Serum vitamin D concentrations at dry-off and close-up predict increased postpartum urine ketone concentrations in dairy cattle.

Vitamin D is commonly supplemented to dairy cows as vitamin D3 to support calcium homeostasis and in times of low sunlight exposure. Vitamin D has beneficial immunomodulatory and anti-inflammatory properties. Serum 25-hydroxyvitamin D [25(OH)D] concentrations fluctuated during lactation, with the lowest concentrations measured in healthy cows within 7 d of calving. However, it is unknown if serum 25(OH)D concentrations measured during the previous lactation are associated with transition diseases or health risk factors in dairy cattle. We collected serum samples from 279 dairy cattle from 5 commercial dairy herds in Michigan at dry-off, close-up, and 2-10 d in milk (DIM). Vitamin D concentrations were determined by measuring serum 25(OH)D by radioimmunoassay. Total serum calcium was measured by colorimetric methods. Body condition scores (BCS) were assigned at the time of blood collection. Clinical disease incidence was monitored until 30 d postparturition. Separate bivariable logistic regression analyses were used to determine if serum 25(OH)D at dry-off, close-up, and 2-10 DIM was associated with various clinical diseases including mastitis, lameness, and uterine disorders (classified as metritis, retained placenta, or both) and increased urine ketone concentrations at P < 0.05. Among all significant bivariable analyses, multivariable logistic regression analyses were built to adjust for potential confounding variables including parity, BCS, season, and calcium. Receiver operator characteristic (ROC) curve analyses were used to determine optimal concentrations of serum 25(OH)D. We found that higher serum 25(OH)D concentrations at dry-off and close-up predicted increased urine ketone concentrations in early lactation, even after adjustment for confounders. Alternatively, we found that lower serum 25(OH)D at 2-10 DIM was associated with uterine diseases. Optimal concentrations for serum 25(OH)D at dry-off and close-up for lower risk of increased urine ketone concentrations were below 103.4 and 91.1 ng/mL, respectively. The optimal concentration for serum 25(OH)D at 2-10 DIM for uterine diseases was above 71.4 ng/mL. These results indicate that serum 25(OH)D at dry-off and close-up may be a novel predictive biomarker for increased urine ketone concentrations during early lactation. Increased urine ketone concentrations are not necessarily harmful or diagnostic for ketosis but do indicate development of negative energy balance, metabolic stress, and increased risk of early lactation diseases. Predicting that dairy cattle are at increased risk of disease facilitates implementation of intervention strategies that may lower disease incidence. Future studies should confirm these findings and determine the utility of serum 25(OH)D concentrations as a predictive biomarker for clinical and subclinical ketosis.

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults.

Throughout history, the only way humans could raise their blood ketone levels was by several days of fasting or by following a strict low-carb, high-fat diet. A recently developed, dietary source of ketones, a ketone monoester, elevates d-ß-hydroxybutyrate (ßHB) to similar concentrations within minutes, with ßHB remaining raised for several hours. To date, the longest human safety study of the exogenous ketone ester was for 5 days, but longer consumption times may be desired. Here we report results for 24 healthy adults, aged 18-70 years, who drank 25 ml (26.8 g) of the ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, three times a day for 28 days (a total of 2.1 L). Anthropomorphic measurements, plus fasting blood and urine analyses were made weekly. It was found that elevating blood ßHB concentrations from 0.1 to 4.1 (±1.1) mM three times a day for 28 days had no effect on body weights or composition, fasting blood glucose, cholesterol, triglyceride or electrolyte concentrations, nor blood gases or kidney function, which were invariably normal. Mild nausea was reported following 6 of the 2,016 drinks consumed. We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.

Sequence variants associating with urinary biomarkers.

Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.5 million sequence variants for association with urinary biomarkers in a set of 150 274 Icelanders with urine dipstick measurements. We detected 20 association signals, of which 14 are novel, associating with at least one of five clinical entities defined by the urine dipstick: glucosuria, ketonuria, proteinuria, hematuria and urine pH. These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes. Two variants associating with proteinuria are in LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal tubule protein uptake. One of the hematuria-associated variants is a rare, previously unreported 2.5 kb exonic deletion in COL4A3. Of the four signals associated with urine pH, we note that the pH-increasing alleles of two variants (POU2AF1, WDR72) associate significantly with increased risk of kidney stones. Our results reveal that genetic factors affect variability in urinary biomarkers, in both a disease dependent and independent context.

Use of cooking oils in a 2:1 ratio classical ketogenic diet for intractable pediatric epilepsy: Long-term effectiveness and tolerability.

BACKGROUND: In many parts of eastern Asia, rice is a dietary staple and therefore the ketogenic diet (KD) can be difficult to administer. The aim of this study was to assess the long-term effectiveness and tolerability of the classical KD using a 2:1 ratio of fat to protein plus net carbohydrates, which is lower than the ratios of 3:1 or 4:1 typically used in classical KD for intractable pediatric epilepsy. MATERIALS: In this prospective study, cooking oils rich in polyunsaturated fatty acid or omega 3 fatty acids, such as olive oil, camellia oil, linseed oil, grape seed oil, and/or perilla oil were used to formulate a classical KD with a 2:1 ratio for infants and children diagnosed with medically intractable epilepsy from April 2002 to April 2018. Subjects received the diet for at least 3 months. The efficacy of the diet was analyzed at 3, 6, 12, and 24 months, and at > 3 years. Tolerability during the period of diet administration was analyzed by medical records and parental reports. RESULTS: Sixty-three subjects, 29 males and 34 females, were enrolled from April 2002 to April 2018. The median age at diet initiation was 2 years 11 months. The median duration of adherence to the diet was 1 year 2 months. The seizure-free rate was 14%, 16%, 17%, 14%, and 14% at 3, 6, 12, and 24 months', and at > 3 years' follow-up, respectively. A greater than 50% seizure reduction was achieved in 52%, 43%, 40%, 33%, and 30% of subjects at each time point. The dietary compliance rate was 100%, 70%, 60%, 35%, and 27% at each follow-up time point. The reasons for discontinuation of the KD were the lack of further improvement in seizure frequency, seizure freedom achieved, food refusal, hyperlipidemia, and poor parental compliance in 38%, 11%, 5%, 2%, and 2% of subjects, respectively. Gastrointestinal discomfort was the most common adverse effect. CONCLUSION: The classical KD with a 2:1 ratio showed clinical effectiveness and tolerability in intractable pediatric epilepsy after long-term follow-up.

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women.

BACKGROUND: Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. METHODS: We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by 1H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. RESULTS: Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. CONCLUSIONS: VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome. Trial Registration ClinicalTrials.gov NCT01699906, 4-Oct-2012, Retrospectively registered. URL- https://clinicaltrials.gov/ct2/show/NCT01699906.

Improving compliance in adults with epilepsy on a modified Atkins diet: A randomized trial.

PURPOSE: To determine whether use of a ketogenic formula during the first month of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy (DRE) improves seizure reduction and compliance compared to MAD alone. METHODS: Eighty adults (age ≥18 years) with DRE and ≥4 reliably quantifiable seizures/month were enrolled. All participants were trained to follow a 20 g/day net carbohydrate limit MAD. Patients were randomized to receive one 8-ounce (237 mL) tetrapak of KetoCal®, a 4:1 ketogenic ratio formula, daily in combination with MAD during the first month (treatment arm) or second month (control/cross-over arm). Patients recorded urine ketones, weight, and seizure frequency and followed up at 1 and 2 months. RESULTS: By 1 month, 84% of patients achieved ketosis (median of 4-4.5 days). At 1 month, the treatment arm had a significantly higher ketogenic ratio and more patients with a ≥1:1 ketogenic ratio compared to the control arm. There was no difference in median seizure frequency, proportion of responders (≥50% seizure reduction), or median seizure reduction from baseline between groups. However, patients treated with KetoCal® during the first month were significantly more likely to continue MAD for 6 months or more. CONCLUSION: Although supplementing MAD with a ketogenic formula in the first month did not increase the likelihood of reducing seizures compared to MAD alone, significantly more adults remained on MAD long-term with this approach. This suggests a potential strategy for encouraging compliance with MAD in adults with DRE.

The Impact of Hyperosmolarity on Long-Term Outcome in Patients Presenting with Severe Hyperglycemic Crisis: A Population Based Study.

AIMS: We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors. METHODS: The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria <1+, and serum osmolarity >320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS). RESULTS: During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome. CONCLUSIONS: Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes.

Screening Mentally Retarded Children for Inborn Errors of Metabolism.

BACKGROUND: Most inborn errors of metabolism result in mental retardation and death due to accumulation of abnormal metabolites in the tissues. The presence of abnormal metabolites in the urine of mentally retarded individuals has been used worldwide for detection of inborn errors of metabolism. The purpose of the study is to determine the prevalence of inborn error of metabolism in mentally retarded children. METHODS: Random urine samples were collected from mentally retarded children at two institutes in Kathmandu, and also from 60 normal children from Duwakot, Nepal after obtaining consent from their parents. Urine was then tested for the presence of amino acids, keto-acids, mucopolysaccharides, fructose, glucose and protein using simple qualitative color reactions in the laboratory. RESULTS: The tests detected eight cases of Phenylketonuria, which turned out to be false positive on paper chromatography. Three cases of presence of ketone bodies (acetoacetate), ten cases of α-ketoaciduria, two cases of mucopolysaccharidosis and twelve cases of fructosuria amongst the sixty-two urine samples were also found. CONCLUSIONS: Certain aminoacidurias, ketoacidurias and mucopolysaccharidoses might be present in the Nepalese population. Within consideration of errors, the samples tested positive should be evaluated by a higher end method to confirm the utility of these simple and cheap chemical tests.

Mass spectral analysis of urine proteomic profiles of dairy cows suffering from clinical ketosis.

BACKGROUND: Ketosis is an important metabolic disorder in dairy cows during the transition period. The urine proteomics of ketosis has not been investigated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). OBJECTIVE: The aim is to determine differences between urine proteomic profiles of healthy cows and those with clinical ketosis, and facilitate studies of the underlying physiological and biochemical mechanisms that lead to liver pathology in ketosis. ANIMALS AND METHODS: We analyzed the urine samples of 20 cows with clinical ketosis (group 1) and 20 control cows (group 2) using SELDI-TOF-MS. RESULTS: Thirty-nine peptide peaks differed between both groups. Polypeptides corresponding to 26 of these differential peptide peaks were identified using the SWISS-PROT protein database. We found that the peaks of 11 distinct polypeptides from the urine samples of the ketosis group were significantly reduced, compared with those of the control group as based on the Wilcoxon rank sum test. Among these were VGF (non-acronymic) protein, amyloid precursor protein, serum amyloid A (SAA), fibrinogen, C1INH, apolipoprotein C-III, cystatin C, transthyretin, hepcidin, human neutrophil peptides, and osteopontin. CONCLUSION: These proteins may represent novel biomarkers of the metabolic changes that occur in dairy cows with ketosis. Our results will help to better understand the physiological changes and pathogenesis observed in cows with ketosis. CLINICAL IMPORTANCE: The SELDI-TOF-MS can be used to understand the physiological and biochemical mechanisms of ketosis and identify biomarkers of the disease.

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

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).

ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

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.

The postmortem diagnosis of alcoholic ketoacidosis.

AIMS: The aim of this article is to review the forensic literature covering the postmortem investigations that are associated with alcoholic ketoacidosis fatalities and report the results of our own analyses. METHODS: Eight cases of suspected alcoholic ketoacidosis that had undergone medico-legal investigations in our facility from 2011 to 2013 were retrospectively selected. A series of laboratory parameters were measured in whole femoral blood, postmortem serum from femoral blood, urine and vitreous humor in order to obtain a more general overview on the biochemical and metabolic changes that occur during alcoholic ketoacidosis. Most of the tested parameters were chosen among those that had been described in clinical and forensic literature associated with alcoholic ketoacidosis and its complications. RESULTS: Ketone bodies and carbohydrate-deficient transferrin levels were increased in all cases. Biochemical markers of generalized inflammation, volume depletion and undernourishment showed higher levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and triiodothyronine were also observed. CONCLUSIONS: Metabolic and biochemical disturbances characterizing alcoholic ketoacidosis can be reliably identified in the postmortem setting. The correlation of medical history, autopsy findings and biochemical results proves therefore decisive in identifying pre-existing disorders, excluding alternative causes of death and diagnosing alcoholic ketoacidosis as the cause of death.

Association between urine osmolality and specific gravity in dogs and the effect of commonly measured urine solutes on that association.

OBJECTIVE: To determine the association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association. ANIMALS: 60 dogs evaluated by an internal medicine service. PROCEDURES: From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at -80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis. RESULTS: The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.

Diagnostic accuracy of fingerstick ß-hydroxybutyrate for ketonuria in pregnant women with nausea and vomiting.

OBJECTIVES: The aim of this study was to determine whether a rapid, fingerstick ß-hydroxybutyrate (ß-OHB) test predicts ketonuria in pregnant women with nausea and vomiting. METHODS: A convenience sample of 82 pregnant women who presented to the Barnes-Jewish Hospital emergency department (ED) with complaints of nausea or vomiting were enrolled into an institutional review board-approved, prospective, observational study. Exclusion criteria were temperature of >38.3°C, altered mental status, prisoners, and >1 L of any intravenous (IV) fluid before screening. Subjects had fingerstick ß-OHB tests, with results reported in increments of 0.1 mmol/L. Urine ketone results were made available once reported as part of standard care and varied from 0 (trace) to +4 values. Ketonuria was defined as a urine ketone value of 3+ or 4+ and was analyzed as a dichotomous, categorical variable. A contingency table and receiver operator characteristic (ROC) curve were constructed for comparing the ß-OHB values to those urine ketone values for each patient. RESULTS: Mean (±SD) ß-OHB was 0.43 (±0.52) mmol/L, and median urine was 1+ for the cohort as a whole. The area under the ROC curve equaled 0.95. The sensitivity and specificity for a fingerstick test of >0.45 mmol/L were 89 and 94.5%, respectively. The positive likelihood ratio (LR) was 16, and the negative LR was 0.12. CONCLUSIONS: Fingerstick ß-OHB is a rapid and reliable diagnostic tool that correlates well with ketonuria and identifies ketonemia in pregnant women with nausea and vomiting. Fingerstick ß-OHB testing has the potential to increase triage efficiency, shorten length-of-stay times, and positively affect patient outcomes in an ED setting.

Low-carbohydrate diet for the treatment of gestational diabetes mellitus: a randomized controlled trial.

OBJECTIVE: Medical nutrition therapy based on the control of the amount and distribution of carbohydrates (CHO) is the initial treatment for gestational diabetes mellitus (GDM), but there is a need for randomized controlled trials comparing different dietary strategies. The purpose of this study was to test the hypothesis that a low-CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet. RESEARCH DESIGN AND METHODS: A total of 152 women with GDM were included in this open, randomized controlled trial and assigned to follow either a diet with low-CHO content (40% of the total diet energy content as CHO) or a control diet (55% of the total diet energy content as CHO). CHO intake was assessed by 3-day food records. The main pregnancy outcomes were also assessed. RESULTS: The rate of women requiring insulin was not significantly different between the treatment groups (low CHO 54.7% vs. control 54.7%; P = 1). Daily food records confirmed a difference in the amount of CHO consumed between the groups (P = 0.0001). No differences were found in the obstetric and perinatal outcomes between the treatment groups. CONCLUSIONS: Treatment of women with GDM using a low-CHO diet did not reduce the number of women needing insulin and produced similar pregnancy outcomes. In GDM, CHO amount (40 vs. 55% of calories) did not influence insulin need or pregnancy outcomes.

Ketoacidosis and trace amounts of isopropanol in a chronic alcoholic patient.

BACKGROUND: Alcohol ketoacidosis is a frequently missed diagnosis, but is well described in the literature. We present a case of ketoacidosis, likely alcohol ketoacidosis, in a 40 y-old chronic alcoholic patient. The detection of trace serum isopropanol prompted a discussion of alcohol ketoacidosis versus toxic isopropanol ingestion or a combination of both, including comparisons with citations in current literature. METHODS: The automated instruments used to analyze the patient's urine, blood, and serum samples are described. RESULTS: The initial impression was severe metabolic acidosis with an increased anion gap and normal serum glucose and whole blood lactate. Testing for potential toxic ingestions detected only increased serum acetone and trace serum isopropanol. A urinalysis positive for ketones and an increased serum ß-hydroxybutyrate concentration clenched the diagnosis of ketoacidosis. CONCLUSION: Ketoacidosis with an increased anion gap in the absence of hyperglycemia or glycosuria in a chronic alcoholic patient should prompt the evaluation for alcohol ketoacidosis. Trace serum isopropanol may be worrisome for a toxic ingestion, but this finding in severe ketoacidosis may be explained by the reversible action of the enzyme alcohol dehydrogenase. Markedly increased serum isopropanol with a low serum acetone:isopropanol ratio would be more indicative of a toxic isopropanol ingestion.

Markedly increased serum and urinary fructose concentrations in diabetic patients with ketoacidosis or ketosis.

To investigate fructose concentrations in diabetic patients with ketoacidosis or ketosis, serum fructose concentrations and daily urinary fructose excretion were measured in 23 patients with ketoacidosis (n = 16) and ketosis (n = 7) on the first day of admission. Seventeen patients were diagnosed with type 1, one patient with mitochondrial, and 4 patients with atypical diabetes. In 16 of the 23 patients, serum and urinary fructose could be assessed after starting treatments. Mean serum fructose concentration was 71.6 ± 108.1 µmol/l, and mean daily urinary fructose excretion was 352.1 ± 473.7 µmol/day. Serum fructose levels in patients with atypical diabetes were much higher (205.0 ± 213.3 µmol/l) than those in patients with type 1 diabetes (45.1 ± 44.5 µmol/l), while urinary fructose levels in atypical diabetes (249.7 ± 92.4 µmol/day) tended to be lower than those in type 1 diabetes (382.6 ± 533.2 µmol/day). Serum fructose concentrations decreased significantly (P < 0.05) from 88.1 ± 126.3 to 18.0 ± 11.0 µmol/l, and daily urinary fructose excretion also decreased significantly (P < 0.05) from 459.8 ± 530.9 to 75.1 ± 62.0 µmol/day in accordance with glycemic normalization after treatment. Marked and reversible increases in serum and urinary fructose concentrations were observed in diabetics with ketoacidosis and ketosis.

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.

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 ß-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)].

A modified Atkins diet is promising as a treatment for glucose transporter type 1 deficiency syndrome.

AIM: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a metabolic encephalopathy that can be effectively treated with a ketogenic diet. The aim of this study was to consolidate the effectiveness of the modified Atkins diet (MAD) as an alternative treatment for GLUT1-DS. METHOD: Six Japanese males with GLUT1-DS were selected for treatment with the MAD. Their age at the time the MAD was instituted ranged from 7 to 16 years and the duration of treatment ranged from 1 to 42 months. All participants had early-onset epilepsy. Each participant's neuropsychological activity, seizure frequency, neurological status, and electroencephalographic (EEG) findings were compared before and after the introduction of the MAD. RESULTS: After initiation of the treatment, all individuals showed +2 to +3 urinary ketosis on a ketostick test check. Epileptic seizures and other paroxysmal events decreased markedly in all individuals. Interictal EEG showed improvement in the background activity and disappearance of epileptic discharges. Along with an increased vigilance level, improvement in motivation and cognitive function was also achieved. Non-paroxysmal permanent ataxia, spasticity, dysarthria, and dystonia were moderately improved in four individuals and slightly improved in the remaining two. Preprandial transient aggravation of neurological symptoms completely disappeared in all participants. There were no significant side effects. INTERPRETATION: For the treatment of GLUT1-DS, the MAD is less restrictive, more palatable, and easier to maintain than the conventional ketogenic diet, but its effectiveness was similar. Thus, MAD treatment is promising for individuals with GLUT1-DS and their families.