RESUMO
High-resolution mass spectrometry is a powerful tool in clinical analysis but remains less explored due to its lower dynamic range and sensitivity compared to triple quadrupoles. Glycated hemoglobin (HbA1c) is the current gold standard biomarker to monitor the control of diabetes, representing long-term plasma glycemic levels. Due to its clinical importance, several methods have been developed for HbA1c quantification, using different principles; however, the results obtained with these techniques may differ according to the method adopted. Hence, there is a great need to standardize the current methods to quantify glycated hemoglobin. A new UPLC-QToF-MS method was fully validated and tested to quantify HbA1c in human samples. The peptides VHLTPE m/z 695.373 and gly-VHLTPE m/z 857.426, obtained via Glu-C digestion, were the selected peptides for quantification of HbA1c (mmol/mol). Chromatographic separation was obtained in a C18 column, maintained at 40 °C. The mobile phase was composed of water and acetonitrile, both containing 0.02% TFA and 0.1% acetic acid, and eluted in gradient mode. The method was fully validated, being considered linear in the range of 25-107 mmol/mol of HbA1c, and was sensitive, selective, precise, accurate, and free of matrix and carryover effects. The method was successfully applied to real samples, reaching about 90% agreement with reference method results, providing accurate and precise information on peptide mass, without laborious sample preparation. These results support the use of HRMS to improve the quality of quantitative results of HbA1c in health services and demonstrate a possible application of peptide investigation for clinical analysis in the near future.
Assuntos
Cromatografia Líquida/métodos , Hemoglobinas Glicadas/análise , Espectrometria de Massas/métodos , Hemoglobinas Glicadas/química , Hemoglobinas Glicadas/metabolismo , Humanos , Limite de Detecção , Modelos Lineares , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Serina Endopeptidases/metabolismoRESUMO
BACKGROUND: The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level. AIM: To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH. METHODS: We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data. RESULTS: We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). CONCLUSION: This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina de Ação Prolongada/uso terapêutico , Hemoglobinas Glicadas/química , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Detemir/uso terapêutico , Insulina Glargina/uso terapêutico , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de RegressãoRESUMO
BACKGROUND: Metabolic syndrome has been associated with nodular goiter. Our aim was to evaluate which metabolic parameters in elderly patients with metabolic syndrome are associated with thyroid enlargement or increased prevalence of thyroid nodules. METHODS: In this cross-sectional study, 77 patients >65 years of age with metabolic syndrome were included. We evaluated the presence of thyroid nodules and thyroid volume by ultrasonography and several biochemical, metabolic and anthropometric parameters. Only patients with thyrotropin (thyroid-stimulating hormone, TSH) levels between 0.3 and 6 mU/L were included. We further divided subjects into two groups-type 2 diabetes mellitus (T2DM) and non-T2DM and established comparisons between them. RESULTS: Among all parameters analyzed we found a significant correlation between glycated hemoglobin (HbA1c) and volume (r=0.261, P=0.027) or number of nodules (r=0.266, P=0.023). Neither sex, age, body mass index (BMI), metformin, nor levothyroxine use were associated with thyroid volume or nodularity. Within the whole cohort, those patients with T2DM had larger thyroid volumes compared to non-T2DM [median (confidence interval, CI) 6.976 (5.220-10.789) vs. 5.034 (3.796-6.034) mL, P<0.008). Furthermore, a larger proportion of T2DM patients presented thyroid volumes >5.8 mL [69 vs. 23%, P<0.001; odds ratio=7.25 (CI 2.04-25.56)]. CONCLUSIONS: In elderly patients with metabolic syndrome, worse metabolic control, represented by higher HbA1c levels, was found associated to increased prevalence of thyroid nodules and larger thyroid volume. Moreover, within the whole metabolic syndrome group, patients with T2DM had the largest thyroid volumes.
Assuntos
Síndrome Metabólica/fisiopatologia , Doenças da Glândula Tireoide/complicações , Glândula Tireoide/fisiologia , Nódulo da Glândula Tireoide/complicações , Idoso , Idoso de 80 Anos ou mais , Antropometria , Argentina , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/química , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Síndrome Metabólica/complicações , Metformina/uso terapêutico , Estudos Prospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/metabolismo , Tireotropina/sangue , Tiroxina/uso terapêutico , UltrassonografiaAssuntos
Humanos , Masculino , Feminino , Diabetes Mellitus/classificação , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Doenças Periodontais/etiologia , Angiopatias Diabéticas/etiologia , Assistência Odontológica para Doentes Crônicos/métodos , Citocinas/fisiologia , Doenças do Colágeno/complicações , Hemoglobinas Glicadas/química , Implantação Dentária , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Doenças Periodontais/terapia , Retinopatia Diabética/etiologia , Fatores de Risco , Tetraciclinas/uso terapêuticoAssuntos
Humanos , Masculino , Feminino , Doenças Periodontais/etiologia , Diabetes Mellitus/classificação , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Tetraciclinas/uso terapêutico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Angiopatias Diabéticas/etiologia , Citocinas/fisiologia , Fatores de Risco , Assistência Odontológica para Doentes Crônicos/métodos , Doenças do Colágeno/complicações , Hemoglobinas Glicadas/química , Implantação Dentária , Doenças Periodontais/terapiaAssuntos
Humanos , Masculino , Feminino , Doenças Periodontais/etiologia , Diabetes Mellitus/classificação , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Tetraciclinas/uso terapêutico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Angiopatias Diabéticas/etiologia , Citocinas/fisiologia , Fatores de Risco , Assistência Odontológica para Doentes Crônicos/métodos , Doenças do Colágeno/complicações , Hemoglobinas Glicadas/química , Implantação Dentária , Doenças Periodontais/terapiaRESUMO
The Q-band (35 GHz) electron paramagnetic resonance (EPR) spectra of nitrosyl hemoglobin (HbNO) and nitrosyl myoglobin (MbNO) were studied as a function of temperature between 19 K and 200 K. The spectra of both heme proteins show two classes of variations as a function of temperature. The first one has previously been associated with the existence of two paramagnetic species, one with rhombic and the other with axial symmetry. The second one manifests itself in changes in the g-factors and linewidths of each species. These changes are correlated with the conformational substates model and associate the variations of g-values with changes in the angle of the N(his)-Fe-N(NO) bond in the rhombic species and with changes in the distance between Fe and N of the proximal (F8) histidine in the axial species.
Assuntos
Hemoglobinas Glicadas/química , Hemeproteínas/química , Mioglobina/análogos & derivados , Óxido Nítrico/química , Fenômenos Biofísicos , Biofísica , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Mioglobina/química , Temperatura , TermodinâmicaRESUMO
La diabetes mellitus es una enfermedad crónica que requiere del cuidado médico constante y de la educación tanto del paciente como de sus familiares. Para su control, el médico se apoya en unas serie de pruebas de laboratorio entre las cuales la hemoglobina glucosilada (HbA1C) juega un papel importante. Esta prueba tiene la ventaja de monitorear las condiciones metabólicas del paciente en las ocho semanas precedentes permitiendo así conocer con mayor certeza la calidad del control de la diabetes. La determinación de hemoglobina glucosilada se debe realizar cada tres o cuatro meses y los valores estimados como normales son de 3 a 6 por ciento