Younger patients and low c-peptide immunoreactivity index but not nutritional states affect fasting blood ketone levels in Japanese with type 1 diabetes after sodium-glucose cotransporter 2 inhibitor administration.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. MATERIALS AND METHODS: In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. RESULTS: All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (ß = -0.504, p = .003) and a low ratio of basal to bolus insulin (ß = -0.420, p = .005). CONCLUSIONS: When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.

Effects of prepartum stocking density and a blind on physiological biomarkers, health, and hygiene of transition Holstein dairy cows.

Many dairy cows succumb to disease after calving. Disease risk may be affected by the cows' social environment and ability to perform maternal behaviors. In nature, cattle isolate from others and find seclusion to give birth; these behaviors may be limited in indoor group pens and could potentially affect the cows' ability to cope. The aim was to determine whether stocking density and a physical blind in prepartum bedded-pack group pens affected physiological biomarkers, disease risk, and hygiene of peripartum dairy cows. A randomized complete block designed with a 2 × 2 factorial arrangement of treatments was used. Approximately 3 wk before calving, 374 cows (primiparous = 127; multiparous = 247) were assigned randomly to 1 of 4 treatment pens with the following 2 factors: (1) high versus low stocking density (7.7 to 12.9 m2 vs. 15.4 to 25.8 m2 lying space per cow), and (2) presence or absence of a blind. The blind was created using plastic road barriers and plywood, a steel gate, and shade cloth. After calving, cows were moved into a freestall pen and milked 3 times per day. Blood was sampled on the day of enrollment (baseline; -24 d) and approximately -14, -7, 3, 7, 10, and 14 d relative to calving, to measure inflammatory (haptoglobin) and metabolic (nonesterified fatty acids and ß-hydroxybutyrate) biomarkers. ß-Hydroxybutyrate (≥1.2 mmol/L) was used to diagnose subclinical ketosis. Vaginal discharge was scored 3, 7, 10, and 14 d after calving, to diagnose metritis (none, mild, or severe). Hygiene was scored on -24, -14, and -7 d before calving. Before calving, haptoglobin was lower in pens with a blind. After calving, cows in pens with low stocking density before calving tended to be at greater odds of being diagnosed with metritis. Cows were more likely to have poorer hygiene scores in high stocking density pens. No treatment effects were detected for pre- and postpartum nonesterified fatty acids, ß-hydroxybutyrate, postpartum haptoglobin, or subclinical ketosis. Results suggest that the provision of a blind and lower stocking density may be beneficial for reducing inflammation before calving. However, low prepartum stocking density might increase the odds of metritis after calving. Although the reason for this paradox is unclear, the effects of prepartum stocking density may require further exploration.

Comparison between two preventive treatments for hyperketonaemia carried out pre-partum: effects on non-esterified fatty acids, ß-hydroxybutyrate and some biochemical parameters during peripartum and early lactation.

The objective of this study was to compare the effect of two different preventive protocols, on serum ß-hydroxybutyrate (BHB) concentration and liver health indices pre-partum and during early-lactation in high-yielding Holstein dairy cows. One hundred cows were randomly divided into three groups: control group (CTRL, n = 20, without preventive treatment), second group (SUPP, n = 40 animals treated with a compound based on acetyl-methionine, inositol, cyanocobalamin, l-alanine, l-arginine, l-threonine, l-glutamic acid supplementation and α-lipoic acid) and third group (MON, n = 40 animals treated with monensin). Blood samples were collected from all cows at on 3 occasions pre-partum and 3 occasions post-partum. Body condition (BCS) score was evaluated and glucose, non-esterified fatty acids (NEFA), BHB, triglycerides, total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin, total proteins, globulins, albumin and urea concentrations were assessed. Two-way repeated measures analysis of variance was applied. Statistically significant differences among the three experimental groups were found in the values of all studied parameters (P < 0.05). Our results confirm the established beneficial effect of MON treatment in decreasing BHB levels and increasing glucose availability after calving. Serum biochemical analysis revealed the expected post-partum alterations attributable to adaptations that influenced the metabolism and liver function in CTRL, whereas these alterations were reduced or absent in SUPP and MON. Results from the present study suggest that both preventive protocols, but in particular SUPP, could positively affect selected indicators of energy metabolism reducing the risk of hyperketonaemia and increase of liver function in Holstein dairy cows, both pre- and post-partum.

Significant reduction of ketoacidosis at diabetes onset in children and adolescents with type 1 diabetes-The Stuttgart Diabetes Awareness Campaign, Germany.

BACKGROUND: To prevent the potentially life-threatening complication, diabetic ketoacidosis (DKA) at type 1 diabetes onset in children and adolescents, awareness campaigns can lead to a significant reduction of DKA. As in Germany, the incidence of DKA at diabetes onset had remained at a constant rate over the last 15 years and increasing numbers of very young children present with higher risk for DKA we decided to set up the Stuttgart Ketoacidosis Awareness Campaign. METHODS: Over 3 years (2015-2017) the campaign was conducted using information flyers and posters illustrating the typical symptoms of diabetes at school entry health examinations at the Public Health Department, in day-care facilities, in all pediatric practices and by regular public activities. The period between 2011 and 2013 was selected as a reference period. RESULTS: Approximately 17 000 children, median age 4.5 years, and their families were informed about the campaign during the preschool health examination. A total of 118 children and adolescents were treated with newly diagnosed type 1 diabetes compared with 127 during the reference period. During the campaign the incidence of DKA decreased significantly from 28% to 16%. CONCLUSIONS: Awareness campaigns like the Stuttgart Ketoacidosis Awareness Campaign about the typical clinical symptoms of type 1 diabetes can significantly reduce the risk for DKA at diabetes onset. Important factors for the success of our campaign were the close cooperation between the children's hospital and the public health department, the targeted approach of families, teachers, and pediatricians and the duration of the campaign over 3 years.

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

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

Sodium-glucose co-transporter type-2 inhibitors: pharmacology and peri-operative considerations.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an emerging class of oral hypoglycaemic agents with therapeutic benefits beyond better glycaemic control. A major concern of the sodium-glucose co-transporter 2 inhibitors is their propensity to cause euglycaemic ketoacidosis in the peri-operative period and the potential for this critical diagnosis to be delayed or missed entirely. This review attempts to collate the case reports of sodium-glucose co-transporter 2 inhibitor ketoacidosis associated with surgery to highlight and put a perspective on this peri-operative issue. Preventive strategies and the management of the ketoacidosis are discussed.

Candidate gene association analyses for ketosis resistance in Holsteins.

High-yielding dairy cattle are susceptible to ketosis, a metabolic disease that negatively affects the health, fertility, and milk production of the cow. Interest in breeding for more robust dairy cattle with improved resistance to disease is global; however, genetic evaluations for ketosis would benefit from the additional information provided by genetic markers. Candidate genes that are proposed to have a biological role in the pathogenesis of ketosis were investigated in silico and a custom panel of 998 putative single nucleotide polymorphism (SNP) markers was developed. The objective of this study was to test the associations of these new markers with deregressed estimated breeding values (EBV) for ketosis. A sample of 653 Canadian Holstein cows that had been previously genotyped with a medium-density SNP chip were regenotyped with the custom panel. The EBV for ketosis in first and later lactations were obtained for each animal and deregressed for use as pseudo-phenotypes for association analyses. Results of the mixed inheritance model for single SNP association analyses suggested 15 markers in 6 unique candidate genes were associated with the studied trait. Genes encoding proteins involved in metabolic processes, including the synthesis and degradation of fatty acids and ketone bodies, gluconeogenesis, lipid mobilization, and the citric acid cycle, were identified to contain SNP associated with ketosis resistance. This work confirmed the presence of previously described quantitative trait loci for dairy cattle, suggested novel markers for ketosis-resistance, and provided insight into the underlying biology of this disease.

A randomized controlled trial on the effect of incomplete milking during early lactation on ketonemia and body condition loss in Holstein dairy cows.

Limiting milk production for a short period of time in early lactation could be a relevant strategy to prevent hyperketonemia (HYK). From December 2013 to March 2015, 838 multiparous Holstein cows from 13 herds were enrolled in a randomized controlled trial evaluating the effect of incomplete milking in early lactation on ketonemia and its effect on body condition score (BCS) loss. Cows were randomly assigned 4 wk before expected calving date to 1 of 2 treatment groups, (1) a conventional milking protocol (CON) for which cows were completely milked or (2) an incomplete milking protocol (INC) for which a maximum of 10 to 14 kg of milk/d were withdrawn during the first 5 d in milk (DIM). ß-Hydroxybutyrate (BHB) concentrations were measured from blood samples collected on each cow 3 times at weekly intervals. Hyperketonemia was defined as BHB ≥1.4 mmol/L. Body condition score variation in the postcalving period was calculated by subtracting BCS assessed at wk 7 from BCS assessed at first week after calving. Effect of treatment on ketonemia and prevalence of HYK were evaluated for 4 specific time periods: 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM. Effect of treatment on ketonemia was investigated using linear mixed models with natural logarithm of BHB measurements as outcome and treatment groups as fixed effect. Generalized linear mixed models with HYK as outcome, using logit link, and treatment groups as fixed effect were used to investigate effect of treatment on odds of HYK. A logistic regression model with BCS loss (<0.75 or ≥0.75) as outcome and treatment groups and herd as fixed effects was used to study effect of INC on odds of having BCS loss ≥0.75. A total of 813 lactations had complete data and were used for statistical analysis of ketonemia and HYK. A total of 709 lactations had complete data and were used for analysis of BCS loss. Geometric means of blood BHB concentrations during the 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM periods were, respectively, 0.72 (95% confidence interval = 0.66, 0.80), 0.66 (0.60, 0.73), 0.90 (0.80, 1.01), and 0.93 (0.83, 1.05) mmol/L for INC, and 0.65 (0.59, 0.72), 0.79 (0.72, 0.87), 0.94 (0.84, 1.06), and 0.92 (0.82, 1.04) mmol/L for CON. Cows in INC group had lower ketonemia during the 4 to 7 DIM period. Predicted prevalence of HYK during the 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM periods were, respectively, 2.8 (3.2, 15.1), 4.6 (2.0, 10.0), 13.4 (8.4, 20.0), and 23.0% (17.4, 29.7) for INC and 2.6 (2.5, 13.8), 10.7 (5.6, 19.3), 19.4 (13.0, 27.9), and 21.3% (16.0, 27.8) for CON. The INC treatment reduced the prevalence of HYK during the 4 to 7 and 8 to 17 DIM periods. No association was observed between INC and BCS loss in the postcalving period. Overall, the incomplete milking protocol was effective for reducing ketonemia and prevalence of HYK during the early postpartum period.

The effect of different treatments for early-lactation hyperketonemia on liver triglycerides, glycogen, and expression of key metabolic enzymes in dairy cattle.

Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism. Multiparous Holstein cows between 3 and 9 d in milk were screened 3 times per week and enrolled in the study when whole-blood ß-hydroxybutyrate concentrations measured ≥1.2 mmol/L. Cows were randomly allocated to 1 of 4 groups: (1) 500 mL of a 50% d-glucose solution intravenously once a day for 3 d (n = 8), (2) 300 mL of propylene glycol orally once a day for 3 d (n = 8), (3) 500 mL of a 50% d-glucose solution intravenously and 300 mL of propylene glycol orally once a day for 3 d (n = 8), or (4) an untreated control group (n = 8). Liver biopsies were taken on the day of enrollment as well as on the day following completion of treatments. Liver triglyceride and glycogen content were determined by colorimetric and fluorometric methods, respectively. Gene and protein expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase 1, glucose-6-phosphatase, 3-hydroxy-3-methylglutaryl-CoA synthase 2, acetyl-CoA carboxylase, and carnitine palmitoyltransferase 1A were compared between groups and time points using quantitative reverse transcriptase PCR and Western blotting techniques, respectively. In addition, the ratio of light chain 3B II:I was determined by Western blotting. Plasma samples from both time points for each enrolled cow were submitted for chemistry analysis. Data were analyzed using a repeated-measures ANOVA taking into account the paired nature of the data, and differences between all groups and time points were controlled for multiple comparisons using the Tukey procedure. No difference was found in triglyceride or glycogen concentration between treatment groups. The gene expression of pyruvate carboxylase decreased in the group receiving both treatments, whereas protein expression of this enzyme increased in all groups over time. The autophagy marker light chain 3B II:I decreased in the group receiving both glucose and propylene glycol. No other changes in gene or protein expression of key hepatic enzymes were associated with treatments. We conclude that intravenous glucose and oral propylene glycol, commonly used treatments for ketosis in postpartum dairy cows, administered alone or in combination for a duration of 3 d did not have important beneficial or detrimental effects on selected indicators of liver composition and function in cows with hyperketonemia.

Ramadan fasting during pregnancy: Obstetric risk stratification.

Some women may wish to fast during pregnancy or lactation, for religious or spiritual reasons. This may pose a dilemma to the obstetric care provider, who has to balance the need for maternal and foetal wellbeing with the wishes and needs of the mother. This communication describes a pragmatic, shared decision making, based on patient centred approach to this challenging clinical situation. It highlights simple clinical and investigation based clues which allow obstetric risk stratification of women in pregnancy or lactation. This clinical and laboratory based assessment allows appropriate decision making regarding fasting, while keeping foeto-maternal safety paramount.

Effects of direct-fed Bacillus pumilus 8G-134 on feed intake, milk yield, milk composition, feed conversion, and health condition of pre- and postpartum Holstein cows.

The usage of direct-fed microbials (DFM) has become common in the dairy industry, but questions regarding choice of strain, mode of action, and efficacy remain prevalent. The objective of this study was to evaluate the effects of a DFM (Bacillus pumilus 8G-134) on pre- and postpartum performance and incidence of subclinical ketosis in early lactation. Forty-three multiparous Holstein cows were assigned to 2 treatments in a randomized complete block design; cows in the direct-fed microbial treatment (DFMt, n=21) received 5.0×10(9) cfu/cow of B. pumilus in 28 g of a maltodextrin carrier, whereas cows in the control treatment (CON, n=22) received 28 g of maltodextrin carrier alone. Treatments were top-dressed on the total mixed ration daily. Treatments were applied from 21 d before expected calving date to 154 d after calving. Cows on treatment DFMt tended to have lower serum haptoglobin concentration than CON cows on d 14. Cows on treatment DFMt had higher IgA concentrations in milk than CON cows during the first week after calving. Cows fed DFMt had higher yields of milk, fat-corrected milk, energy-corrected milk, milk fat, and milk protein during the second week of lactation than CON; however, we found no differences between treatments on milk yield and milk components overall. Cows on DFMt tended to have higher feed conversion and to have lower prevalence of subclinical ketosis (beta-hydroxybutyrate >1.2 mmol/L) on d 5 than cows fed CON. Dry matter intake, body weight, and body condition score were not affected by DFMt supplementation. Milk production efficiencies (calculated based on fat-corrected milk and energy-corrected milk) were higher by 0.1 kg of milk per kilogram of dry matter intake in cows that received DFMt compared with cows that received CON. In conclusion, cows receiving DFMt tended to have lower incidence of subclinical ketosis than cows receiving CON. Cows fed DFMt tended to have higher feed conversion and evidence for greater immunity than CON. Supplementation with B pumilus 8G-134 may provide benefits for transition cow health and milk production efficiency.

Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds.

This study was undertaken to determine the effect of a combined folic acid and vitamin B12 supplement given in early lactation on culling rate, metabolic disorders and other diseases, and reproduction in commercial dairy herds. A total of 805 cows (271 primiparous and 534 multiparous cows) in 15 commercial dairy herds were involved. Every 2mo from February to December 2010 and within each herd, cows were assigned according to parity, previous 305-d milk production, and calving interval to 5mL of either (1) saline 0.9% NaCl (control group) or (2) 320mg of folic acid + 10mg of vitamin B12 (vitamin group). Treatments were administered weekly by intramuscular injections starting 3wk before the expected calving date until 8wk after parturition. A total of 221 cows were culled before the next dry period. Culling rate was not affected by treatment and was 27.5%; culling rate was greater for multiparous (32.2%) than for primiparous cows (18.8%). Within the first 60d in milk (DIM), 47 cows were culled, representing 21.3% of total culling, and no treatment effect was noted. Ketosis incidence based on a threshold ≥100µmol/L of ß-hydroxybutyrate in milk was 38.3±2.9% for the vitamin group and 41.8±3.0% for the control group and was not affected by treatment. The combined supplement of folic acid and vitamin B12 did not decrease incidence of retained placenta, displaced abomasum, milk fever, metritis, or mastitis. However, the incidence of dystocia decreased by 50% in multiparous cows receiving the vitamin supplement, although no effect was observed in primiparous cows. The first breeding postpartum for multiparous cows occurred 3.8d earlier with the vitamin supplement compared with controls, whereas no treatment effect was seen for primiparous cows. Days open, first- and second-breeding conception rates, number of breedings per conception, and percentage of cows pregnant at 150 DIM were not affected by treatment. The reduced percentage of dystocia combined with the earlier DIM at first breeding for multiparous cows receiving the combined supplementation in folic acid and vitamin B12 indicates that the vitamin supplement had a positive effect in older cows.

[Assessment of the natural history and clinical presentation of acetonemic vomiting]. / Ocena przebiegu i obrazu klinicznego wymiotów acetonemicznych u dzieci.

INTRODUCTION: Ketosis in children may result from physiological adaptation to situations like fasting, fat-rich diet, straining physical activity, as well as from serious endocrine or metabolic disorders. The most frequently diagnosed cause of ketoacidosis are states of acetonemia and acetonuria with vomiting, during airways infections. GOAL: Assessment of the natural history and clinical presentation of acetonemic vomiting in children. PATIENTS AND METHODS: 85 children from 18 months to 12 years of age with acetonemic vomiting were incorporated in this study. Detailed anamnesis, clinical examination, and chosen laboratory parameters were analyzed. RESULTS: In 18% of the children a familial pattern of the disease was observed, 75% of the parents declared that their children had fat-rich meals on a regular basis, in 47% there was a tendency to recurrent respiratory tract. The most frequently observed symptoms were incoercible vomiting with nausea (100%), abdominal pain (87%), headaches (35%) and febrile states (62%). Ketosis triggers were: infections with insufficient fluid and food intake (68%), and child overfeeding with fat-rich products (23%). Observed biochemical disturbances were ketosis (mean J3-hydroxybutyric acid serum concentration--1.03 mmol/l, SD +/- 0.83), acetonuria, hypoglycemia (15%), metabolic acidosis (17%) and dyselectrolytemia (14%). The treatment of the children consisted in intravenous and oral rehydration, managing acid-base and electrolyte disturbances. CONCLUSION: In some children acetonemic vomiting is recurrent, and thus prophylactic management is im- portant in children who are at risk.

Incidence of urinary ketosis and the effect of carbohydrate drink supplementation during fasting for elective caesarean section: Audit.

Elective lower segment caesarean section patients are routinely instructed to fast from food for 6h before surgery, with clear fluids up until 2h before surgery. We conducted an audit examining the true fasting times of mothers undergoing an elective caesarean section and the incidence of urinary ketones before and after introducing a preop carbohydrate drink (Nutricia preOp 400ml) to be administered to all patients at 6am on the day of surgery. We audited 50 patients prior to introducing the preop carbohydrate drink and 54 patients after the introduction of a carbohydrate drink. We found the mean fasting time from last caloric intake was reduced from 13h 35min to 5h 5min after the introduction of a preoperative carbohydrate drink. We found that the incidence of urinary ketones was 40.4% prior to the introduction of a preoperative carbohydrate drink and 38.3% after the introduction of a preop drink (p = 1). If fasting times were limited to under 4h, the incidence of urinary ketones is 10%. Our audit demonstrates that reducing preoperative fasting times is possible and preventing metabolic derangements may be possible, requiring an approach targeted at keeping fasting times to a minimum.

Low-carbohydrate diets: a matter of love or hate.

Low-carbohydrate diets (LChD) have become very popular among the general population. These diets have been used to lose body weight and to ameliorate various abnormalities like diabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, narcolepsy, epilepsy, and others. Reports suggest that body weight reduction and glycemic control could be attained while following LChD. However, these advantages are more notably found in short periods of time consuming an LChD. Indeed, the safety and efficacy of the latter diets in the long term have not been sufficiently explored. In contrast to what has been proposed, other mentioned pathologies are not improved or are even worsened by carbohydrate restriction. Therefore, the aim of this review is to define the concept of LChD and to explain their clinical effects in the short and long term, their influence on metabolism, and the opinion of nutrition or health authorities. Finally, evincing the research gaps of LChD that are here exposed will later allow us to reach a consensus with regard to their utilization.

Measurement of fasting ketonuria and capillary blood glucose after main meals in women with gestational diabetes mellitus: How well is the metabolic picture captured?

AIM: Metabolic monitoring of women with gestational diabetes mellitus (GDM) usually consists of measuring fasting ketonuria and postprandial capillary blood glucose (CBG) after main meals. We aimed to evaluate how this monitoring system captures the metabolic picture as compared to a scheme with a greater number of time points. METHODS: Thirty-five women with GDM were recommended to follow a fractionated diet and trained in CBG and ketonuria monitoring. They were asked to monitor ketonuria before a main meal, and to monitor CBG at fasting and 1 h postprandial after any two of the six daily meals. Participants were requested to monitor different meals each day. The goal for 1 h postprandial CBG was <135 mg/dL (7.5 mmol/L). Ketonuria was defined as significant before a certain meal when ≥30% of measurements at that point were positive. Similarly, postprandial CBG was defined as abnormal after a meal when ≥30% measurements exceeded the goal. RESULTS: Ketonuria was significant in 22.5% of the time points and 41.2% of women had significant ketonuria at one or more time points; 61% of the time points and 35.7% of the women with significant ketonuria would have been undetected with monitoring restricted to breakfast. Postprandial CBG was abnormal in 17.6% of meals and 57% of women had abnormal postprandial CBG at one or more meals; 37.8% of points and 15% of women with abnormal postprandial CBG would have been undetected with monitoring restricted to main meals. CONCLUSION: A substantial proportion of metabolic abnormalities in GDM women are not detected with a monitoring program that measures only fasting ketonuria and postprandial CBG after main meals.

Exogenous Ketosis Impairs 30-min Time-Trial Performance Independent of Bicarbonate Supplementation.

PURPOSE: We recently demonstrated that coingestion of NaHCO3 to counteract ketoacidosis resulting from oral ketone ester (KE) intake improves mean power output during a 15-min time trial (TT) at the end of a 3-h cycling race by ~5%. This ergogenic effect occurred at a time when blood ketone levels were low, as ketosis was only induced during the initial ~2 h of the race. Therefore, in the current study, we investigated whether performance also increases if blood ketone levels are increased in the absence of ketoacidosis during high-intensity exercise. METHODS: In a double-blind crossover design, 14 well-trained male cyclists completed a 30-min TT (TT30') followed by an all-out sprint at 175% of lactate threshold (SPRINT). Subjects were randomized to receive (i) 50 g KE, (ii) 180 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON). RESULTS: KE ingestion increased blood d-ß-hydroxybutyrate to ~3-4 mM during the TT30' and SPRINT (P < 0.001 vs CON). In KE, blood pH and bicarbonate concomitantly dropped, causing 0.05 units lower pH and 2.6 mM lower bicarbonate in KE compared with CON during the TT30' and SPRINT (P < 0.001 vs CON). BIC coingestion resulted in 0.9 mM higher blood d-ß-hydroxybutyrate (P < 0.001 vs KE) and completely counteracted ketoacidosis during exercise (P > 0.05 vs CON). Mean power output during TT30' was similar between CON and BIC at 281 W, but was 1.5% lower in the KE conditions (main effect of KE: P = 0.03). Time to exhaustion in the SPRINT was ~64 s in CON and KE and increased by ~8% in the BIC conditions (main effect of BIC: P < 0.01). DISCUSSION: Neutralization of acid-base disturbance by BIC coingestion is insufficient to counteract the slightly negative effect of KE intake during high-intensity exercise.

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats.

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 N(epsilon)-(carboxyethyl)lysine (CEL) and N(epsilon)-(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.

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

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.

Rehydration: role for early use of intravenous dextrose.

Acute gastroenteritis is a common reason for children to seek health care. Among the potential complications of acute gastroenteritis, the most common is dehydration. For mild to moderate dehydration, treatment options include oral and intravenous rehydration. Outpatient treatment failure for either method, when it occurs, is often due to persistent nausea and vomiting. Some authorities have suggested that the early administration of dextrose to patients receiving intravenous rehydration may help terminate vomiting and result in fewer outpatient treatment failures. The purpose of this report was to review the evidence supporting the effectiveness of early intravenous dextrose administration in the outpatient management of dehydration in children with acute gastroenteritis.