Clinical and imaging characteristics of diabetic hemichorea / 中华神经医学杂志

Objective:To explore the clinical manifestations, imaging characteristics, and prognoses of diabetic hemichorea to improve the correct diagnosis and treatment rates.Methods:The clinical data of 8 patients with confirmed diagnosis of diabetic hemichorea in our hospital from May 2019 to February 2022 were collected; and their clinical symptoms, imaging characteristics, and prognoses at 12 months of follow-up were analyzed retrospectively, and the related literature was consulted too to analyze the pathogenesis of diabetic hemichorea.Results:All 8 patients were female, including 5 with a history of diabetes; 7 patients were with hemichorea associated with non-ketotic hyperglycemia (HC-NH), and 1 patient was with hemichorea associated with ketotic hyperglycemia. Seven patients were with hemichorea symptoms, and 1 patient was with bilateral chorea symptoms; 6 patients were with facial abnormalities such as making eyes, tapir mouth and persistent lingual protrusion. At disease onset, the mean random blood glucose was (22.1±3.17) mmol/L, mean glycosylated hemoglobin was (11.8±1.67)%, and urine glucose was (+)-(++++). Cranial CT was performed in 5 patients, and high density in basal ganglia was found in 1 patient. Head MRI showed high signal intensity in T1 of basal ganglia, with unilateral signal intensity in 6 patients and bilateral signal intensity in 2. After controlling blood glucose and symptoms, the condition of these 8 patients got improvement. Seven patients had no recurrence at 12 months of follow-up; 1 patient relapsed after 2 months of remission and did not relapse after treatment during the 12 months of follow-up.Conclusions:Incidence of diabetic hemichorea is relatively high in elderly female diabetic patients whose blood glucose control is not up to standard. By combining with characteristic imaging changes of basal ganglia and hemichorea symptoms, the diagnosis can be made clearly. On the basis of blood glucose control, the combination of dopamine receptor blocker haloperidol and benzodiazepine sedative clonazepam can effectively improve the prognosis.

Subclinical ketosis risk prediction in dairy cows based on prepartum metabolic indices / [Previsão do risco de cetose subclínica em vacas de leite, baseado nos índices metabólicos pré-parto]

Ketosis can seriously impair cow performance. This study detected changes in prepartum blood metabolic parameters for predicting postpartum ketosis occurrence in dairy cows. Body condition score (BCS) was assessed before and after delivery. Blood samples of 63 cows were collected from 10 days before calving to 10 days after calving to measure metabolic parameters including ß-hydroxybutyric acid (BHBA), non-esterified fatty acid (NEFA), glucose (GLU), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total protein (TP), albumin (ALB), globulin (GLO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). There was a postpartum subclinical ketosis incidence of 42.25%. Compared with prepartum, plasma, levels of BHBA, AST, and NEFA significantly increased postpartum, and prepartum AST (R=0.57) and NEFA (R=0.45) showed a significant positive correlation with ketosis postpartum. Plasma GLU level significantly decreased postpartum and was significantly negatively correlated with ketosis (R=-0.21). Receiver operating characteristic curve analysis revealed prepartum BSC < 2.88, and prepartum plasma AST > 68.0 U/L, GLU < 3.97mmol/L, NEFA > 0.27mmol/L, and BHBA > 0.43mmol/L, indicating a high risk of subclinical ketosis postpartum. These levels can be used as risk indicators to predict the occurrence of subclinical ketosis in postpartum cows.(AU)

A cetose pode trazer sérios prejuízos ao desempenho da vaca. Este estudo detectou alterações nos parâmetros metabólicos do sangue pré-parto para prever a cetose pós-parto que ocorre em vacas leiteiras. O escore de condição corporal (ECC) foi avaliado antes e após o parto. Foram coletadas amostras de sangue de 63 vacas entre 10 dias antes e 10 dias após o parto para medir os parâmetros metabólicos, incluindo ácido ß-hidroxibutírico (BHBA), ácido graxo não esterificado (NEFA), glicose (GLU), bilirrubina total (TBIL), bilirrubina direta (DBIL), bilirrubina indireta (IBIL), proteína total (TP), albumina (ALB), globulina (GLO), alanina aminotransferase (ALT) e aspartato aminotransferase (AST). Houve uma incidência de cetose subclínica pós-parto de 42,25%. Em comparação com o pré-parto, o plasma, os níveis de BHBA, AST e NEFA aumentaram significativamente no pós-parto, e AST no pré-parto (R = 0,57) e NEFA (R = 0,45) mostraram uma correlação significativa positiva com cetose pós-parto. O nível plasmático de GLU diminuiu significativamente no pós-parto e foi negativamente correlacionado com a cetose de forma significativa (R = -0,21). A análise da curva característica de operação do receptor revelou BSC pré-parto <2,88 e AST plasmático pré-parto> 68,0 U / L, GLU <3,97mmol / L, NEFA> 0,27mmol / L e BHBA> 0,43mmol / L, indicando um alto risco de cetose subclínica pós-parto. Esses níveis podem ser usados ​​como indicadores de risco para prever a ocorrência de cetose subclínica em vacas no pós-parto.(AU)

Study on the relationship between onset age and ketosis in newly diagnosed type 2 diabetes patients / 公共卫生与预防医学

Objective To explore the relationship between the age of onset and ketosis in patients with newly diagnosed type 2 diabetes mellitus (T2DM), and to provide reference for clinical early intervention and treatment of ketosis according to the characteristics of age. Methods A single center cross-sectional study was conducted to study newly diagnosed T2DM patients who were hospitalized in the Endocrinology Department of Zhongnan Hospital of Wuhan University from January 2016 to December 2019. According to the age of onset, they were divided into young group, middle-aged group and old group. The general clinical data were analyzed and compared. Spearman correlation analysis and multivariate logistic regression were used to analyze the correlation between age and ketosis. Results The proportion of ketosis, males, overweight/obesity, MS, TyG, BMI, β-HB, and TG levels in the young group were significantly higher than those in the middle-aged and old groups, and HbA1c, HOMA-IR, MBS, and OGTT0h were significantly higher than those in the old group. HDL-C in the young group was significantly lower than that in the middle-aged group and old group, and AUGinsulin and IRT2h were significantly lower than those in the old group (P＜0.05). Spearman correlation analysis showed that age was positively correlated with HDL-C and AUGinsulin, and negatively correlated with BMI, TG, HbA1c, β-HB, HOMA-IR, and TyG (P<0.05). Multivariate logistic regression analysis showed that compared with the old group, the OR values of ketosis in the middle-aged group and the young group were 2.584 and 3.870, respectively (P<0.05). Conclusion Early onset age can increase the risk of ketosis in newly diagnosed T2DM patients, and it is necessary to strengthen early intervention and comprehensive treatment for young patients with disease onset.

Relationship between serum 25-hydroxy vitamin D level and ketosis-prone in newly-diagnosed type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To explore relationship between serum 25-hydroxy vitamin D ( 25OHD ) level and ketosis-prone in patients with newly-diagnosed type 2 diabetes mellitus(T2DM).Methods:One hundred and thirty-four patients with newly diagnosed T2DM (103 males, 31 females) admitted in The Third Affiliated Hospital, Southern Medical University from January 2017 to January 2019 were enrolled into this study, including 36 patients with ketosis-prone (KPDM group) and 98 patients without ketosis(NKPDM group). Clinical characteristics, including height, weight, and history of hypertensive disease were collected. Serum 25OHD levels, lipid profile, islet function and glycosylated hemoglobin (HbA 1C)levels, ICA, IAA, GAD-Ab, etc., were measured. Results:Among the 134 patients, the patients with vitamin D deficiency, insufficiency, and sufficiency were 71 cases(52.99%), 52 cases(38.81%), and 11 cases(8.20%), respectively. KPDM group had significantly lower serum 25OHD level than NKPDM group[(44.12±9.77) nmol/L vs (55.35±15.31) nmol/L, P<0.01]. The rate of vitamin D deficiency was significantly higher in KPDM group compared to that in NKPDM group [(77.78% vs 43.88%), P<0.01]. The prevalence of KPDM varied significantly in different vitamin D status groups( P<0.01). Logistic regression analysis suggested that low serum 25OHD, younger age, high HbA 1C, and triglyceride were risk factors to ketosis-prone in newly diagnosed T2DM( P<0.01). Conclusion:Vitamin D deficiency is a common problem in newly diagnosed T2DM, especially in KPDM. Low serum 25OHD level seems to be an independent risk factor for ketosis-prone in patients with newly diagnosed T2DM.

Concentraciones séricas de Beta-hidroxibutirato y su asociación con enfermedades posparto en bovinos de leche / Serum Beta-hydroxybutyrate concentrations and its association with postpartum diseases in dairy cows

RESUMEN Objetivo. Determinar la prevalencia de cetosis bovina según las concentraciones séricas (mmol/Lt) de beta-hidroxibutirato (βHB) y estimar su asociación con enfermedades del posparto temprano en vacas lecheras. Materiales y métodos. Se llevó a cabo un estudio epidemiológico de corte transversal con información individual de los niveles sanguíneos de βHB y presentación clínica de enfermedades puerperales de n=1149 animales; además se evaluó la eficiencia de la prueba como predictora de enfermedad posparto. Posteriormente, se realizó X 2 y un modelo de regresión logística final para explorar los factores asociados con hipercetonemia. La relación entre βHB sanguíneo, la presentación de cetosis y la ocurrencia de enfermedades puerperales se calculó analizando Característica Operativa del Receptor (Receiver Operating Characteristic -ROC). Resultados. Según los niveles de -3HB, la prevalencia de cetosis fue de 7.9%, cetosis clínica 0.6% y cetosis subclínica 7.3%. La prueba fue predictora de enfermedad puerperal (LR+ del 13.6). La condición corporal ≥3.5, número de partos igual a 2 y ≥3, la presentación de retención de placenta, fiebre de leche y la enfermedad posparto, son factores de riesgo de cetosis. El análisis de la curva ROC mostró que la medición de βHB (≥1.2 mmol/Lt) en sangre sirve para diagnosticar cetosis (p<0.0001). Conclusiones. La medición de niveles sanguíneos de βB permitió determinar que la presentación de cetosis es baja, es una alerta no solamente para esta enfermedad sino para las enfermedades del posparto temprano. Los resultados de este estudio confirman lo reportado en estudios previos sobre los factores de riesgo de cetosis.

ABSTRACT Objective. Determine the prevalence of bovine ketosis based on serum concentrations (mmol/Lt) of beta-hydroxybutyrate (βHB) and estimate its association with early postpartum diseases in dairy cows. Materials and methods. An epidemiological cross-sectional study was carried out with individual information on blood levels of βHB and clinical presentation of puerperal diseases in 1149 animals; In addition, the efficiency of the test was evaluated as a predictor of postpartum disease. Subsequently, univariate analysis and a final logistic regression model were performed to explore the factors associated with hyperketonemia. The association between blood βHB, the presentation of ketosis and the occurrence of puerperal diseases was calculated by analyzing the Receiver Operating Characteristic -ROC. Results. According to βHB levels, the prevalence of ketosis was 7.9%, clinical ketosis 0.6% and subclinical ketosis 7.3%. The test was a predictor of puerperal disease (LR+ of 13.6). Body condition score ≥3.5, number of births 2 and ≥3, presentation of retained fetal membranes, milk fever and postpartum disease, are risk factors for ketosis. The analysis of the ROC curve showed that the measurement of βHB (≥1.2 mmol/Lt) in blood serves to diagnose ketosis (p<0.0001). Conclusions. The measurement of βHB blood levels allowed to determine that ketosis presentation is low, it is an alert not only for this disease but for early postpartum diseases. The results of this study confirm risk factors observed in previous studies.

Hipercetonemia: bioquímica de la producción de ácidos grasos volátiles y su metabolismo hepático / Hyperketonemia: Biochemistry of volatile fatty acid production and its hepatic metabolism

RESUMEN La hipercetonemia o cetosis bovina es un desorden metabólico, que se caracteriza por el incremento patológico de cuerpos cetónicos (beta-hidroxibutirato (βHB), Acetoacetato (AcAc) y acetona) y ocurre en el periparto de vacas de leche. El origen primario de la enfermedad es el balance energético negativo (BEN), que puede ser desencadenado por el incremento excesivo de los requerimientos energéticos o la presentación de enfermedades posparto, resultando en la presentación de signos clínicos o disminución de la producción de leche. El objetivo de esta revisión consiste en describir, mediante un modelo, los procesos bioquímicos del rumen y los mecanismos fisiopatológicos, involucrados con incremento excesivo de los cuerpos cetónicos. En resumen, se realizó un modelo fisiológico uniendo literatura fragmentada, sobre la relación entre la función ruminal, hepática y la inducción de lipolisis e incremento de la actividad de Carnitil-Palmitoil transferasa-1 (CPT-1), cuyo resultado puede ser la producción excesiva de Acetil-CoA que, junto con la falta de propionato y oxalacetato (precursores de gluconeogénesis y ciclo de Krebs), dan lugar a la producción patológica de acetoacetato y beta-hidroxibutirato.

ABSTRACT Bovine hyperketonemia or ketosis is a metabolic disorder characterized by high levels of ketone bodies (beta-hydroxybutyrate (βHB), Acetoacetate (AcAc), and acetone) in periparturient dairy cows. A Negative Energy Balance (NEB) is identified as the primary cause of the disease, which is triggered by the excessive increase of energy requirements or the presence of postpartum diseases, resulting in the appearance of clinical signs or decreased milk production. The purpose of this review is to describe the rumen's biochemical Process and the physiopathological mechanisms involved in the excessive production of ketone bodies. After conducting a literature review, a physiological model was carried out in order to understand the relationship between the rumen and liver functions with lipolysis induction and increased CPT-1 activity. The above may result in the overproduction of Acetyl-CoA, which together, with the lack of propionate and oxaloacetate (gluconeogenesis and Krebs cycle precursors), leads to the pathological production of acetoacetate and beta-hydroxybutyrate.

Cetoacidosis por estrés: caso clínico en paciente con atrofia muscular espinal / Stress induced ketoacidosis in spinal muscular atrophy: report of one case

Spinal muscular atrophy is an uncommon cause of ketoacidosis, where there is a decrease in muscle mass, an abnormal metabolism of glucose and fatty acids, and changes in neuroendocrine function. These conditions favor the accumulation of keto acids and the development of metabolic acidosis. We report a 26-year-old female, with a history of spinal muscular atrophy type III, consulting for abdominal pain and vomiting lasting one week. She was admitted to the emergency service somnolent and poorly perfused. She had a pH of 6.98, HCO3- of 3.8 mmol/L, pCO2 of 16.4 mmHg, BE of -26 mmol/L, delta ratio of 1.05, anion gap of 31 mEq/L, creatinine of 0.37 mg/dL, sodium of 147 mEq/L, potassium of 3.7 mEq/L, chloride of 112 mEq/L, lactate of 1.2 mmol/L, glucose of 108 mg/dL, albumin of 4.2 g/dL, ketonemia +++, ketonuria +, measured plasma osmolality of 322 mOsm/kg, estimated osmolality of 314 mOsm/kg, toxilab negative, salicylate levels < 3 µg/mL, acetaminophen levels < 1.2 µg/mL. Intravenous hydration and bicarbonate were started, without satisfactory response. Interpreting the clinical picture as a ketoacidosis induced by stress in a patient with spinal muscular atrophy, it was handled with glucose, amino acids, vitamins and trace elements, with a favorable response.

Effects of low-carbohydrate diet on body weight and glycolipid metabolism in normal rats and obese rats / 上海交通大学学报（医学版）

Objective:To explore the effects of low-carbohydrate diet (LCD) on body weight and glycolipid metabolism in obese rats and normal weight rats. Methods:Eighty male normal weight Sprague-Dawley rats were divided randomly into three groups, i.e., normal control diet group (CD group, n=10), LCD group (n=10) and traditional high-fat diet group (HFD group, n=60). After eight weeks, 30 obese rats were selected from HFD group. Then the obese rats were divided randomly into three groups. The feed of two groups was changed from HFD to LCD (HFD-LCD group) or CD (HFD-CD group), and the rest group was fed with HFD continuously. The experiment lasted for another eight weeks. The feed of CD group and LCD group remained unchanged. The measurement indicators included body weight, feed intake, visceral fat, and blood biochemical indexes (fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and serum β-hydroxybutyrate concentration). Results:In normal rats, from the 6th week, the body weight of LCD group was significantly lower than that of HFD group (P0.05). But at the end of the 16th week, total cholesterol of LCD group was significantly higher than that of CD group (P=0.001) and high-density lipoprotein cholesterol was lower (P=0.021). In the obese rats, at the end of the 16th week, the body weight of HFD-LCD group was significantly lower than that of HFD group and HFD-CD group (P0.05). In the obese rats, compared with HFD group, the intervention of HFD-LCD (β=-88.56, P=0.000) and HFD-CD (β=-39.08, P=0.007) resulted in the decrease of body weight. β-hydroxybutyrate level was helpful to weight loss in the range of 1-2 times of HFD-CD group (β=-34.92, P=0.006). Conclusion:LCD may have different effects on body weight and lipid metabolism between normal weight rats and obese rats, LCD has no weight loss effect on the normal weight rats, but can increase total cholesterol; however, in obese rats LCD can reduce weight and improve the metabolism of glycolipid.

Comparação de métodos para avaliação de beta-hidroxibutirato em ovelhas / Comparison of methods for evaluation of beta-hydroxybutyrate in ewes

Atualmente o uso de sensores portáteis para mensuração de corpos cetônicos está padronizado e difundido na rotina clínica, contudo estudos em ovinos são escassos. Assim, a presente pesquisa objetivou avaliar a acurácia dos sensores portáteis de uso humano e de uso veterinário para a determinação de beta-hidroxibutirato (BHB) em ovelhas no final da gestação e no pós-parto recente. Foram utilizadas 37 amostras de sangue provenientes de nove ovelhas mestiças Corriedale. A determinação bioquímica de BHB no soro, considerada como o padrão-ouro, foi realizada utilizando-se metodologia enzimática colorimétrica. A média obtida na bioquímica sérica foi de 0,497mmol/L; no sensor de uso humano, a média foi igual a 0,537mmol/L, enquanto no sensor de uso veterinário foi de 0,751mmol/L. Foi verificada alta correlação entre o dosímetro de uso humano e o padrão-ouro (r=0,93, P<0,001). A média do aparelho de uso veterinário diferiu das demais (51%; P<0,05), superestimando os resultados em ovelhas. As medições obtidas no aparelho veterinário também apresentaram menor precisão e veracidade. Concluiu-se que o sensor portátil de uso humano é mais acurado e mais preciso no diagnóstico precoce de toxemia da gestação em ovelhas.

Currently the use of portable sensors for measuring ketone bodies is standardized and diffused in the clinical routine, however, studies in sheep are scarce. Therefore, the present study aimed to evaluate the accuracy of the human portable sensor and the veterinary portable sensor for the determination of beta-hydroxybutyrate (BHB) in sheep at the end of gestation and postpartum. We used 37 samples of blood from nine crossbred Corriedale sheep. Biochemical determination of serum BHB, considered gold standard, was performed using colorimetric enzymatic methodology. The mean serum biochemistry was 0.497mmol/L, in the human sensor the mean was 0.537mmol/L, while in the veterinary sensor it was 0.751mmol/L. A high correlation was verified between the dosimeter for human use and the gold standard (r= 0.93, P< 0.001). The mean of the veterinary apparatus differed from the others, being 51% (P< 0,05), higher than the standard, that is, it was less accurate and had lower veracity, overestimating the results in sheep. It was concluded that the portable sensor for human use is more accurate and accurate in the early diagnosis of toxemia of pregnancy in sheep.

Skin eruption induced by dieting – an underdiagnosed skin disease in Malaysia

@#Prurigo pigmentosa is an inflammatory dermatosis characterized by a pruritic, symmetrically distributed erythematous papular or papulo-vesicular eruption on the trunk arranged in a reticulated pattern that resolves with hyperpigmentation. It is typically non-responsive to topical or systemic steroid therapy. The exact etiology is unknown, but it is more commonly described in the Far East countries. Dietary change is one of the predisposing factors. We report on nine young adult patients with prurigo pigmentosa, among whom five were on ketogenic diets prior to the onset of the eruptions. All cases resolved with oral doxycycline with no recurrence. We hope to improve the awareness of this uncommon skin condition among general practitioners and physicians so that disfiguring hyperpigmentation due to delayed diagnosis and treatment can be avoided.

Two cases of ketosis-prone diabetes mellitus in Korean adolescents

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient's lifestyle to preventing recurrent DKA.

Occurrence of subclinical metabolic disorders in dairy cows from western Santa Catarina state, Brazil / Ocorrência de transtornos metabólicos subclínicos em vacas leiteiras da região Oeste do estado de Santa Catarina

The management of dairy herds during the transition period has been studied in several studies due to the severe adjustments to which cows are submitted in the metabolism of carbohydrates, lipids and minerals at early lactation. This is a period when occurs most of the metabolic disorders in dairy cows, especially in their subclinical form. Hitherto a lack of information exists on the occurrence of subclinical metabolic disorders in Brazil. The aim of this study was to determine the occurrence of subclinical metabolic disorders, including ketosis, liver lipidosis, hypocalcemia, lactacidemia and hypomagnesemia, as well as phosphorous, copper and zinc deficiency in dairy cattle from the western region of Santa Catarina state, southern Brazil, during the first 30 days of lactation. Blood samples from 15 dairy herds managed in intensive production (free-stall) and semi-confined systems were collected. Milk yield, reproduction and health data of the herd were recorded in a questionnaire, based on the records of the farm and on the observations during samples collection. Blood samples were collected for the measurement of beta-hydroxybutyrate (BHB) and lactate using portable monitors at the farm and for obtaining serum to perform the following biochemical determinations: total calcium, phosphorus, magnesium, albumin, aspartate transaminase (AST) and creatine kinase (CK) by UV-visible spectrophotometry, and copper and zinc by atomic absorption spectrophotometry. In this study, the cutoff points considered were as follows: serum BHB concentrations >1.2mmol/L for subclinical ketosis, AST >140U/L and CK <94U/L for subclinical liver lipidosis, serum lactate concentrations >2.2mmol/L for lactacidemia, serum total calcium concentrations <7.5mg/dL for subclinical hypocalcemia, serum magnesium concentration <1.7mg/dL for hypomagnesemia, serum phosphorus concentration <2.5mg/dL for phosphorus deficiency, serum copper concentrations <32.8μg/dL for copper deficiency, and serum zinc concentrations <60μg/dL for zinc deficiency. The results showed an occurrence of 9% for subclinical ketosis, 11% for subclinical liver lipidosis, 44.5% for lactacidemia, 11% for subclinical hypocalcemia, 7.4% for subclinical hypomagnesemia, 10.7% for copper deficiency and 8.7% for zinc deficiency. According to the survey results, the occurrence of subclinical ketosis, lipidosis and hypocalcemia in western Santa Catarina differ from data found in the literature(AU)

O manejo dos rebanhos leiteiros durante o período de transição tem sido objeto de estudo de diversas pesquisas devido às severas adaptações sofridas pelas vacas no metabolismo dos carboidratos, lipídeos e minerais no início da lactação. Trata-se de um período em que ocorre a maioria dos transtornos metabólicos em vacas leiteiras, especialmente na sua forma subclínica. Até hoje existe uma falta de informação sobre a ocorrência de transtornos metabólicos subclínicos no Brasil. O objetivo deste estudo foi determinar a ocorrência de transtornos metabólicos subclínicos, dentre eles cetose, lipidose hepática, lactacidemia, hipocalcemia e hipomagnesemia, bem como deficiências de fósforo, cobre e zinco, em bovinos leiteiros da região Oeste do estado de Santa Catarina, durante os primeiros 30 dias de lactação. Foram avaliadas amostras de 15 rebanhos leiteiros manejados em sistemas de produção intensiva (free-stall) e semi-confinamento. Dados de produção, reprodução e sanidade do rebanho e de cada animal utilizado no estudo foram registrados em um questionário, baseando-se nos registros da fazenda e nas observações durante as coletas. Amostras de sangue total foram coletadas para dosagem de beta-hidroxibutirato (BHB) e lactato através de monitores portáteis ao pé das vacas e para obter amostras de soro usadas nas seguintes determinações bioquímicas: cálcio total, fósforo, magnésio, albumina, AST e CK por espectrofotometria UV-visível, e cobre e zinco por espectrofotometria de absorção atômica. No presente trabalho, foram considerados os seguintes pontos de corte: concentrações séricas de BHB >1,2mmol/L para cetose subclínica, atividade sérica de AST >132U/L e de CK <94U/L para lipidose hepática subclínica, concentrações séricas de lactato >2,2mmol/L para lactacidemia, concentrações séricas de cálcio total <7,5mg/dL para hipocalcemia subclínica, concentração sérica de magnésio <1,7mg/dL para hipomagnesemia subclínica, concentração sérica de fósforo <2,5mg/dL para deficiência de fósforo, concentrações séricas de cobre <32,8μg/dL para deficiência de cobre, e concentrações séricas de zinco <60μg/dL para deficiência de zinco. Foi encontrada ocorrência de 9% para cetose subclínica, 11% para lipidose hepática subclínica, 44,5% para lactacidemia, 11% para hipocalcemia subclínica, 7,4% para hipomagnesemia, 10,7% para deficiência de cobre e 8,7% para deficiência de zinco. De acordo com os resultados da pesquisa, as ocorrências de cetose, lipidose hepática e hipocalcemia subclínicas no Oeste Catarinense foram diferentes das encontradas em outros estudos.(AU)

Epidemiología de la cetosis en bovinos: una revisión / Epidemiology of bovine ketosis: a review / Epidemiologia da cetose em bovinos: uma revisão

Resumen La cetosis es una enfermedad metabólica asociada al balance energético negativo que sufren las vacas dedicadas a la producción láctea al inicio de la lactancia y se caracteriza por un aumento en la concentración de cuerpos cetónicos circulantes. La epidemiologia de la enfermedad ha sido ampliamente descrita en diversos países alrededor del mundo, contando con una variación en la prevalencia entre el 4% hasta el 52% y en la incidencia entre 4,9% hasta 72%, con pico de incidencia a la cuarta semana posparto en Las vacas entre segunda y séptima lactancia. Esta entidad tiene una repercusión importante sobre la rentabilidad de los hatos lecheros, por los costos asociados a enfermedades concomitantes, disminución de La producción Láctea, bajo desempeño reproductivo y descartes tempranos. Para disminuir La incidencia de La enfermedad en Los hatos, es necesario realizar el diagnóstico y el tratamiento oportuno, además de reconocer Los factores de riesgo asociados a La misma, el manejo adecuado de La dieta durante el periodo de transición y el tratamiento de las enfermedades concomitantes, entre otros.

Abstract Ketosis is a metabolic disease that occurs during early-lactation in dairy cattle, it is related to negative energy balance, characterized by increased levels of circulating ketones bodies. The epidemiology of the disease has been widely described in several countries around the world, with a prevalence ranging from 4% to 52% and an incidence between 4.9% and 72%, with a peak incidence during the fourth week postpartum in cows between the second and seventh lactation. This condition has an important impact on dairy farms profitability due to increased risk of concomitant diseases, decreased milk yield, poor reproductive performance and early culling. To reduce the disease incidence, it is necessary to perform an early diagnosis and treatment, in addition to recognizing the associated risk factors, the proper nutritional management during the transition period and treatment of periparturient diseases, among others.

Resumo A cetose é uma doença metabóLica associada ao baLanço energético negativo sofrido por vacas dedicadas à produção de Leite no início da Lactação e é caracterizada por um aumento na concentração de corpos cetônicos circulantes. A epidemiologia da doença tem sido amplamente descrita em vários países do mundo, com variação de prevalência entre 4% a 52% e em incidência entre 4,9% e 72%, com pico de incidência ao quarta semana pós-parto em vacas entre a segunda e a sétima lactação. Esta entidade tem um impacto significativo na rentabilidade dos rebanhos leiteiros, os custos associados a doenças concomitantes, diminuição da produção de leite, baixo desempenho reprodutivo e descartes precoces. Para reduzir a incidência da doença em rebanhos, é necessário para fazer o diagnóstico e tratamento imediato, além de reconhecer os fatores de risco associados, gestão de dieta adequada durante o período de transição e o tratamento de doenças concomitantes, entre outros.

Comparação entre vacas puras Holandês e mestiças Holandês x Jersey quanto à sanidade, imunidade e facilidade de parto / Comparison between Holstein and Holstein × Jersey crossbred cows for health, immunity and easy calving

O cruzamento com a raça Jersey vem sendo utilizado principalmente como alternativa para o aumento da concentração de sólidos do leite em rebanhos puros Holandês, sendo a capacidade de produção desses animais conhecida em diversos estudos. Entretanto, ainda existem limitadas informações sobre diversos fatores relevantes para a tomada de decisão e para o manejo de rebanhos cruzados, tais como resistência a doenças e facilidade de parto, sendo esta a motivação do presente trabalho, o qual objetivou avaliar a sanidade, a imunidade e a facilidade de parto de vacas mestiças Holandês x Jersey em relação a vacas puras Holandês. Foram analisados dados de dificuldade de parto, duração da gestação, retenção de placenta, indicadores sanguíneos para doenças metabólicas pós-parto (cetose e paresia puerperal hipocalcêmica) e de imunidade obtidos em vacas mestiças Holandês x Jersey e puras Holandês durante o período de um ano. O grupamento genético não afetou a facilidade de parto (P=0,4376), a retenção de placenta (P=0,7074) e a duração da gestação (P=0,2812). Vacas mestiças apresentaram maiores concentrações de gamaglobulinas (1,776 contra 1,456g/dL) e de proteína total (7,019 contra 6,525g/dL). Quanto à concentração de ß-hidroxibutirato (BHBA), ocorreu diferença somente no dia do parto, com valores mais altos para as vacas mestiças (0,580 contra 0,427mmol/L). Observou-se diferença entre grupamentos genéticos para concentração de cálcio iônico (P=0,082), com vacas mestiças apresentando concentração mais baixa (3,92 contra 4,3 mg/dL). Conclui-se que vacas mestiças apresentam melhor performance em indicadores de imunidade e pior nos indicadores de cetose e paresia puerperal hipocalcêmica no pós-parto em relação às puras Holandês. O cruzamento não aumenta o risco de distocia em vacas inseminadas com touros Holandês.(AU)

The crossbreed with the Jersey breed has been used mainly as an alternative to increasing the concentration of milk solids in Holstein herds, the production capacity of these animals having become the focus of several studies. However, there is still limited information on many relevant factors for decision-making and management of crossbreed herds, such as disease resistance and ease of calving, and this is the motivation for this work, which aimed to evaluate the health, immunity and calving difficulty in Holstein x Jersey crossbred cows compared to pure Holstein cows. Data from calving difficulty, retained placenta, gestation length, blood indicators for postpartum metabolic diseases (ketosis and hypocalcemic puerperal paresis) and immunity in a herd composed by crossbreeds and Holstein cows during one year was analyzed. The genetic groups did not affect ease of calving (P = 0.4376), retained placenta (P = 0.7074) and gestation length (P=0.2812). Crossbred cows had higher concentrations of gammaglobulins (1.776 versus 1.456g/dL) and total protein (7.019 versus 6.525g/dL). For the concentration of BHBA, differences occurred only at calving, with higher values for crossbred cows (0.580 versus 0.427mmol/L). Difference was observed between genetic groups for concentration of ionized calcium (P = 0.082), with crossbred cows presenting lower concentrations (3.92 versus 4.3mg/dL). In conclusion, crossbred cows have superior performance compared to Holstein cows for immunity indicators and lower for hypocalcemic puerperal paresis and ketosis indicators on the day of calving. Crossbred cows do not have an increased risk of dystocia in relation to pure Holstein cows when mated with Holstein bulls.(AU)

Cetosis normoglicémica en adolescente con diabetes tipo 1 recibiendo insulina y dapaglifozina: Reporte de un caso / Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: Case report

Dapaglifozina, un inhibidor del cotransportador de sodio-glucosa 2 (I-SGLT2) induce glucosuria y reduce la glicemia en adultos con diabetes tipo 2. Objetivo: Presentar una cetosis diabética “normoglicémica” en una adolescente con diabetes tipo 1 (DM1) que recibía dapaglifozina y alertar sobre el riesgo del uso I-SGLT2 que parece promisorio, pero no está aprobado en niños ni en DM1. Caso clínico: Paciente de 17 años sin cetosis durante 9 años con DM1, inició dapaglifozina 10 mg/día para reducir la insulina y el peso. Durante 11 meses de tratamiento tuvo cetonas capilares indetectables, redujo el índice de masa corporal 23,9 a 21,1 kg/m², la insulina basal 40 a 17 U, la hemoglobina glicosilada 8,3 a 7,5%, la glicemia capilar 175 a 161 mg/dl y la variabilidad de la glucosa (desvío estándar 85 a 77). Inesperadamente aparecieron náuseas y vómitos. La paciente portaba bomba de insulina con monitorización continua de glucosa, bien calibrada (glucosas intersticiales concordantes con glicemias), que mostraba glucosa estable bajo 200 mg/dl. Recibió insulina pero los vómitos persistieron; en tres horas, aparecieron deshidratación y desmayos, con cetonas 4,6 nmol/l y glicemia 224 mg/dl. Recibió suero fisiológico, ondansetrón, carbohidratos y varias dosis de insulina con pronta recuperación del estado general e hidratación, sin embargo, la cetosis continuó durante 24 horas. Cabe destacar que la bomba estaba funcionando bien y no se cambió la cánula. Al superar la cetosis, continuó con la misma cánula con buen control metabólico. Conclusión: Es importante sospechar la cetosis diabética normoglicémica por ser de riesgo vital.

Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. Objective: To present an “euglycemic” diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. Case report: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg / day to reduce insulin dose and weight. During 11 months on treatment, capillaries ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. Conclusion: Euglycemic ketosis is a life-threatening condition that must be suspected.

Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment

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

A study on the inducing factors of type 2 diabetic ketosis among type 2 diabetes mellitus patients / 预防医学

Objective To investigate the inducing factors of diabetic ketosis(DK)in type 2 diabetes mellitus( T2DM) patients for more effective prevention. Methods A total of 545 T2DM patients with DK who received treatment in Zhejiang Provincial Diabetes Prevention and Treatment Center from June 2011 to June 2015 were enrolled,which contains 297 newly- diagnosed ketosis - prone diabetic(KPD)patients(KPD group)and 248 T2DM patients with DK(T2DM group),the etiological factors and clinical characteristics were analyzed retrospectively. Results The leading causes of DK were long term nonintervetion(71. 71% )and infection(15. 15% )in KPD group,while unadjusted therapeutic regimen(39. 91% )and break - off(22. 98% )and infection(20. 97% )were the leading cause in T2DM group. Compared with T2DM group, patients in KPD group were younger(P ﹤ 0. 01),and had lower BMI index(P ﹤ 0. 01),higher HbA1c level(P ﹤ 0. 01), more serious ketosis patients(urine ketone≥ ﹢ ﹢ ,P ﹤ 0. 05)and more DKA patients(P ﹤ 0. 05). Conclusion T2DM patients with ketosis could not be ignored,especially the KPD patients. More attention should be paid to diabetes health education,and screening of high - risk group and long term follow - up in patients with T2DM are effective means to reduce the incidence of DK in T2DM.

Correlation between blood biochemical indexes and milk composition in early lactation cows in dairy cow / 中国兽医学报

Biochemical indexes and blood composition in early lactation health,ketosis and hypocalcemia dairy cows were analyzed to make sure the milk composition characteristics with related diseases,the correlation analysis between early lactating dairy milk composition and blood biochemical were also make in order to provide support for the cattle health assessment.According to theblood index,72 Holstein cows 7-21 d postpartum,were divided into group subclinical hypocalcemia,ketosis test group and control group,24 heads each group.The blood and milk of cows were collected and used to analyze the correlation between blood biochemical indexes and milk composition.The results showed that ketosis and hypocalcemia induced the level of milk protein and non fat milk solids decreased,while the content of citric acid in milk increased.The correlation equation between citric acid in milk and serum NEFA,BHBA and GLU was y=3.192x-0.802,(R2 =0.363),y=4.594x-0.793,(R2 =0.320),y=1.228x+0.775,(R2 =0.261),in which x was the content of citric acid in milk.The results showed that the content of citric acid in milk had positively related to blood NEFA,which could be used as an early marker for the diagnosis of negative energy balance.The levels of BUN and ALB in blood can be used to evaluate the levels of milk protein and urea.

Prognostic Factors in Patients Hospitalized with Diabetic Ketoacidosis

BACKGROUND: Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of hyperglycemia, acidosis, and ketonemia. This condition is life-threatening despite improvements in diabetic care. The purpose of this study was to evaluate the clinical and biochemical prognostic markers of DKA. We assessed correlations in prognostic markers with DKA-associated morbidity and mortality. METHODS: Two hundred and seventy patients that were hospitalized with DKA over a period of 2 years were evaluated clinically and by laboratory tests. Serial assays of serum electrolytes, glucose, and blood pH were performed, and clinical outcome was noted as either discharged to home or death. RESULTS: The analysis indicated that significant predictors included sex, history of type 1 diabetes mellitus or type 2 diabetes mellitus, systolic blood pressure, diastolic blood pressure, total leukocyte count, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood urea nitrogen, serum creatinine, serum magnesium, serum phosphate, serum osmolality, serum glutamic oxaloacetic transaminases, serum glutamic pyruvic transaminases, serum albumin, which were further regressed and subjected to multivariate logistic regression (MLR) analysis. The MLR analysis indicated that males were 7.93 times more likely to have favorable outcome compared with female patients (odds ratio, 7.93; 95% confidence interval, 3.99 to 13.51), while decreases in mean APACHE II score (14.83) and serum phosphate (4.38) at presentation may lead to 2.86- and 2.71-fold better outcomes, respectively, compared with higher levels (APACHE II score, 25.00; serum phosphate, 6.04). CONCLUSION: Sex, baseline biochemical parameters such as APACHE II score, and phosphate level were important predictors of the DKA-associated mortality.