Hyperglycaemic crises in adults with diabetes: a consensus report.

The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE) and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycaemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment and prevention of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes healthcare professionals and individuals with diabetes.

The oral phenotype and dental management in patients with maple syrup urine disease; case report and scoping review.

BACKGROUND AND OBJECTIVES: The literature about oral manifestations and dental management in maple syrup urine disease (MSUD) is sparse. The aim of this report is to present a new case of MSUD with special emphasis on oral findings and to review the relevant literature. METHOD: A case report of a 4-year-old boy with MSUD was described according to the CARE guidelines for describing case reports. Scoping review of relevant literature was performed, according to the PRISMA-ScR guidelines, by searching PubMed, Medline, Embase, and the grey literature for articles describing dental management and/or oral manifestations in MSUD. RESULTS: The initial search identified 219 articles, but only 4 met the inclusion criteria. Rampant caries and plaque induced gingivitis were the main oro-dental findings in MSUD. Other oral findings included enamel hypoplasia, skeletal abnormalities, and abnormal oral behaviors. Disease-related factors appeared to play a major role in the development of the observed oral phenotype. CONCLUSION: Oral health in MSUD seems to be influenced by the reliance on semi-synthetic diet and associated neurocognitive complications. Tailored oral health promotional interventions should be included in the multidisciplinary management of patients with MSUD.

Idiopathic ketotic hypoglycemia in children: an update.

Idiopathic ketotic hypoglycemia (IKH) is defined as bouts of hypoglycemia with increased blood or urine ketones in certain children after prolonged fasting or during illness. IKH is divided into physiological IKH, which is most frequently observed in normal children with intercurrent acute illness, and pathological IKH, which occurs in children who lack counter-regulatory hormones, have a metabolic disease, or have Silver-Russell syndrome. The typical patient is a young child between the ages of 10 months and 6 years. Episodes nearly always occur in the morning after overnight fasting. Symptoms include those of neuroglycopenia, ketosis, or both. IKH may be diagnosed after ruling out various metabolic and hormonal conditions associated with ketotic hypoglycemia. Sufficient amounts of carbohydrates and protein, avoidance of prolonged fasting, and increased frequency of food ingestion are the main modes of treating IKH. It is crucial to understand the pathogenesis of IKH and to distinguish physiological IKH from pathological IKH. In this mini-review, we present a brief summary of IKH in terms of its definition, types, clinical presentation, diagnosis, and therapeutic approach in children.

A case series of severe symptomatic peripartum hyponatraemia.

This single centre case series describes the presentation and management of six cases of peripartum hyponatraemia in women who were otherwise deemed low-risk at delivery. It highlights presenting symptoms such as fatigue, confusion and seizures as well as the effects on the neonate. It also focuses on areas of interest such as fluid intake, hormonal effects of ADH and oxytocin and the association with birthing pools for future research.

Urinalysis: Interpretation and Clinical Correlations.

Urinalysis is a widely used diagnostic tool to assist clinicians in determining the etiology of various acute or chronic pathologies. Primary care, general internal medicine, and family medicine clinicians should be adept at identifying indications for urinalyses, in addition to appropriately interpreting their results. In this article, we provide an overview of urinalysis for non-nephrologists.

The role of systemic immune-inflammation index in the severity of hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum(HEG) is one of the severe health problems in early pregnancy. Obstetricians should be aware of systemic inflammation in HEG patients to provide better preventive strategies. AIM: Hyperemesis gravidarum(HEG) is one of the most common causes of hospitalization in early pregnancy. Complete blood count parameters can be used as inflammatory markers in patients with HEG. We aimed to investigate the Systemic Immune-Inflammation Index (SII)in predicting the severity of HEG. METHODS: This cross-sectional study was performed with 469 pregnant women diagnosed and hospitalized with HEG. The study parameters were calculated from complete blood count tests and urine analysis. Demographic characteristics, the Pregnancy Unique Quantification of Emesis (PUQE) scale values, and ketonuria levels at hospital admission were recorded. The neutrophil­to­lymphocyte ratio (NLR), platelet­to­lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and SII, calculated by the formula (neutrophil × platelet/lymphocyte), were evaluated for predicting the severity of HEG. RESULTS: There was a positive correlation between the increased degree of ketonuria and SII. The cut-off value of SII for predicting the severity of HEG was 1071.8 (AUC 0.637, 95% CI (0.582-0.693), p<0.001), and sensitivity and specificity were 59% and 59%, respectively. The cut-off value of SII to predict the length of hospitalization was 1073.6(AUC: 0.565, 95% CI: (0.501-0.628), p = 0.039); sensitivity and specificity were 56.3% and 55.5%, respectively. CONCLUSIONS: The clinical utility of SII in predicting HEG severity is limited due to relatively low sensitivity and specificity. Further research is needed to determine the importance of inflammatory indices in HEG patients.

Hematological Parameters to Predict the Severity of Hyperemesis Gravidarum and Ketonuria / Parâmetros hematológicos para prever a gravidade da hiperêmese gravídica e da cetonúria

Abstract Objective Hyperemesis gravidarum (HG) is a pregnancy complication that can progress with persistent nausea and vomiting. The aim of the present study is to evaluate the relationship between hematological parameters and HG. Method A total of 532 pregnant women with HG who were admitted to the Department of Obstetrics and Gynecology between March 2019 and February 2021, and 534 healthy pregnant women with characteristics similar to those of the case group were included in the study. The hematological parameters of both groups were compared. In addition, the hematological parametersof patients with HG according to the severity of ketonuria were compared. Results Themean age of the HG group (n=532) was 26.3 ± 4.1 years, and that of the control group (n=534) was 25.9 ± 4.8 years. Among patients with HG, 46% (n=249) had ketone(+), 33% (n=174), ketone(++), and 21% (n=109), ketone(+++). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were higher in the HG group than in the control group: 3.8 (2.8-5.8)/3.2 (2.6-4.0); p<0.001; and 135.2 ± 30.4/108.9 ± 62.2; p<0.001 respectively. The neutrophil count, NLR, and PLR were higher in the group with ketone(+++) than in the groups with ketone(+) or ketone(++): 7.6 ± 1.9/5.5 ± 2.4; p<0.001; 3.8(2.8-4.6)/2.9(2.3- 3.6); p<0.001; and 149.9 ± 48.0/135.9 ± 65.7; p<0.001 respectively. The mean corpuscular hemoglobin (MCH) level, the NLR, and the PLR were identified as independent predictors of the presence of HG and the level of ketone positivity in HG patients. Conclusion The NLR and PLR were high in patients with HG, suggesting the its inflammatory activity. They may be important markers associated with the presence and severity of HG.

Resumo Objetivo A hiperêmese gravídica (HG) é uma complicação da gravidez que pode evoluir com náuseas e vômitos persistentes. O objetivo deste estudo é avaliar a relação entre os parâmetros hematológicos e a HG. Método Foram incluídas neste estudo 532 gestantes com HG internadas no Departamento de Obstetrícia e Ginecologia entre março de 2019 e fevereiro de 2021, e 534 gestantes saudáveis com características semelhantes às do grupo de caso. Os parâmetros hematológicos foram comparados entre gestantes com e sem HG. Além disso, os parâmetros hematológicos foram comparados entre as pacientes com HG de acordo com a gravidade da cetonúria. Resultados A média de idade do grupo GH (n=532) foi de 26,3 ± 4,1 anos, e a do grupo de controle (n=534) foi de 25,9 ± 4,8 anos. Entre as pacientes com HG, 46% (n=249) tinham cetona(+), 33% (n=174), cetona(++), e 21% (n=109), cetona (+++). A razão de neutrófilos para linfócitos (RNL) e a razão de plaquetas para linfócitos (RPL) forammaiores no grupo HG do que no grupo de controle: 3,8 (2,8-5,8)/3,2 (2,6-4,0); p<0,001; e 135,2 ± 30,4/108,9 ± 62,2; p<0,001, respectivamente). A contagem de neutrófilos, a RNL e a RPL foram maiores no grupo com cetona(+++) do que nos grupos comcetona(+) e cetona(++): 7,6 ± 1,9/5,5 ± 2,4; p<0,001; 3,8 (2,8- 4,6)/2,9 (2,3-3,6); p<0,001; e 149,9 ± 48,0/135,9 ± 65,7; p<0,001, respectivamente. O nível médio de hemoglobina corpuscular (MHC), a RNL e a RPL foram identificados como preditores independentes da presença de HG e do nível de positividade de cetona em pacientes com HG. Conclusão A RNL e RPL estavam elevadas em pacientes com HG, o que sugere a sua atividade inflamatória. Elas podem ser marcadores importantes associados à presença e à gravidade da HG.

Clinical algorithms for the management of intrapartum maternal urine abnormalities.

AIM: To develop evidence-based clinical algorithms for management of common intrapartum urinary abnormalities. POPULATION: Women with singleton, term pregnancies in active labour and immediate postnatal period, at low risk of complications. SETTING: Healthcare facilities in low- and middle-income countries. SEARCH STRATEGY: A systematic search and review were conducted on the current guidelines from WHO, NICE, ACOG and RCOG. Additional search was done on PubMed and The Cochrane Database of Systematic Reviews up to May 2020. CASE SCENARIOS: Four common intrapartum urinary abnormalities were selected: proteinuria, ketonuria, glycosuria and oliguria. Using reagent strip testing, glycosuria was defined as ≥2+ on one occasion or of ≥1+ on two or more occasions. Proteinuria was defined as ≥2+ and presence of ketone indicated ketonuria. Oliguria was defined as hourly urine output ≤30 ml. Thorough initial assessment using history, physical examination and basic investigations helped differentiate most of the underlying causes, which include diabetes mellitus, dehydration, sepsis, pre-eclampsia, shock, anaemia, obstructed labour, underlying cardiac or renal problems. A clinical algorithm was developed for each urinary abnormality to facilitate intrapartum management and referral of complicated cases for specialised care. CONCLUSIONS: Four simple, user-friendly and evidence-based clinical algorithms were developed to enhance intrapartum care of commonly encountered maternal urine abnormalities. These algorithms may be used to support healthcare professionals in clinical decision-making when handling normal and potentially complicated labour, especially in low resource countries. TWEETABLE ABSTRACT: Evidence-based clinical algorithms developed to guide intrapartum management of commonly encountered urinary abnormalities.

The relationship between inflammation markers and ketonuria in hyperemesis gravidarum.

OBJECTIVE: Hyperemesis gravidarum is an illness that starts in early pregnancy and manifests itself with oral intake problems, electrolyte imbalance, ketonuria, and weight loss. Inflammation is closely associated with the hyperemesis gravidarum, and inflammatory indicators have been studied to understand its pathophysiology. This study investigates the relationship of ketonuria levels with inflammatory markers platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) for hyperemesis gravidarum patients. MATERIAL AND METHODS: This retrospective case control study was conducted at Kütahya Medical Sciences University Tertiary Research and Training Hospital between December 2019 and December 2020. A total of 173 pregnancies, 82 of them with hyperemesis gravidarum and 91 of them low-risk pregnancies were included in the study. The patients' demographic profiles and laboratory parameters were recorded. The patients were divided into hyperemesis gravidarum and control groups and the groups were compared for the levels of inflammation markers. For the hyperemesis gravidarum group, the relationship between ketonuria levels and the inflammation severity was investigated. RESULTS: MLR, NLR, PLR levels were higher in the hyperemesis gravidarum group than the control group in a statistically significant way (p < 0.001 for all of the comparisons). The hyperemesis gravidarum group was subdivided into four groups based on their ketonuria levels, and their MLR, NLR, PLR levels were compared. The differences between the groups were statistically significant (p < 0.001) and the indicators increased with the ketonuria levels. Finally, ketonuria levels had a positive and significant correlation with MLR (rho =0.67, p < 0.001), PLR (rho =0.67, p < 0.001), and NLR (rho =0.8, p < 0.001). CONCLUSION: Hyperemesis gravidarum patients have higher levels of hematologic inflammation indicators than healthy pregnant patients. For these patients, the levels of the indicators increase with ketonuria levels.

Two cases of carbonic anhydrase VA deficiency-An ultrarare metabolic decompensation syndrome presenting with hyperammonemia, lactic acidosis, ketonuria, and good clinical outcome.

The combination of neonatal hyperammonemia, lactic acidosis, ketonuria, and hypoglycemia is pathognomonic for carbonic anhydrase VA (CA-VA) deficiency. We present two cases of this rare inborn error of metabolism. Both newborns with South Asian ancestry presented with a metabolic decompensation characterized by hyperammonemia, lactic acidosis and ketonuria; one also had hypoglycemia. Standard metabolic investigations (plasma amino acids, acylcarnitine profile, and urine organic acids) were not indicative of a specific organic aciduria or fatty acid oxidation defect but had some overlapping features with a urea cycle disorder (elevated glutamine, orotic acid, and low arginine). Hyperammonemia was treated initially with nitrogen scavenger therapy and carglumic acid. One patient required hemodialysis. Both have had a favorable long-term prognosis after their initial metabolic decompensation. Genetic testing confirmed the diagnosis of carbonic anhydrase VA (CA-VA) deficiency due to biallelic pathogenic variants in CA5A. These cases are in line with 15 cases previously described in the literature, making the phenotypic presentation pathognomonic for this ultrarare (potentially underdiagnosed) inborn error of metabolism with a good prognosis.

Ketonuria is not associated with hyperemesis gravidarum disease severity.

OBJECTIVE: To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity. STUDY DESIGN: We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point RESULTS: 215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48). CONCLUSIONS: There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG.

The Presence of Urinary Ketones according to Metabolic Status and Obesity.

BACKGROUND: Recently, new concepts about obesity and normal weight subtypes with metabolic conditions are rising and ketone bodies are emerging as a significant indicator of metabolic health. This study aimed to find a relationship between ketonuria and those subtypes. METHODS: The data of 19,036 subjects were analyzed in this cross-sectional study (2013-2017 Korea National Health and Nutrition Examination Survey, KNHANES). Based on body mass index and adult treatment panel III with modification of waist circumference, individuals were categorized into 4 groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). Individuals were divided into 2 groups, positive and negative ketonuria groups, and the metabolic parameters were compared. RESULTS: The metabolic indicators of the positive ketonuria group showed better results than those of the negative ketonuria group and the MHNW group showed the highest proportion of positive ketonuria. The MHNW group showed higher urinary ketones than the MUO group (odds ratio [OR], 0.391; 95% confidence interval [CI], 0.254-0.601) in men. In women, OR of having ketonuria was 0.698 (95% CI, 0.486-1.002) in the MHO group and 0.467 (95% CI, 0.226-0.966) in the MUNW group compared to the MHNW group, respectively. CONCLUSION: Compared to the MHNW group, the MUO group showed lower presence of ketonuria in men, and tendency to have less ketonuria in women.

Alterações urinárias em cães com diabetes mellitus / Urinary alterations in dogs with diabetes mellitus / Alteraciones urinarias en perros con diabetes mellitus

A diabetes mellitus (DM) é uma doença comum na rotina veterinária, de caráter multifatorial, gerando graves consequências na saúde dos pacientes acometidos. O diagnóstico é possível por meio de manifestações clínicas apresentadas e da realização de exames laboratoriais complementares. Entre esses exames, estão a dosagem da glicose sérica e a urinálise, as quais trazem ao clínico diversas informações, que podem ser correlacionadas aos demais achados, tornando possível o diagnóstico conclusivo de DM. Dessa forma, o presente trabalho teve como objetivo avaliar as alterações urinárias e de glicemia em cães com DM. Para isto, foram analisados laudos de amostras urinárias e de glicose sérica de 15 animais, onde o diagnóstico foi conclusivo para DM. Verificou-se presença de glicosúria em 100% dos casos, sendo observado em 66,67% das amostras glicosúria maior que 1000 mg/dL e, em 33,33% amostras, de 500 mg/dL; a cetonúria esteve presente em 66,67 %; proteinúria em 66,67% e bacteriúria presente em 73,33 dos dados analisados. Já a hiperglicemia foi constatada em 13 pacientes (86,67%). Assim, conclui-se que a urinálise é um exame de suma importância para o estabelecimento do diagnóstico, da melhor terapêutica para cada caso e do prognóstico dos pacientes.(AU)

Diabetes mellitus (DM) is a common disease on the veterinary routine. It has a multifactorial character generating severe consequences on the health of the patient. It can be diagnosed by clinical manifestations and by making additional laboratory tests. These tests include the measurement of serum glucose and urinalysis, which provides the physician with additional information to be correlated with other findings, in order to reach a conclusive diagnosis of DM. Therefore, this study aimed at evaluating urinary and glycemic alterations in dogs with DM. It analyzed reports of urine and serum glucose samples from 15 animals with a conclusive diagnosis for DM. Glycosuria was present in 100% of the cases. In addition, it was also observed that in 66.67% of the samples, glycosuria was higher than 1000 mg/dL, and in 33.33%, it was 500 mg/dL. Ketonuria was present in 66.67% of the samples, while proteinuria was observed in 66.67%. Bacteriuria was present in 73.33% of the samples on the analyzed data. Hyperglycemia was observed in 13 of these patients (86.67%), and thus, it can be concluded that urinalysis is an extremely important test for diagnosis, to choose the best therapy for each case and prognosis of the patients.(AU)

Diabetes mellitus (DM) es una enfermedad común en la rutina veterinaria, con un carácter multifactorial, que genera graves consecuencias en la salud de los pacientes afectados. El diagnóstico es posible a través de las manifestaciones clínicas presentadas y mediante realización de pruebas de laboratorio complementarias. Entre esas pruebas, están la medición de la glucosa en suero y el análisis de orina, que brindan al médico informaciones diversas que pueden ser correlacionadas a otros hallazgos, lo que permite hacer un diagnóstico concluyente de DM. Por lo tanto, el presente estudio tuvo como objetivo evaluar las alteraciones urinarias y glucémicas en perros con DM. Para esto, se analizaron informes de muestras de glucosa en suero y orina de 15 animales, donde el diagnóstico fue concluyente para DM. La glucosuria estuvo presente en el 100% de los casos, observándose en el 66,67% de las muestras glucosuria mayor de 1000 mg / dL y, en el 33,33% de las muestras, de 500 mg / dL; la cetonuria estuvo presente en 66.67%; proteinuria en 66.67% y bacteriuria presente en 73.33 de los datos analizados. Se observó hiperglucemia en 13 de esos pacientes (86,67%). Por lo tanto, se concluye que el análisis de orina es una prueba extremadamente importante para establecer el diagnóstico, el mejor tratamiento para cada caso y el pronóstico de los pacientes.(AU)

Type B insulin resistance syndrome in a patient with type 1 diabetes.

SUMMARY: Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. Described here is a patient who within a few months after the onset of autoimmune type 1 diabetes increased her insulin requirements more than 20-fold; despite this she had considerable difficulty maintaining a plasma glucose value of <40-60 mmol/L (720-1100 mg/dL). On suspicion of TBIRS, the patient was started on tapering dose of glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect. Within days, insulin requirements decreased by 80-90% and plasma glucose stabilized around 7-8 mmol/L (126-144 mg/dL). The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses and immune column treatments with temporarily remarkable effect. Mixed and transient results were seen with rituximab, mycophenolic acid and bortezomib, but the glycemic status remained suboptimal. Lack of compliance and recurrent infections may have contributed to this. LEARNING POINTS: Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with acquired polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. We describe here a young patient in whom, a few months after the onset of a regular autoimmune diabetes, insulin requirements in a short time increased more than 20-fold, but despite this, the plasma glucose level could be kept at <40-60 mmol/L only with considerable difficulty. Did this patient have TBIRS? On suspicion of TBIRS, the patient was started on tapering glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect; within days insulin requirements decreased by 80-90% and plasma glucose stabilized around 7-8 mmol/L. The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses with temporarily remarkable effect. TBIRS should be considered in diabetic patients whose glycemia and/or insulin requirements are inexplicably and dramatically increased.

[Starvation ketoacidosis during prolonged fasting of 26 days]. / Hypercétose dans un contexte de jeûne prolongé de 26 jours.

Ketosis is a metabolic situation involving an increase in blood and urine concentrations of ketones that, when prolonged, leads to acidosis. Moderate ketosis usually appears after a fast of a few hours, but its prolongation exposes to hyperketosis. Observation: A 25-year-old woman presented to the emergency department for cohercitive vomiting. She was fasting for a long time in a spiritual setting and had a restricted diet limited to water and vitamin supplements. Clinical and biological assessment was in favour of fasting ketoacidosis. Evolution was favorable with intravenous hydration, poly-ionic and micronutrient supplementation and a gradual resumption of oral feeding. Conclusion: We report the case of a patient with fasting ketoacidosis. Besides consequences of this ketoacidosis, the challenge was also in resuming oral feeding in order to avoid a potentially fatal inappropriate renutrition syndrome.

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

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

Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India-Three Years Experience.

PURPOSE: Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). METHODS: The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. RESULTS: G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. CONCLUSION: The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.

A case of type B insulin resistance syndrome treated with low-dose glucocorticoids.

SUMMARY: Type B insulin resistance syndrome is characterized by the presence of autoantibodies to the insulin receptor. We present a 57-year-old male admitted to a hospital due to body weight loss of 16 kg and hyperglycemia of 13.6 mmol/L. He was diagnosed with type B insulin resistance syndrome because the anti-insulin receptor antibodies were positive. We informed him that some hyperglycemic cases of this syndrome had been reported to be spontaneously remitted in 5 years, and he did not agree to be treated with high-dose glucocorticoids and/or immunosuppressive agents due to his concern for their adverse effects such as hyperglycemia and immunosuppression. He chose to be treated with insulin and voglibose, but fair glucose control could not be obtained. Six years later, he agreed to be treated with low-dose glucocorticoids practicable in outpatient settings. One milligram per day of betamethasone was tried orally and reduced gradually according to the values of glycated hemoglobin. After 30 months of glucocorticoid treatment, the anti-insulin receptor antibodies became undetectable and his fasting plasma glucose and glycated hemoglobin were normalized. This case suggests that low-dose glucocorticoids could be a choice to treat type B insulin resistance syndrome in outpatient settings. LEARNING POINTS: Type B insulin resistance syndrome is an acquired autoimmune disease for insulin receptors. This case suggested the possibility of long-lasting, low-dose glucocorticoid therapy for the syndrome as an alternative for high-dose glucocorticoids or immunosuppressive agents. Since the prevalence of autoimmune nephritis is high in the syndrome, a delay of immunosuppressive therapy initiation might result in an exacerbation of nephropathy.

Prolonged acidosis is a feature of SGLT2i-induced euglycaemic diabetic ketoacidosis.

SUMMARY: We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines. LEARNING POINTS: SGLT2i-induced EDKA is a more protracted and prolonged metabolic derangement and takes approximately twice as long to treat as hyperglycaemic ketoacidosis. Surgical patients ought to stop SGLT2i medications routinely pre-operatively and only resume them after they have made a full recovery from the operation. While the mechanistic basis for EDKA remains unclear, our observation of marked ketonuria in both patients suggests that impaired ketone excretion may not be the predominant metabolic lesion in every case. Measurement of insulin, C-Peptide, blood and urine ketones as well as glucagon and renal function at the time of initial presentation with EDKA may help to establish why this problem occurs in specific patients.

Ketonuria Is Associated with Changes to the Abundance of Roseburia in the Gut Microbiota of Overweight and Obese Women at 16 Weeks Gestation: A Cross-Sectional Observational Study.

The gut microbiome in pregnancy has been associated with various maternal metabolic and hormonal markers involved in glucose metabolism. Maternal ketones are of particular interest due to the rise in popularity of low-carbohydrate diets. We assessed for differences in the composition of the gut microbiota in pregnant women with and without ketonuria at 16 weeks gestation. Fecal samples were obtained from 11 women with fasting ketonuria and 11 matched controls. The samples were analyzed to assess for differences in gut microbiota composition by 16S rRNA sequencing. Supervised hierarchical clustering analysis showed significantly different beta-diversity between women with and without ketonuria, but no difference in the alpha-diversity. Group comparisons and network analysis showed that ketonuria was associated with an increased abundance of the butyrate-producing genus Roseburia. The bacteria that contributed the most to the differences in the composition of the gut microbiota included Roseburia, Methanobrevibacter, Uncl. RF39, and Dialister in women with ketonuria and Eggerthella, Phascolarctobacterium, Butyricimonas, and Uncl. Coriobacteriaceae in women without ketonuria. This study found that the genus Roseburia is more abundant in the gut microbiota of pregnant women with ketonuria. Roseburia is a butyrate producing bacterium and may increase serum ketone levels.