RESUMEN
SUMMARY Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.
RESUMEN
Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.
RESUMEN
The aim of this study was to compare low- and high-viscosity bulk-fill composites for Knoop microhardness (KHN), microtensile bond strength (MTBS) to dentin in occlusal cavities, and fracture strength (FS) in molars with mesialocclusal- distal restoration. Disk-shaped samples with different thicknesses (2 or 4 mm) of low-viscosity (SDR Flow, Dentsply) and high-viscosity bulk-fill composites (Filtek BulkFill, 3M ESPE; and Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) were prepared for top and bottom KHN analysis (n=10). MTBS to dentin and fracture pattern was evaluated in human molars with occlusal cavities restored with (n=10): conventional nanocomposite (Z350XT, 3M ESPE), low-viscosity (Filtek Bulk-fill Flow, 3M ESPE) or high-viscosity bulk-fill composites (Filtek BulkFill). The FS and fracture pattern of human molar with mesial-occlusal-distal restorations submitted or not to thermomechanical cycling were investigated (n=10) using: intact tooth (control), and restoration based on conventional microhybrid composite (Z250, 3M ESPE), low-viscosity (SDR Flow) or high-viscosity bulk-fill composites (Filtek BulkFill). The data were submitted to split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) followed by Tukey's test (α=0.05). For KHN, there was no significant difference for the resin composites between the top and bottom. For MTBS, no significant differences among the materials were detected; however, the low-viscosity composite presented lower frequency of adhesive failures. For FS, there was no significant difference between composites and intact tooth regardless of thermomechanical cycling. Low- and high-viscosity bulk-fill composites have comparable microhardness and microtensile bond strength when used in occlusal restorations. Likewise, the bulk-fill composites present similar fracture strength in molars with mesio-occlusal-distal restorations.
O objetivo deste estudo foi comparar resinas compostas bulk- -fill de baixa e alta viscosidade quanto à microdureza Knoop (KHN), resistência de união a microtração (MTBS) em cavidades oclusais e carga à fratura (FS) em molares com restauração mesio-oclusal-distal. Amostras em forma de disco com diferentes espessuras (2 ou 4 mm) de resinas bulk-fill de baixa viscosidade (SDR Flow, Dentsply) e alta viscosidade (Filtek BulkFill, 3M ESPE; e Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) foram obtidas para análise de KHN no topo e na base (n = 10). A MTBS em dentina e o padrão de fratura foram avaliados em molares humanos com cavidades oclusais restauradas com (n = 10): resina composta nanoparticulada convencional (Z350XT, 3M ESPE), resinas bulk-fill de baixa viscosidade (Filtek Bulk-fill Flow, 3M ESPE) ou alta viscosidade (Filtek BulkFill). Foram investigados a FS e o padrão de fratura de molares humanos em restaurações mesial-ocluso-distais sub metidas ou não à ciclagem termomecânica (n = 10), sendo: dente íntegro (controle), e restaurações baseadas em resina composta microhíbrida convencional (Z250, 3M ESPE); resinas bulk-fill de baixa viscosidade (SDR Flow) ou alta viscosidade (Filtek BulkFill). Os dados foram submetidos a split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) seguidos do teste de Tukey (α = 0,05). Para KHN, não houve diferença significativa entre o topo e a base para as resinas compostas. Para MTBS, não foram detectadas diferenças significativas entre os materiais; entretanto, a resina bulk-fill de baixa viscosidade apresentou menor frequência de falhas adesivas. Para FS, não houve diferença significativa entre os materiais e o dente íntegro, independentemente da ciclagem termomecânica. As resinas bulk-fill de baixa e alta viscosidade têm microdureza e resistência à microtração comparáveis quando usados em restaurações oclusais. Da mesma forma, as resinas bulk-fill apresentam resistência à fratura semelhante em molares com restaurações mesio-oclusal-distais.
Asunto(s)
Resinas Compuestas , Resistencia Flexional , Humanos , Ensayo de Materiales , Diente Molar , ViscosidadRESUMEN
ABSTRACT The aim of this study was to compare low- and high-viscosity bulk-fill composites for Knoop microhardness (KHN), microtensile bond strength (MTBS) to dentin in occlusal cavities, and fracture strength (FS) in molars with mesialocclusal- distal restoration. Disk-shaped samples with different thicknesses (2 or 4 mm) of low-viscosity (SDR Flow, Dentsply) and high-viscosity bulk-fill composites (Filtek BulkFill, 3M ESPE; and Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) were prepared for top and bottom KHN analysis (n=10). MTBS to dentin and fracture pattern was evaluated in human molars with occlusal cavities restored with (n=10): conventional nanocomposite (Z350XT, 3M ESPE), low-viscosity (Filtek Bulk-fill Flow, 3M ESPE) or high-viscosity bulk-fill composites (Filtek BulkFill). The FS and fracture pattern of human molar with mesial-occlusal-distal restorations submitted or not to thermomechanical cycling were investigated (n=10) using: intact tooth (control), and restoration based on conventional microhybrid composite (Z250, 3M ESPE), low-viscosity (SDR Flow) or high-viscosity bulk-fill composites (Filtek BulkFill). The data were submitted to split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) followed by Tukey's test (α=0.05). For KHN, there was no significant difference for the resin composites between the top and bottom. For MTBS, no significant differences among the materials were detected; however, the low-viscosity composite presented lower frequency of adhesive failures. For FS, there was no significant difference between composites and intact tooth regardless of thermomechanical cycling. Low- and high-viscosity bulk-fill composites have comparable microhardness and microtensile bond strength when used in occlusal restorations. Likewise, the bulk-fill composites present similar fracture strength in molars with mesio-occlusal-distal restorations.
RESUMO O objetivo deste estudo foi comparar resinas compostas bulk- -fill de baixa e alta viscosidade quanto à microdureza Knoop (KHN), resistência de união a microtração (MTBS) em cavidades oclusais e carga à fratura (FS) em molares com restauração mesio-oclusal-distal. Amostras em forma de disco com diferentes espessuras (2 ou 4 mm) de resinas bulk-fill de baixa viscosidade (SDR Flow, Dentsply) e alta viscosidade (Filtek BulkFill, 3M ESPE; e Tetric-N Ceram Bulk Fill, Ivoclar Vivadent) foram obtidas para análise de KHN no topo e na base (n = 10). A MTBS em dentina e o padrão de fratura foram avaliados em molares humanos com cavidades oclusais restauradas com (n = 10): resina composta nanoparticulada convencional (Z350XT, 3M ESPE), resinas bulk-fill de baixa viscosidade (Filtek Bulk-fill Flow, 3M ESPE) ou alta viscosidade (Filtek BulkFill). Foram investigados a FS e o padrão de fratura de molares humanos em restaurações mesial-ocluso-distais sub metidas ou não à ciclagem termomecânica (n = 10), sendo: dente íntegro (controle), e restaurações baseadas em resina composta microhíbrida convencional (Z250, 3M ESPE); resinas bulk-fill de baixa viscosidade (SDR Flow) ou alta viscosidade (Filtek BulkFill). Os dados foram submetidos a split-plot ANOVA (KHN), one-way ANOVA (MTBS), two-way ANOVA (FS) seguidos do teste de Tukey (α = 0,05). Para KHN, não houve diferença significativa entre o topo e a base para as resinas compostas. Para MTBS, não foram detectadas diferenças significativas entre os materiais; entretanto, a resina bulk-fill de baixa viscosidade apresentou menor frequência de falhas adesivas. Para FS, não houve diferença significativa entre os materiais e o dente íntegro, independentemente da ciclagem termomecânica. As resinas bulk-fill de baixa e alta viscosidade têm microdureza e resistência à microtração comparáveis quando usados em restaurações oclusais. Da mesma forma, as resinas bulk-fill apresentam resistência à fratura semelhante em molares com restaurações mesio-oclusal-distais.
RESUMEN
AIMS: Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. MATERIALS AND METHODS: Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. RESULTS: Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CONCLUSIONS: CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.
Asunto(s)
Calcio/sangre , Vasos Coronarios/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Factores de Riesgo de Enfermedad Cardiaca , Adulto , Anciano , Calcio/análisis , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Vasos Coronarios/química , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Femenino , Glucoquinasa/genética , Humanos , Hiperglucemia/genética , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
PURPOSE: To perform a clinical and radiographic evaluation comparing Filtek Bulk Fill high viscosity bulk-fill resins with Filtek Z350 XT nanoparticulate for 1 year. METHODS: 58 restorations were performed for each material (bulk-fill and nanoparticulate), for a total of 116 restorations. Among these, 42 Class I and 16 Class II restorations were performed for each group, in molars and premolars. Clinical evaluation was performed 7 days (baseline), 6 months and 1 year after restorations, using the World Dental Federation (FDI) criteria. Radiographs were obtained at 7 days and 1 year after the restoration was placed and the radiopacity was measured using Image J software at the same time interval. RESULTS: Of the 70 restorations available for evaluation at 1 year, the Mann-Whitney and Friedman tests showed no statistically significant difference for the FDI criteria analyzed. Greater radiopacity was observed for bulk-fill resin compared to nanoparticulate (two-way ANOVA, P= 0.022). This same test showed no difference in radiopacity between the groups in the two evaluation periods (P= 0.062). The high viscosity bulk-fill resin composite presented similar clinical performance to nanoparticulate resin in this evaluation period and higher radiopacity was observed for this material when compared to nanoparticulate resin, in both time periods. CLINICAL SIGNIFICANCE: The high viscosity bulk-fill resin composite showed similar performance to the nanoparticulate resin during the evaluation period of 1 year. Radiopacity showed high values for the bulk-fill resin when compared to nanoparticulate resin. The bulk-fill resin has potential to be used in posterior teeth.
Asunto(s)
Materiales Dentales , Restauración Dental Permanente , Diente Premolar , Resinas Compuestas , Diente Molar , ViscosidadRESUMEN
OBJECTIVE: To evaluate the influence of the degree of dentin moisture on interfacial ultramorphology and bond strength (µTBS) of universal adhesives. MATERIALS AND METHODS: Futurabond U (FBU), Scotchbond Universal (SBU), Adhese Universal (ADU), and Prime&Bond active (PBA) were used. After acid-etching, moist or over-dried dentin surfaces were tested. Teeth were restored for scanning and transmission electron microscopy (n = 3) and µTBS evaluation (n = 5). µTBS results were analyzed by two-way ANOVA and Tukey. RESULTS: For moist dentin, a well-formed hybrid layer (HL) was observed. However, when applied to over-dried dentin, remarkable differences were observed. Defects, gaps, and reduced HL thickness were observed mainly for ADU and FBU. When applied to wet dentin, µTBS values were similar for all adhesives, except for FBU, which was significantly lower. When applied to over-dried dentin, PBA presented the highest µTBS values, followed by SBU, ADU, and FBU. ADU presented significantly lower µTBS when applied to over-dried dentin. CONCLUSION: PBA, SBU, and FBU µTBS values were not sensitive to the degree of moisture. Even though application to over-dried dentin revealed defects, gaps and reduced HL thickness for SBU, ADU, and FBU, µTBS analysis only revealed a significant reduction for ADU. CLINICAL SIGNIFICANCE: Universal adhesives can be applied in either self-etching or etch-and-rinse mode. However, clinicians are not aware which universal adhesives should be strictly applied on a moist dentin for bonding in the etch-and-rinse mode.
Asunto(s)
Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Resinas Compuestas , Cementos Dentales , Dentina , Ensayo de Materiales , Cementos de Resina , Resistencia a la TracciónRESUMEN
BACKGROUND: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X). METHODS: We conducted a next-generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY-GCK and 76 were non-GCK MODY. RESULTS: After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY-PDX1/HNF1B. CONCLUSION: A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY-X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adolescente , Adulto , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Brasil , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Humanos , Masculino , Análisis de Secuencia de ADN , Receptores de Sulfonilureas/genética , Transactivadores/genética , Adulto JovenRESUMEN
ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).
Asunto(s)
Humanos , Adulto , Persona de Mediana Edad , Nefropatías Diabéticas/genética , Enfermedades Renales Quísticas/genética , Factor Nuclear 1-beta del Hepatocito/genética , Hiperglucemia/genética , Mutación , Fenotipo , Polimorfismo Genético/genética , Brasil , Estudios de Cohortes , Eliminación de Gen , Nefropatías Diabéticas/complicaciones , Enfermedades Renales Quísticas/complicaciones , Hiperglucemia/complicacionesRESUMEN
OBJECTIVE: To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. SUBJECTS AND METHODS: We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. RESULTS: We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. CONCLUSION: The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).
Asunto(s)
Nefropatías Diabéticas/genética , Factor Nuclear 1-beta del Hepatocito/genética , Hiperglucemia/genética , Enfermedades Renales Quísticas/genética , Mutación , Adulto , Brasil , Estudios de Cohortes , Nefropatías Diabéticas/complicaciones , Eliminación de Gen , Humanos , Hiperglucemia/complicaciones , Enfermedades Renales Quísticas/complicaciones , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético/genéticaRESUMEN
OBJECTIVE: To test the effects of different adhesive protocols and silane application on the adhesive durability to a Lithium Disilicate reinforced glass ceramic. METHODS: Forty disks of 13 mm diameter (E.max Press) were used. After etching with 9.5% HF for 20 seconds, disks were randomly assigned into 4 groups according to the adhesive/silane protocol: silane application only (SIL); silane application followed by adhesive (SILXP-XP Bond); silane-containing adhesive (SBU-ScotchBond Universal); silane application followed by silane-containing adhesive (SILSBU). Four resin composite cylinders of 1-mm diameter and 3-mm height were made on each ceramic disk and tested in shear. Specimens were stored in water for 24 hours or 12 months prior to testing. Results were statistically analyzed by two-way ANOVA and Tukey test. RESULTS: After 24 hours, the highest SBS values were observed for SILXP and SILSBU. However, after 12 months, SILXP and SILSBU presented a significant reduction in SBS, while the highest SBS were observed for SIL. For SBU, no significant reduction in SBS was observed, however, it showed the lowest SBS after 12 months. CONCLUSIONS: Regardless of the presence of silane in the composition of SBU, previous silane application is still recommended prior to cementation of Lithium Disilicate. CLINICAL SIGNIFICANCE: The application of silane as a separate step is recommended prior to cementation of Lithium Disilicate reinforced glass-ceramic, independent of the presence of silane within the universal adhesive solution.
Asunto(s)
Recubrimiento Dental Adhesivo , Silanos , Cerámica , Cementos Dentales , Porcelana Dental , Ensayo de Materiales , Cementos de Resina , Propiedades de SuperficieRESUMEN
SUMMARY Identification of the correct etiology of diabetes brings important implications for clinical management. In this report, we describe a case of a 4-year old asymptomatic girl with diabetes since age 2, along with several individuals in her family with different etiologies for hyperglycemia identified in youth. Genetic analyses were made by Sanger sequencing, laboratory measurements included HbA1c, lipid profile, fasting C-peptide, pancreatic auto-antibodies (glutamic acid decarboxylase [GAD], Islet Antigen 2 [IA-2], and anti-insulin). We found a Gly178Ala substitution in exon 5 of GCK gene in three individuals co-segregating with diabetes, and type 1 diabetes was identified in two other individuals based on clinical and laboratory data. One individual with previous gestational diabetes and other with prediabetes were also described. We discuss difficulties in defining etiology of hyperglycemia in youth in clinical practice, especially monogenic forms of diabetes, in spite of the availability of several genetic, laboratory, and clinical tools.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Adulto , Persona de Mediana Edad , Anciano , Proteínas Serina-Treonina Quinasas/genética , Predisposición Genética a la Enfermedad , Diabetes Mellitus/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/genética , Linaje , Pruebas Genéticas , Diabetes Mellitus/clasificación , Quinasas del Centro Germinal , Genotipo , MutaciónRESUMEN
ABSTRACT Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.
Asunto(s)
Humanos , Síndrome Metabólico/etiología , Diabetes Mellitus Tipo 2/etiología , Adiponectina/metabolismo , Glucosa/metabolismo , Síndrome Metabólico/metabolismo , Diabetes Mellitus Tipo 2/metabolismoRESUMEN
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Adolescente , Adulto , Brasil , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Masculino , Sistema de Registros , Adulto JovenRESUMEN
Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.
Asunto(s)
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/etiología , Glucosa/metabolismo , Síndrome Metabólico/etiología , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Síndrome Metabólico/metabolismoRESUMEN
Identification of the correct etiology of diabetes brings important implications for clinical management. In this report, we describe a case of a 4-year old asymptomatic girl with diabetes since age 2, along with several individuals in her family with different etiologies for hyperglycemia identified in youth. Genetic analyses were made by Sanger sequencing, laboratory measurements included HbA1c, lipid profile, fasting C-peptide, pancreatic auto-antibodies (glutamic acid decarboxylase [GAD], Islet Antigen 2 [IA-2], and anti-insulin). We found a Gly178Ala substitution in exon 5 of GCK gene in three individuals co-segregating with diabetes, and type 1 diabetes was identified in two other individuals based on clinical and laboratory data. One individual with previous gestational diabetes and other with prediabetes were also described. We discuss difficulties in defining etiology of hyperglycemia in youth in clinical practice, especially monogenic forms of diabetes, in spite of the availability of several genetic, laboratory, and clinical tools.
Asunto(s)
Diabetes Mellitus/genética , Predisposición Genética a la Enfermedad , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/genética , Proteínas Serina-Treonina Quinasas/genética , Adulto , Anciano , Preescolar , Diabetes Mellitus/clasificación , Femenino , Pruebas Genéticas , Genotipo , Quinasas del Centro Germinal , Humanos , Masculino , Persona de Mediana Edad , Mutación , LinajeRESUMEN
Thirty-two patients with diabetes negative for point mutations in GCK and HNF1A underwent further molecular screening of GCK, HNF1A, HNF4A, and HNF1B by MLPA analysis. We described the first Brazilian case of MODY5 due to a heterozygous whole-gene deletion in HNF1B, who developed rapidly progressive renal failure and death.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Eliminación de Gen , Factor Nuclear 1-beta del Hepatocito/genética , Adulto , Brasil , Estudios de Casos y Controles , Enfermedades del Sistema Nervioso Central , Esmalte Dental/anomalías , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Glucoquinasa/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Heterocigoto , Humanos , Hallazgos Incidentales , Enfermedades Renales Quísticas , Masculino , FenotipoRESUMEN
INTRODUCTION: Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population. SUBJECTS AND METHODS: Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohen's κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept. RESULTS: Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006). CONCLUSION: a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.