Effects of antidiabetic drugs on bone metabolism Padilla Apuntate, Nuria; Puerto Cabeza, Carmen G.; Gallego Royo, Alba ...
Advances in laboratory medicine,
03/2024, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The prevalence of diabetes mellitus type 2 (DMT2) is increasing exponentially worldwide. DMT2 patients have been found to be at a higher risk for bone fractures than the healthy population. Hence, ...improving our understanding of the impact of antidiabetic drugs on bone metabolism is crucial.
A descriptive, retrospective study involving 106 patients receiving six groups of antidiabetic drugs: insulin; dipeptidylpeptidase four inhibitors (DPP4i); glucagon-like peptide type 1 receptor agonists (GLP1ra); sulfonylureas; sodium-glucose cotransporter two inhibitors (SGLT2i); and pioglitazone, in which osteocalcin (OC), bone alkaline phosphatase (BAP) and C-terminal telopeptide of collagen type 1 or beta-crosslaps (β-CTx) were determined.
β-CTx concentrations were higher in the patients treated with pioglitazone, as compared to patients treated with DPP4i (p=0.035), SGLT2i (p=0.020) or GLP1ra (p<0.001). The lowest β-CTx concentrations were observed in the patients treated with GLP1ra.
Bone remodeling is influenced by the type of antidiabetic drug administered to DMT2 patients. In our study, the patients who received pioglitazone showed higher β-CTx concentrations, as compared to patients treated with other types of antidiabetic drugs. This finding highlights the convenience of avoiding these drugs, especially in postmenopausal women with DMT2. GLP1ra drugs were associated with the lowest β-CTx concentrations, which suggests that these agents could exert beneficial effects on bone metabolism.
Resumen Objetivos La prevalencia de la diabetes mellitus tipo 2 (DMT2) está aumentando de forma exponencial en todo el mundo, habiéndose comprobado que estos pacientes tienen mayor riesgo de ...presentar fracturas óseas, con respecto a la población sana, por lo que resulta de gran relevancia el conocimiento del efecto de los fármacos antidiabéticos sobre el metabolismo óseo. Métodos Estudio estadístico descriptivo, retrospectivo, de 106 pacientes en tratamiento con seis grupos de fármacos antidiabéticos: insulina, inhibidores de dipeptidilpeptidasa 4 (iDPP4), agonistas del receptor del péptido similar al glucagón tipo 1 (arGLP1), sulfonilureas, inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) y pioglitazona, en los que se determinaron osteocalcina (OC), fosfatasa alcalina ósea (FAO) y telopéptido C-terminal del colágeno tipo 1 o beta-crosslaps (β-CTx). Resultados Se encontraron concentraciones más elevadas de β-CTx en los pacientes tratados con pioglitazona que en los tratados con iDPP4 (p=0,035), iSGLT2 (p=0,020) y con arGLP1 (p<0,001), siendo los pacientes tratados con arGLP1 los que presentaron las concentraciones más bajas de β-CTx. Conclusiones El tipo de tratamiento antidiabético recibido en pacientes que padecen DMT2 puede afectar el remodelado óseo. En nuestro estudio los pacientes que fueron tratados con pioglitazona mostraron las concentraciones más elevadas de β-CTx con respecto al resto de grupos de fármacos, lo cual parece indicar la conveniencia de evitar estos fármacos, sobre todo en mujeres postmenopáusicas con DMT2. Los fármacos arGLP1 presentaron los valores más bajos de β-CTx, por lo que podrían ejercer un efecto beneficioso sobre el metabolismo óseo.
Haemochromatosis (HC) is an inherited disorder of iron metabolism. The 85–90% of Hereditary hemochromatosis cases are caused by mutations in HFE gene (HC type 1). The remaining 10–15% of HC cases are ...caused by mutations in other non-HFE genes (HJV, HAMP, TRF2, SLC40A1, BMP6). The study of patients for the diagnosis of HC has an important laboratory approached: analysis of biochemical parameters and genetic studies. To confirm a case, it is necessary to carry out a genetic study of the C282Y and H63D mutations. The presence of C282Y mutation in homozygosis is compatible with the diagnosis of HC type 1. Due to the incomplete penetrance of this mutation and the variable phenotypic expression, the severe forms of the disease are relatively rare. The study of variants in non-HFE genes allows more detailed study of both non-classic HC cases and those with more severe clinical expression. The genotype characterization of a patient not always justified the phenotype expression of the symptoms in this disease. All laboratory clinicians must consider recommendation provide by the experts in the Materia.
Display omitted
Background
Lamb–Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by heterozygous mutation or microdeletion involving the
SOX5
gene. LAMSHF is characterize by developmental ...delay, intellectual disability, poor expressive speech, mild dysmorphic facial features and skeletal abnormalities.
Case presentation
We presented a case of a child with delayed psychomotor development in all areas, scoliosis, peculiar facies, and suspicion of intermittent endotropia, alteration in the alignment of one foot and difficulty in standing. These clinical features lead to genetics studies, in which a novel pathogenic variant in the
SOX5
gene was detected in association with LAMSHF.
Conclusions
LAMSHF should be suspected in patients with developmental delay, speech delay, intellectual disability, behavioural disturbances, ophthalmological alterations and skeletal abnormalities. A novel pathogenic mutation in the
SOX5
gene c.1627del p.(Tyr543IlefsTer14) was identified in this patient as responsible of Lamb–Shaffer syndrome. This case contributes to understanding the genetic characteristics, clinical features, and diagnosis of LAMSHF.
Fish-eye disease (FED) is due to a partial deficiency in LCAT activity. Nevertheless, Familial lecithin-cholesterol acyltransferase deficiency (FLD), also called Norum disease, appears when the ...deficiency is complete. They are both rare genetic disorders inherited in an autosomal recessive manner. Clinical signs include decreased circulating HDL cholesterol and dense corneal opacity. Kidney injuries also affect patients suffering from FLD. The diagnosis of FLD is based on the presence of characteristic signs and symptoms and confirmed by genetic testing.
We present a case of a 63-year-old man showing an altered lipid profile with low HDL cholesterol, chronic kidney disease (CKD) and corneal disorders. He was referred to genetic counseling in order to discard genetic LCAT deficiency due to decreased visual acuity caused by corneal opacity. A massive DNA sequencing was conducted using a multigene panel associated with lipid metabolism disturbances.
Two likely pathogenic variants in
were identified and later confirmed by Sanger sequencing. Both (c.491 G > A and c.496 G > A) were missense variants that originated an amino acid substitution (164Arginine for Histidine and 166Alanine for Threonine, respectively) modifying the protein sequence and its 3D structure.
FLD and FED sharing common biochemical features, and the existence of other diseases with similar clinical profiles underline the need for a timely differential diagnosis aiming to address patients to preventive programs and future available therapies. This case, added to the reduced number of publications previously reported regarding FLD and FED, contributes to better understanding the genetic characteristics, clinical features, and diagnosis of these syndromes.
Myotonic dystrophy type 1 (DM1), also known as Steinert's disease, is a chronic, progressive and disabling multisystemic disorder with a broad spectrum of severity that arises from an ...autosomal-dominant expansion of the Cytosine-Thymine-Guanine (CTG) triplet repeat in the 3' untranslated region of the
gene (19q13.3).
In this study, we report the case of a family with several intergenerational expansions of the CTG repeat, with an additional case of a false suspicion of contraction phenomenon due to TP-PCR limitations.
The meiotic instability of the (CTG)
repeats leads to genetic anticipation where increased size of DM1 mutation and a more severe phenotype have been reported in affected individuals across generations. Even if extremely rare, a decrease in the CTG repeat size during transmission from parents to child can also occur, most frequently during paternal transmissions.
Background
Waardenburg syndrome (WS) is a rare genetic disorder characterized by musculoskeletal abnormalities, deafness and hypopigmentation of hair and skin. This article’s aim is to investigate ...clinical and genetic characteristics of WS in three unrelated Caucasian individuals.
Case presentation
The first patient was a 25-year-old female with congenital bilateral hearing loss, bright-blue-eyes, hypopigmentation of hair and skin, megacolon, language retardation, tenosynovitis and neuromas. The second case was an infant symptomatic from birth, with dysphagia, Hirschsprung disease and neurological abnormalities. The third patient was a 14-year-old boy with congenital bilateral hearing loss and ileocolic Hirschsprung disease. In order to identify variants in potentially causal genes of the patients’ phenotype, genetical testing was conducted: targeted clinical exome, targeted exome and trio exome, respectively. We identified three novel variants spread throughout the coding sequence of
SOX10
. The c.395C>G variant identified de novo in patient 1 was a single nucleotide substitution in exon 2. The c.850G>T variant identified as heterozygous in patient 2 was a loss-of-function variant that generated a premature stop codon. The c.966dupT variant identified in patient 3 was a duplication that generated a premature stop codon. It had been identified in his father, arising a possible germinal mosaicism. According to in silico predictors the variant identified in patient 1 was considered as pathogenic, whereas the other two were classified as likely pathogenic.
Conclusions
An exact description of the mutations responsible for WS provides useful information to explain clinical features of WS and contributes to better genetic counselling of WS patients.
Primary Care (PC) and community are the priority health
sites for the detection and management of frailty. There are
good guidelines (Strategy and consensus of the National
Health Service, ADVANTAGE ...European Joint Action, recommendations
of the Program of Prevention and Health
Promotion Activities of the Spanish Society of Family and
Community Medicine PAPPS-semFYC, Fisterra guideline);
however, its implementation is not taking place with the expected
magnitude or speed, also considering the influence of
the COVID-19 pandemic.
The detection and management of frailty requires multidisciplinary
work by professionals who usually carry out
their activity at the first level of care (physicians, nurses, social
workers), with others whose integration is advisable (nutritionists,
physiotherapists, etc.); and counting on others of
reference (geriatricians). On the other hand, it is necessary to
work with comprehensive approaches based on good coordination
between PC and the Community, with various experiences
in this regard. The support by the Information and
Communication Technologies (ICT) can be very interesting,
with tools for both users and careers (e.g., VIVIFRAIL), as
well as for social and health professionals (e.g., VALINTAN
or WHO ICOPE-Handbook App).
Strategies to intervene in fragility in a more effective and
systematic way must be consolidated: with an adequate professional
training, establishment of campaigns and dissemination
ways for visualizing its relevance and extend their intervention,
prioritization of the most effective programmed
assistance activities (highlighting fragility), multidisciplinary
work with coordination and participation of the different
healthcare and community levels and of the patients themselves,
and providing the PC with adequate resources.
La Atención Primaria (AP) y la comunidad constituyen
el medio asistencial primordial para el manejo de la
fragilidad. Se cuenta con buenas directrices (Estrategia y
Consenso del Sistema Nacional de Salud, Acción Conjunta
Europea ADVANTAGE, recomendaciones del Programa de
Actividades de Prevención y de Promoción de la Salud de
la Sociedad Española de Medicina familiar y Comunitaria:
PAPPS-semFYC, guía Fisterra...); no obstante, su implantación
no se está dando con la magnitud ni rapidez esperada,
considerando también la influencia de la pandemia por
la COVID-19.
La detección y manejo de la fragilidad exige un trabajo
multidisciplinar de profesionales que habitualmente desarrollan
su actividad en el primer nivel asistencial (profesionales
de medicina, enfermería y trabajo social), junto con
otros cuya integración es aconsejable (nutricionistas, fisioterapeutas,
etc...) y contando con otros profesionales de referencia
(geriatras). Por otro lado, es necesario trabajar con
enfoques integrales basados en una buena coordinación entre
AP y la Comunidad, existiendo diversas experiencias en
este sentido. El apoyo de las Tecnologías de la Información
y Comunicación (TIC) puede ser muy interesante, existiendo
herramientas tanto para usuarios y personas cuidadoras
(por ej. VIVIFRAIL), como para profesionales sociosanitarios
(por ej. VALINTAN o WHO ICOPE-Handbook App).
Deben consolidarse las estrategias para intervenir en fragilidad
de una manera más efectiva y sistemática: con la
formación adecuada de los profesionales, establecimiento
de campañas y difusión que hagan visualizar la relevancia
y extender su intervención, priorizando las actividades asistenciales
programadas más efectivas (destacando la fragilidad),
a través del trabajo multidisciplinar con coordinación
y participación de los diferentes niveles asistenciales y comunitarios
y de los propios pacientes, y dotando de medios
y recursos a la AP.
Background
Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced ...by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD.
Objective
We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD.
Methods
A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined.
Results
Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels.
Conclusions
The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.
Resumen Objetivos La distrofia miotónica tipo 1, conocida también como enfermedad de Steinert, es un desorden multisistémico crónico, degenerativo e incapacitante de expresividad clínica muy variable ...provocado por una expansión heredada de manera autosómica dominante de la repetición del triplete citosina-timina-guanina, localizada en la región 3′ no codificante del gen DMPK (19q13.3). Caso clínico En este estudio, presentamos el caso de una familia con varias expansiones de la repetición CTG intergeneracionales, con un caso adicional de falsa sospecha de fenómeno de contracción, debido a las limitaciones de la técnica TP-PCR. Conclusiones La inestabilidad meiótica de las repeticiones de (CTG) n provoca anticipación genética. De este modo, a lo largo de las sucesivas generaciones, se ha hallado un incremento del tamaño de la mutación DM1 y un fenotipo más severo en los individuos afectados. Aunque es extremadamente infrecuente, en la transmisión de padres a hijos, también puede producirse una disminución en el número de repeticiones CTG, siendo esta más frecuente en la transmisión paterna.
PDF
