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1.
J Dairy Sci ; 102(10): 9151-9164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326169

RESUMO

The main objective of this study was to determine the association of dry matter intake as percentage of body weight (DMI%BW) and energy balance (EB) prepartum (-21 d relative to parturition) and postpartum (28 d) with ketosis (n = 189) and clinical mastitis (n = 79). For this, DMI%BW and EB were the independent variables and ketosis and clinical mastitis were the dependent variables. A secondary objective was to evaluate prepartum DMI%BW and EB as predictors of ketosis and clinical mastitis. For this, ketosis and clinical mastitis were the independent variables and DMI%BW and EB were the dependent variables. Data from 476 cows from 9 experiments were compiled. Clinical mastitis was diagnosed if milk from 1 or more quarters was abnormal in color, viscosity, or consistency, with or without accompanying heat, pain, redness, or swelling of the quarter or generalized illness, during the first 28 d postpartum. Ketosis was defined as the presence of acetoacetate in urine that resulted in any color change [5 mg/dL (trace) or higher] in the urine test strip (Ketostix, Bayer, Leverkusen, Germany). Cows that developed ketosis had lesser DMI%BW and lesser EB on d -5, -3, -2, and -1 than cows without ketosis. Each 0.1-percentage point decrease in the average DMI%BW and each 1-Mcal decrease in the average of EB in the last 3 d prepartum increased the odds of having ketosis by 8 and 5%, respectively. Cut-offs for DMI%BW and EB during the last 3 d prepartum to predict ketosis were established and were ≤1.5%/d and ≤1.1 Mcal/d, respectively. Cows that developed ketosis had lesser postpartum DMI%BW and EB and greater energy-corrected milk (ECM) than cows without ketosis. Cows that developed clinical mastitis had lesser DMI%BW but similar prepartum EB compared with cows without clinical mastitis. Each 0.1-percentage point decrease in the average DMI%BW and each 1-Mcal decrease in the average EB in the last 3 d prepartum increased the odds of having clinical mastitis by 10 and 8%, respectively. The average DMI%BW and EB during the last 3 d prepartum produced significant cut-offs to predict clinical mastitis postpartum, which were ≤1.2%/d and ≤1.0 Mcal/d, respectively. Cows that developed clinical mastitis had lesser postpartum DMI%BW from d 3 to 15 and on d 17; greater EB on d 18, from d 21 to 23, and on d 26; and lesser ECM. The main limitation in this study is that the time-order of disease relative to DMI%BW and ECM is inconsistent such that postpartum outcomes were measured before and after disease, which was diagnosed at variable intervals after calving. In summary, measures of prepartum DMI were associated with and were predictors of ketosis and clinical mastitis postpartum, although the effect sizes were small.


Assuntos
Dieta/veterinária , Cetose/veterinária , Mastite Bovina/etiologia , Complicações na Gravidez/veterinária , Animais , Peso Corporal , Bovinos , Metabolismo Energético , Feminino , Alemanha , Cetose/etiologia , Lactação , Leite , Parto , Período Pós-Parto , Gravidez , Complicações na Gravidez/etiologia
2.
Pan Afr Med J ; 33: 7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303952

RESUMO

Sickle cell anaemia (SCA) and type 1 diabetes mellitus (type 1 DM) are chronic medical conditions whose co-existence is uncommon in childhood. Furthermore, complications of SCA such as mesenteric crisis typically present with abdominal pain, which is also common in children with diabetic ketoacidosis (DKA) and this may possess diagnostic challenge. Herewith in, we report a rare case of a nine-year-old child with homozygous sickle cell anaemia, who presented with features of mesenteric crisis and diabetic ketoacidosis. The DKA was diagnosed based on the presence of hyperglycaemia (32.2 mmol/L), ketonaemia (4.6 mmol/L) and acidosis (11.6 mmol/L). The fluids deficit was corrected over 24 hours, with improvement in the vaso-occlusive crises (VOC) without precipitating cerebral oedema.


Assuntos
Anemia Falciforme/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/diagnóstico , Criança , Cetoacidose Diabética/fisiopatologia , Cetoacidose Diabética/terapia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Cetose/diagnóstico , Cetose/etiologia , Masculino
3.
J Pak Med Assoc ; 69(5): 745-746, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31105303

RESUMO

Fasting during Ramadan is obligatory for all able bodiedadult Muslims. Though children are exempt from fasting, many children (and their parents) do observe the Ramadan fast. Responsible diabetes care professionals are expected to offer appropriate and pragmatic advice to children in their care. This communication describes the physiology of fasting in children, and assists physicians in sharing medically accurate information with them. Counselling regarding fasting must be made an integral part of diabetes care in Ramadan-observing families.


Assuntos
Diabetes Mellitus/metabolismo , Jejum/metabolismo , Islamismo , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus/terapia , Jejum/efeitos adversos , Humanos , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Lactente , Recém-Nascido , Cetose/etiologia , Cetose/metabolismo
4.
J Dairy Res ; 86(2): 162-164, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31113526

RESUMO

This research communication describes the possible association between feed sorting and the risk of metabolic disorders in dairy cows. Feed sorting, that is selecting smaller size TMR particles over longer length fibers, can lead to imbalanced energy input. In addition, sorting can lead to lower nutritive value of leftover TMR. To detect a possible relationship between TMR sorting and the occurrence of metabolic disorders in large-scale herds, TMR separation and metabolic profile tests were performed in 22 Hungarian dairies. Feed sorting was defined as >5% alteration in the mass proportion of any of the TMR fractions between the time of feed distribution and 5-6 h later. The prevalence of ketosis and subclinical acidosis differed between feed sorting and non-sorting groups. Inhomogeneous TMR seems to be a predisposing factor for imbalanced energy status. TMR homogeneity measurements should be routinely included in herd health monitoring.


Assuntos
Ração Animal , Doenças dos Bovinos/etiologia , Indústria de Laticínios , Comportamento Alimentar , Cetose/veterinária , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Dieta/veterinária , Ingestão de Energia , Hungria/epidemiologia , Cetose/etiologia
5.
Expert Opin Pharmacother ; 20(7): 781-790, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30835599

RESUMO

INTRODUCTION: Accumulating data from recent studies has altered the gold standard of care for diabetes treatment. In patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or those at high risk for CVD, subsequently to lifestyle changes and metformin therapy, the administration of an SGLT-2 inhibitor with established benefits for cardiovascular outcome (CVOT) should be considered. Areas covered: Tofogliflozin is the most selective SGLT-2 inhibitor and has been approved for the treatment of T2D in Japan. This review summarizes the available data on Tofogliflozin as compared to other SGLT-2 inhibitors, and primarily the three SGLT-2 inhibitors with published CVOT: Empagliflozin, Canagliflozin and Dapagliflozin. Expert opinion: Tofogliflozin's higher selectivity profile increases the positive effects on cardiovascular (CV) outcomes and death and reduces side effects. However, the clinical data on Tofogliflozin from both clinical and real-world studies remain sparse and much less abundant than the other main 3 SGLT-2 inhibitors, thus calling for caution and underscoring the need for further research.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacocinética , Doenças Cardiovasculares/etiologia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/patologia , Glucosídeos/efeitos adversos , Glucosídeos/farmacocinética , Hemoglobina A Glicada/análise , Meia-Vida , Humanos , Hipoglicemia/etiologia , Cetose/etiologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Resultado do Tratamento
6.
Intern Med J ; 49(2): 256-259, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30754085

RESUMO

Ketoacidosis is uncommon in non-diabetic women, but occurs in the postpartum period as a rare complication of continuing to breastfeed during periods of acute illness. We report a case of a lactating woman who presented with severe symptomatic ketoacidosis in the early postpartum period. We also review the pathophysiology and management of lactation ketoacidosis.


Assuntos
Diarreia/fisiopatologia , Cetose/diagnóstico , Cetose/terapia , Lactação , Adulto , Bicarbonatos/administração & dosagem , Feminino , Glucose/administração & dosagem , Humanos , Cetose/etiologia
7.
Yonsei Med J ; 60(3): 308-311, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30799594

RESUMO

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. SCOT deficiency is caused by mutations in the OXCT1 gene, which is mapped to 5p13 and consists of 17 exons. A 12-month-old girl presented with severe ketoacidosis and was treated with continuous renal replacement therapy. She had two previously unrecognized mild-form episodes of ketoacidosis followed by febrile illness. While high levels of ketone bodies were found in her blood and urine, other laboratory investigations, including serum glucose, were unremarkable. We identified novel compound heterozygous mutations in OXCT1:c.1118T>G (p.Ile373Ser) and a large deletion ranging from exon 8 to 16 through targeted exome sequencing and microarray analysis. This is the first Korean case of SCOT deficiency caused by novel mutations in OXCT1, resulting in life-threatening ketoacidosis. In patients with unexplained episodic ketosis, or high anion gap metabolic acidosis in infancy, an inherited disorder in ketone body metabolism should be suspected.


Assuntos
Acidose/genética , Coenzima A-Transferases/deficiência , Cetose/etiologia , Mutação/genética , Sequência de Bases , Coenzima A-Transferases/genética , Éxons/genética , Feminino , Heterozigoto , Humanos , Lactente , Corpos Cetônicos/sangue , Corpos Cetônicos/urina
8.
Trop Anim Health Prod ; 51(6): 1481-1487, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30715655

RESUMO

Ketosis is a metabolic disorder that has an important impact on health and productivity in dairy cattle during early lactation. In Colombia, the incidence and risk factors for ketosis development have not been studied. The objectives of the present study were to determine the incidence of subclinical (SCK) and clinical ketosis (CK) and to determine the risk factors associated with ketosis within the first 6 weeks of lactation in dairy cattle in Colombia. A prospective cohort study was carried out. A convenience sample of 150 lactating dairy cows from ten commercial dairy farms in the Cundi-Boyacencian Andean plateau were tested weekly using a point of care device to measure ß-hydroxybutyrate during the first 6 weeks of lactation. Incidence of SCK and CK was calculated. Risk factors were evaluated using a survey for each animal and for each farm. Potential risk factors were evaluated using a X2 test, Relative Risk was calculated for significant variables by the X2 test (P ≤ 0.05) and these variables were included in the logistic regression model. Cumulative incidence of SCK was 25.33%, 3.33% for CK, and overall incidence of ketosis was 26%. In the logistic regression model, parity 3 or more, herd size > 150 animals, body condition score ≥ 3, retained placenta, and metritis were determined as risk factors for ketosis. The results of this study confirm previous reports in which a high body condition score, increased parity, herd size, retained placenta, and metritis are associated with an increased risk of ketosis in stabled and grazing cattle.


Assuntos
Doenças dos Bovinos/epidemiologia , Cetose/veterinária , Ácido 3-Hidroxibutírico/sangue , Animais , Bovinos , Colômbia/epidemiologia , Feminino , Incidência , Cetose/epidemiologia , Cetose/etiologia , Lactação , Modelos Logísticos , Paridade , Placenta Retida , Gravidez , Estudos Prospectivos , Fatores de Risco
9.
Nat Commun ; 10(1): 548, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710078

RESUMO

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes ketoacidosis in both healthy and type 2 diabetic rats in the setting of insulinopenia through increased plasma catecholamine and corticosterone concentrations secondary to volume depletion. These derangements increase white adipose tissue (WAT) lipolysis and hepatic acetyl-CoA content, rates of hepatic glucose production, and hepatic ketogenesis. Treatment with a loop diuretic, furosemide, under insulinopenic conditions replicates the effect of dapagliflozin and causes ketoacidosis. Furthermore, the effects of SGLT2 inhibition to promote ketoacidosis are independent from hyperglucagonemia. Taken together these data in rats identify the combination of insulinopenia and dehydration as a potential target to prevent euglycemic ketoacidosis associated with SGLT2i.


Assuntos
Desidratação/complicações , Insulina/metabolismo , Cetose/induzido quimicamente , Cetose/etiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Animais , Compostos Benzidrílicos/efeitos adversos , Desidratação/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Glucocorticoides/metabolismo , Glucose/metabolismo , Glucosídeos/efeitos adversos , Humanos , Cetose/patologia , Lipólise/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1/metabolismo
11.
Endocr J ; 66(1): 107-114, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30393272

RESUMO

Soft-drink diabetic ketosis, characterized by acute onset ketosis induced by excessive ingestion of sugar-containing drinks, is often seen in obese, young patients, even with undiagnosed type 2 diabetes. We herein report a 15-year-old obese patient with the apolipoprotein E4/2 phenotype, in whom eruptive xanthomas lead to a diagnosis of soft-drink diabetic ketosis. He developed multiple asymptomatic yellowish papules on the auricles, back, buttocks and the extensor surfaces of the elbows and knees. He initially visited a dermatology clinic and his blood triglyceride and HbA1c levels were found to be 6,490 mg/dL and 16.5%, respectively. He was referred to our hospital for treatment of hyperglycemia and hypertyriglyceridemia. On admission, he had ketonuria and increased blood levels of 3-hydroxybutylate and acetoacetate. He habitually drank 1-3 litters of sweet beverages daily to quench his thirst. Therefore, "soft-drink diabetic ketosis" was diagnosed. Severe hypertriglyceridemia was considered to have been a consequence of impaired insulin action and his apolipoprotein E4/2 phenotype. We treated the diabetic ketosis and hypertriglyceridemia with intensive insulin therapy and a fat-restricted diet. At discharge, he no longer required insulin therapy and his blood glucose levels were controlled with metformin and voglibose. Along with amelioration of the hyperglycemia, triglyceride levels decreased to 247 mg/dL without administration of anti-hyperlipidemia agents. The eruptive xanthoma lesions gradually diminished in size and number and eventually disappeared by 12 months. This case provides an instructive example of eruptive xanthomas serving as a sign of severe dysregulation, not only of lipid, but also glucose, metabolism.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Cetoacidose Diabética/diagnóstico , Hipertrigliceridemia/diagnóstico , Xantomatose/diagnóstico , Ácido 3-Hidroxibutírico/sangue , Acetoacetatos/sangue , Adolescente , Apolipoproteína E2 , Apolipoproteína E4 , Bebidas Gaseificadas/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/metabolismo , Dieta com Restrição de Gorduras , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/dietoterapia , Hipertrigliceridemia/metabolismo , Hipoglicemiantes/uso terapêutico , Inositol/análogos & derivados , Inositol/uso terapêutico , Insulina/uso terapêutico , Cetose/diagnóstico , Cetose/etiologia , Masculino , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/metabolismo , Xantomatose/etiologia , Xantomatose/patologia
12.
Am J Emerg Med ; 37(2): 374.e1, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30414745

RESUMO

We report a case of lactation ketoacidosis in a 22-year-old female who was breastfeeding two infants while dieting. She appeared non-toxic, but had a serum bicarbonate of 7meq/L, a pH of 7.07, and moderate serum ketones. She responded well to simple carbohydrate replenishment and brief cessation of breastfeeding. Emergency Physicians should be aware of this entity so as to avoid unnecessary morbidity and to begin prompt treatment.


Assuntos
Aleitamento Materno , Dieta Redutora/efeitos adversos , Serviço Hospitalar de Emergência , Cetose/diagnóstico , Cetose/etiologia , Carboidratos da Dieta/administração & dosagem , Feminino , Humanos , Cetose/dietoterapia , Adulto Jovem
14.
Rev. esp. anestesiol. reanim ; 65(7): 407-412, ago.-sept. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-177138

RESUMO

Raramente se reporta la acidosis metabólica resistente de riesgo debido a cetoacidosis no diabética por inanición a corto plazo. La cetoacidosis grave debida a inanición es una situación infrecuente y lo es más aún durante el embarazo con situación clínica estresante concomitante. Este informe de un caso presenta a una mujer no diabética ingresada en cuidados intensivos debido a insuficiencia respiratoria tipo 1 durante el tercer trimestre de embarazo, con acidosis metabólica grave resistente a tratamiento médico. Diagnosticamos a la paciente de cetoacidosis por inanición, basándonos en su historia y la ausencia de otras causas de acidosis metabólica con anión gap elevado, tras la realización de un análisis riguroso de su trastorno ácido-base


Threatening refractory metabolic acidosis due to short-term starvation nondiabetic ketoacidosis is rarely reported. Severe ketoacidosis due to starvation itself is a rare occurrence, and more so in pregnancy with a concomitant stressful clinical situation. This case report presents a nondiabetic woman admitted in intensive care for respiratory failure type 1 during the third trimester of pregnancy with a severe metabolic acidosis refractory to medical treatment. We diagnosed the patient with acute starvation ketoacidosis based on her history and the absence of other causes of high anion gap metabolic acidosis after doing a rigorous analysis of her acid-base disorder


Assuntos
Humanos , Feminino , Gravidez , Adulto , Cetose/etiologia , Inanição/complicações , Influenza Humana/complicações , Vírus da Influenza A Subtipo H1N1/patogenicidade , Insuficiência Respiratória/complicações , Complicações na Gravidez , Fatores de Risco
15.
Int J Mol Sci ; 19(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127309

RESUMO

Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.


Assuntos
Antimetabólitos/efeitos adversos , Desoxiglucose/efeitos adversos , Dieta Cetogênica/métodos , Animais , Antimetabólitos/administração & dosagem , Glicemia/metabolismo , Desoxiglucose/administração & dosagem , Feminino , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Corpos Cetônicos/metabolismo , Cetose/etiologia , Cetose/metabolismo , Camundongos Nus , Neoplasias/metabolismo
16.
Neuropediatrics ; 49(6): 369-372, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30045381

RESUMO

Pyruvate carboxylase (PC) is a biotin-containing enzyme that is responsible for the adenosine triphosphate-dependent carboxylation of pyruvate to oxaloacetate, a key intermediate in the tricarboxylic acid cycle. PC deficiency (OMIM 266150) is a rare autosomal recessive metabolic disease, causing elevation of pyruvate, lactate, and alanine. Three types of PC deficiency have been described in the literature; A, B, and C. Type A PC deficiency, also called infantile or North American type, is characterized by infantile onset acidosis, failure to thrive, and developmental delay. The second subtype or type B, the neonatal or French form, presents usually in the neonatal period, mostly in the first 72 hours of life with severe lactic acidosis, truncal hypotonia, and seizures. The third type is called type C, is extremely rare with few cases published in the literature. In this case report, we present an 11-month-old girl who presented with acute flaccid paralysis, lethargy, and constipation with elevated ketones and lactate. She was confirmed genetically and biochemically to have PC deficiency type C. The patient's unusual presentation expands the clinical phenotype of this extremely rare disease.


Assuntos
Acidose Láctica/diagnóstico , Cetose/diagnóstico , Paraplegia/diagnóstico , Doença da Deficiência de Piruvato Carboxilase/diagnóstico , Acidose Láctica/etiologia , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Feminino , Humanos , Lactente , Cetose/etiologia , Letargia/diagnóstico , Letargia/etiologia , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/etiologia , Paraplegia/etiologia , Fenótipo , Doença da Deficiência de Piruvato Carboxilase/complicações
17.
CEN Case Rep ; 7(2): 292-295, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29978296

RESUMO

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease characterized by progressive muscle weakness and atrophy. We report a case of a 36-year-old man with SMA type 3 who presented to our emergency department with epigastric pain and vomiting. He was found to have severe ketoacidosis on laboratory evaluation. The patient's symptoms and ketoacidosis resolved after dextrose infusion and a relatively small amount of sodium bicarbonate infusion. Given the severity of the ketosis that seemed inconsistent with moderate starvation alone, we postulate that there must have been other contributing factors besides moderate starvation that might explain the severity of acidosis in this particular patient. These factors include low muscle mass, disturbed fatty acid metabolism, hormonal imbalances and defective glucose metabolism. Ketoacidosis is an under-recognized entity in patients with neuromuscular diseases and requires a high index of suspicion for prompt diagnosis and management.


Assuntos
Cetose/diagnóstico , Cetose/etiologia , Atrofia Muscular Espinal/complicações , Adulto , Diagnóstico Diferencial , Glucose/administração & dosagem , Glucose/uso terapêutico , Humanos , Infusões Intravenosas , Cetose/sangue , Cetose/terapia , Masculino , Atrofia Muscular Espinal/classificação , Atrofia Muscular Espinal/patologia , Índice de Gravidade de Doença , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/uso terapêutico , Edulcorantes/administração & dosagem , Edulcorantes/uso terapêutico , Resultado do Tratamento
18.
Diabetes ; 67(8): 1471-1480, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29937434

RESUMO

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.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Antígeno B7-H1/antagonistas & inibidores , Diabetes Mellitus Tipo 1/etiologia , Modelos Imunológicos , Pancreatite/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antineoplásicos Imunológicos/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/fisiopatologia , Antígeno B7-H1/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Genótipo , Antígeno HLA-DR4/sangue , Antígeno HLA-DR4/genética , Antígeno HLA-DR4/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Insulina/uso terapêutico , Secreção de Insulina , Isoanticorpos/análise , Cetose/etiologia , Cetose/prevenção & controle , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/metabolismo , Pancreatite/imunologia , Pancreatite/metabolismo , Pancreatite/fisiopatologia , Receptor de Morte Celular Programada 1/metabolismo
19.
BMJ Case Rep ; 20182018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29848523

RESUMO

A 35-year-old woman presented to the emergency department with a 2 days history of malaise and headache. She was breastfeeding her 5-month old infant and had recently started an altered diet based on reducing carbohydrate amount. Moreover, she had also started exercising 2 weeks prior to her illness. Initial blood tests revealed high anion gap metabolic acidosis and hypoglycaemia (pH 7.13 (normal 7.30-7.40), bicarbonate 9.4 mmol/L (normal 21.0-28.0), anion gap 22.6 mmol/L (normal 8-12), glucose 2.9 mmol/L (normal fasting 3.9-5.8) and ketones 6.4 mmol/L (normal <0.6)). The patient was treated with intravenous dextrose and showed complete resolution of ketoacidosis and hypoglycaemia within 48 hours. She was discharged home and remained well with a balanced diet. After excluding all other the causes of hypoglycaemia and ketoacidosis, the diagnosis of lactation ketoacidosis was made and it was considered triggered by altered diet, exercise and skipping meals. All 11 cases of lactation ketoacidosis which has previously been published are reviewed as well.


Assuntos
Aleitamento Materno/efeitos adversos , Dieta com Restrição de Carboidratos/efeitos adversos , Exercício/fisiologia , Hipoglicemia/etiologia , Cetose/etiologia , Lactação/fisiologia , Adulto , Feminino , Humanos
20.
Expert Opin Pharmacother ; 19(8): 895-908, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29799286

RESUMO

INTRODUCTION: Canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, improves various cardiometabolic parameters. Although canagliflozin was originally discovered in Japan, no comprehensive summary of its effects in Japanese patients has been reported. As differences exist in the pathologic features of diabetes between Japanese and non-Japanese populations, it is important to consolidate Japanese data for canagliflozin. Areas covered: The authors summarize Japanese clinical trial and post-marketing surveillance data for canagliflozin, and make comparisons with non-Japanese data. They also consider the therapeutic potential of canagliflozin in Japanese patients by presenting results from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Expert opinion: In Japanese patients, canagliflozin 100 mg, administered as monotherapy or combination therapy, improved blood glucose, body weight, and blood pressure, and was well tolerated; the efficacy and safety profiles were comparable to previous clinical studies in other countries. In the CANVAS Program, canagliflozin reduced major cardiovascular events, and although Japan was not included in this program, canagliflozin may have cardiovascular benefits in Japanese patients, in whom control of multiple risk factors is important for preventing diabetic complications. Patients with high cardiovascular risk often have multiple comorbidities, so it is important to consider the risk-benefit balance of using SGLT2 inhibitors in individual patients.


Assuntos
Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Pressão Sanguínea , Peso Corporal , Canagliflozina/efeitos adversos , Canagliflozina/farmacocinética , Hemoglobina A Glicada/análise , Meia-Vida , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Japão , Cetose/etiologia , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose , Resultado do Tratamento
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