RESUMEN
Pathogenic variants in the LRP5, PLS3, or WNT1 genes can significantly affect bone mineral density, causing monogenic osteoporosis. Much remains to be discovered about the phenotype and medical care needs of these patients. The purpose of this study was to examine the use of medical care among Dutch individuals identified between 2014 and 2021 with a pathogenic or suspicious rare variant in LRP5, PLS3, or WNT1. In addition, the aim was to compare their medical care utilization to both the overall Dutch population and the Dutch Osteogenesis Imperfecta (OI) population. The Amsterdam UMC Genome Database was used to match 92 patients with the Statistics Netherlands (CBS) cohort. Patients were categorized based on their harbored variants: LRP5, PLS3, or WNT1. Hospital admissions, outpatient visits, medication data, and diagnosis treatment combinations (DTCs) were compared between the variant groups and, when possible, to the total population and OI population. Compared to the total population, patients with an LRP5, PLS3, or WNT1 variant had 1.63 times more hospital admissions, 2.0 times more opened DTCs, and a greater proportion using medication. Compared to OI patients, they had 0.62 times fewer admissions. Dutch patients with an LRP5, PLS3, or WNT1 variant appear to require on average more medical care than the total population. As expected, they made higher use of care at the surgical and orthopedic departments. Additionally, they used more care at the audiological centers and the otorhinolaryngology (ENT) department, suggesting a higher risk of hearing-related problems.
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Osteogénesis Imperfecta , Osteoporosis , Humanos , Proteína Wnt1/genética , Osteoporosis/genética , Osteogénesis Imperfecta/genética , Densidad Ósea/genética , Fenotipo , Mutación , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genéticaRESUMEN
AIMS: To investigate the feasibility, safety and efficacy of the Nurse-Driven Diabetes In-Hospital Treatment protocol (N-DIABIT), which consists of nurse-driven correctional therapy, in addition to physician-guided basal therapy, and is carried out by trained ward nurses. METHODS: Data on 210 patients with diabetes consecutively admitted in the 5-month period after the introduction of N-DIABIT (intervention group) were compared with the retrospectively collected data on 200 consecutive patients with diabetes admitted in the 5-month period before N-DIABIT was introduced (control group). Additional per-protocol analyses were performed in patients in whom mean patient-based protocol adherence was ≥ 70% (intervention subgroup, n = 173 vs. control subgroup, n = 196). RESULTS: There was no difference between the intervention and the control group in mean blood glucose levels (8.9 ± 0.1 and 9.1 ± 0.2 mmol/l, respectively; P = 0.38), consecutive hyperglycaemic (blood glucose ≥ 10.0 mmol/l) episodes; P = 0.15), admission duration (P = 0.79), mean number of blood glucose measurements (P = 0.21) and incidence of severe hypoglycaemia (P = 0.29). Per-protocol analyses showed significant reductions in mean blood glucose levels and consecutive hypoglycaemia and hyperglycaemia in the intervention compared with the control group. CONCLUSIONS: Implementation of N-DIABIT by trained ward nurses in non-intensive care unit diabetes care is feasible, safe and non-inferior to physician-driven care alone. High protocol adherence was associated with improved glycaemic control.
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Diabetes Mellitus Tipo 1/enfermería , Diabetes Mellitus Tipo 2/enfermería , Anciano , Glucemia/metabolismo , Estudios de Casos y Controles , Protocolos Clínicos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Factibilidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Hiperglucemia/enfermería , Hiperglucemia/prevención & control , Hipoglucemia/enfermería , Hipoglucemia/prevención & control , Masculino , Rol de la Enfermera , Admisión del Paciente/estadística & datos numéricos , Responsabilidad SocialRESUMEN
AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic ß-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans. METHODS: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*104) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*104) but again not in men (P = 0.34). CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene.
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Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Polimorfismo de Nucleótido Simple , Receptores de Dopamina D2/genética , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Dinamarca , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Sitios Genéticos , Humanos , Hiperglucemia/sangre , Hiperglucemia/genética , Hiperglucemia/metabolismo , Insulina/sangre , Secreción de Insulina , Masculino , Persona de Mediana Edad , Países Bajos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Dopamina D2/metabolismo , Caracteres SexualesRESUMEN
AIMS/HYPOTHESIS: We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control. METHODS: Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine). RESULTS: Serum insulin level was positively associated with HR at all time points during the clamps except the first-phase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log10HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures. CONCLUSION/INTERPRETATION: Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.
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Hiperglucemia/metabolismo , Hiperinsulinismo/metabolismo , Miocardio/metabolismo , Nervio Vago/efectos de los fármacos , Adulto , Índice de Masa Corporal , Estudios Transversales , Electrocardiografía , Ayuno , Femenino , Péptido 1 Similar al Glucagón/metabolismo , Técnica de Clampeo de la Glucosa , Corazón/fisiología , Frecuencia Cardíaca , Humanos , Hiperglucemia/fisiopatología , Hiperinsulinismo/fisiopatología , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Pulmonary hypoplasia and respiratory failure are primary causes of death in patients with osteogenesis imperfecta (OI) type II. OI is a genetic skeletal disorder caused by pathogenic variants in genes encoding collagen type I. It is still unknown if the collagen defect also affects lung development and structure, causing lung hypoplasia in OI type II. The aim of this study was to investigate the intrinsic characteristics of OI embryonic lung parenchyma and to determine whether altered collagen type I may compromise airway development and lung structure. Lung tissue from nine fetuses with OI type II and six control fetuses, matched by gestational age, was analyzed for TTF-1 and collagen type I expression by immunohistochemistry, to evaluate the state of lung development and amount of collagen. The differentiation of epithelium into type 2 pneumocytes during embryonic development was premature in OI type II fetuses compared to controls (p < 0.05). Collagen type I showed no significant differences between the two groups. However, the amount of alpha2(I) chains was higher in fetuses with OI and the ratio of alpha1(I) to alpha2(I) lower in OI compared to controls. Cell differentiation during lung embryonic development in patients with OI type II is premature and impaired. This may be the underlying cause of pulmonary hypoplasia. Altered cell differentiation can be secondary to mechanical chest factors or a consequence of disrupted type I collagen synthesis. Our findings suggest that collagen type I is a biochemical regulator of pulmonary cell differentiation, influencing lung development.
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Colágeno Tipo I , Osteogénesis Imperfecta , Humanos , Colágeno Tipo I/genética , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Colágeno/metabolismo , Diferenciación CelularRESUMEN
AIM: Glucocorticoids are efficacious anti-inflammatory agents, but, in susceptible individuals, these drugs may induce glucose intolerance and diabetes by affecting ß-cell function and insulin sensitivity. We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of ß-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance. METHODS: A cross-sectional cohort study was conducted in four academic medical centres in the Netherlands and Germany. Four hundred and forty-nine volunteers (188 men; 261 women) were recruited with normal glucose tolerance (n=261) and impaired glucose tolerance (n=188). From 2-h hyperglycaemic clamps, first- and second-phase glucose-stimulated insulin secretion, as well as insulin sensitivity index and disposition index, were calculated. All participants were genotyped for the functional NR3C1 polymorphisms N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/6190), 9ß A/G (rs6198) and ThtIIII (rs10052957). Associations between these polymorphisms and ß-cell function parameters were assessed. RESULTS: In women, but not in men, the N363S polymorphism was associated with reduced disposition index (P=1.06 10(-4) ). Also only in women, the ER22/23EK polymorphism was associated with reduced first-phase glucose-stimulated insulin secretion (P=0.011) and disposition index (P=0.003). The other single-nucleotide polymorphisms were not associated with ß-cell function. Finally, none of the polymorphisms was related to insulin sensitivity. CONCLUSION: The N363S and ER22/23EK polymorphisms of the NR3C1 gene are negatively associated with parameters of ß-cell function in women, but not in men.
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Intolerancia a la Glucosa/genética , Resistencia a la Insulina/genética , Células Secretoras de Insulina/fisiología , Polimorfismo de Nucleótido Simple/genética , Receptores de Glucocorticoides/genética , Estudios Transversales , Femenino , Genotipo , Haplotipos , Humanos , Hiperglucemia/genética , Insulina/metabolismo , Secreción de Insulina , Masculino , Factores SexualesRESUMEN
OBJECTIVE: To evaluate the effectiveness of an exercise programme for pregnant women who were overweight or obese and at risk for gestational diabetes mellitus (GDM). DESIGN: Randomised controlled trial. SETTING: Hospitals and midwifery practices in the Netherlands. POPULATION: Pregnant women who were overweight or obese and at risk for GDM between 2007 and 2011. METHODS: Normal care was compared with an exercise training programme during pregnancy. The training consisted of aerobic and strength exercises, and was aimed at improving maternal fasting blood glucose, insulin sensitivity, and birthweight. Linear regression analyses were performed to determine the effects. MAIN OUTCOME MEASURES: Maternal outcome measures were fasting blood glucose (mmol/l), fasting insulin (pmol/l) and HbA1c (%), body weight (kg), body mass index (kg/m(2) ), and daily physical activity (minute/week). Offspring outcome measures were birthweight and fetal growth. RESULTS: A total of 121 women were randomly allocated to either a control (n = 59) or an intervention (n = 62) group. Intention-to-treat analysis showed that the exercise programme did not reduce maternal fasting blood glucose levels nor insulin sensitivity. Also, no effect was found on birthweight. CONCLUSIONS: The exercise intervention performed over the second and third trimester of pregnancy had no effects on fasting blood glucose, insulin sensitivity, and birthweight, most probably because of low compliance. The high prevalence of women at risk for GDM calls for further research on possible interventions that can prevent GDM, and other types of interventions to engage this target group in physical activity and exercise.
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Peso al Nacer/fisiología , Glucemia/metabolismo , Diabetes Gestacional/prevención & control , Terapia por Ejercicio/métodos , Resistencia a la Insulina/fisiología , Sobrepeso/terapia , Adulto , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/sangre , Diabetes Gestacional/fisiopatología , Ayuno/sangre , Femenino , Edad Gestacional , Hemoglobina Glucada/metabolismo , Humanos , Sobrepeso/sangre , Sobrepeso/fisiopatología , Cooperación del Paciente , Linaje , Embarazo , Resultado del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
After a diagnostic study involving computer tomography and bone scintigraphy, a 16-year-old boy appeared to be suffering from the monostotic type of fibrous dysplasia of the maxilla. The diagnosis was confirmed by histopathological examination ofa biopsy. During a follow-up period of 8 years, no signs of progression were evident. Fibrous dysplasia is a rather poorly understood benign bone disease which may occur anywhere in the skeleton. In general, histopathological confirmation using a bone biopsy is recommended. Fibrous dysplasia can be divided into 3 types: 1. monostotic, 2. polyostotic, and 3. polyostotic with endocrine problems. In the majority of cases, a wait-and-watch strategy is sufficient. Malignant transformation is extremely rare and appears almost exclusively in polyostotic cases.
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Displasia Fibrosa Monostótica/diagnóstico , Maxilar/patología , Adolescente , Displasia Fibrosa Monostótica/complicaciones , Humanos , Masculino , Cintigrafía , Tomografía Computarizada por Rayos X , Espera VigilanteRESUMEN
In this issue, we outline the developments that have increasingly enabled people with insulin-dependent diabetes to professionally operate a vehicle. We focus on all professions in passenger transport in the Netherlands, with the pilot as a reference. A protocol has been developed in the UK to enable safe and responsible flying by selected pilots with type 1 diabetes mellitus and insulin dependent type 2 diabetes mellitus. It is used in several countries within and outside Europe, but not yet in the Netherlands. Modern diabetes care, innovative monitoring, good medical supervision and support ensure that patients with insulin-dependent diabetes in the Netherlands can work under certain circumstances as train, ship, tram, metro and bus transporters, but not as a pilot. Based on sufficient data and good arguments, introducing the ''pilot-diabetes'' protocol in the Netherlands would be a good and responsible step forward.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insulinas , Pilotos , Europa (Continente) , HumanosRESUMEN
AIMS/HYPOTHESIS: Traditional blood glucose lowering agents do not prevent the progressive loss of beta cell function in patients with type 2 diabetes. The dipeptidylpeptidase (DPP)-4 inhibitor vildagliptin improves beta cell function both acutely and chronically (up to 2 years). Whether this effect persists after cessation of treatment remains unknown. Here, we assessed the insulin secretory capacity in drug-naive patients with type 2 diabetes after a 52 week treatment period with vildagliptin or placebo, and again after a 12 week washout period. METHODS: This study was conducted at a single university medical centre, and was a double-blind, randomised clinical trial in 59 drug-naive patients with type 2 diabetes and mild hyperglycaemia to either vildagliptin 100 mg (n = 29) or placebo (n = 30). Randomisation was performed by a validated 1:1 system. Neither patient, nor caregiver, was informed about the assigned treatment. Inclusion criteria were drug-naive patients ≥30 years, with HbA(1c) ≤7.5% and BMI of 22-45 kg/m(2). The mildly hyperglycaemic patient population was chosen to minimise glucose toxicity as a confounding variable. Beta-cell function was measured during an arginine-stimulated hyperglycaemic clamp at week 0, week 52 and after a 12 week washout period. All patients with at least one post-randomisation measure were analysed (intent-to-treat). RESULTS: Fifty-two week vildagliptin 100 mg (n = 26) treatment increased the primary efficacy variable, combined hyperglycaemia and arginine-stimulated C-peptide secretion (AIR(arg)), by 5.0 ± 1.8 nmol/l × min, while it decreased by 0.8 ± 1.8 nmol/l × min with placebo (n = 25) (between-group difference p = 0.030). No significant between-group difference in AIR(arg) was seen after the 12 week washout period. The between-group difference adjusted mean 52 week changes from baseline was -0.19 ± 0.11, p = 0.098 and -0.22 ± 0.23%, p = 0.343 for HbA(1c) and fasting plasma glucose, respectively. There were no suspected drug treatment-related serious adverse events. CONCLUSIONS/INTERPRETATION: One year treatment with vildagliptin significantly increased beta cell secretory capacity. This effect was not maintained after the washout, indicating that this increased capacity was not a disease modifying effect on beta cell mass and/or function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00260156.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Nitrilos/farmacología , Nitrilos/uso terapéutico , Pirrolidinas/farmacología , Pirrolidinas/uso terapéutico , Adamantano/farmacología , Adamantano/uso terapéutico , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Ayuno/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hiperglucemia/sangre , Hiperglucemia/metabolismo , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , VildagliptinaRESUMEN
AIMS/HYPOTHESIS: We estimated the heritability of individual differences in beta cell function after a mixed meal test designed to assess a wide range of classical and model-derived beta cell function parameters. METHODS: A total of 183 healthy participants (77 men), recruited from the Netherlands Twin Register, took part in a 4 h protocol, which included a mixed meal test. Participants were Dutch twin pairs and their siblings, aged 20 to 49 years. All members within a family were of the same sex. Insulin sensitivity, insulinogenic index, insulin response and postprandial glycaemia were assessed, as well as model-derived parameters of beta cell function, in particular beta cell glucose sensitivity and insulin secretion rates. Genetic modelling provided the heritability of all traits. Multivariate genetic analyses were performed to test for overlap in the genetic factors influencing beta cell function, waist circumference and insulin sensitivity. RESULTS: Significant heritabilities were found for insulinogenic index (63%), beta cell glucose sensitivity (50%), insulin secretion during the first 2 h postprandial (42-47%) and postprandial glycaemia (43-52%). Genetic factors influencing beta cell glucose sensitivity and insulin secretion during the first 30 postprandial min showed only negligible overlap with the genetic factors that influence waist circumference and insulin sensitivity. CONCLUSIONS/INTERPRETATION: The highest heritability for postprandial beta cell function was found for the insulinogenic index, but the most specific indices of heritability of beta cell function appeared to be beta cell glucose sensitivity and the insulin secretion rate during the first 30 min after a mixed meal.
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Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiología , Periodo Posprandial , Adulto , Femenino , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Secreción de Insulina , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Respiratory failure is a major cause of death in patients with Osteogenesis Imperfecta. Moreover, respiratory symptoms seem to have a dramatic impact on their quality of life. It has long been thought that lung function disorders in OI are mainly due to changes in the thoracic wall, caused by bone deformities. However, recent studies indicate that alterations in the lung itself can also undermine respiratory health. OBJECTIVES: Is there any intrapulmonary alteration in Osteogenesis Imperfecta that can explain decreased pulmonary function? The aim of this systematic literature review is to investigate to what extent intrapulmonary or extrapulmonary thoracic changes contribute to respiratory dysfunction in Osteogenesis Imperfecta. METHODS: A literature search (in PubMed, Embase, Web of Science, and Cochrane), which included articles from inception to December 2020, was performed in accordance with the PRISMA guidelines. RESULTS: Pulmonary function disorders have been described in many studies as secondary to scoliosis or to thoracic skeletal deformities. The findings of this systematic review suggest that reduced pulmonary function can also be caused by a primary pulmonary problem due to intrinsic collagen alterations. CONCLUSIONS: Based on the most recent studies, the review indicates that pulmonary defects may be a consequence of abnormal collagen type I distorting the intrapulmonary structure of the lung. Lung function deteriorates further when intrapulmonary defects are combined with severe thoracic abnormalities. This systematic review reveals novel findings of the underlying pathological mechanism which have clinical and diagnostic implications for the assessment and treatment of pulmonary function disorders in Osteogenesis Imperfecta.KEY MESSAGESDecreased pulmonary function in Osteogenesis Imperfecta can be attributed to primary pulmonary defects due to intrapulmonary collagen alterations and not solely to secondary problems arising from thoracic skeletal dysplasia.Type I collagen defects play a crucial role in the development of the lung parenchyma and defects, therefore, affect pulmonary function. More awareness is needed among physicians about pulmonary complications in Osteogenesis Imperfecta to develop novel concepts on clinical and diagnostic assessment of pulmonary functional disorders.
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Osteogénesis Imperfecta/complicaciones , Insuficiencia Respiratoria/fisiopatología , Humanos , Pulmón , Osteogénesis Imperfecta/patología , Calidad de Vida , Pruebas de Función Respiratoria , Insuficiencia Respiratoria/etiología , EscoliosisRESUMEN
AIMS/HYPOTHESIS: The aim of the present study was to estimate the heritability of the beta cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine. METHODS: This was a twin-family study that included 54 families from the Netherlands Twin Register. The participants were healthy twin pairs and their siblings of the same sex, aged 20 to 50 years. Insulin response of the beta cell was assessed by a modified hyperglycaemic clamp with additional GLP-1 and arginine. Insulin sensitivity index (ISI) was assessed by the euglycaemic-hyperinsulinaemic clamp. Multivariate structural equation modelling was used to obtain heritabilities and the genetic factors underlying individual differences in BMI, ISI and secretory responses of the beta cell. RESULTS: The heritability of insulin levels in response to glucose was 52% and 77% for the first and second phase, respectively, 53% in response to glucose + GLP-1 and 80% in response to an additional arginine bolus. Insulin responses to the administration of glucose, glucose + GLP-1 and glucose + GLP-1 + arginine were highly correlated (0.62< r <0.79). Heritability of BMI and ISI was 74% and 60% respectively. The genetic factors that influenced BMI and ISI explained about half of the heritability of insulin levels in response to the three secretagogues. The other half was due to genetic factors specific to the beta cell. CONCLUSIONS/INTERPRETATION: In healthy adults, genetic factors explain most of the individual differences in the secretory capacity of the beta cell. These genetic influences are partly independent from the genes that influence BMI and ISI.
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Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adulto , Índice de Masa Corporal , Peso Corporal , Péptido 1 Similar al Glucagón/farmacología , Receptor del Péptido 1 Similar al Glucagón , Técnica de Clampeo de la Glucosa , Humanos , Hiperinsulinismo , Insulina/genética , Insulina/farmacología , Secreción de Insulina , Células Secretoras de Insulina/efectos de los fármacos , Cinética , Persona de Mediana Edad , Análisis Multivariante , Receptores de Glucagón/fisiología , Adulto JovenRESUMEN
Fibrodysplasia ossificans progressiva (FOP) is a very rare devastating heterotopic ossification disorder, classically caused by a heterozygous single point mutation (c.617G>A) in the ACVR1gene, encoding the Bone morphogenetic protein (BMP) type I receptor, also termed activin receptor-like kinase (ALK)2. FOP patients develop heterotopic ossification episodically in response to inflammatory insults, thereby compromising tissue sampling and the development of in vitro surrogate models for FOP. Here we describe the generation and characterization of a control and a classical FOP induced pluripotent stem cell (iPSC) line derived from periodontal ligament fibroblast cells using Sendai virus vectors.
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Técnicas de Cultivo de Célula/métodos , Línea Celular/patología , Fibroblastos/patología , Células Madre Pluripotentes Inducidas/patología , Ligamento Periodontal/patología , Adulto , Secuencia de Bases , Femenino , Humanos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
As a consequence of the increased prevalence of type 2 diabetes mellitus in younger age groups, the combination of this form of diabetes and pregnancy is seen more often. Three cases are described. A 31-year-old Caucasian woman with preconceptional type 2 diabetes mellitus presented at gestational week 8. She was receiving chronic treatment with oral hypoglycaemic drugs, and methyldopa due to the pregnancy. She was switched immediately to intensive insulin therapy, which resulted in reasonable glycaemic control. Delivery occurred prematurely at week 30 due to preeclampsia; the neonate died due to sepsis after 1 week. A 32-year-old Moroccan woman with previous gestational diabetes mellitus presented with hyperglycaemia during the first trimester, which suggested possible preconceptional type 2 diabetes mellitus. Insulin treatment was initiated, and the pregnancy continued without further consequence. A 34-year-old Moroccan woman with preconceptional type 2 diabetes mellitus was switched to intensive insulin treatment; conception was delayed until adequate glycaemic control was achieved. The pregnancy continued without further consequence. Insulin therapy should be initiated before conception in women with preconceptional type 2 diabetes mellitus that requires glucose-lowering therapy. Counselling and care are similar to that for women with type 1 diabetes mellitus. Women with a history of gestational diabetes should be counselled and tested before conception to detect silent type 2 diabetes mellitus. Given the high-risk nature oftype 2 diabetes mellitus and pregnancy, specialist team care is mandatory.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Atención Preconceptiva , Embarazo en Diabéticas/tratamiento farmacológico , Adulto , Femenino , Humanos , Embarazo , Resultado del EmbarazoRESUMEN
The treatment of cancer can have a negative influence on bone metabolism. This can result in the development of early osteoporosis or the aggravation of existing osteoporosis, with an increased risk of fractures. Depending on the duration and type of cancer therapy, prophylactic or therapeutic measures against osteoporosis may become necessary. The risk of osteoporosis may be assessed by screening with osteodensitometry, among other methods. Effective treatment is possible, for example with bisphosphonates.
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Antineoplásicos/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Osteoporosis/inducido químicamente , Antineoplásicos/uso terapéutico , Humanos , Neoplasias/terapia , Osteoporosis/prevención & controlRESUMEN
Bisphosphonates are generally administered either orally or intravenously. Orally administered bisphosphonates are primarilly used in the treatment of postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and Paget's disease. When orally administered, only about 1% is absorbed from the tractus from the tractus digestivus. With intravenous administration, higher blood levels levels are reached. Intravenously administered bisphosphonates are used in the treatment of hypercalcaemia, Kahler's disease, and bone metastases of other malignancies. A few cases of osteonecrosis of the jaw(s) are seen especially when more powerful bisphosphonates are administered intravenously. This osteonecrosis is most often provoked by means of an invasive oral treatment. Bisphosphonate-associated osteonecrosis is very difficult to treat. Therefore, dental preventive measures and treatment of dental foci and other inflammations are recommended before starting bisphosphonate therapy.
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Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Osteonecrosis/inducido químicamente , Administración Oral , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/uso terapéutico , Relación Dosis-Respuesta a Droga , Humanos , Inyecciones Intravenosas , Enfermedades Maxilomandibulares/inducido químicamente , Enfermedades Maxilomandibulares/prevención & control , Cuidados a Largo Plazo , Osteonecrosis/prevención & control , Osteoporosis/tratamiento farmacológicoRESUMEN
A 71-year-old male was admitted to our hospital with heart failure, cachexia and biochemical disturbances due to a diet consisting of exclusively vegetables, oil and water. Our investigations showed that this diet was a consequence of an excessive preoccupation with health. The patient did not meet criteria for an eating disorder or other DSM-IV psychiatric disorder. We conclude that malnutrition due to health fad diets may be an underestimated medical problem. There is no specific psychopathological disorder that covers this behaviour, and there is no knowledge of its epidemiology. Popular literature is paying a great deal attention to orthorexia nervosa, an alleged eating disorder that describes a pathological obsession with healthy food. In medical literature this concept has been largely neglected, although eating disorder specialists frequently observe this behaviour in their practice. More clinical and scientific attention for this phenomenon is necessary to determine its epidemiology, validity and clinical picture.
Asunto(s)
Dieta Saludable/efectos adversos , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Desnutrición/etiología , Anciano , Conducta Alimentaria , Humanos , Masculino , VerdurasRESUMEN
This clinical case presentation describes the disease trajectory in two patients who presented with psychiatric symptoms as a result of abnormal serum glucocorticoid levels. One case involves a 58-year-old man with hypercortisolism, the other case concerns a 55-year-old woman with hypocortisolism. In both cases there was a considerable diagnostic delay in recognizing the underlying adrenal gland pathology. Abnormal glucocorticoid levels, caused by endocrine disorders, often results in psychiatric symptoms. Delay in diagnosis may have adverse consequences. Hyper- or hypocortisolism should be considered in patients who present with an atypical presentation of psychiatric symptoms. Moreover, the absence of specific physical signs or symptoms at first presentation in such patients does not exclude an underlying endocrinological cause. Therefore, physical and psychiatric reassessment of such patients should be considered at regular intervals.
Asunto(s)
Glucocorticoides/sangre , Trastornos Mentales/diagnóstico , Trastornos Mentales/etiología , Diagnóstico Tardío , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Trastornos Mentales/terapia , Persona de Mediana EdadRESUMEN
Paget's disease of bone is a focal disorder of bone remodelling that leads to changes in the shape and size of affected bones, and is associated with articular and vascular complications. The disorder is characterised by a localised increase in osteoclast number and activity in one or more affected sites while the rest of the skeleton remains unaffected. The excessive bone resorption leads to recruitment of osteoblasts to the remodelling sites, resulting in increased bone formation. This accelerated bone turnover causes deposition of bone with disorganised architecture and structural weakness. The precise aetiology is unknown. It is thought that the disease is caused by interactions between environmental and genetic factors; the nature of this interaction still has to be determined. The disease is progressive, but can be treated with a single infusion of zoledronic acid. In this manuscript three cases are described, along with a review of the current diagnostic tools and treatment.