Antihyperglycemic Effects of Annona cherimola Miller and the Flavonoid Rutin in Combination with Oral Antidiabetic Drugs on Streptozocin-Induced Diabetic Mice.

Ethanolic extract obtained from Annona cherimola Miller (EEAc) and the flavonoid rutin (Rut) were evaluated in this study to determine their antihyperglycemic content, % HbA1c reduction, and antihyperlipidemic activities. Both treatments were evaluated separately and in combination with the oral antidiabetic drugs (OADs) acarbose (Aca), metformin (Met), glibenclamide (Gli), and canagliflozin (Cana) in acute and subchronic assays. The evaluation of the acute assay showed that EEAc and Rut administered separately significantly reduce hyperglycemia in a manner similar to OADs and help to reduce % HbA1c and hyperlipidemia in the subchronic assay. The combination of EEAc + Met showed the best activity by reducing the hyperglycemia content, % HbA1c, Chol, HDL-c, and LDL-c. Rutin in combination with OADs used in all treatments significantly reduced the hyperglycemia content that is reflected in the reduction in % HbA1c. In relation to the lipid profiles, all combinate treatments helped to avoid an increase in the measured parameters. The results show the importance of evaluating the activity of herbal remedies in combination with drugs to determine their activities and possible side effects. Moreover, the combination of rutin with antidiabetic drugs presented considerable activity, and this is the first step for the development of novel DM treatments.

Hipoglucemia grave en pacientes con diabetes mellitus 2 y azoados normales / Severe hypoglycemia in patients with diabetes mellitus type 2 and normal creatinine serum values

Resumen: ANTECEDENTES: la hipoglucemia grave es causa frecuente de hospitalización en México. OBJETIVO: identificar las características clínicas y de laboratorio asociadas con hipoglucemia grave en pacientes consecutivos con hipoglucemia grave y azoados normales. PACIENTES Y MÉTODO: estudio prospectivo en el que del 11 agosto de 2011 al 31 mayo de 2013 se incluyeron pacientes con hipoglucemia grave y creatinina normal. Se registró edad, sexo, tiempo de evolución de la diabetes mellitus, tratamiento antidiabético, comorbilidades y depuración de creatinina en orina de 24 horas. RESULTADOS: ingresaron 234 pacientes con hipoglucemia grave, 21 9% tenían creatinina normal: 13 mujeres 62% y 8 38% hombres, con edad promedio de 64.76 años límites: 42-84; 13 62% eran mayores de 60 años; 15 71% tenían más de 5 años con diabetes mellitus 2 promedio de evolución de 9.2 años; 15 recibían glibenclamida 71%, 4 en combinación con insulina 19% y 8 con metformina 38%; 2 recibían rosiglitazona más insulina. Cuatro no tenían comorbilidades 19%; 14 tenían hipertensión arterial 71% y 3 neoplasia adenocarcinoma, carcinoma gástrico y carcinoma esofágico; 11 52% ingresaron con pérdida del estado de alerta; 5 con desorientación 24%, 4 con trastornos de conducta 19%, uno con dislalia 5%; 15 de 21 71% tenían grado avanzado de deterioro renal, a pesar de tener azoados normales. CONCLUSIONES: es importante determinar la depuración de creatinina en todos los niveles de atención, única guía para prescribir tratamientos seguros de acuerdo con la función renal. La glibenclamida debe prescribirse con cautela en adultos mayores, con más de 10 años de evolución de la diabetes mellitus 2 y evitarse en los sujetos con insuficiencia renal crónica documentada.

Abstract: BACKGROUND: Severe hypoglycemia is a frequent cause of hospitalization in Mexico. OBJECTIVE: To identify the clinical and laboratory characteristics associated to severe hypoglycemia in consecutive patients with severe hypoglycemia and normal creatinine serum values. PATIENTS AND METHOD: A prospective study was done from August 11, 2011 to May 31, 2013, including patients with severe hypoglycemia and normal creatinine serum values. Age, sex, time of evolution of diabetes mellitus 2, antidiabetic treatment, comorbidities and 24-hour urine creatinine clearance were recorded. RESULTS: From 234 patients with severe hypoglycemia admitted, 21 9% had normal creatinine: 13 women 62% and 8 38% men, with a mean age of 64.76 years range: 42-84; 13 62% were older than 60 years; 15 71% had more than 5 years with DM2 mean evolution of 9.2 years; 15 received glibenclamide 71%, 4 in combination with insulin 19% and 8 with metformin 38%. Two received rosiglitazone plus insulin. Four patients had not comorbidities 19%; 16 had arterial hypertension 71% and 3, neoplasms adenocarcinoma, gastric carcinoma and esophageal carcinoma. Eleven patients 52% were admitted with syncope, 5 with disorientation 24%, 4 with conduct disorders 19% and one with dyslalia 5%; 15 of 21 patients 71% had advanced degrees of renal impairment, despite normal creatinine serum values. CONCLUSIONS: It is important to perform creatinine clearance at all levels of care, the only guide for safe treatments according to kidney function. Glibenclamide should be cautiously prescribed in older adults with a history of more than 10 years of diabetes mellitus 2 and should be avoided in those with documented chronic renal failure.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Simultaneous determination of oral antidiabetic drugs in human plasma using microextraction by packed sorbent and high-performance liquid chromatography.

In this study, a simple method using microextraction by packed sorbent and high-performance liquid chromatography with ultraviolet detection for simultaneous determination of chlorpropamide, gliclazide and glimepiride in human plasma was developed and validated. A fractional factorial design and a complete factorial design were applied to evaluate the parameters which could affect the extraction and desorption steps, respectively. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration/ejection cycles) and in the desorption step (percentage of acetonitrile in the elution solvent and number of aspirations of elution solvent through the device) were statistically significant (p>0.05) when recovery was used as response. The developed method allowed the use of small volumes of sample and solvents and rapid separation by using a fused core column (only 2.2min were needed). This method was fully validated showing selectivity, precision, accuracy and linearity over the range 1.0-50.0µgmL(-1) for chlorpropamide, 1.0-10.0µgmL(-1) for gliclazide and 0.1-1.0µgmL(-1) for glimepiride. Finally, the validated method was applied in the analysis of samples from volunteers containing the three tested analytes.