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.

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.

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.

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.

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.

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.

[Overview on the relationship between changes in activity and ketosis in dairy cows]. / Übersicht zu Zusammenhängen zwischen Änderungen der Bewegungsintensität und Ketose bei Milchkühen.

With a prevalence of up to 43 % subclinical ketosis is one of the most common diseases in dairy cows in their transition period. In itself, this may cause subsequent diseases such as clinical ketosis or lameness. Therefore, monitoring of animals in this stage is of importance. In addition to the measurement of ß-hydroxybutyrate or acetoacetate in blood, milk, and urine as well as the observation of the animals, computer-assisted systems are suitable means of monitoring. Information such as animal identification and activity data are recorded on a data logger and transmitted to a computer. A change in activity may be an indication of an underlying disease days before the onset of additional clinical signs. In cases of ketosis, a decrease in activity may be observed 5 days before the clinical diagnosis is made. Thus, these data are a valuable contribution in monitoring the cattle herd's health status for both the farmer and the veterinarian. Activity measurement may also be employed for the detection of a beginning lameness. In the presence of lameness, the individual's activity decreases and periods of lying are longer. Activity measurement via transponder as a part of the herd monitoring provides important information on lameness prevalence in the herd. In the presence of a lameness a visual assessment should additionally be made. Lameness scores (Locomotion score, Gait score) have been developed for this purpose and add to determining the lameness status of the herd. This way the animals are divided into different lameness classes. Based on this classification those individuals in need of claw trimming or further treatment may be identified leading to amelioration or prevention of secondary diseases. Due to lameness and subsequent reduction of activity and feed intake, the animals may develop subclinical or clinical ketosis. Therefore, under consideration of both animal welfare and economic factors early disease detection and prophylaxis is desirable and should be a main objective of herd monitoring.

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.

Added dietary cobalt or vitamin B12, or injecting vitamin B12 does not improve performance or indicators of ketosis in pre- and post-partum Holstein-Friesian dairy cows.

Vitamin B12 is synthesised in the rumen from cobalt (Co) and has a major role in metabolism in the peri-paturient period, although few studies have evaluated the effect of the dietary inclusion of Co, vitamin B12 or injecting vitamin B12 on the metabolism, health and performance of high yielding dairy cows. A total of 56 Holstein-Friesian dairy cows received one of four treatments from 8 weeks before calving to 8 weeks post-calving: C, no added Co; DC, additional 0.2 mg Co/kg dry matter (DM); DB, additional 0.68 mg vitamin B12/kg DM; IB, intra-muscular injection of vitamin B12 to supply 0.71 mg/cow per day prepartum and 1.42 mg/cow per day post-partum. The basal and lactation rations both contained 0.21 mg Co/kg DM. Cows were weighed and condition scored at drying off, 4 weeks before calving, within 24 h of calving and at 2, 4 and 8 weeks post-calving, with blood samples collected at drying off, 2 weeks pre-calving, calving and 2, 4 and 8 weeks post-calving. Liver biopsy samples were collected from all animals at drying off and 4 weeks post-calving. Live weight changed with time, but there was no effect of treatment (P>0.05), whereas cows receiving IB had the lowest mean body condition score and DB the highest (P0.05) with mean values of 21.6 kg/day, 39.6 kg/day and 40.4 g/kg, respectively. Cows receiving IB had a higher plasma vitamin B12 concentration than those receiving any of the other treatments (P0.05) of treatment on homocysteine or succinate concentrations, although mean plasma methylmalonic acid concentrations were lower (P=0.019) for cows receiving IB than for Control cows. Plasma ß-hydroxybutyrate concentrations increased sharply at calving followed by a decline, but there was no effect of treatment. Similarly, there was no effect (P>0.05) of treatment on plasma non-esterified fatty acids or glucose. Whole tract digestibility of DM and fibre measured at week 7 of lactation were similar between treatments, and there was little effect of treatment on the milk fatty acid profile except for C15:0, which was lower in cows receiving DC than IB (P<0.05). It is concluded that a basal dietary concentration of 0.21 mg Co/kg DM is sufficient to meet the requirements of high yielding dairy cows during the transition period, and there is little benefit from additional Co or vitamin B12.

The effects of crossbreeding with Norwegian Red dairy cattle on common postpartum diseases, fertility and body condition score.

Norwegian Red bulls, selected in Norway, have been used for crossbreeding with Israeli Holstein on commercial farms. The aim of this project was to investigate Norwegian Red×Israeli Holstein (NRX) performance to see how the daughters perform in a different environment than the one their sires were selected in. This was done by comparing health and fertility of NRX with their Israeli Holstein (HO) counterparts. The data consisted of 71 911 HO records and 10 595 NRX records from 33 855 cows in 23 Israeli dairy herds. Calving events took place between 2006 and 2016. Five postpartum disorders (mean frequency in HO v. NRX, %) recorded by veterinarians were analyzed: anestrus (37.4 v. 41.2), metritis (40.1 v. 28.6), ketosis (11.9 v. 7.1), lameness (7.1 v. 3.1) and retained placenta (6.2 v. 4.0). The incidence of abortions was also analyzed; HO had a mean frequency of 9.9% and NRX 8.2%. These traits were defined as binary traits, with '1' indicating that the disorder was present and a treatment took place at least once, or '0' if the cow did not show signs of that disorder. Days open (i.e. the number of days from calving to conception), body condition score (BCS) recorded on a 1 to 5 scale and changes in BCS from calving to peak lactation were also analyzed. A logistic model was used for the health traits, while days open and BCS were analyzed with linear models. The model included breed group, herd-year of calving, birth year and parity as fixed effects. There was a significantly higher risk (odds ratio for HO v. NRX in parentheses) of ketosis (1.46), metritis (1.78), lameness (2.07), retained placenta (1.41) and abortion (1.13) in HO compared with NRX. Israeli Holstein heifers and cows in parity 3 to 6 had fewer cases of anestrus than NRX but no differences were found between the groups in parities 1 and 2. Body condition score was higher for NRX than HO and there was less change in BCS from calving to peak lactation in NRX compared with HO. Likewise, NRX had fewer days open than HO. Results indicate that crossbreeding can produce cows with better fertility that are less susceptible to postpartum disorders.

Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors.

Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.

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.

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.

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.

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.

Efectividad del sistema MiniMed 640G con SmartGuard(R) para la prevención de hipoglucemia en pacientes pediátricos con diabetes mellitus tipo 1 / Effectiveness of MiniMed 640G with SmartGuard(R) System for prevention of hypoglycemia in pediatric patients with type 1 diabetes mellitus

Introducción/objetivos: El tratamiento con el sistema MiniMed 640G-SmartGuard(R) (640G-SG, infusión subcutánea continua de insulina con sensor de monitorización continua de glucosa intersticial implementado con suspensión automática por predicción de hipoglucemia) ha demostrado en estudios previos, disminución del riesgo de hipoglucemia sin producir alteraciones en el control metabólico en pacientes con DM1. El objetivo del estudio fue evaluar la efectividad del sistema 640G-SG sobre la frecuencia de hipoglucemia y su impacto sobre el control metabólico en una población pediátrica con DM1. Pacientes/métodos: Estudio retrospectivo que incluyó 21 niños tratados con 640G-SG. Se analizaron previo y durante su uso: HbA1c, glucemia media (mg/dl), coeficiente de variación de glucosa, frecuencia de hipoglucemia (<70mg/dl) e hiperglucemia (>180mg/dl), controles de glucemia capilar/día, episodios de cetosis/cetoacidosis e hipoglucemias graves. En el último mes de uso: glucemia en ayunas, frecuencia de uso del sensor y número y duración de eventos de suspensión. Resultados: Los pacientes llevaron el sistema continuamente durante 5,0±2,1 meses con mediana de uso del 92%. Objetivamos disminución significativa de la frecuencia de hipoglucemia (10,4±5,2% a 7,6±3,3%, p=0,044) y del número de controles de glucemia capilar/día (11,3±2,2 a 8,1±2,1, p<0,001), sin aumento de hiperglucemia (p=0,65). Duración media de suspensión de infusión de insulina 3,1±1,2 h/día (37,3% suspensión nocturna). Sin cambios significativos en HbA1c, glucemia media, ni coeficiente de variación. Ningún paciente presentó cetosis/cetoacidosis ni hipoglucemia grave. Conclusiones: La suspensión automática de infusión de insulina por predicción de hipoglucemia implementada en MiniMed 640G-SmartGuard(R) ayuda a evitar el riesgo de hipoglucemia, sin empeorar el control metabólico ni provocar cetosis/cetoacidosis, y reduce la carga de controles adicionales de glucemia en nuestra cohorte pediátrica (AU)

Introduction/aims: Treatment with the MiniMed 640G-SmartGuard(R) 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. Patients/methods: 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. Results: 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. Conclusions: 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 (AU)

Attitude, complications, ability of fasting and glycemic control in fasting Ramadan by children and adolescents with type 1 diabetes mellitus.

OBJECTIVES: Sick individuals and children are exempted from fasting Ramadan. Fasting by type 1 diabetes patients might predispose to acute complications. There are no guidelines on fasting safety or its impact on diabetes control in children and adolescents. We aim to assess patients' attitude towards fasting, frequency of complications and impact on glycemic control in children with type 1 diabetes. RESEARCH DESIGN & METHODS: 65 children with type 1 diabetes were enrolled. The study involved 2 hospital visits. Questionnaires were filled in each visit and HbA1c was recorded. Log books indicating symptomatic hypoglycemia and hyperglycemia leading to breaking fast were obtained. RESULTS: Majority of subjects were willing to fast and 75% were encouraged by parents to do. 57% and 26% fasted more than half and all through the month respectively. 52% had, at least, one episode of hypoglycemia and 29% had hyperglycemia with one episode of ketoacidosis. All patients broke fast in response to symptomatic hypoglycemia/hyperglycemia. There was no significant difference between the frequency of complications in the pump or the Multiple Daily Injection (MDI) groups. Mean HbA1c increased from 70mmol/mol to 73mmol/mol. The difference was not statistically significant. CONCLUSION: Children and adolescents with type 1 diabetes are keen to fast Ramadan and they are able to fast a significant number of days. Hypoglycemia and hyperglycemia are not uncommon with no difference between Pump or in MDI users. Breaking fast on occurrence of complications makes fasting safe. Glycemic control might deteriorate during the month and the following Eid.

Escenarios de simulación clínica creados por alumnos de medicina: descripción de la experiencia de 2 años / Clinical simulation scenarios designed by medical students: The description of a two-year experience

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Calcifilaxis tratada con tiosulfato sódico intralesional / Intralesional Sodium Thiosulfate to Treat Calciphylaxis

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