Cetoacidosis por empagliflozina post histerectomía / Post hysterectomy ketoacidosis due to empagliflozin

RESUMEN Paciente de sexo femenino de 42 años, con diagnóstico de diabetes mellitus tipo 2, de 3 años de evolución, era tratada con empagliflozina/metformina. Intervenida quirúrgicamente por miomatosis uterina, presentó en el postoperatorio inmediato deterioro neurológico y acidosis metabólica, sin hiperglicemia, pero con desequilibrio hidroelectrolítico. Fue ingresada a terapia intensiva, requiriendo manejo invasivo con hemodiálisis y diálisis peritoneal por acidosis refractaria. Egresó luego de 17 días de estancia intrahospitalaria, en buenas condiciones generales.

ABSTRACT A 42-year-old female patient received a diagnosis of type 2 diabetes mellitus 3 years ago, and was treated with empagliflozin/metformin. She had a surgical intervention for uterine myomatosis, and presented immediately after the surgery neurological deterioration, metabolic acidosis without hyperglycemia, and hydroelectrolytic imbalance. She was admitted to the intensive care unit and required treatment with hemodialysis and peritoneal dialysis due to refractory acidosis. She was discharged in good condition after 17 days of hospitalization.

A Journey to Understand Glucose Homeostasis: Starting from Rat Glucose Transporter Type 2 Promoter Cloning to Hyperglycemia

My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.

Identification and Functional Characterization of P159L Mutation in HNF1B in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5)

Mutation in HNF1B, the hepatocyte nuclear factor-1beta (HNF-1beta) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-1beta in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic beta-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in beta-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

A Case of Fanconi-Bickel Syndrome with Mild Clinical Signs / 대한내과학회지

Fanconi-Bickel syndrome is a rare autosomal recessive disorder caused by a mutation in the facilitative glucose transporter 2 gene (GLUT2 or SLC2A2 gene) that codes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic beta-cells, enterocytes, and renal tubular cells. Mutation of this gene leads to defective carbohydrate metabolism, hepatomegaly, glucose intolerance, proximal renal tubular dysfunction, and hypophosphatemic rickets. We report a case of Fanconi-Bickel syndrome in an 18-year-old man who presented due to renal glycosuria; a mutation was identified in the GLUT2 gene (c.482C > A + c.1556G > A). To the best of our knowledge, unlike previous reports of Fanconi-Bickel syndrome, this case was relatively unusual in that it caused only mild clinical signs.