydrate avoidance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation

PubMed Central

Cotter, David G.; Schugar, Rebecca C.; Wentz, Anna E.; André d'Avignon, D.

2013-01-01

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1+/− mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states. PMID:23233542

Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

PubMed

Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

2013-02-15

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

On the role of mid-infrared predicted phenotypes in fertility and health dairy breeding programs.

PubMed

Bastin, C; Théron, L; Lainé, A; Gengler, N

2016-05-01

Fertility and health traits are of prime importance in dairy breeding programs. However, these traits are generally complex, difficult to record, and lowly heritable (<0.10), thereby hampering genetic improvement in disease resistance and fertility. Hence, indicators are useful in the prediction of genetic merit for fertility and health traits as long as they are easier to measure than direct fitness traits, heritable, and genetically correlated. Considering that changes in (fine) milk composition over a lactation reflect the physiological status of the cow, mid-infrared (MIR) analysis of milk opens the door to a wide range of potential indicator traits of fertility and health. Previous studies investigated the phenotypic and genetic relationships between fertility and MIR-predicted phenotypes, most being related to negative postpartum energy balance and body fat mobilization (e.g., fat:protein ratio, urea, fatty acids profile). Results showed that a combination of various fatty acid traits (e.g., C18:1 cis-9 and C10:0) could be used to improve fertility. Furthermore, occurrence of (sub)clinical ketosis has been related to milk-based phenotypes such as fat:protein ratio, fatty acids, and ketone bodies. Hence, MIR-predicted acetone and β-hydroxybutyrate contents in milk could be useful for breeding cows less susceptible to ketosis. Although studies investigating the genetic association among mastitis and MIR-predicted phenotypes are scarce, a wide range of traits, potentially predicted by MIR spectrometry, are worthy of consideration. These include traits related to the disease response of the cow (e.g., lactoferrin), reduced secretory activity (e.g., casein), and the alteration of the blood-milk barrier (e.g., minerals). Moreover, direct MIR prediction of fertility and health traits should be further considered. To conclude, MIR-predicted phenotypes have a role to play in the improvement of dairy cow fertility and health. However, further studies are warranted to

Glucose concentration in capillary blood of dairy cows obtained by a minimally invasive lancet technique and determined with three different hand-held devices.

PubMed

Mair, B; Drillich, M; Klein-Jöbstl, D; Kanz, P; Borchardt, S; Meyer, L; Schwendenwein, I; Iwersen, M

2016-02-24

Dairy cows have a massive demand for glucose at the onset of lactation. A poor adaption to this period leads to an excessive negative energy balance with an increased risk for ketosis and impaired animal health and production. Besides the measurement of ketones, analysing the glucose concentration in blood is reported as helpful instrument for diagnosis and differentiation of ketosis. Monitoring metabolic parameters requires multiple blood sampling. In other species, new blood sampling techniques have been introduced in which small amounts of blood are rapidly analysed using electronic hand-held devices. The objective of this study was to evaluate the suitability of capillary blood for blood glucose measurement in dairy cows using the hand-held devices FreeStyle Precision (FSP, Abbott), GlucoMen LX Plus (GLX, A. Menarini) and the WellionVet GLUCO CALEA, (WGC, MED TRUST). In total, 240 capillary blood samples were obtained from dry and fresh lactating Holstein-Friesian cows. Blood was collected from the skin of the exterior vulva by using a lancet. For method comparison, additional blood samples were taken from a coccygeal vessel and analyzed in a laboratory. Glucose concentrations measured by a standard laboratory method were defined as the criterion standard. The Pearson correlation coefficients between the glucose concentrations analyzed in capillary blood with the devices and the reference were 73% for the FSP, 81% for the GLX and 41% for the WGC. Bland-Altman plots showed biases of -18.8 mg/dL for the FSP, -11.2 mg/dL for the GLX and +20.82 mg/dL for the WGC. The optimized threshold determined by a Receiver Operating Characteristics analysis to detect hyperglycemia using the FSP was 43 mg/dL with a sensitivity (Se) and specificity (Sp) of 76 and 80%. Using the GLX and WGC optimized thresholds were 49 mg/dL (Se = 92%, Sp = 85%) and 95 mg/dL (Se = 39%, Sp = 92%). The results of this study demonstrate good performance characteristics for the GLX

Neuronal-glial interactions in rats fed a ketogenic diet.

PubMed

Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

2006-01-01

Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

Intermittent metabolic switching, neuroplasticity and brain health

PubMed Central

Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

2018-01-01

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting.

PubMed

Ham, Melissa R; Okada, Pamela; White, Perrin C

2004-03-01

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus marked by characteristic biochemical derangements. Diagnosis and management involve frequent evaluation of these biochemical parameters. Reliable bedside equivalents for these laboratory studies may help reduce the time to treatment and reduce costs. We evaluated the precision and bias of a bedside serum ketone meter in the acute care setting. Serum ketone results using the Precision Xtra glucometer/ketone meter (Abbott Laboratories, MediSense Products Inc., Bedford, MA, USA) correlated strongly with the Children's Medical Center of Dallas' laboratory values within the meter's value range. Meter ketone values steadily decreased during the treatment of DKA as pH and CO(2) levels increased and acidosis resolved. Therefore, the meter may be useful in monitoring therapy for DKA. This meter may also prove useful in identifying patients at risk for DKA in physicians' offices or at home.

The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

PubMed

Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

2015-02-01

Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

Paracentric Inversion of Chromosome 21 Leading to Disruption of the HLCS Gene in a Family with Holocarboxylase Synthetase Deficiency.

PubMed

Quinonez, Shane C; Seeley, Andrea H; Lam, Cindy; Glover, Thomas W; Barshop, Bruce A; Keegan, Catherine E

2017-01-01

Holocarboxylase synthetase (HLCS) deficiency is a rare autosomal recessive disorder that presents with multiple life-threatening metabolic derangements including metabolic acidosis, ketosis, and hyperammonemia. A majority of HLCS deficiency patients respond to biotin therapy; however, some patients show only a partial or no response to biotin therapy. Here, we report a neonatal presentation of HLCS deficiency with partial response to biotin therapy. Sequencing of HLCS showed a novel heterozygous mutation in exon 5, c.996G>C (p.Gln332His), which likely abolishes the normal intron 6 splice donor site. Cytogenetic analysis revealed that the defect of the other allele is a paracentric inversion on chromosome 21 that disrupts HLCS. This case illustrates that in addition to facilitating necessary family testing, a molecular diagnosis can optimize management by providing a better explanation of the enzyme's underlying defect. It also emphasizes the potential benefit of a karyotype in cases in which molecular genetic testing fails to provide an explanation.

Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association

PubMed Central

Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

2015-01-01

The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS. PMID:26123455

Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors

PubMed Central

Strowd, Roy E.; Cervenka, Mackenzie C.; Henry, Bobbie J.; Kossoff, Eric H.; Hartman, Adam L.; Blakeley, Jaishri O.

2015-01-01

Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study. PMID:26649186

[Hepatomegaly due to glycogen storage disease and type 1 diabetes mellitus].

PubMed

Flotats Bastardas, M; Miserachs Barba, M; Ricart Cumeras, A; Clemente León, M; Gussinyer Canadell, M; Yeste Fernández, D; Albisu Aparicio, María A; Carrascosa Lezcano, A

2007-08-01

Patients with type 1 diabetes and poor metabolic control can develop hepatomegaly due to intrahepatic glycogen deposition. If these patients also have elevated liver enzymes, dyslipidemia, cushingoid features and delayed growth or sexual maturation, Mauriac syndrome can be diagnosed. This disorder is common and reversible with optimization of insulin therapy. We report three adolescents with type 1 diabetes and a long-standing history of poor glycemic control, who developed hepatomegaly, elevated liver enzymes and dyslipidemia with preserved liver function. One of these patients also had delayed growth and another had hypogonadotropic hypogonadism. Liver ultrasound showed changes suggestive of glycogenosis. In all three patients, optimization of insulin therapy achieved good glycemic control and reversed the manifestations within 2 weeks. The etiology of Mauriac syndrome is controversial since both prolonged hyperglycemia and hyperinsulinization produce glycogen accumulation in the liver. Hypercortisolism (due to ketosis or hypoglycemia) contributes to glycogen storage and also causes growth and sexual maturation delay.

[Neonatal diabetes mellitus and KCNJ11 gene mutation: report of a family case].

PubMed

Orío Hernández, M; de la Serna Martínez, M; González Casado, I; Lapunzina, P; Gracia Bouthelier, R

2008-06-01

Neonatal diabetes mellitus (NDM) is characterized by hyperglycemia within the first month of life and insulin dependence for at least two weeks. There are two types of NDM, transient (TNDM) and permanent (PNDM), which are genetically different. We report the case of two brothers who developed hyperglycemia without ketosis on the 18th day and 2 h of life, respectively. Thyroid function tests, abdominal ultrasound and karyotype where normal and there were no pancreatic antibodies. The first one required insulin therapy for the first 92 days of life and the second for 5 months. The mother developed gestational diabetes during both pregnancies and she was later diagnosed diabetes mellitus (without antibodies). They were studied for mutations in KCNJ11 gene (principally related to the permanent form). The three of them showed the E229K mutation (frequently associated with the transient form). A genetic study is essential in NDM to achieve the most accurate prognosis possible.

Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association.

PubMed

Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

2015-06-29

The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS. 2015 BMJ Publishing Group Ltd.

Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis.

PubMed

Aboulhosn, Kewan; Arnason, Terra

2013-09-04

A healthy 18-year-old girl presented to a local emergency room with 48 h of abdominal pain and vomiting. A radiological and biochemical diagnosis of moderate acute pancreatitis was made. Bloodwork demonstrated prominent hypertriglyceridaemia (HTG) of 19.5 mmol/L (severe HTG: 11.2-22.4), detectable urine ketones and a random blood glucose of 13 mmol/L dropping to 10.5 mmol/L on repeat (normal random <11). Ketone levels were deemed consistent with fasting ketosis after 48 h of vomiting. There was no known history of diabetes in the patient. Management included aggressive rehydration and pain control, yet the patient rapidly decompensated into shock requiring intensive care unit support. Blood gases revealed severe metabolic acidosis (pH 6.99) and unsuspected underlying diabetic ketoacidosis was diagnosed. The HTG gradually resolved following intravenous fluids and insulin infusion with slower correction of the metabolic acidosis. Importantly, her glycated haemoglobin was 12%, indicating the silent presence of chronic glucose elevations.

Short communication: Rumination and feeding behaviors differ between healthy and sick dairy cows during the transition period.

PubMed

Schirmann, K; Weary, D M; Heuwieser, W; Chapinal, N; Cerri, R L A; von Keyserlingk, M A G

2016-12-01

The objectives of this study were: (1) to describe the rumination and feeding behavior of freestall-housed Holstein dairy cows in the weeks around parturition, and (2) to determine the relationship between postpartum disease and precalving rumination and feeding behavior. Eighty cows were enrolled at approximately 2wk (18±7d, mean ± standard deviation) before calving. Using automatic monitoring systems, rumination and feeding behavior were recorded continuously from 10d before until 3wk after calving. Postpartum health checks were performed each day, and metritis assessment was conducted 2 times/wk. Blood β-hydroxybutyrate was measured 3 times/week, and cows with ≥1.2mmol/L during the first 14d postpartum were diagnosed as having subclinical ketosis. The final data set included 64 cows in 5 groups: healthy (n=20), metritis (n=18), subclinical ketosis (SCK; n=9), metritis+SCK (n=9), and >1 health problem and not included before (MULT, n=8). We compared rumination and feeding data between healthy cows and the 4 categories of ill animals in each of 4 periods relative to calving: precalving (d -7 to -2), period 1 (d 3 to 8 postpartum), period 2 (d 9 to 14 postpartum), and period 3 (d 15 to 20 postpartum). Cows with SCK spent less time ruminating during the precalving period. Compared with healthy cows, those with SCK and metritis+SCK had lower dry matter intake during the precalving period and continued to eat less until d 14 and d 20 postpartum, respectively. Cows with metritis and MULT cows had lower dry matter intake during the first 2wk postpartum. Precalving feeding time was lower for SCK, metritis+SCK, and MULT cows compared with healthy cows. The difference in feeding time between healthy and metritis+SCK cows had disappeared by period 2 and between all health categories except MULT by period 3. MULT cows visited the feed bins less often and were less often replaced at the feed bin throughout all 4 periods of the study. Automatic monitoring of intake and

Separate housing for one month after calving improves production and health in primiparous cows but not in multiparous cows.

PubMed

Østergaard, S; Thomsen, P T; Burow, E

2010-08-01

The hypothesis was that dairy cows housed for 1 mo after calving in a separate group with herd mates would produce more milk and would be healthier than cows integrated in a group of all lactating cows immediately after calving. The experiment was conducted with 489 cows in 6 commercial loose-housing dairy herds where cows were randomly selected for treatment (separate housing) or control. Cows selected for treatment were housed for 1 mo after calving in a separate section, and controls were housed in the remaining section of the barn for lactating cows. Data were compared for milk yield, somatic cell count, medical treatments, reproductive performance, culling, mortality, and clinical observation of scores for body condition, leg and udder hygiene, lameness, hock lesions, other cutaneous lesions, vaginal discharge, and condition of the hair coat. The analysis of the effect of separate housing showed that primiparous cows produced more milk [approximately 230 kg of energy-corrected milk from 0 to 305 d in milk (DIM)], whereas multiparous and especially parity 3+ cows produced less milk (approximately 394 kg of energy-corrected milk from 0 to 305 DIM) during the lactation. Separate housing had no effect on mortality or reproductive efficiency. In primiparous cows, the number of medical treatments for ketosis was reduced by separate housing [hazard ratio 0.33, 95% confidence interval (CI): 0.13-0.83]. Clinical evaluations showed that separate housing decreased the scores for hock lesions in cows at 0 to 30 DIM (odds ratio 0.41, CI: 0.19-0.91), whereas the scoring of leg cleanliness showed more dirty legs in separated cows at 0 to 30 DIM (odds ratio 3.61, CI: 2.01-6.47) compared with cows integrated into the herd immediately. The body condition score in separated cows was reduced from 0 to 30 DIM (score reduced by 0.16, CI: 0.07-0.25) and from 31 to 60 DIM (score reduced by 0.13, CI: 0.04-0.23) compared with cows integrated immediately. We concluded that separate

Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

PubMed Central

Ruderman, Neil B.; Ross, Peter S.; Berger, Michael; Goodman, Michael N.

1974-01-01

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the

Role of carbohydrate metabolism in grass tetany

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, J.K.; Madsen, F.C.; Lentz, D.E.

1977-01-01

Clinical hypomagnesemia is confined primarily to beef cattle in the United States but also occurs in dairy cattle in other countries, probably due to different management practices. During periods when grass tetany is likely, early vegetative temperate zone grasses are usually low in total readily available carbohydrates and magnesium but high in potassium and nitrogen. The tetany syndrome may include hypoglycemia and ketosis, suggesting an imbalance in intermediary energy metabolism. Many enzyme systems critical to cellular metabolism, including those which hydrolyze and transfer phosphate groups, are activated by Mg. Thus, by inference, Mg is required for normal glucose utilization, fat,more » protein, nucleic acid and coenzyme synthesis, muscle contraction, methyl group transfer, and sulfate, acetate, and formate activation. Numerous clinical and experimental studies suggest an intimate relationship between metabolism of Mg and that of carbohydrate, glucagon, and insulin. The objective is to review this literature and suggest ways in which these relationships might contribute to a chain of events leading to grass tetany.« less

Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis

PubMed Central

Aboulhosn, Kewan; Arnason, Terra

2013-01-01

A healthy 18-year-old girl presented to a local emergency room with 48 h of abdominal pain and vomiting. A radiological and biochemical diagnosis of moderate acute pancreatitis was made. Bloodwork demonstrated prominent hypertriglyceridaemia (HTG) of 19.5 mmol/L (severe HTG: 11.2–22.4), detectable urine ketones and a random blood glucose of 13 mmol/L dropping to 10.5 mmol/L on repeat (normal random <11). Ketone levels were deemed consistent with fasting ketosis after 48 h of vomiting. There was no known history of diabetes in the patient. Management included aggressive rehydration and pain control, yet the patient rapidly decompensated into shock requiring intensive care unit support. Blood gases revealed severe metabolic acidosis (pH 6.99) and unsuspected underlying diabetic ketoacidosis was diagnosed. The HTG gradually resolved following intravenous fluids and insulin infusion with slower correction of the metabolic acidosis. Importantly, her glycated haemoglobin was 12%, indicating the silent presence of chronic glucose elevations. PMID:24005972

Effects of time and sampling location on concentrations of β-hydroxybutyric acid in dairy cows.

PubMed

Mahrt, A; Burfeind, O; Heuwieser, W

2014-01-01

Two trials were conducted to examine factors potentially influencing the measurement of blood β-hydroxybutyric acid (BHBA) in dairy cows. The objective of the first trial was to study effects of sampling time on BHBA concentration in continuously fed dairy cows. Furthermore, we determined test characteristics of a single BHBA measurement at a random time of the day to diagnose subclinical ketosis considering commonly used cut-points (1.2 and 1.4 mmol/L). Finally, we set out to evaluate if test characteristics could be enhanced by repeating measurements after different time intervals. During 4 herd visits, a total of 128 cows (8 to 28 d in milk) fed 10 times daily were screened at 0900 h and preselected by BHBA concentration. Blood samples were drawn from the tail vessels and BHBA concentrations were measured using an electronic BHBA meter (Precision Xceed, Abbott Diabetes Care Ltd., Witney, UK). Cows with BHBA concentrations ≥0.8 mmol/L at this time were enrolled in the trial (n=92). Subsequent BHBA measurements took place every 3h for a total of 8 measurements during 24 h. The effect of sampling time on BHBA concentrations was tested in a repeated-measures ANOVA repeating sampling time. Sampling time did not affect BHBA concentrations in continuously fed dairy cows. Defining the average daily BHBA concentration calculated from the 8 measurements as the gold standard, a single measurement at a random time of the day to diagnose subclinical ketosis had a sensitivity of 0.90 or 0.89 at the 2 BHBA cut-points (1.2 and 1.4 mmol/L). Specificity was 0.88 or 0.90 using the same cut-points. Repeating measurements after different time intervals improved test characteristics only slightly. In the second experiment, we compared BHBA concentrations of samples drawn from 3 different blood sampling locations (tail vessels, jugular vein, and mammary vein) of 116 lactating dairy cows. Concentrations of BHBA differed in samples from the 3 sampling locations. Mean BHBA

Thresholds of whole-blood β-hydroxybutyrate and glucose concentrations measured with an electronic hand-held device to identify ovine hyperketonemia.

PubMed

Pichler, M; Damberger, A; Schwendenwein, I; Gasteiner, J; Drillich, M; Iwersen, M

2014-03-01

Metabolic disorders, especially hyperketonemia, are very common in dairy sheep. The whole-blood concentrations of β-hydroxybutyrate (BHBA) and glucose can be determined by commercially available electronic hand-held devices, which are used in human medicine and for the detection of ketosis in dairy cows. The aim of this study was to evaluate the suitability of the hand-held device Precision Xceed (PX; Abbott Diabetes Care Inc., Abbott Park, IL) to detect hyperketonemia in ewes. An additional objective of this study 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, v. jug.). Blood samples taken from the v. jug. were collected from 358 ewes on 4 different farms. These samples and a blood drop obtained from an ear vein were analyzed simultaneously on farm with the PX. For method comparison, the samples obtained from the v. jug. were also analyzed by standard methods, which served as the gold standard at the Central Laboratory of the University of Veterinary Medicine Vienna, Austria. The correlation coefficients between the serum BHBA concentration and the concentrations measured with the hand-held meter in the whole blood from an ear vein and the v. jug. were 0.94 and 0.96, respectively. The correlation coefficients of plasma and whole-blood glucose concentration were 0.68 for the v. jug. and 0.47 for the ear vein. The mean glucose concentration was significantly lower in animals classified as hyperketonemic (BHBA ≥ 1.6 mmol/L) compared with healthy ewes. Whole-blood concentrations of BHBA and glucose measured with the PX from v. jug. showed a constant negative bias of 0.15 mmol/L and 8.4 mg/dL, respectively. Hence, a receiver operating characteristic analysis was performed to determine thresholds for the PX to detect hyperketonemia in ewes. This resulted in thresholds for moderate ketosis of BHBA concentrations of 0.7 mmol/L in blood

An audit of the contribution to post-mortem examination diagnosis of individual analyte results obtained from biochemical analysis of the vitreous.

PubMed

Mitchell, Rebecca; Charlwood, Cheryl; Thomas, Sunethra Devika; Bellis, Maria; Langlois, Neil E I

2013-12-01

Biochemical analysis of the vitreous humor from the eye is an accepted accessory test for post-mortem investigation of cause of death. Modern biochemical analyzers allow testing of a range of analytes from a sample. However, it is not clear which analytes should be requested in order to prevent unnecessary testing (and expense). The means and standard deviation of the values obtained from analysis of the vitreous humor for sodium, potassium, chloride, osmolality, glucose, ketones (β-hydroxybutyrate), creatinine, urea, calcium, lactate, and ammonia were calculated from which the contribution of each analyte was reviewed in the context of post-mortem findings and final cause of death. For sodium 32 cases were regarded as high (more than one standard deviation above the mean), from which 9 contributed to post-mortem diagnosis [drowning (4), heat related death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values (greater than one standard deviation below the mean) made no contribution. For chloride 29 high values contributed to 4 cases--3 drowning and 1 heat-related, but these were all previously identified by a high sodium level. There were 29 high and 35 low potassium values, none of which contributed to determining the final cause of death. Of 22 high values of creatinine, 12 contributed to a diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16 cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat-related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values. There was no contribution from 32 high values and 19 low values of calcium and there was no contribution from 4 high and 2 low values of ammonia. There were 11 high values of glucose, which contributed to the diagnosis of 6 cases of diabetic hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic ketosis, 3 hypothermia, 3

Short communication: survey of fresh cow management practices of dairy cattle on small and large commercial farms.

PubMed

Heuwieser, W; Iwersen, M; Gossellin, J; Drillich, M

2010-03-01

The objective was to conduct a survey of current fresh cow management practices that have an effect on health and diseases postpartum considering different herd sizes of commercial dairy farms. A mail survey regarding aspects of the fresh cow program including general management issues, calving, diseases, and veterinary service was conducted utilizing a convenience sample. A total of 429 survey forms were returned (12.0% response rate) and could be used for final analysis. Only 21.6% of the farms had a designated fresh cow pen. Almost every farm executed some type of fresh cow examination. Only 18.5% of farm managers documented the observations. Most of the dairy managers used more or less subjective criteria such as general appearance (97.0%) and appetite (69.7%). Only a minority of the responding dairy managers monitored their fresh cows using objective (fever 33.6%) or semiquantitative measures (subclinical ketosis 2.8%; body condition score 36.4%). On most farms, the veterinarian visited the herd only if needed (72.6%). Most cases of retained fetal membranes were treated by manual removal (72.3%) and antibiotic pills (89.5%). Several challenges and opportunities were identified to improve cow management practices.

Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

PubMed Central

Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

2013-01-01

Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP)

PubMed Central

Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R. Max; Tu, Benjamin P.; MacMillan, John B.; De Brabander, Jef K.; Veech, Richard L.; Uyeda, Kosaku

2016-01-01

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. PMID:26984404

[3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].

PubMed

Eirís, J; Ribes, A; Fernández-Prieto, R; Rodríguez-García, J; Rodríguez-Segade, S; Castro-Gago, M

1998-06-01

3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids. Here, we report the case of a 17-year-old girl who presented in both ten months and five years of age a clinical picture characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia, metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding of hepatic steatosis and clinical and biochemical data. As of 11 years old, laboratory investigations revealed carnitine deficiency and characteristic aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was made in cultured fibroblasts. Our report constitutes an example of the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.

Hyperemesis gravidarum presenting as jaundice and transient hyperthyroidism complicated with acute pancreatitis.

PubMed

Weng, Meng Tzu; Wei, Shu Chen; Wong, Jau Min; Chang, Tien Chun

2005-03-01

Hyperemesis gravidarum is an extreme form of nausea and vomiting during pregnancy. Its presenting symptoms include vomiting, disturbed nutrition, electrolyte imbalance, ketosis, extreme weight loss, renal and/or liver damage. It is rare for a hyperemesis gravidarum patient to present with jaundice, hyperthyroidism and idiopathic acute pancreatitis during the same hospitalization period. Here, we report such a case. A 25-year-old pregnant woman without underlying liver or thyroid disease was admitted due to jaundice noted for 2 days at 8 weeks of gestational age. Hyperthyroidism symptoms of tachycardia and finger tremor also bothered her. After treatment with parenteral fluid and antithyroid agents, her clinical condition improved. However, an episode of idiopathic pancreatitis occurred after nausea and vomiting subsided. Bowel rest with parenteral fluid and nutrition supplement was given and the increased pancreatic enzyme level gradually subsided. Follow-up liver and thyroid function were normal after gestational age of 26 weeks. She delivered a healthy female baby without low birth body weight at gestational age of 39 weeks. Rapid diagnosis and supportive care are important for the hyperemesis gravidarum patient with the complication of acute pancreatitis.

Internist, anesthesiologist and surgeon use of ketogenic diet.

PubMed

Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R; Dalvi, Prachiti; Camporesi, Enrico M; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo

2018-03-01

Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.

Master Amino acid Pattern as substitute for dietary proteins during a weight-loss diet to achieve the body's nitrogen balance equilibrium with essentially no calories.

PubMed

Lucà-Moretti, M; Grandi, A; Lucà, E; Muratori, G; Nofroni, M G; Mucci, M P; Gambetta, P; Stimolo, R; Drago, P; Giudice, G; Tamburlin, N

2003-01-01

Results of this multicentric study have shown that by giving 10 g (10 tablets) of Master Amino acid Pattern (MAP) as a substitute for dietary proteins, once a day, to 114 overweight participants undergoing the American Nutrition Clinics/Overweight Management Program (ANC/OMP), the participants' nitrogen balance could be maintained in equilibrium with essentially no calories (MAP 1 g=0.04 kcal), thereby preserving the body's structural and functional proteins, eliminating excessive water retention from the interstitial compartment, and preventing the sudden weight increase after study conclusion commonly known as the yo-yo effect. Study results have shown that the use of MAP, in conjunction with the ANC/OMP, has proven to be safe and effective by preventing those adverse effects associated with a negative nitrogen balance, such as oversized or flabby tissue, stretch marks, sagging of breast tissue, increased hair loss, faded hair color, and fragile or brittle nails. Also preventing those anomalies commonly associated with weight-loss diets, such as hunger, weakness, headache caused by ketosis, constipation, or decreased libido, the use of MAP, in conjunction with the ANC/OMP, allowed for mean weight loss of 1.4 kg (3 lb) per week.

PAX6 maintains β cell identity by repressing genes of alternative islet cell types.

PubMed

Swisa, Avital; Avrahami, Dana; Eden, Noa; Zhang, Jia; Feleke, Eseye; Dahan, Tehila; Cohen-Tayar, Yamit; Stolovich-Rain, Miri; Kaestner, Klaus H; Glaser, Benjamin; Ashery-Padan, Ruth; Dor, Yuval

2017-01-03

Type 2 diabetes is thought to involve a compromised β cell differentiation state, but the mechanisms underlying this dysfunction remain unclear. Here, we report a key role for the TF PAX6 in the maintenance of adult β cell identity and function. PAX6 was downregulated in β cells of diabetic db/db mice and in WT mice treated with an insulin receptor antagonist, revealing metabolic control of expression. Deletion of Pax6 in β cells of adult mice led to lethal hyperglycemia and ketosis that were attributed to loss of β cell function and expansion of α cells. Lineage-tracing, transcriptome, and chromatin analyses showed that PAX6 is a direct activator of β cell genes, thus maintaining mature β cell function and identity. In parallel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes including ghrelin, glucagon, and somatostatin. Chromatin analysis and shRNA-mediated gene suppression experiments indicated a similar function of PAX6 in human β cells. We conclude that reduced expression of PAX6 in metabolically stressed β cells may contribute to β cell failure and α cell dysfunction in diabetes.

PAX6 maintains β cell identity by repressing genes of alternative islet cell types

PubMed Central

Swisa, Avital; Avrahami, Dana; Eden, Noa; Zhang, Jia; Feleke, Eseye; Dahan, Tehila; Cohen-Tayar, Yamit; Stolovich-Rain, Miri; Kaestner, Klaus H.; Glaser, Benjamin; Ashery-Padan, Ruth

2016-01-01

Type 2 diabetes is thought to involve a compromised β cell differentiation state, but the mechanisms underlying this dysfunction remain unclear. Here, we report a key role for the TF PAX6 in the maintenance of adult β cell identity and function. PAX6 was downregulated in β cells of diabetic db/db mice and in WT mice treated with an insulin receptor antagonist, revealing metabolic control of expression. Deletion of Pax6 in β cells of adult mice led to lethal hyperglycemia and ketosis that were attributed to loss of β cell function and expansion of α cells. Lineage-tracing, transcriptome, and chromatin analyses showed that PAX6 is a direct activator of β cell genes, thus maintaining mature β cell function and identity. In parallel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes including ghrelin, glucagon, and somatostatin. Chromatin analysis and shRNA-mediated gene suppression experiments indicated a similar function of PAX6 in human β cells. We conclude that reduced expression of PAX6 in metabolically stressed β cells may contribute to β cell failure and α cell dysfunction in diabetes. PMID:27941241

Study on some risk factors and effects of bovine ketosis on dairy cows from the Galicia region (Spain).

PubMed

Viña, C; Fouz, R; Camino, F; Sanjuán, M L; Yus, E; Diéguez, F J

2017-10-01

The study was designed to determine the relation between β-hydroxybutyrate (BHB) concentrations in milk from dairy cows after calving and the length of the previous lactation, the dry period and the 305-day normalized production, and to assess the influence of BHB concentrations on culling and test-day milk productions and somatic cell counts (SCC) throughout the lactation that followed the BHB measurement. The data used in the study were obtained from 59 187 cows in the Galicia region (Spain). BHB determination was performed using Fourier-transformed infrared spectrometry from the milk samples collected from each cow on the first post-partum test day. For statistical analysis, the following methods were applied: (i) ordinal regression to assess the effect of the length of the previous lactation, the dry period and the 305-day normalized milk production on milk BHB, (ii) a Cox model to estimate the influence of the BHB concentration on risk of culling (overall and for a variety of reasons) and (iii) linear regression to assess the link between BHB and the milk yield and SCC obtained from each of the tests day performed throughout lactation. The probability of having higher BHB concentrations increased when the length of the previous lactation (p = 0.006), the dry period (p = 0.003) and the 305-day normalized milk yield (p = 0.005) increased. However, the slight increase observed (especially for the case of the dry period and the 305-day milk yield) would not justify that measures be implemented to reduce these traits. Higher concentrations of BHB led to an increased risk of culling due to 'death' (p ≤ 0.001) and 'urgent slaughter' (p ≤ 0.002) (both causes of involuntary culling). It also led to a reduction in milk production (p < 0.001) and an increase in SCC (p < 0.001) in the post-partum; from that moment onward (including peak lactation), there were no differences in those two parameters depending on the BHB levels. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Accuracy of capillary blood 3-β-hydroxybutyrate determination for the detection and treatment of canine diabetic ketoacidosis.

PubMed

Bresciani, Francesca; Pietra, Marco; Corradini, Sara; Giunti, Massimo; Fracassi, Federico

2014-01-01

In human medicine, diagnosis of diabetic ketoacidosis (DKA) is usually based on measurement of capillary 3-β-hydroxybutyrate (3-HB) with a hand held ketone sensor. This study was conducted to determine if measurement of capillary 3-HB could be useful for the diagnosis and monitoring of canine DKA. Fifteen dogs with diabetic ketosis and 10 with DKA were evaluated. Paired measurements of 3-HB of capillary and venous blood samples were analysed by the electrochemical sensor and reference method. Use of capillary 3-HB measurement during DKA management was then evaluated through simultaneous measurements of capillary 3-HB, urinary AcAc and venous blood gas analysis. Good agreement between capillary and venous 3-HB measurement was detected by the electrochemical sensor and reference method. Monitoring treatment of DKA revealed a significant correlation between capillary 3-HB and acidosis markers, while no significant correlation was observed between AcAc and acidosis markers. A cut-off value of capillary blood 3-HB > 3.8 mmol/L for diagnosis of DKA resulted in 70% and 92% sensitivity and specificity. The electrochemical sensor accurately measures 3-HB concentration in both capillary and venous blood samples, is accurate in diagnosing canine DKA, and appears to reflect the patient's metabolic status during DKA treatment.

Acute intractable vomiting and severe ketoacidosis secondary to the Dukan Diet©.

PubMed

Freeman, Thomas F; Willis, Blake; Krywko, Diann M

2014-10-01

The benefits of low-carbohydrate, high-protein diets, such as the Dukan Diet©, are well documented, whereas reported adverse effects are rare in literature. Such diets mimic starvation states in that they promote the breakdown of fat and the production of ketones secondary to fatty acid metabolism. In fact, one measure of the effectiveness of such diets is the presence of ketosis. To our knowledge, there have been no reported cases of ketoacidosis resulting from the Dukan Diet. The purpose of this case report is to illustrate the importance of a detailed dietary history in patients with severe ketoacidosis secondary to the Dukan Diet and suggest treatment that may allow outpatient management. A 42-year-old Iranian woman with no prior medical problems presented with 10 h of intractable nausea and vomiting secondary to ketoacidosis 2 days after starting the Dukan Diet. Although rare, ketoacidosis secondary to a low-carbohydrate, high-protein diet can have serious complications if untreated. Clinical suspicion should arise in any patient presenting with intractable nausea and vomiting after starting a diet such as the Dukan Diet. Early recognition and intervention is essential to quicken patient recovery and outpatient management. Published by Elsevier Inc.

Measuring breath acetone for monitoring fat loss: Review

PubMed Central

2015-01-01

Objective Endogenous acetone production is a by‐product of the fat metabolism process. Because of its small size, acetone appears in exhaled breath. Historically, endogenous acetone has been measured in exhaled breath to monitor ketosis in healthy and diabetic subjects. Recently, breath acetone concentration (BrAce) has been shown to correlate with the rate of fat loss in healthy individuals. In this review, the measurement of breath acetone in healthy subjects is evaluated for its utility in predicting fat loss and its sensitivity to changes in physiologic parameters. Results BrAce can range from 1 ppm in healthy non‐dieting subjects to 1,250 ppm in diabetic ketoacidosis. A strong correlation exists between increased BrAce and the rate of fat loss. Multiple metabolic and respiratory factors affect the measurement of BrAce. BrAce is most affected by changes in the following factors (in descending order): dietary macronutrient composition, caloric restriction, exercise, pulmonary factors, and other assorted factors that increase fat metabolism or inhibit acetone metabolism. Pulmonary factors affecting acetone exchange in the lung should be controlled to optimize the breath sample for measurement. Conclusions When biologic factors are controlled, BrAce measurement provides a non‐invasive tool for monitoring the rate of fat loss in healthy subjects. PMID:26524104

Effect of potassium and hypomagnesemia on insulin in the bovine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lentz, D.E.; Madsen, F.C.; Miller, J.K.

1976-01-01

Grass tetany in cattle has been associated with the consumption of early spring forages high in potassium (K) and low in magnesium (Mg). Alterations in serum Mg and K may affect intermediary carbohydrate metabolism, resulting in hypoglycemia and ketosis that often accompany grass tetany. We investigated these interrelationships by infusing potassium chloride (KCl) intravenously in normal (plasma Mg greater than 2.1 mg/100 ml) and Mg-deficient (plasma Mg less than .7 mg/100 ml) 9-month-old Holstein bull calves and intraruminally into nonpregnant, nonlactating Holstein cows. Plasma levels of both K and immunoreactive insulin (IRI) were elevated (P less than .01) by 1.14,more » 2, and 3 percent KCl (51, 64, and 135 mg K/kg) in calves and by 550 g KCl (440 mg K/kg body weight) in cows. Plasma K was lower (P less than .01) and IRI higher (P less than .01) in Mg-deficient calves than in normal calves during 2 percent KCl infusion. These results suggest that prolonged elevation of K and insulin in ruminants could lead to a series of metabolic disturbances that may play an important role in the etiology of grass tetany.« less

Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR.

PubMed

Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R Max; Tu, Benjamin P; MacMillan, John B; De Brabander, Jef K; Veech, Richard L; Uyeda, Kosaku

2016-05-13

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Fasting: The History, Pathophysiology and Complications

PubMed Central

Kerndt, Peter R.; Naughton, James L.; Driscoll, Charles E.; Loxterkamp, David A.

1982-01-01

An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T3 levels and a rise in glucagon and reverse T3 levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias. ImagesFigure 4. PMID:6758355

Master Amino acid Pattern as sole and total substitute for dietary proteins during a weight-loss diet to achieve the body's nitrogen balance equilibrium.

PubMed

Lucà-Moretti, M; Grandi, A; Lucà, E; Muratori, G; Nofroni, M G; Mucci, M P; Gambetta, P; Stimolo, R; Drago, P; Giudice, G; Tamburlin, N; Karbalai, M; Valente, C; Moras, G

2003-01-01

Results of this multicentric study have shown that by giving Master Amino acid Pattern (MAP) as a sole and total substitute of dietary proteins to 500 overweight participants undergoing the American Nutrition Clinics/Overweight Management Program (ANC/OMP), the participants' body nitrogen balance could be maintained in equilibrium with essentially no calories (MAP 1 g=0.04 kcal), thereby preserving the body's structural and functional proteins, eliminating excessive water retention from the interstitial compartment, and preventing the sudden weight increase after study conclusion commonly known as the yo-yo effect. Study results have shown that the use of MAP, in conjunction with the ANC/OMP regimen, has proven to be safe and effective by preventing those adverse effects associated with a negative nitrogen balance, such as oversized or flabby tissue, stretch marks, the sagging of breast tissue, increased hair loss, faded hair color, and fragile or brittle nails. Also prevented were those anomalies commonly associated with weight-loss diets, such as hunger, weakness, headache caused by ketosis, constipation, and decreased libido. The use of MAP in conjunction with the ANC/OMP also allowed for mean weight loss of 2.5 kg (5.5 lb) per week, achieved through reduction of excessive fat tissue and elimination of excessive water retention from the interstitial compartment.

Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats.

PubMed

Abdelhamid, Amir Mohamed; Abdelaziz, Rania Ramadan; Salem, Hatem Abdelrahman Ali

2018-03-06

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA 1c . It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

PubMed

Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

2014-01-30

The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Nonpharmacological treatment of epilepsy

PubMed Central

Saxena, V. S.; Nadkarni, V. V.

2011-01-01

Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG) biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine). Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70–80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment. PMID:22028523

Ketogenic diets, mitochondria, and neurological diseases

PubMed Central

Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

2014-01-01

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

Epinephrine deficiency results in intact glucose counter-regulation, severe hepatic steatosis and possible defective autophagy in fasting mice

PubMed Central

Sharara-Chami, Rana I.; Zhou, Yingjiang; Ebert, Steven; Pacak, Karel; Ozcan, Umut; Majzoub, Joseph A.

2016-01-01

Epinephrine is one of the major hormones involved in glucose counter-regulation and gluconeogenesis. However, little is known about its importance in energy homeostasis during fasting. Our objective is to study the specific role of epinephrine in glucose and lipid metabolism during starvation. In our experiment, we subject regular mice and epinephrine-deficient mice to a 48-h fast then we evaluate the different metabolic responses to fasting. Our results show that epinephrine is not required for glucose counter-regulation: epinephrine-deficient mice maintain their blood glucose at normal fasting levels via glycogenolysis and gluconeogenesis, with normal fasting-induced changes in the peroxisomal activators: peroxisome proliferator activated receptor γ coactivator α (PGC-1α), fibroblast growth factor 21 (FGF-21), peroxisome proliferator activated receptor α (PPAR-α), and sterol regulatory element binding protein (SREBP-1c). However, fasted epinephrine-deficient mice develop severe ketosis and hepatic steatosis, with evidence for inhibition of hepatic autophagy, a process that normally provides essential energy via degradation of hepatic triglycerides during starvation. We conclude that, during fasting, epinephrine is not required for glucose homeostasis, lipolysis or ketogenesis. Epinephrine may have an essential role in lipid handling, possibly via an autophagy-dependent mechanism. PMID:22405854

Differential metabolite levels in response to spawning-induced inappetence in Atlantic salmon Salmo salar.

PubMed

Cipriano, Rocco C; Smith, McKenzie L; Vermeersch, Kathleen A; Dove, Alistair D M; Styczynski, Mark P

2015-03-01

Atlantic salmon Salmo salar undergo months-long inappetence during spawning, but it is not known whether this inappetence is a pathological state or one for which the fish are adapted. Recent work has shown that inappetent whale sharks can exhibit circulating metabolite profiles similar to ketosis known to occur in humans during starvation. In this work, metabolite profiling was used to explore differences in analyte profiles between a cohort of inappetent spawning run Atlantic salmon and captively reared animals that were fed up to and through the time of sampling. The two classes of animals were easily distinguished by their metabolite profiles. The sea-run fish had elevated ɷ-9 fatty acids relative to the domestic feeding animals, while other fatty acid concentrations were reduced. Sugar alcohols were generally elevated in inappetent animals, suggesting potentially novel metabolic responses or pathways in fish that feature these compounds. Compounds expected to indicate a pathological catabolic state were not more abundant in the sea-run fish, suggesting that the animals, while inappetent, were not stressed in an unnatural way. These findings demonstrate the power of discovery-based metabolomics for exploring biochemistry in poorly understood animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

Seizure tests distinguish intermittent fasting from the ketogenic diet

PubMed Central

Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

2010-01-01

Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

A theoretical comparison between two ruminal electron sinks

PubMed Central

Ungerfeld, Emilio M.

2013-01-01

Dihydrogen accumulation resulting from methanogenesis inhibition in the rumen is an energy loss and can inhibit fermentation. The objective of this analysis was to compare the energetic and nutritional consequences of incorporating H2 into reductive acetogenesis or additional propionate production beyond the acetate to propionate shift occurring along with methanogenesis inhibition. Stoichiometric consequences were calculated for a simulated fermentation example. Possible nutritional consequences are discussed. Incorporating H2 into reductive acetogenesis or additional propionate production resulted in equal heat of combustion output in volatile fatty acids (VFA). Incorporation of H2 into reductive acetogenesis could result in moderate decrease in ruminal pH, although whole-animal buffering mechanisms make pH response difficult to predict. Research would be needed to compare the microbial protein production output. There could be post-absorptive implications due to differences in VFA profile. Electron incorporation into reductive acetogenesis could favor energy partition toward milk, but increase risk of ketosis in high-producing dairy cows on ketogenic diets. Greater propionate production could favor milk protein production, but may be less desirable in animals whose intake is metabolically constrained, like feedlot steers. Because of the different nutritional implications, and because practical solutions to incorporate H2 into either pathway are not yet available, it is recommended to research both alternatives. PMID:24198813

Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.

PubMed

Chung, Hae-Yun; Park, Yoo Kyoung

2017-09-01

Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

Characterization of the management practices of the top milk producing herds in the country.

PubMed

Jordan, E R; Fourdraine, R H

1993-10-01

Out of 128 surveys mailed to dairy farms that had been identified by the nine DHI processing centers as the top milk producing herds in the country, 61 surveys were returned. The predominant forage being fed was corn silage, followed by legume hay and haylage. On average, 6.7 feed additives and 3.5 alternative feeds were fed. Producers reported the following incidences of metabolic disorders: parturient paresis, 7.2%; displaced abomasum, 3.3%; ketosis, 3.7%; and nonspecific downer cow syndrome, 1.1%. Producers scheduled detection of estrus 3.1 times per day. Only 18.3% of the herds used routine synchronization of estrus. Artificial insemination was used on 94.8% of the cows and 88.5% of the heifers. The most important trait in sire selection was PTA for milk. For mastitis control, 75.4% of the producers practiced predipping, 85.2% used individual paper towels, 93.4% practiced postdipping, and 95.1% treated all cows at cessation of milking. Increased profitability and lower costs or higher returns were the primary motivators of these producers. Veterinarians were the most frequent source of information, followed by farm magazines. Satellite delivery of educational programs was the least acceptable delivery method. Extension professionals need to be cognizant of the producers' preferred information sources and delivery systems to ensure accurate, timely, cost-effective transfer of technological advances.

Management of diabetes mellitus: is the pump mightier than the pen?

PubMed

Pickup, John C

2012-02-28

Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) compared with multiple daily insulin injections (MDI). The greatest reduction in HbA(1c) levels with CSII occurs in patients with the worst glycaemic control; therefore, the most appropriate and cost-effective use of CSII in adults with T1DM is in those who have continued, elevated HbA(1c) levels or disabling hypoglycaemic episodes with MDI (including the use of long-acting insulin analogues and structured patient education). The disadvantages of CSII include higher costs than MDI and the risk of ketosis in the event of pump failure. In children with T1DM, CSII may be used when MDI is considered impractical or inappropriate. Pumps are not generally recommended for patients with type 2 diabetes mellitus but may improve control in some subgroups. A new generation of smaller insulin infusion pumps with an integrated cannula, called patch pumps, could improve uptake of CSII in general. The important clinical question is not whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII further improves glycaemic control when this control continues to be poor with MDI, and evidence exists that in most cases it does.

Rethinking fat as a fuel for endurance exercise.

PubMed

Volek, Jeff S; Noakes, Timothy; Phinney, Stephen D

2015-01-01

A key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced carbohydrate availability coupled with an inability to effectively utilize alternative lipid fuel sources. Paradoxically, cognitive and physical decline associated with glycogen depletion occurs in the presence of an over-abundance of fuel stored as body fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high-carbohydrate intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body's ability to oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels >0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low-carbohydrate availability is referred to as keto-adaptation. Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto-adaptation that could extend human physical and mental performance beyond current expectation. In this paper, we review these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is restricted could be of benefit for some athletes.

Measuring breath acetone for monitoring fat loss: Review.

PubMed

Anderson, Joseph C

2015-12-01

Endogenous acetone production is a by-product of the fat metabolism process. Because of its small size, acetone appears in exhaled breath. Historically, endogenous acetone has been measured in exhaled breath to monitor ketosis in healthy and diabetic subjects. Recently, breath acetone concentration (BrAce) has been shown to correlate with the rate of fat loss in healthy individuals. In this review, the measurement of breath acetone in healthy subjects is evaluated for its utility in predicting fat loss and its sensitivity to changes in physiologic parameters. BrAce can range from 1 ppm in healthy non-dieting subjects to 1,250 ppm in diabetic ketoacidosis. A strong correlation exists between increased BrAce and the rate of fat loss. Multiple metabolic and respiratory factors affect the measurement of BrAce. BrAce is most affected by changes in the following factors (in descending order): dietary macronutrient composition, caloric restriction, exercise, pulmonary factors, and other assorted factors that increase fat metabolism or inhibit acetone metabolism. Pulmonary factors affecting acetone exchange in the lung should be controlled to optimize the breath sample for measurement. When biologic factors are controlled, BrAce measurement provides a non-invasive tool for monitoring the rate of fat loss in healthy subjects. © 2015 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Eating and rumination activities two weeks prepartum to one month postpartum in 100 healthy cows and cows with peripartum diseases.

PubMed

Braun, U; Buchli, H; Hässig, M

2017-10-01

Eating and rumination activities were investigated in 100 cows from 14 days prepartum to 30 days postpartum. All cows were clinically healthy at the start of the study. A pressure sensor incorporated into the noseband of a halter was used to record jaw movements, which allowed the quantification of the daily duration of eating and rumination, number of regurgitated cuds and number of chewing cycles per cud. The cows were retrospectively divided into 2 main groups healthy (n = 24) and ill cows (n = 76), and the latter were further divided into the following subgroups: cows with periparturient paresis (n = 12), retained placenta (n = 13), metritis (n = 17), primary ketosis (n = 19) and lameness (n = 6). Healthy cows had the shortest eating and rumination times on the day of calving; duration of eating decreased continually before and increased steadily after calving. In contrast, duration of rumination varied little except for a significant drop on the days of calving. Compared with healthy cows, eating times of ill cows were significantly shorter before and after calving and rumination time was reduced on days 2 to 4 postpartum. The duration of eating differed between healthy and ill cows before calving, and therefore the usefulness of eating and rumination variables for early recognition of periparturient diseases in cows requires further investigation.

Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination: a case report.

PubMed

Yasuda, H; Nagata, M; Moriyama, H; Kobayashi, H; Akisaki, T; Ueda, H; Hara, K; Yokono, K

2012-01-01

Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported. We report a case of fulminant Type 1 diabetes with thrombocytopenia following influenza vaccination. A 54-year-old man was admitted to hospital with hyperglycaemia and diabetic ketosis. Seven days before admission, he received a seasonal influenza vaccine for the prevention of influenza infection. On admission, blood glucose was 29 mmol/L and HbA1c 40 mmol/mol (5.9%). Fasting and 2-h C-peptide immunoreactivity were <0.0333 nmol/L and 0.0999 nmol/L, respectively. Anti-GAD and anti-IA-2 antibodies were negative, so no autoimmunity seemed to participate in the etiology. ELISPOT assay also showed no association with T cell-mediated autoimmunity. HLA genotypes were consistent with susceptibility to fulminant Type 1 diabetes. After the abrupt onset of diabetes, he showed mild thrombocytopenia, which has been observed for approximately 5 years after diabetes development. This is the first description of fulminant Type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?

PubMed

Pinckaers, Philippe J M; Churchward-Venne, Tyler A; Bailey, David; van Loon, Luc J C

2017-03-01

Elite athletes and coaches are in a constant search for training methods and nutritional strategies to support training and recovery efforts that may ultimately maximize athletes' performance. Recently, there has been a re-emerging interest in the role of ketone bodies in exercise metabolism, with considerable media speculation about ketone body supplements being routinely used by professional cyclists. Ketone bodies can serve as an important energy substrate under certain conditions, such as starvation, and can modulate carbohydrate and lipid metabolism. Dietary strategies to increase endogenous ketone body availability (i.e., a ketogenic diet) require a diet high in lipids and low in carbohydrates for ~4 days to induce nutritional ketosis. However, a high fat, low carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrate, which forms a key fuel source for skeletal muscle during intense endurance-type exercise. Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes' performance under conditions where evidence-based nutritional strategies are applied appropriately.

Hypertension despite dehydration during severe pediatric diabetic ketoacidosis.

PubMed

Deeter, Kristina H; Roberts, Joan S; Bradford, Heidi; Richards, Todd; Shaw, Dennis; Marro, Kenneth; Chiu, Harvey; Pihoker, Catherine; Lynn, Anne; Vavilala, Monica S

2011-06-01

Diabetic ketoacidosis (DKA) may result in both dehydration and cerebral edema but these processes may have opposing effects on blood pressure. We examined the relationship between dehydration and blood pressure in pediatric DKA. A retrospective review was performed at Seattle Children's Hospital, Seattle, WA. Participants were hospitalized children less than 18 yr. Intervention(s) or main exposure was to patients with DKA (venous pH < 7.3, glucose > 300 mg/dL, HCO(3) < 15 mEq/L, and urinary ketosis). Dehydration was calculated as percent body weight lost at admission compared to discharge. Hypertension (systolic and/or diastolic blood pressure (DBP) percentile > 95%) was defined based on National Heart, Lung, and Blood Institute (NHLBI, 2004) nomograms and hypotension was defined as systolic blood pressure (SBP) <70 + 2 [age]. Thirty-three patients (median 10.9 yr; range 10 months to 17 yr) were included. Fifty-eight percent of patients (19/33) had hypertension on admission before treatment and 82% had hypertension during the first 6 h of admission. None had admission hypotension. Hypertension 48 h after treatment and weeks after discharge was common (28 and 19%, respectively). Based on weight gained by discharge, 27% of patients had mild, 61% had moderate, and 12% presented with severe dehydration. Despite dehydration, most children admitted with severe DKA had hypertension. © 2011 John Wiley & Sons A/S.

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

PubMed

Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

2017-09-01

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes.

PubMed

Sofou, Kalliopi; Dahlin, Maria; Hallböök, Tove; Lindefeldt, Marie; Viggedal, Gerd; Darin, Niklas

2017-03-01

Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed. Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe-except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients. Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

Relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against Neospora caninum infection in different stages of lactation

PubMed

Alekish, Myassar O.; Talafha, Abdelsalam Q; Alshehabat, Musa A; Ismail, Zuhair A Bani

Neospora caninum is an important cause of abortion in dairy cattle. The general health of affected cows has not been investigated before. Therefore, the main objective of this study was to identify possible relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against N. caninum antibodies in different stages of lactation. The study was carried out using 72 N. caninum seropositive cows and 61 seronegative dairy cows (control). Serum from all cows was tested to determine their N. caninum status (seropositive vs seronegative) using commercially available indirect enzyme-linked immunosorbent assay test kit (iELISA). In addition, serum biochemical parameters including beta-hydroxybutyrate (BHB), glucose, creatinine, blood urea nitrogen, total protein, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyltranspeptidase (GGT) were determined using routine laboratory methods. The stage of lactation was obtained at the time of sampling from farm records. Student independent t-test showed that there was a significant difference in the serum concentrations of BHB, AST, ALT, and LDH between seropositive and seronegative cows. There was no significant association between seropositivity and the stage of lactation. However, multivariable logistic regression analysis showed that there was a strong association between seropositivity and BHB concentrations. Results of this study indicate a possible relationship between N. caninum seropositivity and certain metabolic diseases such as ketosis and fatty liver syndrome in dairy cows.

Efficacy of an Overnight Predictive Low-Glucose Suspend System in Relation to Hypoglycemia Risk Factors in Youth and Adults With Type 1 Diabetes.

PubMed

Calhoun, Peter M; Buckingham, Bruce A; Maahs, David M; Hramiak, Irene; Wilson, Darrell M; Aye, Tandy; Clinton, Paula; Chase, Peter; Messer, Laurel; Kollman, Craig; Beck, Roy W; Lum, John

2016-11-01

We developed a system to suspend insulin pump delivery overnight when the glucose trend predicts hypoglycemia. This predictive low-glucose suspend (PLGS) system substantially reduces nocturnal hypoglycemia without an increase in morning ketosis. Evaluation of hypoglycemia risk factors that could potentially influence the efficacy of the system remains critical for understanding possible problems with the system and identifying patients that may have the greatest benefit when using the system. The at-home randomized trial consisted of 127 study participants with hemoglobin A1c (A1C) of ≤8.5% (mmol/mol) for patients aged 4-14 years and ≤8.0% for patient aged 15-45 years. Factors assessed included age, gender, A1C, diabetes duration, daily percentage basal insulin, total daily dose of insulin (units/kg-day), bedtime BG, bedtime snack, insulin on board, continuous glucose monitor (CGM) rate of change (ROC), day of the week, time system activated, daytime exercise intensity, and daytime CGM-measured hypoglycemia. The PLGS system was effective in preventing hypoglycemia for each factor subgroup. There was no evidence that the PLGS system was more or less effective in preventing hypoglycemia in any one subgroup compared with the other subgroups based on that factor. In addition, the effect of the system on overnight hyperglycemia did not differ in subgroups. The PLGS system tested in this study effectively reduced hypoglycemia without a meaningful increase in hyperglycemia across a variety of factors. © 2016 Diabetes Technology Society.

Ketone body metabolism and its defects.

PubMed

Fukao, Toshiyuki; Mitchell, Grant; Sass, Jörn Oliver; Hori, Tomohiro; Orii, Kenji; Aoyama, Yuka

2014-07-01

Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with "mild" SCOT mutations may have nonketotic periods. T2-deficient patients with "mild" mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.

The associations between culling due to clinical Johne's disease or the detection of Mycobacterium avium subsp. paratuberculosis fecal shedding and the diagnosis of clinical or subclinical diseases in two dairy herds in Minnesota, USA.

PubMed

Raizman, Eran A; Wells, Scott J; Godden, Sandra M; Fetrow, John; Oakes, J Michael

2007-07-16

Our objectives were to identify associations between clinical or subclinical diseases and subsequent culling because of clinical Johne's disease (JD) or the detection of fecal shedding of Mycobacterium paratuberculosis (Map) after 305 days in milk (DIM). A total of 1297 cows from two Minnesota dairies were enrolled in the study. From study cows, fecal samples were obtained prior to calving (close-up period) and after at least 305 DIM or at the time of leaving the herd (sold/dead). Between 3 and 21 DIM, blood samples were obtained for serum betahydroxybutyrate (BHB) and serum total-protein testing. Body-condition score (BCS) was evaluated during the close-up period, between 3 and 21 DIM, and at the end of lactation. The diagnosis time (DIM) of clinical disease events (culling because of JD clinical signs, ketosis, lameness, mastitis, displacement abomasum, injury, metritis, milk fever, pneumonia, and retained placenta) was recorded. Sixty-six cows were culled because of JD clinical signs (CCDJ) with average DIM of 209. CCDJ was associated with event of pneumonia (n=131) (OR=3.0, 95% CI=1.0-6.0) and level of fecal shedding (light: OR=13.0, 95% CI=5.3-30.0; moderate: OR=34.0, 95% CI=13.0-89.0; heavy: OR=66.0, 95% CI=26.0-171.0). Detection of fecal shedding at the end of the lactation (n=79) was associated only with event of pneumonia (OR=2.0, 95% CI=1.0-4.0).

The role of rumen-protected choline in hepatic function and performance of transition dairy cows.

PubMed

Shahsavari, Arash; D'Occhio, Michael J; Al Jassim, Rafat

2016-07-01

High-producing dairy cows enter a period of negative energy balance during the first weeks of lactation. Energy intake is usually sufficient to cover the increase in energy requirements for fetal growth during the period before calving, but meeting the demand for energy is often difficult during the early stages of lactation. A catabolic state predominates during the transition period, leading to the mobilisation of energy reserves (NEFA and amino acids) that are utilised mainly by the liver and muscle. Increased uptake of mobilised NEFA by the liver, combined with the limited capacity of hepatocytes to either oxidise fatty acids for energy or to incorporate esterified fatty acids into VLDL results in fatty liver syndrome and ketosis. This metabolic disturbance can affect the general health, and it causes economic losses. Different nutritional strategies have been used to restrict negative effects associated with the energy challenge in transition cows. The provision of choline in the form of rumen-protected choline (RPC) can potentially improve liver function by increasing VLDL exportation from the liver. RPC increases gene expression of microsomal TAG transfer protein and APOB100 that are required for VLDL synthesis and secretion. Studies with RPC have looked at gene expression, metabolic hormones, metabolite profiles, milk production and postpartum reproduction. A reduction in liver fat and enhanced milk production has been observed with RPC supplementation. However, the effects of RPC on health and reproduction are equivocal, which could reflect the lack of sufficient dose-response studies.

Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature.

PubMed

Hickmott, Laura; De La Peña, Hugo; Turner, Helen; Ahmed, Fathelrahman; Protheroe, Andrew; Grossman, Ashley; Gupta, Avinash

2017-04-01

Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.

Role of yoga in diabetes.

PubMed

Sahay, B K

2007-02-01

The science of yoga is an ancient one. It is a rich heritage of our culture. Several older books make a mention of the usefulness of yoga in the treatment of certain diseases and preservation of health in normal individuals. The effect of yogic practices on the management of diabetes has not been investigated well. We carried out well designed studies in normal individuals and those with diabetes to assess the role of yogic practices on glycaemic control, insulin kinetics, body composition exercise tolerance and various co-morbidities like hypertension and dyslipidemia. These studies were both short term and long-term. These studies have confirmed the useful role of yoga in the control of diabetes mellitus. Fasting and postprandial blood glucose levels came down significantly. Good glycaemic status can be maintained for long periods of time. There was a lowering of drug requirement and the incidence of acute complications like infection and ketosis was significantly reduced. There were significant changes in the insulin kinetics and those of counter-regulatory hormones like cortisol. There was a decrease in free fatty acids. There was an increase in lean body mass and decrease in body fat percentage. The number of insulin receptors was also increased. There was an improvement in insulin sensitivity and decline in insulin resistance. All these suggest that yogic practices have a role even in the prevention of diabetes. There is a beneficial effect on the co-morbid conditions like hypertension and dyslipidemia.

Bicarbonate in diabetic ketoacidosis - a systematic review

PubMed Central

2011-01-01

Objective This study was designed to examine the efficacy and risk of bicarbonate administration in the emergent treatment of severe acidemia in diabetic ketoacidosis (DKA). Methods PUBMED database was used to identify potentially relevant articles in the pediatric and adult DKA populations. DKA intervention studies on bicarbonate administration versus no bicarbonate in the emergent therapy, acid-base studies, studies on risk association with cerebral edema, and related case reports, were selected for review. Two reviewers independently conducted data extraction and assessed the citation relevance for inclusion. Results From 508 potentially relevant articles, 44 were included in the systematic review, including three adult randomized controlled trials (RCT) on bicarbonate administration versus no bicarbonate in DKA. We observed a marked heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate administration in various studies. Two RCTs demonstrated transient improvement in metabolic acidosis with bicarbonate treatment within the initial 2 hours. There was no evidence of improved glycemic control or clinical efficacy. There was retrospective evidence of increased risk for cerebral edema and prolonged hospitalization in children who received bicarbonate, and weak evidence of transient paradoxical worsening of ketosis, and increased need for potassium supplementation. No studies involved patients with an initial pH < 6.85. Conclusions The evidence to date does not justify the administration of bicarbonate for the emergent treatment of DKA, especially in the pediatric population, in view of possible clinical harm and lack of sustained benefits. PMID:21906367

Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families.

PubMed

Ijaz, Sadaqat; Zahoor, Muhammad Yasir; Imran, Muhammad; Ramzan, Khushnooda; Bhinder, Munir Ahmad; Shakeel, Hussain; Iqbal, Muhammad; Aslam, Asim; Shehzad, Wasim; Cheema, Huma Arshad; Rehman, Habib

2017-10-26

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency. Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis. Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals. FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.

CELL BIOLOGY SYMPOSIUM: Practical application of the basic aspects of GLUT4 membrane trafficking and insulin signaling on issues related to animal agriculture.

PubMed

Smith, S B

2017-05-01

Because of the relatively short lifespans of beef cattle, membrane trafficking in relation to inflammation is not considered important unless it overtly affects productivity. However, glucose uptake and utilization is important for adipose tissue development in beef cattle, and increasing glucose utilization in intramuscular adipose tissue can increase carcass quality. Research from the 1980s demonstrated a lack of insulin sensitivity in isolated bovine adipocytes and adipose tissue explants incubated in vitro. Insulin did not stimulate glucose or acetate incorporation into fatty acids, nor did it increase concentrations of glycolytic intermediates in bovine adipose tissue incubated with exogenous glucose. Specific binding of [I] iodoinsulin and insulin degradation in bovine isolated adipocytes was low to non-detectable. These early studies indicated that insulin-dependent receptor-mediated signaling was less important in bovine adipose tissue than in adipose tissues of humans, swine, or laboratory species. More recent research demonstrated that glucose transporter protein 4 (GLUT4) expression in muscle and adipose tissue declines markedly after birth in calves, indicating the development of insulin resistance as cattle transition from suckling to functional ruminants. Insulin resistance is important in dairy cattle, causing ketosis and fatty liver. Consistent with this, subcutaneous adipose tissue expression decreases 50% following parturition in dairy cattle, although expression of genes associated with insulin responsiveness (, , and ) is up-regulated by 21 d postpartum. Understanding the underlying mechanisms of insulin resistance in beef and dairy cattle would increase animal health and thereby improve productivity.

Interactions of Fat and Carbohydrate Metabolism—New Aspects and Therapies

PubMed Central

Lawrence, R. D.

1941-01-01

NO one has so far produced anything approaching a clear picture of either fat or carbohydrate metabolism and the interactions of the two are still more involved and elusive although they clearly exist. Plants and animals build up reserves of fat from carbohydrate, but the reverse process (fat into carbohydrate), proved in plant seeds, is still unproven in animals, although theoretically possible. In normal human metabolism fat-carbohydrate interactions are almost hidden. The disturbances shown in the metabolism of a diabetic seem to give us the clearest indications of these interactions. Either carbohydrate or fat can be used as the main source of body fuel, but their metabolic course is very different, both as regards chemistry and function. It is only whep carbohydrate is not available, either in starvation or severe diabetes, that fat provides the fuel of the body; this contrast is also manifest in the blood and internal organs, especially the liver. Under the commonest normal conditions of diet carbohydrate is predominantly and preferentially used for metabolism. The liver is rich in glycogen, poor in fat; the blood fat is minimal and ketone bodies, although perhaps present in small amount in the blood at most times, are absent on common tests. As soon as carbohydrate is insufficiently available for the needs of metabolism, depot fat flows to the liver and is there catabolized to ketone bodies which recent proof has shown to be burned peripherally in the muscles independent of carbohydrate metabolism. This is a normal process, harmful only in diabetes, and especially harmful when it occurs suddenly, e.g. when insulin is cut off from a fat diabetic dog or human patient. A diabetic supports with ease a prolonged severe ketosis but suffers from one of sudden onset, although of milder severity. Insulin in the diabetic and sugar in the starved switches metabolism from fat to carbohydrate usage very quickly and ketonuria usually disappears in three to six hours. �

Different ketogenesis strategies lead to disparate seizure outcomes.

PubMed

Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

2018-07-01

Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

Nutritional strategies to optimize dairy cattle immunity.

PubMed

Sordillo, L M

2016-06-01

Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities.

PubMed

Cebra, C K; Garry, F B; Getzy, D M; Fettman, M J

1997-01-01

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.

Potent anti-seizure effects of D-leucine

PubMed Central

Hartman, Adam L.; Santos, Polan; O’Riordan, Kenneth J.; Stafstrom, Carl E.; Hardwick, J. Marie

2015-01-01

There are no effective treatments for millions of patients with intractable epilepsy. High-fat ketogenic diets may provide significant clinical benefit but are challenging to implement. Low carbohydrate levels appear to be essential for the ketogenic diet to work, but the active ingredients in dietary interventions remain elusive, and a role for ketogenesis has been challenged. A potential antiseizure role of dietary protein or of individual amino acids in the ketogenic diet is understudied. We investigated the two exclusively ketogenic amino acids, L-leucine and L-lysine, and found that only L-leucine potently protects mice when administered prior to the onset of seizures induced by kainic acid injection, but not by inducing ketosis. Unexpectedly, the D-enantiomer of leucine, which is found in trace amounts in the brain, worked as well or better than L-leucine against both kainic acid and 6 Hz electroshock-induced seizures. However, unlike L-leucine, D-leucine potently terminated seizures even after the onset of seizure activity. Furthermore, D-leucine, but not L-leucine, reduced long-term potentiation but had no effect on basal synaptic transmission in vitro. In a screen of candidate neuronal receptors, D-leucine failed to compete for binding by cognate ligands, potentially suggesting a novel target. Even at low doses, D-leucine suppressed ongoing seizures at least as effectively as diazepam but without sedative effects. These studies raise the possibility that D-leucine may represent a new class of anti-seizure agents, and that D-leucine may have a previously unknown function in eukaryotes. PMID:26054437

New Nordic Diet versus Average Danish Diet: A Randomized Controlled Trial Revealed Healthy Long-Term Effects of the New Nordic Diet by GC-MS Blood Plasma Metabolomics.

PubMed

Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco; Acar, Evrim; Gürdeniz, Gözde; Larsen, Thomas M; Astrup, Arne; Dragsted, Lars O; Engelsen, Søren Balling

2016-06-03

A previous study has shown effects of the New Nordic Diet (NND) to stimulate weight loss and lower systolic and diastolic blood pressure in obese Danish women and men in a randomized, controlled dietary intervention study. This work demonstrates long-term metabolic effects of the NND as compared with an Average Danish Diet (ADD) in blood plasma and reveals associations between metabolic changes and health beneficial effects of the NND including weight loss. A total of 145 individuals completed the intervention and blood samples were taken along with clinical examinations before the intervention started (week 0) and after 12 and 26 weeks. The plasma metabolome was measured using GC-MS, and the final metabolite table contained 144 variables. Significant and novel metabolic effects of the diet, resulting weight loss, gender, and intervention study season were revealed using PLS-DA and ASCA. Several metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects, higher levels of vaccenic acid and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic, and N-aspartic acids and 1,5-anhydro-d-sorbitol were related to a lower weight loss. Specific gender and seasonal differences were also observed. The study strongly indicates that healthy diets high in fish, vegetables, fruit, and whole grain facilitated weight loss and improved insulin sensitivity by increasing ketosis and gluconeogenesis in the fasting state.

Real-Time Detection of Infusion Site Failures in a Closed-Loop Artificial Pancreas.

PubMed

Howsmon, Daniel P; Baysal, Nihat; Buckingham, Bruce A; Forlenza, Gregory P; Ly, Trang T; Maahs, David M; Marcal, Tatiana; Towers, Lindsey; Mauritzen, Eric; Deshpande, Sunil; Huyett, Lauren M; Pinsker, Jordan E; Gondhalekar, Ravi; Doyle, Francis J; Dassau, Eyal; Hahn, Juergen; Bequette, B Wayne

2018-05-01

As evidence emerges that artificial pancreas systems improve clinical outcomes for patients with type 1 diabetes, the burden of this disease will hopefully begin to be alleviated for many patients and caregivers. However, reliance on automated insulin delivery potentially means patients will be slower to act when devices stop functioning appropriately. One such scenario involves an insulin infusion site failure, where the insulin that is recorded as delivered fails to affect the patient's glucose as expected. Alerting patients to these events in real time would potentially reduce hyperglycemia and ketosis associated with infusion site failures. An infusion site failure detection algorithm was deployed in a randomized crossover study with artificial pancreas and sensor-augmented pump arms in an outpatient setting. Each arm lasted two weeks. Nineteen participants wore infusion sets for up to 7 days. Clinicians contacted patients to confirm infusion site failures detected by the algorithm and instructed on set replacement if failure was confirmed. In real time and under zone model predictive control, the infusion site failure detection algorithm achieved a sensitivity of 88.0% (n = 25) while issuing only 0.22 false positives per day, compared with a sensitivity of 73.3% (n = 15) and 0.27 false positives per day in the SAP arm (as indicated by retrospective analysis). No association between intervention strategy and duration of infusion sets was observed ( P = .58). As patient burden is reduced by each generation of advanced diabetes technology, fault detection algorithms will help ensure that patients are alerted when they need to manually intervene. Clinical Trial Identifier: www.clinicaltrials.gov,NCT02773875.

Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset.

PubMed

Triolo, Taylor M; Chase, H Peter; Barker, Jennifer M

2009-05-01

Upon diagnosis of type 1 diabetes, patients are usually symptomatic, and many have ketoacidosis. Screening for islet autoantibodies (IAs) has been shown to decrease A1C level and rate of hospitalization at diabetes onset. Metabolic tests and the presence of symptoms were described at diabetes onset during the Diabetes Prevention Trial-Type 1 (DPT-1). The DPT-1 screened relatives of patients with type 1 diabetes for islet cell autoantiobodies (ICAs). Those with positive ICAs had intravenous and oral glucose tolerance tests (IVGTTs and OGTTs) and were randomized into one of two prevention trials. Throughout the DPT-1 parenteral and oral insulin study, 246 people were diagnosed with type 1 diabetes. Of the 246 subjects diagnosed with diabetes, 218 had data regarding the presence of symptoms, and 138 (63.3%) reported no symptoms suggestive of diabetes. Eight subjects (3.67%) presented with ketosis. Subjects presented with a mean +/- SD A1C of 6.41 +/- 1.15%. At diagnosis, 90 subjects (50.8%) had A1C in the normal range (<6.2%). OGTT data at the time of diagnosis indicate that 35.4% had a glucose result of <100 mg/dl at 0 min. The majority of subjects diagnosed with type 1 diabetes through the DPT-1 were asymptomatic at onset and had normal fasting glucose and A1C levels. This suggests that intermittent screening (IA followed by OGTT) may allow diagnosis of diabetes before severe metabolic decompensation. Screening with A1C will miss identifying many of the subjects with newly diagnosed type 1 diabetes in this cohort.

Mortality of live export cattle on long-haul voyages: pathologic changes and pathogens.

PubMed

Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; Barnes, Anne; O'Hara, Amanda J

2014-03-01

The cause of death in 215 cattle on 20 long-haul live export voyages from Australia to the Middle East, Russia, and China was investigated between 2010 and 2012 using gross, histologic, and/or molecular pathology techniques. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect nucleic acids from viruses and bacteria known to be associated with respiratory disease in cattle: Bovine coronavirus (Betacoronavirus 1), Bovine herpesvirus 1, Bovine viral diarrhea virus 1 and 2, Bovine respiratory syncytial virus, Bovine parainfluenza virus 3, Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. The most commonly diagnosed cause of death was respiratory disease (107/180, 59.4%), followed by lameness (n = 22, 12.2%), ketosis (n = 12, 6.7%), septicemia (n = 11, 6.1%), and enteric disease (n = 10, 5.6%). Two thirds (130/195) of animals from which lung samples were collected had histologic changes and/or positive qRT-PCR results indicative of infectious lung disease: 93 out of 130 (72%) had evidence of bacterial infection, 4 (3%) had viral infection, and 29 (22%) had mixed bacterial and viral infections, and for 4 (3%) the causative organism could not be identified. Bovine coronavirus was detected in up to 13% of cattle tested, and this finding is likely to have important implications for the management and treatment of respiratory disease in live export cattle. Results from the current study indicate that although overall mortality during live export voyages is low, further research into risk factors for developing respiratory disease is required.

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation

PubMed Central

Evans, Mark; Cogan, Karl E.

2016-01-01

Abstract Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β‐hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post‐exercise recovery period, and the ability to utilise ketone bodies is higher in exercise‐trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti‐lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes. PMID:27861911

Alterations in Hepatic Glucose and Energy Metabolism as a Result of Calorie and Carbohydrate Restriction

PubMed Central

Browning, Jeffrey D.; Weis, Brian; Davis, Jeannie; Satapati, Santhosh; Merritt, Matthew; Malloy, Craig R.; Burgess, Shawn C.

2009-01-01

Carbohydrate-restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis and ketosis. Because little is known regarding the effect of carbohydrate-restriction on the origin of gluconeogenic precursors (gluconeogenesis from glycerol (GNGglycerol) and lactate/amino acids (GNGPEP)) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used 2H and 13C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and TCA cycle flux in weight-stable subjects(n=7) and subjects following carbohydrate-(n=7) or calorie-restriction(n=7). The majority of hepatic glucose production in carbohydrate-restricted subjects came from GNGPEP. The contribution of glycerol to gluconeogenesis was similar in all groups despite evidence of increased fat oxidation in carbohydrate-restricted subjects. A strong correlation between TCA cycle flux and GNGPEP was found, though the reliance on TCA cycle energy production for gluconeogenesis was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of gluconeogenesis. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNGPEP is maximal. In conclusion, carbohydrate-restriction modifies hepatic gluconeogenesis by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic β-oxidation. PMID:18925642

Postpartum body condition score and results from the first test day milk as predictors of disease, fertility, yield, and culling in commercial dairy herds.

PubMed

Heuer, C; Schukken, Y H; Dobbelaar, P

1999-02-01

The study used field data from a regular herd health service to investigate the relationships between body condition scores or first test day milk data and disease incidence, milk yield, fertility, and culling. Path model analysis with adjustment for time at risk was applied to delineate the time sequence of events. Milk fever occurred more often in fat cows, and endometritis occurred between calving and 20 d of lactation more often in thin cows. Fat cows were less likely to conceive at first service than were cows in normal condition. Fat body condition postpartum, higher first test day milk yield, and a fat to protein ratio of > 1.5 increased body condition loss. Fat or thin condition or condition loss was not related to other lactation diseases, fertility parameters, milk yield, or culling. First test day milk yield was 1.3 kg higher after milk fever and was 7.1 kg lower after displaced abomasum. Higher first test day milk yield directly increased the risk of ovarian cyst and lameness, increased 100-d milk yield, and reduced the risk of culling and indirectly decreased reproductive performance. Cows with a fat to protein ratio of > 1.5 had higher risks for ketosis, displaced abomasum, ovarian cyst, lameness, and mastitis. Those cows produced more milk but showed poor reproductive performance. Given this type of herd health data, we concluded that the first test day milk yield and the fat to protein ratio were more reliable indicators of disease, fertility, and milk yield than was body condition score or loss of body condition score.

Thioredoxin-interacting protein (Txnip) is a critical regulator of hepatic glucose production.

PubMed

Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

2008-01-25

Thioredoxin-interacting protein (Txnip) has been recently described as a possible link between cellular redox state and metabolism; Txnip binds thioredoxin and inhibits its disulfide reductase activity in vitro, while a naturally occurring strain of Txnip-deficient mice has hyperlipidemia, hypoglycemia, and ketosis exacerbated by fasting. We generated Txnip-null mice to investigate the role of Txnip in glucose homeostasis. Txnip-null mice were hypoglycemic, hypoinsulinemic, and had blunted glucose production following a glucagon challenge, consistent with a central liver glucose-handling defect. Glucose release from isolated Txnip-null hepatocytes was 2-fold lower than wild-type hepatocytes, whereas beta-hydroxybutyrate release was increased 2-fold, supporting an intrinsic defect in hepatocyte glucose metabolism. While hepatocyte-specific gene deletion of Txnip did not alter glucose clearance compared with littermate controls, Txnip expression in the liver was required for maintaining normal fasting glycemia and glucose production. In addition, hepatic overexpression of a Txnip transgene in wild-type mice resulted in elevated serum glucose levels and decreased ketone levels. Liver homogenates from Txnip-null mice had no significant differences in the glutathione oxidation state or in the amount of available thioredoxin. However, overexpression of wild-type Txnip in Txnip-null hepatocytes rescued cellular glucose production, whereas overexpression of a C247S mutant Txnip, which does not bind thioredoxin, had no effect. These data demonstrate that Txnip is required for normal glucose homeostasis in the liver. While available thioredoxin is not changed in Txnip-null mice, the effects of Txnip on glucose homeostasis are abolished by a single cysteine mutation that inhibits binding to thioredoxin.

Nursing sickness in lactating mink (Mustela vison). II. Pathophysiology and changes in body fluid composition.

PubMed Central

Wamberg, S; Clausen, T N; Olesen, C R; Hansen, O

1992-01-01

An investigation of the pathophysiological characteristics of nursing sickness in mink was carried out as a follow-up study of a previous epidemiological survey at a Danish fur research farm during the 1989 breeding season. In a total of 48 nursing females of the Standard Black and Pastel type, concentrations of several pertinent biochemical constituents of whole blood, plasma, urine and skeletal muscle were determined in order to identify nutritional and metabolic factors involved in the origin and development of the disease. Compared to the reference data obtained in 17 apparently normal lactating dams the findings in 31 females suffering from nursing sickness presented varying clinical and biochemical signs of progressive dehydration and emaciation: aldosteronism, hypovolemia, hyponatremia, hyperkalemia (in the face of muscle potassium depletion), hyperglycemia and azotemic acidemia. Neither ketosis nor severe lactacidemia was observed. The urine was almost devoid of sodium and chloride, and urinary potassium concentration diminished by approximately 50%. The concentrating ability of the kidneys was reduced to less than one third of the maximum value. The results were consistent with severe dehydration and emaciation due to heavy losses of energy, water and body mass along with increasing milk production. The progressive nature of the disease supported the hypothesis that nursing sickness is due to the combined effects of heavy milk production and excessive tissue catabolism along with reduced or ceased dietary intake, and maybe increasing environmental stress. In the advanced stage of the disease coma and death appear to be the inevitable outcome of the metabolic strains for continuing milk production. PMID:1591662

Reveal genes functionally associated with ACADS by a network study.

PubMed

Chen, Yulong; Su, Zhiguang

2015-09-15

Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

Bariatric surgery is not contraindicated in obese patients suffering from glycogen storage disease type IXa. A case report with follow-up at three years.

PubMed

Musella, Mario; Milone, Marco; Maietta, Paola; Bianco, Paolo; Pisapia, Anna; Gaudioso, Dario; Palumbo, Rubina

2014-01-01

Glucose storage disease type IXa (GSD IXa) is an uncommon condition presenting with childhood onset hepatomegaly, growth retardation, and often, fasting ketosis and hypoglycemia. Despite its benign course, the lack of dietary counseling may favor uncontrolled weight gain. We investigated the efficacy of bariatric surgery in one 17 years old female suffering from GSD IXa and morbid obesity. The diagnosis was GSD type IXa in a patient with a body mass index (BMI) of 45.5kg/m(2). Onset of hypoglycemia was reported twice each month. She was treated her implanting an adjustable gastric banding through laparoscopy. Three years after surgery the patient presents a BMI of 30.1kg/m(2) and an excess of weight loss (EWL) of 71.1%. Only once, following surgery, she had to deflate her band to allow a faster transit of food through her stomach, thus reaching a prompt euglycemic condition, due to an incoming hypoglycemic crisis. Laparoscopic adjustable gastric banding (LAGB) is one of the most used approaches to treat morbid obesity. It is a restrictive procedure unable to affect the absorption of any nutrient, presenting a very low intra and perioperative complication rate. In our GSD IXa patient, it offered a prompt modification of food intake restriction whenever requested, thus avoiding hypoglycemia. LAGB is effective in determining weight loss without inducing significant side effects or worsening hypoglycemia, in this morbid obese patient, suffering from GSD type IXa. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

AMPK induced memory improvements in the diabetic population: A case study.

PubMed

Halikas, Alicia; Gibas, Kelly J

2018-04-27

Diabetics in mid-life carry a 1.5 times higher risk of developing Alzheimer's disease than those diagnosed with diabetes (T2D) later in life [1]. Recent research points to accelerated cognitive decline within a range of 20%-50% for middle-aged diabetics as compared to non-diabetic populations [2,3]. Metabolic syndrome (MetS), a type 2 diabetes (T2D) precursor, is also linked to MCI and AD pathologies via hypo-metabolic brain circuitry that inhibits glucose metabolism and attenuates cognitive function [4]. Dysregulation of intracellular and extracellular signaling as mediated by the mTOR and AMPK pathways is the result. These critical nutrient sensing pathways modulate epigenetic shifts in the genome by channeling fuel substrates either towards mitochondrial fatty acid oxidation (AMPK) or cytosolic glycolysis and substrate level phosphorylation (mTOR) [5]. This case study was designed to examine the link between peripheral insulin resistance and early stage memory loss in a type 2 diabetic male. Reactivating the AMPK pathway via induced and controlled nutritional ketosis combined with high intensity interval training (HIIT) (in order to inhibit mTOR signaling) were primary features of the 10 week intervention. Post intervention results revealed statistically significant reductions in HgA1c, fasting insulin and HOMA-IR (homeostatic model assessment of insulin resistance). Restoring peripheral and hypothalamic insulin sensitivity by way of AMPK activation may restore memory function, improve neuroplasticity, and normalize MetS biomarkers (Demetrius and Driver, 2014; [4,6]). Copyright © 2018. Published by Elsevier Ltd.

Predictors for pregnancy outcomes in Romanian women with Type 1 Diabetes Mellitus: a prospective study.

PubMed

Timar, Bogdan; Timar, Romulus; Albai, Alin; Stoian, Dana; Nitu, Razvan; Craina, Marius

2014-01-01

Type 1 diabetes mellitus in pregnant women is associated with an increased risk of congenital malformations, obstetric complications, neonatal morbidity, and mortality. Our aim was to evaluate which factors from the first trimester of pregnancy have a significant impact on the pregnancy outcomes of women with type 1 diabetes. We included 94 pregnant women with type 1 diabetes in this study. In these patients, we analyzed the influence of several diabetes-related parameters on the pregnancy outcome. We compared the parameters between two cohorts: those with successful pregnancies and those with adverse pregnancy outcomes, defined as spontaneous abortion or congenital malformations. The influence of several factors on the pregnancy outcome was assessed using multivariate and univariate logistic regressions. The prevalence of adverse pregnancy outcomes was 28.7%, and was associated with poorer glycemic control (p <0.001), lower frequency of daily self-monitoring tests (p <0.001), smoking status (p <0.001), alcohol consumption (p <0.001), increased prevalence of chronic complications of diabetes, and the presence of ketosis. However, the adverse outcomes were not significantly associated with age, duration of diabetes, presence of thyroid disease, or body mass index. Furthermore, planned pregnancy was found to be a significant protective factor (odds ratio, 0.15; p <0.001). These results indicate that by carefully planning the pregnancy, ensuring optimal glycemic control, and eliminating habitual risk factors, the fetal risk in pregnancies among women with type 1 diabetes may decrease to a value similar to that noted in women without diabetes.

Anorexia nervosa in children and adolescents: diagnosis, treatment and the role of the pediatrician.

PubMed

Silber, T J

2013-02-01

The diagnosis and treatment of anorexia nervosa (AN) in children and adolescents has some commonality but also differs from that of this condition in adults. A new understanding of AN is emerging: research data from the fields of epidemiology, genetics, and brain biology, suggest that there may be an underlying brain diathesis predisposing towards AN. It is now proposed that that what starts as a harmless diet, once it turns into a more prolonged food restriction may trigger an eating disorder in a genetically neurobiologically predisposed population. The condition may be then perpetuated by the biochemical changes induced by weight loss, ketosis, and the impact of the ensuing malnutrition on the brain (starvation illness). This change of paradigm from a psychological understanding to a neurobiological conceptualization calls for an early intervention to assure nutritional rehabilitation as soon as an eating disorder is suspected in children, without needing to wait for all the classical features of the diagnosis as seen in adults. This new model is agnostic about the origins of the disease and questions the classic assumption of "an underlying family pathology". It gives strong support to treatments such as Family Based Treatment, also referred to as the "Maudsley method". Essentially this consists of empowering parents to monitor and supervise the nutritional rehabilitation of their children. Hence pediatricians no longer need to be bystanders when treating these children and adolescents. They now have a clearly defined role: early diagnosticians, clinical monitors (of potential medical complications), nutrition advisors, and as members of a multidisciplinary team, patient and family advocates and educators.

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

PubMed

Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P < .001) concentrations, decreased SSGIR (HEC-II, P = .002; HEC-IV, P = .033), ISI (HEC-I, P < .015; HEC-II, P = .004), and insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P < .001). Dexamethasone decreases whole body insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Efficacy of the ketogenic diet in the 6-Hz seizure test

PubMed Central

Hartman, Adam L.; Lyle, Megan; Rogawski, Michael A.; Gasior, Maciej

2008-01-01

SUMMARY Purpose Since the ketogenic diet is effective in drug-resistant epilepsies, we sought to determine whether it is active in the 6-Hz seizure test, which identifies agents with a broader spectrum of activity than conventional antiepileptic screening tests. Methods Male (3–4 week old) NIH Swiss mice were fed a normal or ketogenic diet ad libitum for 2–21 days. The intensity of the corneal stimulation current required to elicit seizures in the 6-Hz test was measured. Blood glucose and β-hydroxybutyrate were measured on the day of seizure testing. Results CC50 (current intensity producing seizures in 50% of mice tested) was 50.6 mA and 15 mA in mice fed for 12 days with a ketogenic or normal diet, respectively (p < 0.001). CC50 was elevated in separate experiments after 16, but not 2, 5, and 21 days of ketogenic diet exposure. CC50 values of growing mice fed the normal diet does not differ, indicating CC50 does not vary with mouse weight during a rapid growth phase. β-Hydroxybutyrate was significantly higher, and glucose was significantly lower in mice fed the ketogenic diet than those fed the normal diet. Blood glucose and β-hydroxybutyrate levels did not correlate with CC50. Discussion The ketogenic diet significantly elevates the seizure threshold in the 6-Hz test in a time-specific manner. Protection from seizures in this model was not related to level of ketosis. CC50 was insensitive to body weight in mice fed the normal diet, demonstrating that the 6-Hz model can assess anticonvulsant regimens where weight is a confounding factor. PMID:18070095

Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

PubMed

Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

2018-05-01

This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.

PubMed

De Feyter, Henk M; Behar, Kevin L; Rao, Jyotsna U; Madden-Hennessey, Kirby; Ip, Kevan L; Hyder, Fahmeed; Drewes, Lester R; Geschwind, Jean-François; de Graaf, Robin A; Rothman, Douglas L

2016-08-01

The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure

PubMed Central

Selfridge, J. Eva; Wilkins, Heather M.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

2014-01-01

Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated. PMID:25104046

Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

PubMed

Ruoff, J; Borchardt, S; Heuwieser, W

2017-07-01

The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows.

PubMed

Xu, Chuang; Xu, Qiushi; Chen, Yuanyuan; Yang, Wei; Xia, Cheng; Yu, Hongjiang; Zhu, Kuilin; Shen, Taiyu; Zhang, Ziyang

2015-10-24

Negative energy balance (NEB) is a common pathological foundation of ketosis and fatty liver. Liver and fat tissue are the major organs of lipid metabolism and take part in modulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB develop during perinatal period. Fibroblast growth factor-21 (FGF-21) is a recently discovered protein hormone that plays an important and specific regulating role in adipose lipid metabolism and liver gluconeogenesis for human and mouse. Our aim is to investigate the variation and relationship between serum FGF-21 concentration and characteristic parameters related to negative energy balance in different energy metabolism state. In this research, five non-pregnant, non-lactating Holstein-Friesian dairy cows were randomly allocated into two groups. The interventions were a controlled-energy diet (30% of maintenance energy requirements) and a moderate-energy diet (120% of predicted energy requirements) that lasted for the duration of the experiment. We measured biochemical parameters, serum FGF-21, leptin and insulin levels by commercial ELISA kits. The results showed that serum FGF-21 levels were significantly higher in both groups treated with a controlled-energy diet, while FGF-21 levels in both groups treated with moderate-energy diet were low. FGF-21 levels exhibited a significant positive correlation with serum leptin levels, while an inverse relationship was found between FGF-21 and blood glucose and β-hydroxybutyrate acid (BHBA) levels. An increase in FGF-21 levels after a controlled-energy diet treatment may contribute to a positive metabolic effect which could result in a new theoretical and practical basis for the preventive strategy of dairy cows with NEB.

[Influence of feeding rumen-protected choline to transition dairy cows. Part 1: metabolism and milk yield].

PubMed

Furken, C; Hoedemaker, M

2014-01-01

The effects of rumen-protected choline (RPC) on energy metabolism and milk production in dairy cows were analyzed. Two hundred and ninety-eight primiparous and multiparous cows of a high producing dairy herd (mean daily milk yield: 32 l) were randomly assigned to control or treatment groups and were fed with 0 or 15 g RPC, respectively, (corresponding to 0 and 60 g/d ReaShure®, respectively) from 21 days before expected calving to 21 days postpartum (p. p.). Blood metabolites were determined for either all cows (glucose, β-hydroxybutyrate [BHB]) or randomly (insulin, insulin-like growth factor-1 [IGF-1], non-esterified fatty acids [NEFA]) during the periparturient period. An index for insulin sensitivity (RQUICKI) was calculated and milk production data (dairy herd improvement tests, 100-days-, 305-days-, milk peak yield, colostrum quality) was analyzed. In the statistical analysis, a distinction was made between the feeding groups and between the parity, and their interactions were analyzed. With the exception of a lower 305-day-milk yield in the treatment group (p < 0.05), the evaluated variables did not show statistically significant differences between the feeding groups and no interactions could be found. In comparison to heifers, multiparous cows had less cases of subclinical ketosis a. p. and p. p. (OR a. p.: 0.178; OR p. p.: 0.310), more of them were above the threshold for somatic cell counts (OR 2.584-3.298), and their milk yields were higher (p < 0.05). Supplementing RPC did not affect the energy metabolism or the milk production in this herd. Further research in other dairy herds should focus on this topic.

Clinical review: insulin pump-associated adverse events in adults and children.

PubMed

Ross, P L; Milburn, J; Reith, D M; Wiltshire, E; Wheeler, B J

2015-12-01

Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity.

PubMed

McCarty, Mark F; DiNicolantonio, James J

2016-01-01

Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)-about 30%-have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to 'ectopic fat' metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6-C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate.

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes.

PubMed

Saslow, Laura R; Kim, Sarah; Daubenmier, Jennifer J; Moskowitz, Judith T; Phinney, Stephen D; Goldman, Veronica; Murphy, Elizabeth J; Cox, Rachel M; Moran, Patricia; Hecht, Fredrick M

2014-01-01

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.

Considering choline as methionine precursor, lipoproteins transporter, hepatic promoter and antioxidant agent in dairy cows.

PubMed

Abbasi, Imtiaz Hussain Raja; Abbasi, Farzana; Soomro, Rab N; Abd El-Hack, Mohamed E; Abdel-Latif, Mervat A; Li, Wen; Hao, Ren; Sun, Feifei; Bodinga, Bello M; Hayat, Khawar; Yao, Junhu; Cao, Yangchun

2017-11-25

During the transition period, fatty liver syndrome may be caused in cows undergo negative energy balance, ketosis or hypocalcemia, retained placenta or mastitis problems. During the transition stage, movement of non-esterified fatty acids (NEFA) increases into blood which declines the hepatic metabolism or reproduction and consequently, lactation performance of dairy cows deteriorates. Most of studies documented that, choline is an essential nutrient which plays a key role to decrease fatty liver, NEFA proportion, improve synthesis of phosphatidylcholine, maintain lactation or physiological function and work as anti-oxidant in the transition period of dairy cows. Also, it has a role in the regulation of homocysteine absorption through betaine metabolite which significantly improves plasma α-tocopherol and interaction among choline, methionine and vitamin E. Many studies reported that, supplementation of rumen protected form of choline during transition time is a sustainable method as rumen protected choline (RPC) perform diverse functions like, increase glucose level or energy balance, fertility or milk production, methyl group metabolism, or signaling of cell methionine expansion or methylation reactions, neurotransmitter synthesis or betaine methylation, increase transport of lipids or lipoproteins efficiency and reduce NEFA or triacylglycerol, clinical or sub clinical mastitis and general morbidity in the transition dairy cows. The purpose of this review is that to elucidate the choline importance and functions in the transition period of dairy cows and deal all morbidity during transition or lactation period. Furthermore, further work is needed to conduct more studies on RPC requirements in dairy cows ration under different feeding conditions and also to elucidate the genetic and molecular mechanisms of choline in ruminants industry.

Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.

PubMed

Andrews, Tory J; Cox, Robert D; Parker, Christina; Kolb, James

2017-02-01

Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality. Copyright © 2016 Elsevier Inc. All rights reserved.

Testing for monogenic diabetes among children and adolescents with antibody-negative clinically defined Type 1 diabetes.

PubMed

Rubio-Cabezas, O; Edghill, E L; Argente, J; Hattersley, A T

2009-10-01

Monogenic diabetes is frequently misdiagnosed as Type 1 diabetes. We aimed to screen for undiagnosed monogenic diabetes in a cohort of children who had a clinical diagnosis of Type 1 diabetes but were pancreatic autoantibody-negative. We studied 252 patients diagnosed clinically with Type 1 diabetes between 6 months and 17 years of age. Pancreatic autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase antibodies (GADA) and/or insulinoma-associated antigen-2 antibodies (IA2A)] were absent in 25 cases (9.9%). The most frequent genes involved in monogenic diabetes [KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity-onset diabetes of the young (MODY)] were directly sequenced. Two of the 25 (8%) antibody-negative patients had de novo heterozygous mutations in INS; c.94G>A (G32S) and c.265C>T (R89C). The two patients presented with non-ketotic hyperglycaemia at 8 and 11 months of age. In contrast, the four antibody-positive patients who presented at a similar age (6-12 months) had a more severe metabolic derangement, manifested as ketosis in all four cases, with ketoacidosis in two. At ages 15 and 5 years, both INS mutation patients were prescribed a replacement dose of insulin with good glycaemic control [glycated haemoglobin (HbA(1c)) 7.0 and 7.2%]. No mutations were found in KCNJ11, HNF1A or HNF4A. The identification of patients with monogenic diabetes from children with clinically defined Type 1 diabetes may be helped by clinical criteria including the absence of pancreatic autoantibodies.

Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity

PubMed Central

McCarty, Mark F; DiNicolantonio, James J

2016-01-01

Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)—about 30%—have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to ‘ectopic fat’ metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6–C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate. PMID:27547436

The role of changes in the sensitivity of hepatic mitochondrial overt carnitine palmitoyltransferase in determining the onset of the ketosis of starvation in the rat.

PubMed Central

Drynan, L; Quant, P A; Zammit, V A

1996-01-01

The relationships between the increase in blood ketone-body concentrations and several parameters that can potentially influence the rate of hepatic fatty acid oxidation were studied during progressive starvation (up to 24 h) in the rat in order to discover whether the sensitivity of mitochondrial overt carnitine palmitoyltransferase (CPT I) to malonyl-CoA plays an important part in determining the intrahepatic potential for fatty acid oxidation during the onset of ketogenic conditions. A rapid increase in blood ketone-body concentration occurred between 12 and 16 h of starvation, several hours after the marked fall in hepatic malonyl-CoA and in serum insulin concentrations and doubling of plasma non-esterfied fatty acid (NEFA) concentration. Consequently, both the changes in hepatic malonyl-CoA and serum NEFA preceded the increase in blood ketone-body concentration by several hours. The maximal activity of CPT I increased gradually throughout the 24 h period of starvation, but the increases did not become significant before 18 h of starvation. By contrast, the sensitivity of CPT I to malonyl-CoA and the increase in blood ketone-body concentration followed an identical time course, demonstrating the central importance of this parameter in determining the ketogenic response of the liver to the onset of the starved state. PMID:8836117

Effects of treatment of periparturient dairy cows with recombinant bovine somatotropin on health and productive and reproductive parameters.

PubMed

Silva, P R B; Soares, H F; Braz, W D; Bombardelli, G D; Clapper, J A; Keisler, D H; Chebel, R C

2017-04-01

of metritis (HO-control = 26.2, HO-rbST125 = 16.6, JS-control = 19.9, JS-rbST125 = 13.3%) compared with control cows. Ketosis incidence tended to be higher for rbST125 cows (HO-control = 9.4, HO-rbST125 = 11.3, JS-control = 8.5, JS-rbST125 = 13.4%) compared with control cows. The interaction between treatment and herd tended to affect yield of ECM during the first 30 DIM because HO cows treated with rbST during the periparturient period had greater yield than control HO cows (HO-control = 35.5 ± 1.0 vs. HO-rbST125 = 39.4 ± 1.0 kg/d), but treatment with rbST did not affect yield of ECM of JS cows (JS-control = 26.7 ± 0.6 vs. JS-rbST125 = 27.8 ± 0.6 kg/d). Treatment of periparturient dairy cows with 125 mg of rbST decreased the incidence of uterine disorders in HO and JS cows and increased yield of ECM during the first 30 DIM among HO cows, despite slightly increasing the incidence of ketosis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A comparative study of the metabolic profile, insulin sensitivity and inflammatory response between organically and conventionally managed dairy cattle during the periparturient period.

PubMed

Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

2014-09-01

The number of organically managed cattle (OMC) within the European Union has increased tremendously in the last decade. However, there are still some concerns about animals under this farming system meeting their dietary requirements for milk production. The aim of this study was to compare the metabolic adaptations to the onset of lactation in three different herds, one conventional and two organic ones. Twenty-two conventionally managed cattle (CMC) and 20 from each organic farm were sampled throughout the periparturient period. These samplings were grouped into four different stages: (i) far-off dry, (ii) close-up dry, (iii) fresh and (iv) peak of lactation and compared among them. In addition, the results of periparturient animals were also compared within each management type with a control group (animals between the 4th and 5th months of pregnancy). Metabolic profiles were used to assess the health status of the herds, along with the quantification of the acute phase proteins haptoglobin and serum amyloid A, insulin and the calculation of different surrogate indices of insulin sensitivity. Generalised linear mixed models with repeated measurements were used to study the effect of the stage, management type or their interaction on the serum variables studied. The prevalence of subclinical ketosis was higher in OMC, although they showed better insulin sensitivity, a lower degree of inflammation and less liver injury, without a higher risk of macromineral deficiencies. Therefore, attention should be paid on organic farms to the nutritional management of cows around the time of calving in order to prevent the harmful consequences of excessive negative energy balance. Moreover, it must be taken into account that most of the common practices used to treat this condition in CMC are not allowed on a systematic basis in OMC.

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

PubMed

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

[Juvenile onset diabetes: the effect of education for metabolic control].

PubMed

Gúrpide Arraya, N; Durá Travé, T; Moya Benavent, M

1998-03-01

This study analyzes the repercusions that education about diabetes and frequent periodical checkups or intensive followups have on the metabolic control of this disease. A group of 13 young diabetics, ranging in age from 5 to 13.4, were submitted to trimestral clinical and analytical controls during a continuous 36-month period starting at the outset of their illnesses. Each received conventional insulin therapy, two daily injections of a mixture of regular insulin/NPH. Annual checkups registered 3.8 +/- 0.4. Four patients, or 30.8%, had an attack of symptomatic hypoglycemia. None of these required hospitalization for ketosis. The HblAc level at the outset of their illnesses was very high, 11.2 +/- 2.7%, but this dropped to normal levels, 7.1 +/- 1.5%, during the first trimester of treatment, and stayed quite normal for the duration of the study except at the 21-month checkup, 8.7 +/- 1.8%, and at the 33-month checkup, 8.6 +/- 1.4%. As soon as metabolic irregularities were detected, all that was necessary so that the succeeding checkups improved notably was to review the items which the patient had neglected such as diet and self-checks. The impact of the initial medical report and the educational component of the periodical checkups seem to be the keys for the quality of a child's metabolical control over time. To sum up, bear in mind that a young diabetic tends to begin to show difficulties in his/her metabolic control about 21 months after the outset of his/her disease, in spite of an intensive checkup program. To a large degree, a solution will depend on the professional competence of the medical team treating the patient, and moreover, on the degree of knowledge about diabetes which the patient and/or his/her family have received.

[Evaluation of a new electronic handheld meter for measurement of β-hydroxybutyric acid in dairy cows].

PubMed

Mahrt, A; Burfeind, O; Voigtsberger, R; Müller, A; Heuwieser, W

2014-01-01

Subclinical ketosis (SCK), an important disease in lactating dairy cows, is defined as the presence of elevated concentrations of circulating ketone bodies without the development of clinical signs. Therefore, diagnostic methods are limited to the detection of the concentrations of ketone bodies in different body fluids. The objective of this study was to evaluate a recently developed electronic hand- held meter (NovaVet) for the determination of β-hydroxybutyric acid (BHB) in the blood of dairy cows. A total of 155 lactating dairy cows were included in the trial. Blood samples were taken from each cow and analyzed using the BHB meter. The obtained concentrations were compared to the results determined by a commercial laboratory. The Spearman's rank correlation coefficient was determined between the two methods. A Wilcoxon test was performed and a Bland-Altman plot was generated. Test characteristics (sensitivity, specificity, positive and negative predictive value) for established BHB cut points for the diagnosis of SCK were calculated using receiver operating characteristic (ROC) analysis. The two methods were highly correlated (rs = 0.87; p < 0.05). A difference (median 0.0 mmol/l; interquartile range [IQR] -0.1 to 0.2 mmol/l; p < 0.05) was found between BHB concentrations determined using the BHB meter (median 1.0 mmol/l; IQR 0.7-1.3 mmol/l) and by the laboratory (median 0.9 mmol/l; IQR 0.7-1.1 mmol/l). Using a cut point of 1.2 mmol/l, sensitivity and specificity of the BHB meter were 97% and 82%, respectively. There was a good agreement between BHB concentrations determined using the BHB meter and the laboratory. Furthermore, the BHB meter displayed good test characteristics. The specificity of 82% results in a number of false-positive results. However, this new device can be recommended for the detection of SCK in cows under practical conditions.

Prediction of whole-genome risk for selection and management of hyperketonemia in Holstein dairy cattle.

PubMed

Weigel, K A; Pralle, R S; Adams, H; Cho, K; Do, C; White, H M

2017-06-01

Hyperketonemia (HYK), a common early postpartum health disorder characterized by elevated blood concentrations of β-hydroxybutyrate (BHB), affects millions of dairy cows worldwide and leads to significant economic losses and animal welfare concerns. In this study, blood concentrations of BHB were assessed for 1,453 Holstein cows using electronic handheld meters at four time points between 5 and 18 days postpartum. Incidence rates of subclinical (1.2 ≤ maximum BHB ≤ 2.9 mmol/L) and clinical ketosis (maximum BHB ≥ 3.0 mmol/L) were 24.0 and 2.4%, respectively. Variance components, estimated breeding values, and predicted HYK phenotypes were computed on the original, square-root, and binary scales. Heritability estimates for HYK ranged from 0.058 to 0.072 in pedigree-based analyses, as compared to estimates that ranged from 0.071 to 0.093 when pedigrees were augmented with 60,671 single nucleotide polymorphism genotypes of 959 cows and 801 male ancestors. On average, predicted HYK phenotypes from the genome-enhanced analysis ranged from 0.55 mmol/L for first-parity cows in the best contemporary group to 1.40 mmol/L for fourth-parity cows in the worst contemporary group. Genome-enhanced predictions of HYK phenotypes were more closely associated with actual phenotypes than pedigree-based predictions in five-fold cross-validation, and transforming phenotypes to reduce skewness and kurtosis also improved predictive ability. This study demonstrates the feasibility of using repeated cowside measurement of blood BHB concentration in early lactation to construct a reference population that can be used to estimate HYK breeding values for genomic selection programmes and predict HYK phenotypes for genome-guided management decisions. © 2017 Blackwell Verlag GmbH.

Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes

PubMed Central

Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

2018-01-01

Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows. PMID:29593725

The effect of grape seed and grape marc meal extract on milk performance and the expression of genes of endoplasmic reticulum stress and inflammation in the liver of dairy cows in early lactation.

PubMed

Gessner, D K; Koch, C; Romberg, F-J; Winkler, A; Dusel, G; Herzog, E; Most, E; Eder, K

2015-12-01

During the periparturient phase, cows are typically in an inflammation-like condition, and it has been suggested that inflammation associated with the development of stress of the endoplasmic reticulum (ER) in the liver contributes to the development of fatty liver syndrome and ketosis. In the present study, we investigated the hypothesis that feeding grape seed and grape marc meal extract (GSGME) as a plant extract rich in flavonoids attenuates inflammation and ER stress in the liver of dairy cows. Two groups of cows received either a total mixed ration as a control diet or the same total mixed ration supplemented with 1% of GSGME over the period from wk 3 prepartum to wk 9 postpartum. Dry matter intake during wk 3 to 9 postpartum was not different between the 2 groups. However, the cows fed the diet supplemented with GSGME had an increased milk yield and an increased daily milk protein yield. Cows supplemented with GSGME moreover had a significantly reduced mRNA abundancy of fibroblast growth factor (FGF) 21, a stress hormone induced by various stress conditions, in the liver in wk 1 and 3 postpartum. In contrast, mRNA abundances of a total of 3 genes involved in inflammation and 14 genes involved in ER stress response, as well as concentrations of triacylglycerols and cholesterol, in liver samples of wk 1 and 3 postpartum did not differ between the 2 groups. Overall, this study shows that supplementation of GSGME did not influence inflammation or ER stress in the liver but increased milk yield, an effect that could be due to effects on ruminal metabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

PubMed

Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

2015-07-01

Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

A Non-Traditional Model of the Metabolic Syndrome: The Adaptive Significance of Insulin Resistance in Fasting-Adapted Seals

PubMed Central

Houser, Dorian S.; Champagne, Cory D.; Crocker, Daniel E.

2013-01-01

Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7–3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies

Symposium review: Modulating adipose tissue lipolysis and remodeling to improve immune function during the transition period and early lactation of dairy cows.

PubMed

Contreras, G Andres; Strieder-Barboza, Clarissa; De Koster, Jenne

2018-03-01

Despite major advances in our understanding of transition and early lactation cow physiology and the use of advanced dietary, medical, and management tools, at least half of early lactation cows are reported to develop disease and over half of cow deaths occur during the first week of lactation. Excessive lipolysis, usually measured as plasma concentrations of free fatty acids (FFA), is a major risk factor for the development of displaced abomasum, ketosis, fatty liver, and metritis, and may also lead to poor lactation performance. Lipolysis triggers adipose tissue (AT) remodeling that is characterized by enhanced humoral and cell-mediated inflammatory responses and changes in its distribution of cellular populations and extracellular matrix composition. Uncontrolled AT inflammation could perpetuate lipolysis, as we have observed in cows with displaced abomasum, especially in those animals with genetic predisposition for excessive lipolysis responses. Efficient transition cow management ensures a moderate rate of lipolysis that is rapidly reduced as lactation progresses. Limiting FFA release from AT benefits immune function as several FFA are known to promote dysregulation of inflammation. Adequate formulation of pre- and postpartum diet reduces the intensity of AT lipolysis. Additionally, supplementation with niacin, monensin, and rumen-protected methyl donors (choline and methionine) during the transition period is reported to minimize FFA release into systemic circulation. Targeted supplementation of energy sources during early lactation improves energy balance and increases insulin concentration, which limits AT lipolytic responses. This review elaborates on the mechanisms by which uncontrolled lipolysis triggers inflammatory disorders. Details on current nutritional and pharmacological interventions that aid the modulation of FFA release from AT and their effect on immune function are provided. Understanding the inherent characteristics of AT biology in

Innovative dairy cow management to improve resistance to metabolic and infectious diseases during the transition period.

PubMed

Lacasse, P; Vanacker, N; Ollier, S; Ster, C

2018-02-01

The incidence of metabolic and infectious diseases varies greatly during the lactation cycle. Most new cases of clinical mastitis appear at the beginning of lactation, and the incidence increases with the level of milk production. In addition to mastitis, many other infectious diseases become clinically apparent during the first 2weeks of lactation. During this time, cows are in a negative energy balance and must mobilize body reserves to balance the deficit between food energy intake and energy required for milk production. The relationships between energy deficit and metabolic diseases, such as ketosis and hepatic lipidosis, are well known. Furthermore, cows in energy deficit have a weakened immune system and are therefore more susceptible to infections. There is now good evidence that the increase in circulating non-esterified fatty acids impairs immune cell functions. Therefore, management approaches that reduce the negative energy balance and the increase in non-esterified fatty acids at the beginning of lactation are likely to improve resistance to infection. Improving the nutrient supply through periparturient nutritional management has been the subject of considerable research. However, another way to reduce the imbalance between nutrient supply and demand is to temporarily decrease the latter. In this review, we examine how management strategies such as conjugated linoleic acid feeding, prepartum milking, or limiting postpartum milk production could be used to reduce metabolic perturbations and immunosuppression during the transition period. At this stage, it appears that reducing the amount of milk harvested postpartum by means of partial milking in the first days after calving is the most promising approach to reduce metabolic stress and immunosuppression without compromising the productivity of high-yielding dairy cows. Copyright © 2017. Published by Elsevier Ltd.

Breath acetone as a potential marker in clinical practice.

PubMed

Ruzsányi, Veronika; Péter Kalapos, Miklós

2017-06-01

In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

Medium-chain triglycerides in infant formulas and their relation to plasma ketone body concentrations.

PubMed

Wu, P Y; Edmond, J; Auestad, N; Rambathla, S; Benson, J; Picone, T

1986-04-01

A mild ketosis is known to prevail in the mother, fetus, and newborn infant during the 3rd trimester and in the early neonatal period. It has been shown that during an equivalent period in the rat ketone bodies are readily oxidized and serve as key substrates for lipogenesis in brain. Since medium-chain triglycerides are known to be ketogenic, preterm infants may benefit from dietary medium-chain triglycerides beyond the point of enhanced fat absorption. Our objective was to determine the ketogenic response in preterm infants (gestational age: 33 +/- 0.8 wk) fed three different isocaloric formulas by measuring the concentrations of 3-hydroxybutyrate and acetoacetate in the plasma of these infants. At the time of entrance to the study the infants were receiving 110 kcal/kg/24 h. Study I (11 infants): the infants were fed sequentially in the order; PM 60/40 (PM), Special Care Formula (SCF), and Similac 20 (SIM). In SCF greater than 50% of the fat consists of medium-chain length fatty acids while PM and SIM contain about 25%. The concentration of 3-hydroxybutyrate in plasma was significantly higher when infants were fed SCF than PM and SIM [0.14 +/- 0.03, 0.06 +/- 0.01, and 0.05 +/- 0.01 mM, respectively (p less than 0.01)]. Study II (12 infants); the infants were fed SCF, then SIM, or the reverse. The concentration of acetoacetate in plasma was 0.05 +/- 0.01 and 0.03 +/- 0.01 mM when infants were fed SCF and SIM, respectively (0.1 greater than p greater than 0.05). The concentrations of 3-hydroxybutyrate in plasma were similar to those measured in study I for the respective formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

State of the science: VLED (Very Low Energy Diet) for obesity.

PubMed

Delbridge, Elizabeth; Proietto, Joseph

2006-01-01

It is often stated, "the faster you lose weight, the faster it is regained ". A review of existing literature does not support such a statement--indeed if anything the reverse is true. The origins of this erroneous view are the misconceptions that weight regain is a simple matter of bad dietary and social habits and that it takes time to change these, that physiological adaptations to rapid weight loss are different to those of gradual weight loss and that weight regain is simply due to a return to old habits. Indeed there are many advantages to rapid weight loss achieved with the use of a modern very low energy diet, including the fact that rapid weight loss is a motivating factor, that the mild ketosis that occurs not only suppresses hunger, but also slows protein loss and that adherence is easier with a structured dietary regime. VLEDs are dietary preparations that provide all nutritional requirements together with between 1845 and 3280 KJ (450 and 800 Kcal) per day. An individual takes this meal replacement three times daily as a substitute for breakfast, lunch and dinner. In addition, a bowl of non-starchy vegetables once daily provides some fibre and helps to satisfy the social aspect of eating. A teaspoon of oil on the vegetables contracts the gall bladder to minimise the risk of gall stone formation. Since weight loss, at whatever rate, results in physiological adaptations leading to weight regain, careful attention must be paid to the period after the VLED regime is completed. Lifestyle modification, diet and exercise are instituted optimally with behaviour modification. If, despite the subject's best efforts, weight regain occurs, an appetite suppressant is advisable to help control the drive to eat.

Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes.

PubMed

Zhang, Shiqi; Liu, Guowen; Xu, Chuang; Liu, Lei; Zhang, Qiang; Xu, Qiushi; Jia, Hongdou; Li, Xiaobing; Li, Xinwei

2018-01-01

Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes

PubMed Central

Saslow, Laura R.; Kim, Sarah; Daubenmier, Jennifer J.; Moskowitz, Judith T.; Phinney, Stephen D.; Goldman, Veronica; Murphy, Elizabeth J.; Cox, Rachel M.; Moran, Patricia; Hecht, Fredrick M.

2014-01-01

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (−0.6%, 95% CI, −1.1% to −0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764. PMID:24717684

A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

PubMed

Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

2013-11-01

Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

Energetic Constraints Produce Self-sustained Oscillatory Dynamics in Neuronal Networks

PubMed Central

Burroni, Javier; Taylor, P.; Corey, Cassian; Vachnadze, Tengiz; Siegelmann, Hava T.

2017-01-01

Overview: We model energy constraints in a network of spiking neurons, while exploring general questions of resource limitation on network function abstractly. Background: Metabolic states like dietary ketosis or hypoglycemia have a large impact on brain function and disease outcomes. Glia provide metabolic support for neurons, among other functions. Yet, in computational models of glia-neuron cooperation, there have been no previous attempts to explore the effects of direct realistic energy costs on network activity in spiking neurons. Currently, biologically realistic spiking neural networks assume that membrane potential is the main driving factor for neural spiking, and do not take into consideration energetic costs. Methods: We define local energy pools to constrain a neuron model, termed Spiking Neuron Energy Pool (SNEP), which explicitly incorporates energy limitations. Each neuron requires energy to spike, and resources in the pool regenerate over time. Our simulation displays an easy-to-use GUI, which can be run locally in a web browser, and is freely available. Results: Energy dependence drastically changes behavior of these neural networks, causing emergent oscillations similar to those in networks of biological neurons. We analyze the system via Lotka-Volterra equations, producing several observations: (1) energy can drive self-sustained oscillations, (2) the energetic cost of spiking modulates the degree and type of oscillations, (3) harmonics emerge with frequencies determined by energy parameters, and (4) varying energetic costs have non-linear effects on energy consumption and firing rates. Conclusions: Models of neuron function which attempt biological realism may benefit from including energy constraints. Further, we assert that observed oscillatory effects of energy limitations exist in networks of many kinds, and that these findings generalize to abstract graphs and technological applications. PMID:28289370

Short-term fasting, seizure control and brain amino acid metabolism.

PubMed

Yudkoff, Marc; Daikhin, Yevgeny; Nissim, Ilana; Horyn, Oksana; Luhovyy, Bogdan; Lazarow, Adam; Nissim, Itzhak

2006-01-01

The ketogenic diet is an effective treatment for seizures, but the mechanism of action is unknown. It is uncertain whether the anti-epileptic effect presupposes ketosis, or whether the restriction of calories and/or carbohydrate might be sufficient. We found that a relatively brief (24 h) period of low glucose and low calorie intake significantly attenuated the severity of seizures in young Sprague-Dawley rats (50-70 gms) in whom convulsions were induced by administration of pentylenetetrazole (PTZ). The blood glucose concentration was lower in animals that received less dietary glucose, but the brain glucose level did not differ from control blood [3-OH-butyrate] tended to be higher in blood, but not in brain, of animals on a low-glucose intake. The concentration in brain of glutamine increased and that of alanine declined significantly with low-glucose intake. The blood alanine level fell more than that of brain alanine, resulting in a marked increase ( approximately 50%) in the brain:blood ratio for alanine. In contrast, the brain:blood ratio for leucine declined by about 35% in the low-glucose group. When animals received [1-(13)C]glucose, a metabolic precursor of alanine, the appearance of (13)C in alanine and glutamine increased significantly relative to control. The brain:blood ratio for [(13)C]alanine exceeded 1, indicating that the alanine must have been formed in brain and not transported from blood. The elevated brain(alanine):blood(alanine) could mean that a component of the anti-epileptic effect of low carbohydrate intake is release of alanine from brain-to-blood, in the process abetting the disposal of glutamate, excess levels of which in the synaptic cleft would contribute to the development of seizures.

Evaluation of nonesterified fatty acids and beta-hydroxybutyrate in transition dairy cattle in the northeastern United States: Critical thresholds for prediction of clinical diseases.

PubMed

Ospina, P A; Nydam, D V; Stokol, T; Overton, T R

2010-02-01

The objectives of this study were to 1) establish cow-level critical thresholds for serum concentrations of nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) to predict periparturient diseases [displaced abomasa (DA), clinical ketosis (CK), metritis and retained placenta, or any of these three], and 2) investigate the magnitude of the metabolites' association with these diseases within 30 d in milk. In a prospective cohort study of 100 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd, for a total of 2,758 samples. Serum NEFA concentrations were measured in the prepartum group, and both NEFA and BHBA were measured in the postpartum group. The critical thresholds for NEFA or BHBA were evaluated with receiver operator characteristic analysis for all diseases in both cohorts. The risk ratios (RR) of a disease outcome given NEFA or BHBA concentrations and other covariates were modeled with multivariable regression techniques, accounting for clustering of cows within herds. The NEFA critical threshold that predicted any of the 3 diseases in the prepartum cohort was 0.29mEq/L and in the postpartum cohort was 0.57mEq/L. The critical threshold for serum BHBA in the postpartum cohort was 10mg/dL, which predicted any of the 3 diseases. All RR with NEFA as a predictor of disease were >1.8; however, RR were greatest in animals sampled postpartum (e.g., RR for DA=9.7; 95% CI=4.2 to 22.4. All RR with BHBA as the predictor of disease were >2.3 (e.g., RR for DA=6.9; 95% CI=3.7 to 12.9). Although prepartum NEFA and postpartum BHBA were both significantly associated with development of clinical disease, postpartum serum NEFA concentration was most associated with the risk of developing DA, CK, metritis, or retained placenta during the first 30 d in milk. Copyright 2010 American Dairy Science Association. Published by

Incidence of complications in young-onset diabetes: Comparing type 2 with type 1 (the young diab study).

PubMed

Amutha, Anandakumar; Anjana, Ranjit Mohan; Venkatesan, Ulagamathesan; Ranjani, Harish; Unnikrishnan, Ranjit; Venkat Narayan, K M; Mohan, Viswanathan; Ali, Mohammed K

2017-01-01

There is little data on the incidence of diabetes complications in young onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in non European populations. From a tertiary diabetes centre, Chennai, India, we recruited 108 T1DM (defined by abrupt onset of symptoms or diabetic ketoacidosis, absent insulin reserve requiring insulin treatment) and 90 T2DM participants (defined by absence of ketosis, good beta-cell reserve, and good response to oral agents) who were diagnosed between the ages of 10 and 25years, and without any evidence of diabetes complications at diagnosis. We estimated the incidence of various complications (median follow up of five years); retinopathy was defined by presence of at least one definite microaneurysm by retinal photography, nephropathy by urinary albumin excretion ⩾30μg/mg of creatinine, neuropathy by vibration perception threshold ⩾20V on biothesiometry, peripheral vascular disease by an ankle-brachial index <0.9, and ischemic heart disease (IHD) by history of myocardial infarction or coronary revascularization or Q waves on ECG or on drug treatment for IHD. The mean ages at diagnosis of T1DM and T2DM participants were 17.1±4.2vs. 21.6±3.6years respectively. The incidence of various complications reported in numbers/1000 person years of follow up of T1DM and T2DM were: retinopathy 77.4vs. 78.0/1000 person years, nephropathy, 62.0vs. 58.8, neuropathy 7.8 vs. 13.9 and ischemic heart disease 1.2vs. 5.4. In Cox regression analysis, after adjustment for age, glycated hemoglobin, systolic blood pressure and serum cholesterol, T2DM participants had 2.11 times (95%CI: 1.27-3.51) higher risk of developing any diabetes complication, compared to T1DM. Young-onset T2DM have a more aggressive disease course than T1DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

PubMed

Moreno, Basilio; Crujeiras, Ana B; Bellido, Diego; Sajoux, Ignacio; Casanueva, Felipe F

2016-12-01

The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p < 0.001). Interestingly, a selective reduction in visceral fat measured by a specific software of dual-energy x-ray absorptiometry (DEXA)-scan (-600 g vs. -202 g; p < 0.001) was observed. Moreover, the very low-calorie-ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p < 0.001). In conclusion, a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

PubMed

Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

2017-04-01

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Effects of a plant product consisting of green tea and curcuma extract on milk production and the expression of hepatic genes involved in endoplasmic stress response and inflammation in dairy cows.

PubMed

Winkler, Anne; Gessner, Denise K; Koch, Christian; Romberg, Franz-Josef; Dusel, Georg; Herzog, Eva; Most, Erika; Eder, Klaus

2015-01-01

During the periparturient phase, cows are typically in an inflammation-like condition, and it has been proposed that inflammation associated with the induction of stress of the endoplasmic reticulum (ER) in the liver contributes to the development of fatty liver syndrome and ketosis. In the present study, the hypothesis that supplementation of dairy cows with a plant product consisting of green tea (95%) and curcuma extract (5%) rich in polyphenols attenuates inflammation and ER stress in the liver during early lactation was investigated. Twenty-seven cows were assigned to two groups, either a control group (n=14) or a treatment group (n=13). Both groups of cows received a total mixed ration, and the ration of the treatment group was supplemented with 0.175 g of the plant product per kg dry matter from week 3 prepartum to week 9 postpartum. Dry matter intake and energy balance during week 2 to week 9 postpartum were not different between the two groups. However, cows supplemented with the plant product had a greater amount of energy-corrected milk during week 2 to week 9 postpartum and lower concentrations of triacylglycerols and cholesterol in the liver in week 1 and week 3 postpartum than cows of the control group (p<0.05). Cows supplemented with the plant product showed a trend towards a reduced mRNA concentration of haptoglobin (p<0.10), while relative mRNA concentrations of eight genes of the unfolded protein response considered in the liver were not different between the two groups of cows. Relative hepatic mRNA concentration of fibroblast growth factor, a stress hormone induced by various stress conditions, was reduced at week 1 and week 3 postpartum in cows supplemented with the plant product (p<0.05). Overall, the data of this study suggest that--although there were only minor effects on the occurrence of ER stress and inflammation--a supplementation of polyphenols might be useful to improve milk yield and prevent fatty liver syndrome in dairy cows.

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function

PubMed Central

Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

2016-01-01

Introduction Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. Methods and analysis The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the ‘Suspend before low’ feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics and dissemination Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. Trial registration number ACTRN12614000510640, Pre-results. PMID:27084290

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function.

PubMed

Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

2016-04-15

Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the 'Suspend before low' feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. ACTRN12614000510640, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of low carbohydrate diets on energy and nitrogen balance and body composition in rats depend on dietary protein-to-energy ratio.

PubMed

Frommelt, Lena; Bielohuby, Maximilian; Menhofer, Dominik; Stoehr, Barbara J M; Bidlingmaier, Martin; Kienzle, Ellen

2014-01-01

Truly ketogenic rodent diets are low in carbohydrates but also low in protein. The aim of this study was to differentiate effects of ketosis, low carbohydrate (LC) and/or low-protein intake on energy and nitrogen metabolism. We studied the nitrogen balance of rats fed LC diets with varying protein contents: LC diets consisted of 75/10, 65/20 and 55/30 percent of fat to protein (dry matter), respectively, and were iso-energetically pair-fed to a control (chow) diet to 12-wk-old male Wistar rats (n = 6 per diet). Previous studies demonstrated only LC75/10 was truly ketogenic. Food, fecal, and urine samples, as well as carcasses were collected and analyzed for heat of combustion and nitrogen (Kjeldahl method). Blood samples were analyzed for plasma protein, albumin, and triacylglycerol. All LC groups displayed less body weight gain, and the degree of reduction was inversely related to digestible crude protein intake (daily weight gain compared with chow: LC75/10: -50%; LC55/30: -20%). Nitrogen excretion by urine was related to digestible protein intake (chow: 0.23 ± 0.02 g nitrogen/d; LC75/10: 0.05 ± 0.01 g nitrogen/d). Renal energy excretion was closely associated with intake of digestible crude protein (r = 0.697) and renal nitrogen excretion (r = 0.769). Energy-to-nitrogen ratio in urine was nearly doubled with LC75/10 compared with all other groups. Total body protein was highest with chow and lowest with LC75/10. Rats fed with LC75/10 displayed features of protein deficiency (reduced growth and nitrogen balance, hypoproteinemia, depletion of body protein, and increased body and liver fat), whereas the effects with the non-ketogenic diets LC65/20 and LC55/30 were less pronounced. These results suggest that truly ketogenic LC diets in growing rats are LC diets that are also deficient in protein for growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain.

PubMed

Canis, Martin; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-02-27

The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased

Events occurring during the previous lactation, the dry period, and peripartum as risk factors for early lactation mastitis in cows receiving 2 different intramammary dry cow therapies.

PubMed

Pinedo, P J; Fleming, C; Risco, C A

2012-12-01

The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur

Obesity and youth diabetes: distinguishing characteristics between islet cell antibody positive vs. negative patients over time.

PubMed

Rivera-Vega, Michelle Y; Flint, Amanda; Winger, Daniel G; Libman, Ingrid; Arslanian, Silva

2015-08-01

Obese youth clinically diagnosed with type 2 diabetes mellitus (T2DM) frequently have evidence of islet cell autoimmunity. We investigated the clinical and biochemical differences, and therapeutic modalities among autoantibody positive (Ab+) vs. autoantibody negative (Ab-) youth at the time of diagnosis and over time in a multi-provider clinical setting. Chart review of 145 obese youth diagnosed with T2DM from January 2003 to July 2012. Of these, 70 patients were Ab+ and 75 Ab-. The two groups were compared with respect to clinical presentation, physical characteristics, laboratory data, and therapeutic modalities at diagnosis and during follow up to assess the changes in these parameters associated with disease progression. At presentation, Ab+ youth with a clinical diagnosis of T2DM were younger, had higher rates of ketosis, higher hemoglobin A1c (HbA1c) and glucose levels, and lower insulin and c-peptide concentrations compared with the Ab- group. The Ab- group had a higher body mass index (BMI) z-score and cardiometabolic risk factors at diagnosis and such difference remained over time. Univariate analysis revealed that treatment modality had no effect on BMI in either group. Generalized estimating equations for longitudinal data analysis revealed that (i) BMI z-score and diastolic blood pressure (DBP) were significantly affected by duration of diabetes; (ii) systolic blood pressure (SBP) and ALT were affected by changes in BMI z-score; and (iii) changes in HbA1c had an effect on lipid profile and cardiometabolic risk factors regardless of antibody status. Irrespective of antibody status and treatment modality, youth who present with obesity and diabetes, show no improvement in obesity status over time, with the deterioration in BMI z-score affecting blood pressure (BP) and ALT, but the lipid profile being mostly impacted by HbA1c and glycemic control. Effective control of BMI and glycemia are needed to lessen the future macrovascular complications irrespective

Livestock disease threats associated with intensification of pastoral dairy farming.

PubMed

Lean, Ij; Westwood, Ct; Playford, Mc

2008-12-01

This paper provides an overview of the changes in the pasture-based dairy systems of New Zealand and Australia that may influence the health of cattle. There are relatively few available data that can be used to quantify the effects of increased intensification of milk production on the health of cattle. There is evidence that increased production increases the risk of mastitis and culling for udder health. Increased risks of mastitis with treatment with somatotropin support these findings; however, the risk of mastitis may decrease with increased milking frequency. Larger herds with greater stocking density should increase the risk for infectious disease, but evidence to support this contention is sparse. Very intensive grazing patterns associated with higher grass yields achieved using better cultivars and greater use of fertilisers favour nematode parasites. There is some evidence of anthelmintic resistance in both nematodes and liver fluke. Veterinarians will need to be aware of the potential for these to reduce the productivity of cattle. There have been benefits of improved nutrition on the efficiency of energy use for dairy production. Diseases such as bloat and ketosis appear to be of lower prevalence. It also appears that mineral nutrition of pasture-fed cattle is being better addressed, with gains in the control of milk fever, hypomagnesaemia and trace-element deficiencies. However, acidosis is a condition with a high point prevalence in pasture-based dairy systems where cows are fed supplements; one study in Australia found a point prevalence of approximately 11% of cows with acidosis. There is evidence from this study that the neutral detergent fibre (NDF) in pasture-based diets may need to be higher than 30% of the diet to maintain rumen stability. Laminitis and acidosis are different conditions with a similar pathogenesis, specifically highly fermentable diets. The prevalence of lameness was 28% in herds in Australia, suggesting that this condition

Effectiveness of MiniMed 640G with SmartGuard® System for prevention of hypoglycemia in pediatric patients with type 1 diabetes mellitus.

PubMed

Villafuerte Quispe, Beatriz; Martín Frías, María; Roldán Martín, M Belén; Yelmo Valverde, Rosa; Álvarez Gómez, M Ángeles; Barrio Castellanos, Raquel

2017-04-01

Treatment with the MiniMed 640G-SmartGuard ® system (640G-SG, sensor-augmented insulin pump system with low predicted glucose suspension feature) has been shown to decrease risk of hypoglycemia without altering metabolic control in patients with T1DM. The study purpose was to assess the impact of 640G-SG on hipoglycemia frequency and on metabolic control in a pediatric population with T1DM. A retrospective study on 21 children treated with 640G-SG. HbA1C, mean blood glucose (mg/dl), glucose variation coefficient, frequency of hypoglycemia (<70mg/dl) and hyperglycemia (>180mg/dl), daily capillary blood glucose measurements, ketosis/diabetic ketoacidosis, and severe hypoglycemic episodes were analyzed and compared before and during use of the system. Fasting blood glucose, frequency of sensor use and number and duration of system suspension events were also assessed in the last month of use of the system. All patients used the system continuously (5.0±2.1 months), with a median sensor use of 92%. Significant decreases were seen in hypoglycemia frequency (10.4±5.2% to 7.6±3.3%, p=.044) and number of capillary blood glucose measurements (11.3±2,2 to 8.1±2,1, p<.001), and there was no increase in hyperglycemia frequency (p=.65). Mean system suspension time was 3.1±1.2hours/day (37.3% of overnight stops). Changes in HbA1c, mean blood glucose, and variation coefficient were not significant. No patient experienced diabetic ketoacidosis or severe hypoglycemia. The sensor-augmented pump with the predictive low glucose suspension management system, as implemented in the 640G-SG system, can help avoid risk of hypoglycemia without significantly affecting metabolic control or causing diabetic ketoacidosis, and decrease the burden of additional capillary blood glucose measurements in our pediatric cohort. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Prediction of insemination outcomes in Holstein dairy cattle using alternative machine learning algorithms.

PubMed

Shahinfar, Saleh; Page, David; Guenther, Jerry; Cabrera, Victor; Fricke, Paul; Weigel, Kent

2014-02-01

When making the decision about whether or not to breed a given cow, knowledge about the expected outcome would have an economic impact on profitability of the breeding program and net income of the farm. The outcome of each breeding can be affected by many management and physiological features that vary between farms and interact with each other. Hence, the ability of machine learning algorithms to accommodate complex relationships in the data and missing values for explanatory variables makes these algorithms well suited for investigation of reproduction performance in dairy cattle. The objective of this study was to develop a user-friendly and intuitive on-farm tool to help farmers make reproduction management decisions. Several different machine learning algorithms were applied to predict the insemination outcomes of individual cows based on phenotypic and genotypic data. Data from 26 dairy farms in the Alta Genetics (Watertown, WI) Advantage Progeny Testing Program were used, representing a 10-yr period from 2000 to 2010. Health, reproduction, and production data were extracted from on-farm dairy management software, and estimated breeding values were downloaded from the US Department of Agriculture Agricultural Research Service Animal Improvement Programs Laboratory (Beltsville, MD) database. The edited data set consisted of 129,245 breeding records from primiparous Holstein cows and 195,128 breeding records from multiparous Holstein cows. Each data point in the final data set included 23 and 25 explanatory variables and 1 binary outcome for of 0.756 ± 0.005 and 0.736 ± 0.005 for primiparous and multiparous cows, respectively. The naïve Bayes algorithm, Bayesian network, and decision tree algorithms showed somewhat poorer classification performance. An information-based variable selection procedure identified herd average conception rate, incidence of ketosis, number of previous (failed) inseminations, days in milk at breeding, and mastitis as the most

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

PubMed

van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

2017-03-07

North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified

Effects of propylene glycol on the metabolic status and milk production of dairy buffaloes.

PubMed

Hussein, H A; Abdel-Raheem, S M; Abd-Allah, M; Senosy, W

2015-01-01

The study was designed to investigate the effects of drenching with propylene glycol (PG) on body condition, serum metabolites and milk production during the transition period of dairy buffaloes. Animals were randomly allocated to a control group (n=5) and a PG group of 10 buffaloes that were drenched with 500 ml of propylene glycol once daily from 10 (9±3) days prepartum until 2 weeks postpartum. Ultrasound measurements of backfat thickness (BFT) were performed weekly, while blood samples were taken at -4, -2, 2, 4, 6, and 8 weeks from parturition for estimation of hematological and biochemical metabolites. At -4, -3, and -2 weeks from calving, BFT did not differ between the two groups, but decreased after calving and was higher for the control group than the PG group at weeks -1 and 1. Hematological analysis revealed insignificant changes between the two groups. Serum concentrations of non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose did not differ between the two groups before parturition. At 2 and 4 weeks from parturition, NEFA was higher for the control group than the PG group. Serum concentrations of BHBA were higher at 2, 4, 6, and 8 weeks in control animals than in treated buffaloes. In contrast, the glucose level was significantly increased in PG group when compared to the control group at week 2 postpartum (p<0.05). Serum concentrations of total cholesterol, triglycerides, total proteins, albumin, and globulins did not differ significantly between the two groups (p>0.05). Serum enzyme activities of aspartate aminotransferase and γ-glutamyl transferase were significantly higher in the control than in the PG group. In treated buffaloes significantly (p<0.05) higher average 60-day milk yields were recorded (8.4±0.22 vs. 10.7±0.40 kg/day). Milk composition did not differ between the two groups. Drenching of dairy buffaloes with propylene glycol may reduce the risk of ketosis, improve the metabolic status, and increase the milk

The effects of energy concentration in roughage and allowance of concentrates on performance, health and energy efficiency of pluriparous dairy cows during early lactation.

PubMed

Schmitz, Rolf; Schnabel, Karina; von Soosten, Dirk; Meyer, Ulrich; Spiekers, Hubert; Rehage, Jürgen; Dänicke, Sven

2018-04-01

The aim of this study was to investigate the effects of different energy supplies from roughage and concentrates on performance, health and energy efficiency during early lactation. For this purpose an experiment was conducted containing 64 pluriparous German Holstein cows from 3 weeks prepartum until 16 weeks postpartum. During dry period all cows received an equal dry cow ration. After calving, cows were assigned in a 2 × 2 factorial arrangement to one of four groups, receiving either a moderate (MR, 6.0 MJ NE L ) or a high (HR, 6.4 MJ NE L ) energy concentration in roughage and furthermore moderate (MC, 150 g/kg energy-corrected milk (ECM)) or high amounts of concentrates (HC, 250 g/kg ECM) on dry matter (DM) basis, which were allocated from an automatic feeding system. Higher allocation of concentrates resulted in an increase of DM intake at expense of roughage intake. HC cows had a higher milk yield than MC cows, whereas ECM was higher in HR cows due to a decrease of milk fat yield in MR groups. Energy balance and body condition score were elevated in HC cows, but no differences occurred in development of subclinical ketosis. Furthermore, energy efficiency variables were lower in HC groups because the greater energy intake was not associated with a considerable elevation of milk yield. Consistency of faeces did not indicate digestive disorders in any of the treatment groups although the faecal manure score was significantly lower in HR groups. Our results underline the importance of a high energy uptake from roughage, which can contribute to an adequate performance and beneficial efficiency, especially at lower amounts of concentrates in ration. Feeding concentrates on an average amount of 9.4 kg/d compared to 6.4 kg/d on DM basis improved the energy balance in our trial, but without consequences for metabolic blood variables and general health of the cows.

Changes in milk urea around insemination are negatively associated with conception success in dairy cows.

PubMed

Albaaj, A; Foucras, G; Raboisson, D

2017-04-01

Dietary protein levels are a risk factor for poor reproductive performance. Conception is particularly impaired in cases of high blood or milk urea. The objective of this study was to investigate the association between conception and low milk urea or changes in milk urea around artificial insemination (AI). Data were obtained from the French Milk Control Program for a 4-yr period (2009-2012). Milk urea values between 250 and 450 mg/kg (4.3 and 7.7 mM) were considered intermediate (I), and values ≤150 mg/kg (2.6 mM) were considered low (L). Milk urea values before and after each AI were allocated into 4 classes representing the dynamics of milk urea (before-after; I-I, I-L, L-I, and L-L). Subclinical ketosis was defined using milk fat and protein contents before AI as proxies. A logistic regression with a Poisson correction and herd as a random variable was then performed on data from Holstein or all breeds of cows. The success of conception was decreased [relative risk (95% confidence interval) = 0.96 (0.94-0.99)] in low-urea cows compared with intermediate-urea cows after AI; no significant association was found for urea levels before AI. When combining data on urea before and after AI, I-L urea cows exhibited a 5 to 9% decrease in conception compared with I-I urea cows, and L-I urea cows showed no difference in conception success compared with I-I urea cows. A decreased conception success for L-L urea cows compared with I-I urea cows was observed for the analysis with cows of all breeds. This work revealed that a decrease in urea from intermediate (before AI) to low (after AI) is a risk factor for conception failure. Surveys of variation in milk urea in dairy cows close to breeding are highly recommended. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ethnoveterinary medicines used for ruminants in British Columbia, Canada.

PubMed

Lans, Cheryl; Turner, Nancy; Khan, Tonya; Brauer, Gerhard; Boepple, Willi

2007-02-26

The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis. Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production. Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera helix and Alchemilla

Caloric stress alters fat characteristics and Hsp70 expression in milk somatic cells of lactating beef cows

PubMed Central

Eitam, Harel; Brosh, Arieh; Orlov, Alla; Izhaki, Ido

2008-01-01

Selection for higher production rate in cattle inhabiting challenging habitats may be considered disadvantageous because of possible deleterious effects on immunity and reproduction and, consequently, on calf crop percentage. In Israel, free-grazing high productive beef cows experience reduction in nutritional quality of forage during up to 8 months of the year. As milk production by dams dictates calf performance, dam’s nutritional needs and rebreeding rates, the aim of the present study was to test how lactating beef cows deal with combined caloric and protein stress both at the productive and self protective levels. For this purpose, we studied the effect of long-term caloric stress on milk characteristics and gene expression of stress and milk components producing proteins. Lactating dams responded to caloric stress by decreased body weight, milk, and milk protein production. To compensate for total energy loses in milk, they produced milk of higher fat concentration and shifted the proportions of its fatty acids towards long and unsaturated ones. This was reflected by increased mRNA transcription of the fatty acid binding protein. Prolonged low-energy diet promoted cell-specific heat shock protein (Hsp) response; whereas significant increase of Hsp90 but unchanged levels of Hsp70 proteins were observed in white blood cells, the expression of Hsp70 in milk somatic cells was markedly attenuated, in parallel with a marked increase of αs1-casein expression. At the mammary gland level, these results may indicate a decrease in turnover of proteins and a shift to an exclusive expression of milk components producing factors. Similar responses to caloric stress were revealed also in ketotic dairy cows. Ketosis promoted a shift towards long and unsaturated fatty acids and an increased expression of αs1-casein in milk somatic cells. These findings may reflect an evolutionary-preserved mechanism in lactating cows for coping with caloric restriction. Overall, our

Effects of pathogen-specific clinical mastitis on probability of conception in Holstein dairy cows.

PubMed

Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

2014-11-01

The objective of this study was to estimate the effects of pathogen-specific clinical mastitis (CM), occurring in different weekly intervals before or after artificial insemination (AI), on the probability of conception in Holstein cows. Clinical mastitis occurring in weekly intervals from 6 wk before until 6 wk after AI was modeled. The first 4 AI in a cow's lactation were included. The following categories of pathogens were studied: Streptococcus spp. (comprising Streptococcus dysgalactiae, Streptococcus uberis, and other Streptococcus spp.); Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level that can be detected from our microbiological procedures) observed in the culture sample and cases with contamination (≥ 3 pathogens in the sample); and other pathogens [including Citrobacter, yeasts, Trueperella pyogenes, gram-negative bacilli (i.e., gram-negative organisms other than E. coli, Klebsiella spp., Enterobacter, and Citrobacter), Corynebacterium bovis, Corynebacterium spp., Pasteurella, Enterococcus, Pseudomonas, Mycoplasma, Prototheca, and others]. Other factors included in the model were parity (1, 2, 3, 4 and higher), season of AI (winter, spring, summer, autumn), day in lactation of first AI, farm, and other non-CM diseases (retained placenta, metritis, ketosis, displaced abomasum). Data from 90,271 AI in 39,361 lactations in 20,328 cows collected from 2003/2004 to 2011 from 5 New York State dairy farms were analyzed in a generalized linear mixed model with a Poisson distribution. The largest reductions in probability of conception were associated with CM occurring in the week before AI or in the 2 wk following AI. Escherichia coli and Klebsiella spp. had the greatest adverse effects on probability of conception. The probability of conception for a cow with any combination of characteristics may be calculated based on the parameter estimates. These

Overnutrition in spiny mice (Acomys cahirinus): beta-cell expansion leading to rupture and overt diabetes on fat-rich diet and protective energy-wasting elevation in thyroid hormone on sucrose-rich diet.

PubMed

Shafrir, E

2000-01-01

The investigation of diabetes propensity in spiny mice, performed in Geneva and Jerusalem colonies, is reviewed. Spiny mice live in semi-desert regions of the eastern Mediterranean countries. Those transferred to Geneva in the 1950s were maintained on a rodent diet supplemented by fat-rich seeds. They became obese, exhibited pancreatic islet hyperplasia and hypertrophy. Low insulin secretion response was characteristic of this species, despite ample pancreatic content of insulin. After a few months, diabetes with ketosis occurred, often suddenly, in association with islet cell disintegration. In Jerusalem the spiny mice were collected from their native habitat and placed on diets containing 50% sucrose or fat-rich seed diets. On a sucrose-rich diet, spiny mice developed hepatomegaly, lipogenic enzyme hyperactivity, and elevation in very low density lipoproteins as a result of metabolism of the fructose component mainly in the liver. No overt diabetes or pancreatic islet disintegration were observed, although insulin content and beta-cell hypertrophy and hyperplasia were apparent. On a fat-rich diet, spiny mice exhibited marked weight gain, adipose tissue growth and low hepatic lipogenesis. The obesity was accompanied by mild hyperglycemia and hyperinsulinemia with glucose intolerance leading to an occasional glucosuria after several months on the diet. The sucrose diet induced an extrathyroidal elevation of triiodothyronine (T(3)). Serum T(3) level and hepatic T(4)-T(3) conversion were increased, while serum T(4) levels tended to decrease. The activity of the T(3)-inducible hepatic mitochondrial FAD-glycerophosphate oxidase and K(+)/Na(+)-ATPase, as well as body temperature were increased, indicating that the sucrose diet was associated with enhanced thermogenesis and energy-wasting metabolic cycling. The sucrose-rich diet might exert an adaptive thermogenesis-mediated defense mechanism, protecting against excessive weight gain and disruptive pancreatic islet

E-mail management of the modified Atkins Diet for adults with epilepsy is feasible and effective.

PubMed

Cervenka, Mackenzie C; Terao, Natalie N; Bosarge, Jennifer L; Henry, Bobbie J; Klees, Angela A; Morrison, Peter F; Kossoff, Eric H

2012-04-01

The modified Atkins Diet (MAD) is an effective dietary treatment for children with epilepsy. However, adults may have limited access to this therapy because of lack of availability of dietitian or nutrition support or familiarity with the diet by their treating neurologist. This study was designed to investigate the tolerability and efficacy of the MAD administered solely via e-mail to adults with pharmacoresistant epilepsy. A prospective, open-label, proof-of-principle 3-month study design was employed. Adults were enrolled, instructed on how to self-administer a 20 g carbohydrate per day MAD, and followed by the investigators only via e-mail. There were no clinic visits or dietitian contacts during the study period. Twenty-five participants (median age 30 years [range 18-66 years], 68% female) consented and 22 started the MAD. The median prior anticonvulsants was 5 (range 2-10) and seizure frequency was 5 per week (range 1-140). Urinary ketosis was achieved in 21 participants (95%), of which 16 (76%) reported at least 40 mg/dl (moderate). Twenty-one participants (95%) remained on the MAD at 1 month and 14 (64%) at 3 months. After 1 month, 9 (41%) had >50% seizure reduction including one (5%) with >90% seizure reduction using intent-to-treat analysis. After 3 months, 6 (27%) had >50% seizure reduction including 3 (14%) with >90% seizure reduction. The mean ketogenic ratio was 1.1:1 (fat:carbohydrates and protein) for those who provided a MAD food record at follow-up. Over the study period, the median number of e-mails sent by the participants was 6 (range 1-19). The most frequent side effect was weight loss. E-mail administration of the MAD to adults with refractory epilepsy appears to be feasible and effective. Therefore, when dietitian or physician support is limited for adult patients with epilepsy, remote access via telemedicine could provide an alternative. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

PubMed

Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients.

PubMed

Sandström, R; Hyltander, A; Körner, U; Lundholm, K

1995-01-01

It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients. The results demonstrated for the first time in man that provision of structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions

Ethnoveterinary medicines used for ruminants in British Columbia, Canada

PubMed Central

Lans, Cheryl; Turner, Nancy; Khan, Tonya; Brauer, Gerhard; Boepple, Willi

2007-01-01

Background The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. Methods In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. Results There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera

Capitalizing on fine milk composition for breeding and management of dairy cows.

PubMed

Gengler, N; Soyeurt, H; Dehareng, F; Bastin, C; Colinet, F; Hammami, H; Vanrobays, M-L; Lainé, A; Vanderick, S; Grelet, C; Vanlierde, A; Froidmont, E; Dardenne, P

2016-05-01

The challenge of managing and breeding dairy cows is permanently adapting to changing production circumstances under socio-economic constraints. If managing and breeding address different timeframes of action, both need relevant phenotypes that allow for precise monitoring of the status of the cows, and their health, behavior, and well-being as well as their environmental impact and the quality of their products (i.e., milk and subsequently dairy products). Milk composition has been identified as an important source of information because it could reflect, at least partially, all these elements. Major conventional milk components such as fat, protein, urea, and lactose contents are routinely predicted by mid-infrared (MIR) spectrometry and have been widely used for these purposes. But, milk composition is much more complex and other nonconventional milk components, potentially predicted by MIR, might be informative. Such new milk-based phenotypes should be considered given that they are cheap, rapidly obtained, usable on a large scale, robust, and reliable. In a first approach, new phenotypes can be predicted from MIR spectra using techniques based on classical prediction equations. This method was used successfully for many novel traits (e.g., fatty acids, lactoferrin, minerals, milk technological properties, citrate) that can be then useful for management and breeding purposes. An innovation was to consider the longitudinal nature of the relationship between the trait of interest and the MIR spectra (e.g., to predict methane from MIR). By avoiding intermediate steps, prediction errors can be minimized when traits of interest (e.g., methane, energy balance, ketosis) are predicted directly from MIR spectra. In a second approach, research is ongoing to detect and exploit patterns in an innovative manner, by comparing observed with expected MIR spectra directly (e.g., pregnancy). All of these traits can then be used to define best practices, adjust feeding and health

[Influence of feeding rumen-protected choline to transition dairy cows. Part 2: Health and reproduction].

PubMed

Furken, C; Hoedemaker, M

2014-01-01

To determine the effects of rumen-protected choline (RPC) on health and reproduction in dairy cows. A total of 298 primi- and multiparous German Holstein cows of a high-production dairy herd (average daily milk yield: 32 l) were assigned randomly to a control or treatment group and were hand fed with 0 or 60 g/d of RPC as ReaShure®, respectively, from 21 days before expected calving to 21 days post partum (p. p.) as a top dressing. Health data was analyzed for the incidence of fever within the first 10 days in milk (DIM) as well as the incidence of diseases and the culling rate within the first 200 DIM. Reproduction data were evaluated in terms of the calving data, uterine involution on days 10, 21 and 42 p. p., uterine cytology at day 42 p. p., progesterone concentrations during weeks 3 and 5 p. p. and certain fertility measures. In the statistical analysis, it was differentiated between the control and treatment groups and between primi- and multiparous animals, and their interactions were analyzed. The treatment group had less cows with subclinical endometritis, higher sickness rates after day 100 p. p., lower numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the control group (p  <  0.05). Primipara in contrast to multipara had fever more frequently, higher rates of subclinical ketosis p. p., metritis and lameness, higher numbers of sick cows in the first 30 DIM, higher rates of stillbirths and dystocia, showed impaired involution of the uterus on day 10 p. p., fewer animals were cyclic during week 5 p. p. and less animals were culled (p < 0.05). Statistically significant interactions indicated that more heifers of the treatment group were lame, more heifers of the control group developed fever and subclinical endometritis, cows of the treatment group suffered more metritis and were sick more often in the first 30 DIM, and cows of the control group had more dystocia (p < 0.05). Overall, supplementing RPC had only minor effects on

Trial Protocol: randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking.

PubMed

Lycett, Deborah; Hajek, Peter; Aveyard, Paul

2010-10-07

Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/m2), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months.Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily

Endogenous and dietary lipids influencing feed intake and energy metabolism of periparturient dairy cows.

PubMed

Kuhla, B; Metges, C C; Hammon, H M

2016-07-01

The high metabolic priority of the mammary gland for milk production, accompanied by limited feed intake around parturition results in a high propensity to mobilize body fat reserves. Under these conditions, fuel selection of many peripheral organs is switched, for example, from carbohydrate to fat utilization to spare glucose for milk production and to ensure partitioning of tissue- and dietary-derived nutrients toward the mammary gland. For example, muscle tissue uses nonesterified fatty acids (NEFA) but releases lactate and amino acids in a coordinated order, thereby providing precursors for milk synthesis or hepatic gluconeogenesis. Tissue metabolism and in concert, nutrient partitioning are controlled by the endocrine system involving a reduction in insulin secretion and systemic insulin sensitivity and orchestrated changes in plasma hormones such as insulin, adiponectin, insulin growth factor-I, growth hormone, glucagon, leptin, glucocorticoids, and catecholamines. However, the endocrine system is highly sensitive and responsive to an overload of fatty acids no matter if excessive NEFA supply originates from exogenous or endogenous sources. Feeding a diet containing rumen-protected fat from late lactation to calving and beyond exerts similar negative effects on energy intake, glucose and insulin concentrations as does a high extent of body fat mobilization around parturition in regard to the risk for ketosis and fatty liver development. High plasma NEFA concentrations are thought not to act directly at the brain level, but they increase the energy charge of the liver which is, signaled to the brain to diminish feed intake. Cows differing in fat mobilization during the transition phase differ in their hepatic energy charge, whole body fat oxidation, glucose metabolism, plasma ghrelin, and leptin concentrations and in feed intake several week before parturition. Hence, a high lipid load, no matter if stored, mobilized or fed, affects the endocrine system

Effect of monensin and essential oils on performance and energy metabolism of transition dairy cows.

PubMed

Drong, C; Meyer, U; von Soosten, D; Frahm, J; Rehage, J; Breves, G; Dänicke, S

2016-06-01

This work examined preventive effects of a dietary and a medical intervention measure on postpartum (p.p.) ketogenesis in dairy cows overconditioned in late pregnancy. Sixty German Holstein cows were allocated 6 weeks antepartum (a.p.) to three high body condition score (BCS) groups (BCS 3.95 ± 0.08) and one low BCS group (LC, BCS 2.77 ± 0.14). Concentrate proportion in diet a.p. was higher (60% vs. 20%) and increase in proportion p.p. from 30% up to 50% decelerated (3 vs. 2 weeks) in high BCS groups. High BCS cows received a monensin controlled-release capsule (CRC) (HC/MO), a blend of essential oils (HC/EO) or formed a control group (HC). Performance parameters and energy status were evaluated in three periods [day (d) -42 until calving, one until 14 days in milk (DIM), 15 until 56 DIM]. Feed efficiency was 65% and 53% higher in HC/MO than in LC (p < 0.001) and HC groups (p = 0.002) in the second period. Milk fat content was higher in HC/EO (5.60 vs. 4.82%; p = 0.012) and milk urea higher in HC/MO (135 mg/kg) than in LC cows (107 mg/kg; p < 0.001). Increased p.p. levels of non-esterified fatty acids in serum were found in HC (p = 0.003), HC/MO (p = 0.068) and HC/EO (p = 0.002) in comparison with LC cows. Prevalence of subclinical and clinical ketosis was 54% and 46%, respectively, in HC group. Monensin decreased the prevalence to 50% and 7% respectively. Ruminal fermentation pattern showed higher proportions of propionate (23.43 mol % and 17.75 mol %, respectively; p < 0.008) and lower acetate:propionate ratio (2.66 vs. 3.76; p < 0.001) in HC/MO than HC group. Results suggest that a monensin CRC improved energy status and feed efficiency of transition dairy cows while essential oils failed to elicit any effect. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Norwegian mastitis control programme

PubMed Central

2009-01-01

This paper describes the methods and results of the Norwegian Mastitis Control Program implemented in 1982. The program has formed an integral part of the Norwegian Cattle Health Services (NCHS) since 1995. The NCHS also have specific programs for milk fever, ketosis, reproduction and calf diseases. The goal of the program is to improve udder health by keeping the bulk milk somatic cell count (BMSCC) low, to reduce the use of antibiotics, to keep the cost of mastitis low at herd level and improve the consumers' attitude to milk products. In 1996, a decision was made to reduce the use of antibiotics in all animal production enterprises in Norway by 25% within five years. Relevant data has been collected through the Norwegian Cattle Herd Recording System (NCHRS); including health records since 1975 and somatic cell count (SCC) data since 1980. These data have been integrated within the NCHRS. Since 2000, mastitis laboratory data have also been included in the NCHRS. Data on clinical disease, SCC and mastitis bacteriology have been presented to farmers and advisors in monthly health periodicals since 1996, and on the internet since 2005. In 1996, Norwegian recommendations on the treatment of mastitis were implemented. Optimal milking protocols and milking machine function have been emphasised and less emphasis has been placed on dry cow therapy. A selective dry cow therapy program (SDCTP) was implemented in 2006, and is still being implemented in new areas. Research demonstrates that the rate of clinical mastitis could be reduced by 15% after implementing SDCTP. The results so far show a 60% reduction in the clinical treatment of mastitis between 1994 and 2007, a reduction in BMSCC from 250,000 cells/ml to 114,000 cells/ml, and a total reduction in the mastitis cost from 0.23 NOK to 0.13 NOK per litre of milk delivered to the processors, corresponding to a fall from 9.2% to 1.7% of the milk price, respectively. This reduction is attributed to changes in attitude and

Association between the proportion of sampled transition cows with increased nonesterified fatty acids and beta-hydroxybutyrate and disease incidence, pregnancy rate, and milk production at the herd level.

PubMed

Ospina, P A; Nydam, D V; Stokol, T; Overton, T R

2010-08-01

In this study the herd alarm level was defined as the proportion of sampled transition cows per herd with increased prepartum nonesterified fatty acid (NEFA), postpartum beta-hydroxybutyrate (BHBA), or NEFA concentrations that were associated with herd-level incidence of displaced abomasum (DA) or clinical ketosis (CK), pregnancy rate (PR), and milk production. The objectives were to 1) identify the herd alarm level for excessive negative energy balance and 2) describe the herd-level prevalence of this proportion. This was a prospective cohort study of 60 free-stall herds fed total mixed rations in the northeast United States. Two cohorts of approximately 15 animals were assessed for prepartum NEFA and postpartum BHBA and NEFA. The herd alarm level (i.e., the proportion of sampled animals above a certain metabolite threshold) was as follows: 15% had prepartum NEFA of 0.27 mEq/L; 15 and 20% had BHBA of 10 and 12 mg/dL, respectively; and 15% had postpartum NEFA of 0.60 and 0.70 mEq/L. The different herd alarm levels correspond to differences between the metabolites and respective herd-level effect. The herd-level effects for herds above the herd alarm level for prepartum NEFA were 3.6% increase in DA and CK incidence, 1.2% decrease in PR, and 282 kg decrease in average mature equivalent 305-d (ME 305) milk. For BHBA, the herd-level effects were a 1.8% increase in DA and CK, 0.8% decrease in PR, and 534 and 358 kg decrease in projected ME 305 milk yield for heifers and cows, respectively. For postpartum NEFA, the herd-level effects were 1.7% increase in DA and CK, 0.9% decrease in PR, and 288 and 593 kg decrease in projected ME 305 milk yield for heifers and cows, respectively. The prevalence of herds in which more than 15% of animals sampled had prepartum NEFA concentration >or=0.30 mEq/L was 75%, BHBA >or=12 mg/dL was 40%, and postpartum NEFA >or=0.70 mEq/L was 65%. This study showed that there were detrimental herd-level effects if a large enough proportion of cows

Dairy cow disability weights.

PubMed

McConnel, Craig S; McNeil, Ashleigh A; Hadrich, Joleen C; Lombard, Jason E; Garry, Franklyn B; Heller, Jane

2017-08-01

Over the past 175 years, data related to human disease and death have progressed to a summary measure of population health, the Disability-Adjusted Life Year (DALY). As dairies have intensified there has been no equivalent measure of the impact of disease on the productive life and well-being of animals. The development of a disease-adjusted metric requires a consistent set of disability weights that reflect the relative severity of important diseases. The objective of this study was to use an international survey of dairy authorities to derive disability weights for primary disease categories recorded on dairies. National and international dairy health and management authorities were contacted through professional organizations, dairy industry publications and conferences, and industry contacts. Estimates of minimum, most likely, and maximum disability weights were derived for 12 common dairy cow diseases. Survey participants were asked to estimate the impact of each disease on overall health and milk production. Diseases were classified from 1 (minimal adverse effects) to 10 (death). The data was modelled using BetaPERT distributions to demonstrate the variation in these dynamic disease processes, and to identify the most likely aggregated disability weights for each disease classification. A single disability weight was assigned to each disease using the average of the combined medians for the minimum, most likely, and maximum severity scores. A total of 96 respondents provided estimates of disability weights. The final disability weight values resulted in the following order from least to most severe: retained placenta, diarrhea, ketosis, metritis, mastitis, milk fever, lame (hoof only), calving trauma, left displaced abomasum, pneumonia, musculoskeletal injury (leg, hip, back), and right displaced abomasum. The peaks of the probability density functions indicated that for certain disease states such as retained placenta there was a relatively narrow range of

The effect of conjugated linoleic acid supplements on oxidative and antioxidative status of dairy cows.

PubMed

Hanschke, N; Kankofer, M; Ruda, L; Höltershinken, M; Meyer, U; Frank, J; Dänicke, S; Rehage, J

2016-10-01

Dairy cows develop frequently negative energy balance around parturition and in early lactation, resulting in excessive mobilization of body fat and subsequently in increased risk of ketosis and other diseases. Dietary conjugated linoleic acid (CLA) supplements are used in dairy cows mainly for their depressing effect on milk fat content, but are also proposed to have antioxidative properties. As negative energy balance is associated with oxidative stress, which is also assumed to contribute to disease development, the present study was conducted to examine effects of CLA on oxidative and antioxidative status of lactating dairy cows. German Holstein cows (primiparous n=13, multiparous n=32) were divided into 3 dietary treatment groups receiving 100g/d of control fat supplement, containing 87% stearic acid (CON; n=14), 50g/d of control fat supplement and 50g/d of CLA supplement (CLA 50; n=15), or 100g/d of CLA supplement (CLA 100; n=16). The CLA supplement was lipid-encapsulated and contained 12% of trans-10,cis-12 CLA and cis-9,trans-11 CLA each. Supplementation took place between d1 and 182 postpartum; d 182 until 252 postpartum served as a depletion period. Blood was sampled at d -21, 1, 21, 70, 105, 140, 182, 224, and 252 relative to calving. The antioxidative status was determined using the ferric-reducing ability of plasma, α-tocopherol, α-tocopherol-to-cholesterol mass ratio, and retinol. For determination of oxidative status concentrations of hydroperoxides, thiobarbituric acid-reactive substances (TBARS), N'-formylkynurenine, and bityrosine were measured. Mixed models of fixed and random effects with repeated measures were used to evaluate period 1 (d -21 to 140) and 2 (d182-252) separately. Cows showed increased oxidative stress and lipid peroxidation during the periparturient period in terms of increased serum concentrations of hydroperoxides and TBARS, which decreased throughout lactation. During period 1, the supplemented cows had lower TBARS

Measurement of β-hydroxybutyrate in capillary blood obtained from an ear to detect hyperketonemia in dairy cows by using an electronic handheld device.

PubMed

Süss, D; Drillich, M; Klein-Jöbstl, D; Wagener, K; Krieger, S; Thiel, A; Meyer, L; Schwendenwein, I; Iwersen, M

2016-09-01

The primary objective of the present study was to test whether capillary blood obtained by puncturing the skin of an ear with a minimal invasive lancet technique is able to detect hyperketonemia (HYK) in dairy cows. Furthermore, test characteristics of a new available handheld device, the FreeStyle Precision Neo (FSP-Neo, Abbott GmbH & Co. KG, Wiesbaden, Germany) for determination of β-hydroxybutyrate (BHB) concentrations in bovine blood were evaluated by comparing the measurements with a laboratory reference. The BHB concentration was determined with the FSP-Neo device in 720 capillary blood samples from 3 different sampling sites (left, right ear, and repeated measurement) and in 240 samples from a coccygeal vessel. The concentration of BHB in serum harvested from the coccygeal blood samples was analyzed at the laboratory and was used as reference. The Spearman correlation coefficient (ρs) between the BHB concentrations in capillary blood measured with the handheld device and the reference test was between 0.76 and 0.81. Using capillary blood, the mean ± standard deviation BHB difference compared with the reference test was 0.20±0.47 mmol/L for all 3 sampling locations at the ears. The receiver operating characteristic analyses for the FSP-Neo device resulted in an optimized threshold for the detection of subclinical ketosis (SCK) in capillary blood of 1.3 mmol/L (left and right ear) and 1.2 mmol/L (repeated measurements). Applying these adjusted threshold sensitivities (Se) for all 3 capillary sampling sites at the ear were 100%, and specificities (Sp) ranged between 93 and 94%. Hence, we conclude that all sampling locations were suitable to identify cows suffering from SCK. The reference test compared with BHB measurements in coccygeal blood resulted in a ρs of 0.92 with a mean ± standard deviation of 0.02±0.21 mmol/L. The receiver operating characteristic analyses for the FSP-Neo device resulted in an optimized threshold for the detection of SCK in

Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.

PubMed

Ly, Trang T; Nicholas, Jennifer A; Retterath, Adam; Lim, Ee Mun; Davis, Elizabeth A; Jones, Timothy W

2013-09-25

. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. anzctr.org.au Identifier: ACTRN12610000024044.

Insulin therapy in children and adolescents with type 1 diabetes.

PubMed

Malik, Faisal S; Taplin, Craig E

2014-04-01

Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system

Diagnostic performance of cytology for assessment of hepatic lipid content in dairy cattle.

PubMed

Fry, M M; Yao, B; Ríos, C; Wong, C; Mann, S; McArt, J A A; Nydam, D V; Leal Yepes, F A; Viesselmann, L; Geick, A; Goldin, K; Jordan, A; Behling-Kelly, E

2018-02-01

The objective of our study was to characterize the diagnostic performance of cytology for assessing hepatic lipid content (HLC) in dairy cows by comparing microscopic evaluation of lipid vacuolation in touch imprint slide preparations of liver biopsies with quantitative measurement of triglyceride concentration ([TG]; mg/mg of wet weight) in paired biopsy samples. Our study also sought to compare the diagnostic performance of liver cytology, plasma nonesterified fatty acid concentration ([NEFA]), and plasma β-hydroxybutyrate concentration ([BHB]) derived from a measurement performed on whole blood, for assessing HLC. Chemical extraction of TG from liver tissue remains the gold standard for quantifying HLC, largely because available blood tests, although useful for detecting some types of pathology, such as increased lipid mobilization, ketosis, or hepatocellular injury, are nonspecific as to etiology. Veterinary practitioners can sample bovine liver for cytological evaluation in a fast, minimally invasive, and inexpensive manner. Thus, if highly predictive of HLC, cytology would be a practical diagnostic tool for dairy veterinarians. In our study, liver biopsy samples from Holstein cows (219 samples from 105 cows: 52 from cows 2 to 20 d prepartum, 105 from cows 0 to 10 d in milk, 62 from cows 18 to 25 d in milk) were used to prepare cytology slides and to quantify [TG] using the Folch extraction method followed by the Hantzch condensation reaction and spectrophotometric measurement. An ordinal scale (0-4) based on amount of hepatocellular cytoplasm occupied by discrete clear vacuoles was used by 3 blinded, independent observers to rank HLC in Wright-Giemsa-stained slides. Interobserver agreement in cytology scoring was good. Corresponding plasma [NEFA] and [BHB] measurements were available for 187 and 195 of the 219 samples, respectively. Liver [TG] correlated more strongly with cytology score than with NEFA or BHB, and receiver operating characteristic curve

The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

PubMed Central

Kephart, Wesley C.; Pledge, Coree D.; Roberson, Paul A.; Mumford, Petey W.; Romero, Matthew A.; Mobley, Christopher B.; Young, Kaelin C.; Lowery, Ryan P.; Wilson, Jacob M.; Huggins, Kevin W.; Roberts, Michael D.

2018-01-01

Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; n = 5) and a KD group (n = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest that

Albert Renold Memorial Lecture: Molecular Background of Nutritionally Induced Insulin Resistance Leading to Type 2 Diabetes – From Animal Models to Humans

PubMed Central

Shafrir, Eleazar

2001-01-01

Albert Renold strived to gain insight into the abnormalities of human diabetes by defining the pathophysiology of the disease peculiar to a given animal. He investigated the Israeli desert-derived spiny mice (Acomys cahirinus), which became obese on fat-rich seed diet. After a few months hyperplasia and hypertrophy of β-cells occurred leading to a sudden rupture, insulin loss and ketosis. Spiny mice were low insulin responders, which is probably a characteristic of certain desert animals, protecting against insulin oversecretion when placed on an abundant diet. We have compared the response to overstimulation of several mutant diabetic species and nutritionally induced nonmutant animals when placed on affluent diet. Some endowed with resilient β-cells sustain long-lasting oversecretion, compensating for the insulin resistance, without lapsing into overt diabetes. Some with labile beta cells exhibit apoptosis and lose their capacity of coping with insulin resistance after a relatively short period. The wide spectrum of response to insulin resistance among different diabetes prone species seems to represent the varying response of human beta cells among the populations. In search for the molecular background of insulin resistance resulting from overnutrition we have studied the Israeli desert gerbil Psammomys obesus (sand rat), which progresses through hyperinsulinemia, followed by hyperglycemia and irreversible beta cell loss. Insulin resistance was found to be the outcome of reduced activation of muscle insulin receptor tyrosine kinase by insulin, in association with diminished GLUT4 protein and DNA content and overexpression of PKC isoenzymes, notably of PKCε. This overexpression and translocation to the membrane was discernible even prior to hyperinsulinemia and may reflect the propensity to diabetes in nondiabetic species and represent a marker for preventive action. By promoting the phosphorylation of serine/threonine residues on certain proteins of the

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

PubMed Central

2010-01-01

Background Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. Methods This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/m2), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones

Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

PubMed

Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

2014-03-01

The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of

Fresh-cow handling practices and methods for identification of health disorders on 45 dairy farms in California.

PubMed

Espadamala, A; Pallarés, P; Lago, A; Silva-Del-Río, N

2016-11-01

The aim of the present study was to describe fresh-cow handling practices and techniques used during fresh cow evaluations to identify postpartum health disorders on 45 dairy farms in California ranging from 450 to 9,500 cows. Fresh cow practices were surveyed regarding (a) grouping and housing, (b) scheduling and work organization, (c) screening for health disorders, and (d) physical examination methods. Information was collected based on cow-side observations and responses from fresh cow evaluators. Cows were housed in the fresh cow pen for 3 to 14 (20%), 15 to 30 (49%), or >31 (31%) d in milk. Fresh cow evaluations were performed daily (78%), 6 times a week (11%), 2 to 5 times a week (9%), or were not routinely performed (2%). There was significant correlation between the duration of fresh cow evaluations and the number of cows housed in the fresh pen. Across all farms, the duration of evaluations ranged from 5 to 240 min, with an average of 16 s spent per cow. During fresh cow checks, evaluators always looked for abnormal vaginal discharge, retained fetal membranes, and down cows. Dairies evaluated appetite based on rumen fill (11%), reduction of feed in the feed bunk (20%), rumination sensors (2%), or a combination of these (29%). Milk yield was evaluated based on udder fill at fresh cow checks (40%), milk flow during milking (11%), milk yield records collected by milk meters (2%), or a combination of udder fill and milk meters (5%). Depressed attitude was evaluated on 64% of the dairies. Health-monitoring exams for early detection of metritis were implemented on 42% of the dairies based on rectal examination (13%), rectal temperature (22%), or both (7%). Dairies implementing health-monitoring exams took longer to perform fresh cow evaluations. Physical examination methods such as rectal examination, auscultation, rectal temperature evaluation, and cow-side ketosis tests were used on 76, 67, 38, and 9% of dairies, respectively. Across dairies, we found large

Effect of administration of recombinant bovine somatotropin on health and performance of lactating dairy cows diagnosed with hyperketonemia.

PubMed

Gohary, K; Leslie, K E; Ford, J; Capel, M; LeBlanc, S J; Duffield, T F

2015-07-01

The effect of administering recombinant bovine somatotropin (rbST) to cows with hyperketonemia during the early postpartum period on health, metabolic parameters, milk production, and early reproductive performance was evaluated in a double-blinded clinical trial. Cows from 8 dairy herds in New York State were tested weekly between 3 and 16d in milk for elevated serum β-hydroxybutyrate. Cows were enrolled in the study when blood β-hydroxybutyrate was ≥1.3mmol/L for the first time. Enrolled cows were randomly assigned to a treatment (n=273) or placebo control (n=270) group. Treated cows were given 325mg of rbST subcutaneously on the day of enrollment and again 14d later. Control cows received the same regimen except the syringe contained only the carrier without somatotropin. After enrollment, blood samples were collected weekly for 4wk and submitted to the laboratory to be analyzed for selected metabolites. Risk ratios for clinical diseases subsequent to treatment were calculated using Poisson regression. Continuous data were analyzed using linear mixed models. Time to first insemination was assessed with survival analysis. In the 42d following the first administration of rbST, incidence risks of displaced abomasum, clinical ketosis, metritis, clinical mastitis, and lameness were not different between treatment groups. Cows treated with rbST had a slightly lower body condition score 28d after enrollment compared with control cows. In the 4wk following enrollment, serum nonesterified fatty acids and aspartate amino-transferase were slightly higher for treated than control cows, respectively. Serum glucose, calcium, haptoglobin, and β-hydroxybutyrate were similar between groups. Treatment had no effect on resolution of hyperketonemia in any of the 4wk after enrollment. Milk production in either of the 2-wk periods after each treatment was not different between treated and control cows. Furthermore, milk production was not different between groups from enrollment

Technical note: Validation of a handheld meter for measuring β-hydroxybutyrate concentrations in plasma and serum from dairy cows.

PubMed

Pineda, A; Cardoso, F C

2015-12-01

The use of handheld meters for cow-side tests for β-hydroxybutyrate (BHB) concentrations in whole blood has become common. The aim of this study was to compare serum BHB (sBHB) and plasma BHB (pBHB) concentrations analyzed using either a "gold standard" enzymatic laboratory method (LM; Randox Laboratories Ltd., Antrim, UK; cat. no. RB1007) or a handheld meter (PX; Precision Xtra, Abbott Diabetes Care Inc., Alameda, CA). Results from 374 (187 serum and 187 plasma) samples taken from Holstein cows from 11 d before (52 samples) to 5 d after parturition (137 samples) were used for the analysis. Statistical analysis was performed using the MIXED, REG, and LOGISTIC procedures of SAS (v9.4; SAS Institute Inc., Cary, NC). A linear mixed model with repeated measures was fitted for LM and PX. Regression and correlation analyses were completed to estimate the relationship and agreement between the 2 methods. Lin's concordance correlation coefficient (CCC) and Bland-Altman plots were used to evaluate agreement between LM and PX. Cross-validation by randomly splitting the data in model-building and validation sets was performed to estimate and validate the equation that predicted the LM results using PX. Receiver operating characteristic (ROC) curves were used to estimate the sensitivity (Se) and specificity (Sp) of PX at different threshold levels. The CCC was 0.74 for pBHB and 0.68 for sBHB. The 95% confidence interval of agreement of the Bland-Altman plot encompassed 96% of the difference between LM and PX for pBHB and 95% for sBHB. The mean difference for pBHB was -0.50±0.25mmol, and that for sBHB was -0.63±0.41mmol. The highest Se and Sp for PX were achieved when the threshold for ketosis was set to 1.8mmol/L for pBHB and 2.1mmol/L for sBHB. The area under the ROC curve was 0.97 for pBHB and 0.96 for sBHB. The negative bias shown by the Bland-Altman plots suggested that PX yielded higher pBHB and sBHB concentrations than the LM. However, the excellent test

Association between body energy content in the dry period and post-calving production disease status in dairy cattle.

PubMed

Smith, G L; Friggens, N C; Ashworth, C J; Chagunda, M G G

2017-09-01

The transition from gestation to lactation is marked by significant physiological changes for the individual cow such that disease incidence is highest in early lactation. Around the time of calving, cows rely on mobilisation of body energy reserves to fill the energy deficit created by an increase in nutrient demands at a time of restricted feed intake. It is well established that monitoring of body energy reserves in lactation is an important component of herd health management. However, despite their influence on future health and productivity, monitoring of body energy reserves in the dry period is often sparse. Further, there is increasing concern that current dry off management is inappropriate for modern cattle and may influence future disease risk. This study aimed to identify candidate indicators of early lactation production disease from body energy data collected in the dry period and production data recorded at the time of dry off. Retrospective analysis was performed on 482 cow-lactations collected from a long-term Holstein-Friesian genetic and management systems project, the Langhill herd in Scotland. Cow-lactations were assigned to one of four health groups based on health status in the first 30 days of lactation. These four groups were as follows: healthy, reproductive tract disorders (retained placenta and metritis), subclinical mastitis and metabolic disorders (ketosis, hypocalcaemia, hypomagnesaemia and left displaced abomasum). ANOVA, employing a GLM was used to determine effects for the candidate indicator traits. Cows which were diagnosed with a reproductive tract disorder in the first 30 days of lactation experienced a significantly greater loss in body energy content, body condition score and weight in the preceding dry period than healthy cows. The rate of change in body energy content during the first 15 days of the dry period was -18.26 MJ/day for cows which developed reproductive tract disorder compared with +0.63 MJ/day for healthy cows

High somatic cell counts and changes in milk fat and protein contents around insemination are negatively associated with conception in dairy cows.

PubMed

Albaaj, Ahmad; Foucras, Gilles; Raboisson, Didier

2017-01-15

The fertility of dairy cows has decreased dramatically worldwide over the last few decades, and several causes of this trend have been reported. Several studies have associated compromised udder health with deteriorating reproduction performance. Subclinical ketosis (SCK) has also been reported to be a risk factor for decreased conception. The objective of the present study was to describe how SCK might interact with the reported association between udder health and conception in dairy cows. Data from the French Milk Control Program and data on 8,549,667 instances of artificial insemination (AI) and their corresponding preceding and subsequent test-days from 5,979,701 Holstein cows were examined over a 5-year period (2008-2012). The effect of udder health was evaluated through a low (L) or high (H) somatic cell count (SCC) before and after AI using a threshold of 200,000 cells/mL, and transformed into four groups (LL, LH, HL, and HH). Three proxies for defining SCK were proposed based on the milk fat and protein content (or their ratio) before AI. Statistical analysis first included a generalized additive model to help define the optimal threshold values. Next, a logistic regression with a Poisson correction was performed. On average, the risk of conception at first AI was reduced by 14% for LH or HH cows (relative risk [and 95% CI] = 0.86 [0.85-0.87]) when the SCC increased or remained high within 40 days before and after AI, relative to LL group. The reduction of conception success associated with SCK (fat and protein contents changes) varied from 3% to 17% depending on the used SCK proxy. Including the interaction term SCC ∗ SCK clearly showed that the association of increased SCC around AI with conception success was modified by the presence of SCK. A cow that already has SCK and experiences an increase in SCC around or after AI exhibits up to 2 times further decrease in conception success compared with a cow with a high SCC and no SCK. In conclusion