Terapia complementaria a la insulina en el tratamiento de niños y adolescentes con diabetes mellitus tipo 1- (DM1) / Therapies complementaries to insulin in the treatment of children and adolescents with type 1 diabetes mellitus (T1DM)

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.

Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.

A Case of Isolated Glycosuria Mediated by an SLC5A2 Gene Mutation and Characterized by Postprandial Heavy Glycosuria Without Salt Wasting

Familial renal glycosuria (FRG) is an inherited disorder characterized by persistent glycosuria in the absence of hyperglycemia. It is caused by mutations in the sodium-glucose co-transporter, leading to increase in the renal excretion of glucose and sodium. However, there have been no studies on the role of fasting and postprandial changes in the urinary sodium excretion in patients with FRG. We report a case of renal glycosuria, which was confirmed by a SLC5A2 mutation via gene sequencing, and compared the postprandial urinary glucose and sodium excretion. A 26-year-old man sometimes experienced glycosuria on routine screening; however, other laboratory findings were normal. His fasting and postprandial urinary glucose excretion levels were 295mg/dL and 2,170mg/dL, respectively. The fasting and postprandial urinary sodium excretion levels were 200mEq/L and 89mEq/L, respectively. In patients with FRG, excessive diuresis might be prevented by a compensatory mechanism that reduces postprandial sodium excretion.

Interaction of carbohydrate derivatives and sodium-glucose cotransporters 2 by molecular dynamic simulation / 中草药

Objective: To investigate the interactions between carbohydrate derivatives and sodium-glucose cotransporters 2 (SGLT2) using molecular dynamic (MD) method and to explore the mechanisms and structure-activity relationship of SGLT2 inhibitors. Methods: The homologous structure of SGLT2 was modeled, the GROMACS program was used to model eight structures, such as SGLT2, SGLT2-glucose compound, and SGLT2-carbohydrate compound. And the root mean square fluctuation (RMSF) of the key residues and ligands and the interaction energy between the ligands and SGLT2 was investigated by trajectory analysis. Results: The interaction energy calculated by MD method had the higher correlation with experimental results than that by molecular docking method. H80, K154, D158, and Y290 were the key residues involved in the interaction, N75 and F453 were the important residues, and W291, Q295, and S393 might be the auxiliary residues. The ligands had a relatively consistent conformation, and fragments A and C played the more important roles in receptor binding. And the size, rigidity, and polarity increasing could elevate the bonding strength. Conclusion: MD simulation results could display the good performance of the interaction between the ligands and SGLT2, and could give clear guidance for the design of new SGLT2 inhibitors.

Novel therapeutic agents for diabetes mellitus / 中国实用内科杂志

Current therapies of diabetes proven to lowering glucose include metformin,TZDs,sulphanylureas,nateglinide,Repaglinide,acarbose and insulin analogues.Given our better understanding of the beta cell function are slowly emerging.Recently,the gastrointestinal peptide hormones glucagon-like peptide 1 analogues and inhibitors of dipeptidyl peptidase-4(DPP-4) have been shown to significantly contribute to glucose homeostasis.Meanwhile,other novel prospect for diabetes such as selective peroxisome proliferator-activated receptor(PPAR) gamma modulators,inhibitors of sodium glucose co-transporters 2 have been proven to be attractive drug candidates.The therapeutic potential of these molecules are discussed in this review.