RESUMO
The GCM2 gene encodes a transcription factor predominantly expressed in parathyroid cells that is known to be critical for development, proliferation and maintenance of the parathyroid cells. A cohort of 127 Spanish patients with a disorder of calcium metabolism were screened for mutations by Next-Generation Sequencing (NGS). A targeted panel for disorders of calcium and phosphorus metabolism was designed to include 65 genes associated with these disorders. We observed two variants of uncertain significance (p.(Ser487Phe) and p.Asn315Asp), one likely pathogenic (p.Val382Met) and one benign variant (p.Ala393_Gln395dup) in the GCM2 gene in the heterozygous state in five families (two index cases had hypocalcemia and hypoparathyroidism, respectively, and three index cases had primary hyperparathyroidism). Our study shows the utility of NGS in unravelling the genetic origin of some disorders of the calcium and phosphorus metabolism, and confirms the GCM2 gene as an important element for the maintenance of calcium homeostasis. Importantly, a novel variant in the GCM2 gene (p.(Ser487Phe)) has been found in a patient with hypocalcemia.
Assuntos
Cálcio/metabolismo , Hiperparatireoidismo Primário/genética , Hipocalcemia/genética , Hipoparatireoidismo/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Cálcio/sangue , Sinalização do Cálcio/genética , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico , Hipocalcemia/sangue , Hipocalcemia/diagnóstico , Hipoparatireoidismo/sangue , Hipoparatireoidismo/diagnóstico , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Glândulas Paratireoides , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Background:Telephone-delivered intervention can provide support in diabetes self-management to improve glycemic control. "eStar® program" is a telephone support platform for type 2 diabetes on glargine insulin treatment. Its objective is to help patients to perform insulin titration to reach target fasting blood glucose levels. Patients are contacted by trained nurses on a regular basis to adjust the basal insulin dose and reinforce the diabetes education. This study aimed to evaluate if eStar program was effective in helping patients reach their optimal insulin glargine dose within 6 months.Materials and Methods:An observational prospective study was conducted with type 2 diabetes patients who were initiating insulin glargine or requiring dose titration and were eligible to be included in the eStar program. Those participants who followed the program comprised the intervention group, while those who discontinued, the control group. The primary outcome was to evaluate if this program was effective in helping patients reach their optimal insulin glargine dose within 6 months. Secondary outcomes included changes in glycosylated hemoglobin (HbA1C), fasting plasma glucose (FPG), insulin dose, and body mass index after 6 months.Results:A total of 228 subjects [intervention group, 143 (62.7%); control group, 85 (37.3%)] were included in the study. A significantly greater percentage of patients in the intervention group reached their optimal glargine dose than in the control group (83.8% vs. 31.5%; p < 0.001). After 6 months, significant reductions in mean HbA1C levels were observed in both groups: 1.49% (p < 0.001) for the intervention group and 1.08% (p < 0.001) for the control group. Furthermore, a mean reduction in FPG between group was achieved (34.96 mg/dL; p < 0.001).Conclusions:The eStar program is an effective way to help patients reach their optimal insulin glargine dose, besides improving their glycemic control.
