Cyperus esculentus L. protects testis and sperm morphology of hyperglycaemic rats / Cyperus esculentus L. protege la morfología de los testículos y los espermatozoides de ratas hiperglicémicas

Cyperus esculentus L. (tiger nut) is a tuberous plant that promotes and protects reproductive functions, which are usually hampered in diabetics. The present study investigated the effect of Cyperus esculentus tuber extract (CETE) on testicular histology and sperm viability of alloxan-induced hyperglycaemic Wistar rats. Twenty-five adult male Wistar rats weighing 150-200g and grouped into five (n=5): Group 1, the control, administered tap water (20mL/kg), while groups 2-5 were administered a single intraperitoneal dose (120mg/kg b.w.) of alloxan, and each further received orally tap water (20mL/kg), CETE (100mg/kg), CETE (500 mg/kg) and metformin (500 mg/kg), respectively for 21 days. The animals were sacrificed, their sperm collected for analysis, while the testes were harvested, and processed for histology. Results showed significantly increased (p<0.05) blood glucose and testosterone, and significantly decreased (p<0.05) sperm pH, motility, count, morphology and density, as well as disruptions and hypertrophy of the spermatogenic and Sertoli cells of the hyperglycaemic group. There were significant (p<0.05) blood glucose decline, while the sperm parameters and testicular weight improved with normal testicular histology in the 100 mg/kg CETE, 500 mg/kg CETE, and metformin-treated groups compared to the control and hyperglycaemic group. Treatment with CETE showed blood glucose amelioration and improved sperm quality, as well as testicular damage attenuation.

Cyperus esculentus L. es una planta tuberosa que promueve y protege las funciones reproductivas, que generalmente se ven afectadas en los diabéticos. El presente estudio investigó el efecto del extracto de tubérculo de Cyperus esculentus (CETE) sobre la histología testicular y la viabilidad de los espermatozoides de ratas wistar con hiperglicemia inducida por alloxan. Veinticinco ratas Wistar macho adultas que pesaban 150-200 g y se agruparon en cinco (n = 5): el grupo 1, el control, administró agua del grifo (20ml / kg), mientras que los grupos 2-5 se les administró una dosis intraperitoneal única (120 mg / kg p.v.) de alloxan, y agua del grifo por vía oral (20ml/kg), CETE (100 mg/kg), CETE (500 mg/kg) y metformina (500 mg/kg), respectivamente durante 21 días. Los animales fueron sacrificados, su esperma recolectada para su análisis, mientras que los testículos fueron retirados y procesados para histología. Los resultados mostraron un aumento significativo (p<0,05) de la glucosa en sangre y la testosterona, y una disminución significativa (p<0,05) del pH, la motilidad, el recuento, la morfología y la densidad de los espermatozoides, así como interrupciones e hipertrofia de las células espermatogénicas y sertoli del grupo hiperglucémico. Hubo una disminución significativa (p<0,05) de la glucosa en sangre, mientras que los parámetros espermáticos y el peso testicular mejoraron con la histología testicular normal en los grupos de 100 mg / kg de CETE, 500 mg / kg de CETE y tratados con metformina en comparación con el grupo de control e hiperglucémico. El tratamiento con CETE mostró una mejora de la glucosa en sangre y una mejora de la calidad de los espermatozoides, así como atenuación del daño testicular.

Metformin and resveratrol suppress type 2 diabetes mellitus-induced articular cartilage damage in rats associated with the inhibition of inflammation and augmentation of proteoglycans / La metformina y el resveratrol suprimen el daño del cartílago articular inducido por la diabetes mellitus tipo 2 en ratas asociado con la inhibición de la inflamación y el aumento de proteoglicanos

SUMMARY: Induction of osteoarthritis (OA) following diabetes is characterized by a sever inflammation of the joints that can lead to disability. The cartilage content of proteoglycans can substantially be reduced, following the induction of diabetes mellitus associated with inflammation as well as knee joint injury, and the antidiabetic drug metformin combined with the anti-inflammatory agent resveratrol can prevent these deleterious effects. Therefore, insulin-independent diabetes, type 2 diabetes mellitus (T2DM) was induced in Albino rats by streptozotocin (STZ) injection (50 mg/kg) after being fed on a high carbohydrate and fat diets for 2 weeks. The protective group of rats which also received a single injection of STZ was treated daily with metformin (Met; 200 mg/kg) and resveratrol (Res; 30 mg/kg) for 12 weeks. Harvested knee joint tissues were prepared for basic histology stain and for proteoglycans staining using light microscopy. Histology images showed in diabetic rats (T2DM) OA development as demonstrated by profound injury to the knee joint and severe decrease of articular cartilage proteoglycans content, which were substantialy protected by Met+Res. Met+Res also significantly (p< 0.0001) decreased diabetes induced glycemia, dyslipidemia, and the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). In addition, there was a significant correlation between OA and glycemia, dyslipidemia, and inflammation. Collectively, we demonstrate an association between knee joint damage and biomarkers of glycemia, dyslipidemia, and inflammation in diabetes-induced OA, with metformin plus resveratrol providing protective effects.

RESUMEN: La inducción de osteoartritis (OA) después de la diabetes se caracteriza por una inflamación severa de las articulaciones que puede conducir a la discapacidad. El contenido de cartílago de proteoglicanos se puede reducir sustancialmente, luego de la inducción de diabetes mellitus asociada con inflamación y lesión en la articulación de la rodilla sin embargo, el fármaco antidiabético metformina combinado con el agente antiinflamatorio resveratrol puede prevenir estos efectos nocivos. Por lo tanto, se indujo diabetes insulino dependiente, diabetes mellitus tipo 2 (T2DM) en ratas albinas mediante inyección de estreptozotocina (STZ) (50 mg/kg) después de haber sido alimentadas con dietas ricas en carbohidratos y grasas durante 2 semanas. El grupo protector de ratas que también recibió una inyección única de STZ fue tratado diariamente con metformina (Met; 200 mg/kg) y resveratrol (Res; 30 mg/kg) durante 12 semanas. Tejidos de la articulación de la rodilla fueon retirados y teñidos con histología básica y tinción de proteoglicanos usando microscopía óptica. Las imágenes histológicas en ratas diabéticas mostraban (T2DM) desarrollo de OA visualizadas por una lesión profunda en la articulación de la rodilla y una disminución severa del contenido de proteoglicanos del cartílago articular, los cuales estaban sustancialmente protegidos por Met+Res. Met+Res. También disminuyó significativamente (p< 0,0001) la glucemia inducida por la diabetes, la dislipidemia y los biomarcadores inflamatorios, el factor de necrosis tumoral alfa (TNF-α), la interleucina-6 (IL-6) y la proteína C reactiva de alta sensibilidad (PCR-hs). Además, hubo una correlación significativa entre la OA y la glucemia, la dislipidemia y la inflamación. En conjunto, demostramos una asociación entre el daño de la articulación de la rodilla y los biomarcadores de glucemia, dislipidemia e inflamación en la OA inducida por diabetes, con metformina más resveratrol que brindan efectos protectores.

Suppression of diabetes-induced renal inflammatory cell infiltration by metformin associated with the amelioration of renal injury biomarkers / Supresión de la infiltración de células inflamatorias renales de diabetes-inducida, por metformina asociada con la mejora de los biomarcadores de lesión renal

SUMMARY: Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.

RESUMEN: La diabetes y la hipertensión representan la mayoría de los casos de lesión renal crónica que pueden provocar insuficiencia renal. El vínculo entre el antígeno común de los leucocitos (CD45) y la enfermedad renal diabética (DKD) con y sin incorporación de metformina en un modelo animal no se había anteriormente investigado. El objetivo fue evaluar el grado de infiltración de leucocitos en los tejidos renales 10 semanas después de la inducción de diabetes en ratas tratadas con metformina. Además, monitoreamos los parámetros de sangre y orina asociados con la diabetes. El grupo modelo de ratas recibió una inyección de estreptozotocina (STZ; 50 mg/kg) después de ser alimentadas durante 14 días con una dieta alta en grasas (HFD) y continuamente alimentadas con un HFD hasta que fueron sacrificadas, en la semana 12. El grupo protector fue tratado de la misma manera excepto que estos animales fueron recibieron desde el día 1 metformina (200 mg/kg) hasta ser sacrificados, en la semana 12. Los riñones fueron inmunoteñidos con CD45 como marcador de infiltración de leucocitos y examinados por microscopía óptica. Las muestras de orina se analizaron en busca de albúmina y la sangre recolectada se analizó en busca de glucosa, urea, creatinina y biomarcadores de estrés oxidativo y antioxidantes. La lesión renal secundaria a la diabetes se desarrolló como lo demuestra (i) el aumento de la glucosa en sangre, la urea y el malondialdehído (MDA) como marcador de la peroxidación lipídica; y (ii) daño del tejido renal y marcado aumento en los tejidos renales que expresan células positivas para CD45. Los marcadores anteriores fueron inhibidos (p≤0.0006) por metformina. Además, se observó una correlación significativa entre la puntuación de CD45 y la glucemia, la urea, la MDA y la superóxido dismutasa antioxidante (SOD). Por lo tanto, nuestros datos demuestran una asociación entre la infiltración de células inflamatorias CD45+ en los tejidos renales y biomarcadores de daño renal en un modelo de rata con DKD, que fue protegido de manera efectiva por metformina.

Evaluación de la prescripción de hipoglucemiantes orales en población adulta con Diabetes Mellitus Tipo 2 / Evaluation of the prescription of oral hypoglycemic agents in the adult population with type 2 diabetes mellitus

En el nivel primario de atención se detectan errores en la prescripción del tratamiento farmacológico de la diabetes tipo 2. El objetivo de este estudio fue evaluar la calidad de la prescripción de hipoglucemiantes orales en pacientes atendidos en consultorios del médico de la familia del Policlínico Universitario Hermanos Cruz, municipio Pinar del Río, Cuba. Se realizó un estudio de utilización de medicamentos de tipo descriptivo y transversal clasificado dentro de estos como de indicación-prescripción con elementos de esquema terapéutico y de factores que condicionan los hábitos de prescripción. El universo estuvo conformado por 1575 pacientes con diagnóstico de diabetes mellitus tipo 2 tratados con hipoglucemiantes orales que pertenecían a los 20 consultorios médicos de la familia.La muestra de estudio se obtuvo por el método de muestreo no probabilístico (por conveniencia) (n=846). La información se obtuvo de la historia clínica y tarjeta control de los pacientes para adquirir estos medicamentos. Predominó la edad de 40-49 años, el sexo femenino y entre 5-10 años de evolución de la enfermedad. No se usó la primera línea de tratamiento en el 43,6 % de los casos, ningún caso tenía estudios de laboratorio para el uso de la Metformina. La prescripción y dosis fue adecuada no así su uso racional. Las interacciones más frecuentes fueron las farmacocinéticas.El uso racional de hipoglucemiantes orales fue deficiente lo que hace necesario ampliar la divulgación de un protocolo de tratamiento para mejorar el uso de estos fármacos en el nivel primario de atención.

Errors in the prescription of drug treatment for type 2 diabetes are detected at the primary level of care. the purpose of this study was to evaluate the quality of the prescription of oral hypoglycemic agents in patients attended in the family doctor's offices of the Hermanos Cruz University Polyclinic, Pinar del Río distrit, Cuba. A descriptive and cross-sectional study of the use of medications was carried out, classified within these as indication-prescription with elements of the therapeutic scheme and factors that condition prescription habits. The universe was made up of 1575 patients diagnosed with type 2 diabetes mellitus treated with oral hypoglycemic agents who belonged to the 20 family medical offices. The study sample was carried out by the non-probabilistic sampling method (for convenience) (n = 846). The information was obtained from the clinical history and control card of the patients to acquire these medications. The age of 40-49 years, the female sex and between 5-10 years of evolution of the disease predominated. The first line of treatment was not used in 43.6% of the cases; no case had laboratory studies for the use of Metformin. The prescription and dose was adequate, but not its rational use. The most frequent interactions were pharmacokinetic ones.The rational use of oral hypoglycemic agents was deficient, which makes it necessary to expand the dissemination of a treatment protocol to improve the use of these drugs at the primary level of care.

Prevalência de hiperglicemia de estresse em uma unidade de terapia intensiva / Prevalence of stress hyperglycemia in an intensive care unit

Objetivo: Avaliar a prevalência e o manejo da hiperglicemia de estresse em pacientes internados em uma unidade de terapia intensiva. Métodos: Estudo retrospectivo, realizado de janeiro a junho de 2018. Os dados foram obtidos a partir de 582 prontuá- rios eletrônicos, considerando os valores glicêmicos durante a hospitalização, história prévia ou não de diabetes mellitus, causas do internamento, tempo de permanência na unidade de terapia intensiva, presença de complicações durante o internamento e conduta utilizada em caso de hiperglicemia de estresse. Resulta- dos: Dos 582 pacientes internados na unidade de terapia intensi- va, 579 tiveram sua glicemia indicada nos prontuários analisados; 341 (58,9%) apresentaram hiperglicemia em algum momento da internação, sendo a hiperglicemia de estresse caracterizada em 200 pacientes (35%). A duração média de internamento desses pacientes foi de 8,39±10,9 dias, e a causa mais frequente de inter- namento foi devido a pós-operatório por diversas causas, somando 148 indivíduos (74%). Dentro os pacientes, 72 (36%) apresenta- ram alguma complicação. Além disso, 13 casos (6,5%) evoluíram para óbito. Conclusão: Estudos disponíveis sobre alvos de gli- cose em pacientes críticos das unidades de terapia intensiva apresentam difícil interpretação devido às diferenças subs- tanciais no grupo de populações e aos protocolos de gestão de pacientes utilizados em vários centros. Todavia, a prevalência da hiperglicemia de estresse encontrada nesta amostra é se- melhante à de outras casuísticas estudadas. O índice eleva- do de complicações enfatiza a necessidade de padronização nos critérios para diagnóstico e tratamento da hiperglicemia de estresse objetivando melhor prognóstico desses pacientes independentemente da causa do internamento.

Objective: To evaluate the prevalence and management of stress hyperglycemia in patients hospitalized in anintensive care unit. Methods: Retrospective study, carried out from January to June 2018. Data were obtained from 582 electronic medical records, considering glycemic values during hospitalization, existence of previous history of Diabetes Mellitus, causes of hospitalization, length of stay in the intensive care unit, presence of complications during hospitalization, and behavior used in case of stress hyper- glycemia. Results: Of the 582 patients admitted in the ICU, 579 had their glycemia indicated in the charts analyzed: 341 (58,9%) had hyperglycemia in a certain moment of hospitalization, with stress hyperglycemia being present in 200 patients (35%). The average duration of hospitalization of these patients was 8,39 ± 10,9 days, and the most frequent cause of hospitalization was postoperative for various causes, totaling 148 individuals (74%). Of the patients, 72 (36%) presented some type of complication and 13 patients (6,5%) died. Conclusion: Available studies on glucose targets in critical intensive care unit patients are difficult to be interpre- ted because of substantial differences in the study populations and of patient management protocols used at various centers. However, the prevalence of stress hyperglycemia found in this sample is similar to that of other study groups. The high com- plication rate emphasizes the need for standardization of the criteria for diagnosis and treatment of stress hyperglycemia aiming at a better prognosis of these patients regardless of the cause of hospitalization.

Control glicémico perioperatorio / Perioperatory glycemic control

Diabetes is the most common endocrinopathy, in 2014, 8.6% of the population suffered from diabetes, and it was responsible for at least 3.7 million deaths per year. It is estimated that by that by 2050 more than 30% of the population will have this disease. In cardiovascular surgery, it is described that 5.2% of patients are undiagnosed diabetics and this rises to 10% -28% in non-cardiac surgeries. The adverse results are markedly high in those patients with poor glycemic control including an increase of more than 50% in mortality, as well as an increase in respiratory infections, surgical site infection, urinary infection, heart attack and acute kidney injury among others. During the preoperative period of patients with diabetes, it is important to review glycemic control and its current treatment, in addition to providing the patient instructions on how to adjust medications. Intraoperatively, any condition that leads to an uncontrolled increase in surgical stress must be controlled, since this in turn generates hyperglycemia. Knowledge of insulins, their pharmacology and schedules is essential to maintain blood glucose intraoperatively in normal ranges. Different practical algorithms are proposed for the correct and safe management of hyperglycemia in the perioperative period. All care should be continued in the postoperative period defining the continuity of the insulin therapies established and the postoperative care of the patient.

La diabetes es la endocrinopatía más común, en 2014, el 8,6% de la población padecía diabetes siendo responsable de 3,7 millones de muertes por año. Se estima que para el 2050 más del 30% de la población tendrá diabetes. En cirugía cardiovascular el 5,2% de los pacientes son diabéticos no diagnosticados, cifra que aumenta hasta 10%-28% en cirugías no cardíacas. Los resultados adversos son marcadamente elevados en aquellos pacientes con mal control incluyendo un aumento del 50% en la mortalidad, así mismo, incremento de infecciones respiratorias, infección del sitio quirúrgico, infección urinaria, infarto agudo de miocardio y lesión renal aguda, entre otros. Durante el preoperatorio de pacientes con diabetes, es importante revisar el control glucémico y su tratamiento, además de proporcionar al paciente instrucciones por escrito sobre cómo ajustarlo. En el intraoperatorio se debe controlar cualquier condición que lleve a un aumento del estrés quirúrgico pues este a su vez genera hiperglucemia. Es fundamental el conocimiento de las insulinas, su farmacología y esquemas para mantener glucemias en el intraoperatorio en rangos normales. Se proponen diferentes algoritmos prácticos para el correcto y seguro manejo de la hiperglucemia en el perioperatorio. La atención debe continuarse en el posoperatorio definiendo continuidad de terapias insulínicas instauradas y el adecuado cuidado del paciente.

Hypolipidemic, hipoglycemiant and antioxidant effects of Myrcia splendens (Sw) DC in an animal type 2 diabetes model induced by streptozotocin / Efectos hipolipemiante, hipoglucemiante y antioxidante de Myrcia splendens (Sw) DC en un modelo animal de diabetes tipo 2 inducido por estreptozotocina

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.

Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.

Metformin for prevention of cesarean delivery and large-for-gestational-age newborns in non-diabetic obese pregnant women: a randomized clinical trial

ABSTRACT Objective To evaluate the use of metformin for preventing cesarean deliveries and large-for-gestational-age (LGA) newborn (NB) outcomes in non-diabetic obese pregnant women. Subjects and methods This is a randomized clinical trial with obese pregnant women, divided into 2 groups: metformin group and control group, with followed-up prenatal routine. The gestational age of participants was less than or equal to 20 weeks and were monitored throughout entire prenatal period. For outcomes of delivery and LGA newborns, absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated with a 95% confidence interval (CI). Results 357 pregnant women were evaluated. From the metformin group (n = 171), 68 (39.8%) subjects underwent cesarean delivery, and 117 (62.9%) subjects from the control group (n = 186) had intercurrence (p < 0.01). As for the mothers' general characteristics, there was significance for marital status (p < 0.01). Maternal-fetal results presented reduced preeclampsia (p < 0,01). Primary prophylactic results presented an ARR of 23.1 times (95% CI: 13.0-33.4) with NNT of 4 (95% CI: 3.0-7.7) and no significant values for LGA NB (p > 0.01). Secondary prophylactic outcomes presented decreased odds ratio for preeclampsia (OR = 0.17, 95% CI: 0.10-0.41). Conclusion The use of metformin reduced cesarean section rates, resulted in a small number of patients to be treated, but it did not reduce LGA NB. Administering a lower dosage of metformin from the early stages to the end of treatment may yield significant results with fewer side effects. Arch Endocrinol Metab. 2020;64(3):290-7

Underutilization of insulin and better metabolic control. A NOVA clinic experience

SUMMARY OBJECTIVE To present the results of metabolic control in patients with type 2 Diabetes Mellitus from a private clinic in Northern Mexico, METHODS This cross-sectional study used retrospective data obtained from electronic records from a private outpatient clinic at the end of 2018. Inclusion criteria were a diagnosis of T2DM and age ≥ 18 years. Baseline characteristics (age, gender, drug use) were reported. The achievement of glycated hemoglobin goals was established as <7%. RESULTS A total of 3820 patients were evaluated. Their mean age was 59.86 years (+/-15.01). Of the population, 46.72% were men, and 53.28% were women. Glycated hemoglobin goals were adequate in 1872 (54%) patients. There were 3247 patients (85%) treated with oral medications, of which 1948 (60%) reported glycated hemoglobin less than 7%. Insulin use was reported in 573 (15%) patients, with 115 (20%) reporting glycated hemoglobin less than 7%. The most frequently used basal insulin was glargine in 401 (70%) patients. CONCLUSIONS Our findings are clearly higher than the control rate reported by our national health surveys of 25% with glycated hemoglobin < 7%, but similar to that reported in other countries. The most commonly used therapeutic scheme was the combination of oral hypoglycemic agents. The percentage of cases that include insulin in their treatment was lower. Clinical inertia to insulin initiation and intensification has been defined as an important cause of this problem.

RESUMO OBJETIVO Apresentar os resultados do controle metabólico de pacientes com Diabetes Mellitus tipo 2 em uma clínica privada no norte do México, MÉTODOS Este estudo transversal utilizou dados retrospectivos obtidos em prontuários eletrônicos de um ambulatório privado no final de 2018. Os critérios de inclusão foram o diagnóstico de DM2 e idade ≥ 18 anos. Características basais (idade, sexo, uso de drogas) foram relatadas. A realização de metas de hemoglobina glicada foi estabelecida como <7%. RESULTADOS Um total de 3820 pacientes foram avaliados. A média de idade foi de 59,86 anos (+/- 15,01). Da população, 46,72% eram homens e 53,28% eram mulheres. Objetivos de hemoglobina glicada foram adequados em 1872 (54%) pacientes. Havia 3247 pacientes (85%) tratados com medicamentos orais relatando em 1948 (60%) menos de 7%. O uso de insulina foi relatado em 573 (15%) pacientes, com 115 (20%) relatando menos de 7%. A insulina basal mais utilizada foi a glargina, em 401 (70%) pacientes. CONCLUSÕES Nossos resultados são claramente mais altos do que a taxa de controle relatada por nossos levantamentos nacionais de saúde de 25% com hemoglobina glicada <7%, mas semelhante à relatada em outros países. O esquema terapêutico mais utilizado foi a combinação de hipoglicemiantes orais. A porcentagem de casos que incluem insulina no tratamento foi menor. A inércia clínica à iniciação e intensificação da insulina tem sido definida como uma importante causa desse problema.

Physical exercise and metformin in gestational obesity and prevention on gestational diabetes mellitus: a systematic review / Exercício físico e metformina na obesidade gestacional e prevenção diabetes mellitus gestacional: revisão sistemática

Abstract Objectives: identify the action of metformin and physical activities to reduce weight gain and prevent mellitus diabetes in obese pregnant women. Methods: the electronic search was performed in PubMed / MEDLINE, LILACS, Web of Science, Scopus and Cochrane library databases between 2008 and 2018. The selection took place between April and July 2018, through the descriptors "pregnancy, obesity, metformin, treatment, exercise". A protocol was programmed and consecutively a selective research on the inclusion / exclusion phase. The "PICO" strategy was used. Population: obese pregnant women. Intervention: physical exercises and metformin. Control: The main indicator established was therapeutic outcomes with physical activity and metformin. Outcome of interest: body weight control. Results: by selecting the database, 3,983 articles were identified on the topic of interest. After selecting and eligibility, only 16 scientific studies were selected, of which 81.25% were clinical trials related to diet programs, physical activity, metformin use and possible outcomes, 18.75% were prospective cohort on causes of obesity in gestation and its association with gestational mellitus diabetes and preventive therapies. The study pointed out the possibility of adapting physical therapy programs with the correct metformin dosage for a greater control in gestational weight gain. However, there is a need for greater awareness and changes in habits for obese woman during the gestational period. Conclusions: the drug presents similarity to physical activity by activating AMPK and may be added to treatments that propose changes in pregnant women's lifestyle to reduce weight gain and prevent gestational diabetes mellitus with a better understanding of the optimal dosage. Thus, the study suggests the use of metformin is not only for the prevention and the intercurrence of gestational diabetes mellitus, but a strictly careful investigation allowing its use to non-diabetic obese pregnant women.

Resumo Objetivos: identificar a ação da metformina e da atividade física para redução do ganho de peso e prevenção do diabetes mellitus em gestantes obesas. Métodos: a busca eletrônica foi realizada nas bases de dados PubMed/MEDLINE, LILACS, Web of Science, Scopus e biblioteca Cochrane entre 2008 e 2018. A seleção ocorreu entre abril e julho de 2018, através dos descritores "gravidez, obesidade, metformina, tratamento, exercício". Programou-se um protocolo e consecutivamente uma etapa seletiva de inclusão/exclusão das pesquisas. Utilizou-se a estratégia "PICO". População: gestantes obesas. Intervenção: exercícios fisicos e metformina. Controle: o principal comparador estabelecido foi o desfecho terapêutico com atividade fisica e metformina. Desfecho de interesse: controle do peso corporal. Resultados: através da seleção do banco de dados, 3.983 artigos foram identificados sobre o tema de interesse. Após as etapas de seleção e elegibilidade, apenas 16 estudos científicos foram selecionados, dos quais 81,25% ensaios clinicos referentes aos programas de dieta, atividade física, uso da metformina e possíveis desfechos, 18,75% coorte prospectiva sobre as causas da obesidade na gestação e sua associação com o diabetes mellitus gestacional e terapêutica preventiva. O estudo apontou a possibilidade de se adequar programas de terapias físicas com a dosagem correta de metformina para um maior controle no ganho de peso gestacional. No entanto, existe a necessidade de uma maior concientização e mudanças de hábitos da mulher obesa durante o período gestacional. Conclusões: a droga apresenta semelhança com a atividade física ao ativar o AMPK e pode somar aos tratamentos que propõem mudanças no estilo de vida das gestantes para reduzir o ganho de peso e prevenir o diabetes mellitus gestacional com a necessidade de um melhor entendimento sobre a dosagem ideal. Desta forma, o estudo sugere que o uso da metformina não seja apenas para prevenção e intercorrências do DMG, mas também com uma investigação estritamente cuidadosa para possibilitar o seu uso em grávidas obesas não diabéticas.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

Use of flash glucose-sensing technology in patients with type 2 diabetes treated with liraglutide combined with CSII: a pilot study

Glycemic variability (GV) may be linked to the development of diabetic complications by inducing inflammation, oxidative stress, and endothelial dysfunction. Flash glucose monitoring (FGM) provides a novel method of continuously monitoring interstitial glucose levels for up to 14 days. This study randomly assigned poorly controlled type 2 diabetes mellitus patients treated with metformin and multiple daily injections of insulin (n=60) to either continuous subcutaneous insulin infusion (CSII) treatment or CSII in combination with liraglutide (CSII+Lira) treatment for 14 days during hospitalization. GV was assessed using a FGM system; weight and cardiometabolic biomarkers were also evaluated. The coefficient of variation was significantly reduced in the CSII+Lira group (P<0.001), while no significant change was observed in the CSII group. The changes differed significantly between the two groups in mean amplitude of glycemic excursions (P=0.004), standard deviation (P=0.006), and the percentage of time in the target range (4-10 mmol/L, P=0.005 and >10 mmol/L, P=0.028). The changes in mean of daily differences, interquartile range, and percentage of time in hypoglycemia (<3.3 mmol/L) and hyperglycemia (>13.9 mmol/L) identified by FGM showed no difference. Treatment with liraglutide increased serum adiponectin [33.5 (3.5, 47.7) pg/mL, P=0.003] and heme oxygenase-1 levels [0.4 (-0.0, 1.8) ng/mL, P=0.001] and reduced serum leptin levels [-2.8 (3.9) pg/mL, P<0.001]. Adding the glucagon-like peptide-1 analog liraglutide improved GV, weight, and some cardiometabolic risk markers. The FGM system is, therefore, shown to be a novel and useful method for glucose monitoring.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

Nueva generación de insulinas: glargina U300: Resumen de evidencia clínica / New generation of insulins: glargine U300. Summary of clinical evidence

La diabetes mellitus tipo 2 tiene evolución crónica y progresiva, prevalencia creciente y aún es diagnosticada tardíamente. Esto conlleva mayor incidencia de complicaciones crónicas, con incremento de costos en salud. Existe retraso en el inicio de insulinoterapia por causas relacionadas tanto al paciente como al médico. A pesar de los avances en su tratamiento, una baja proporción de enfermos logra control glucémico adecuado. La alta prevalencia de hipoglucemia en pacientes insulino-tratados, impulsó el desarrollo de una nueva generación de insulinas basales de acción prolongada, mayor estabilidad con menor variabilidad y riesgo de hipoglucemias. El programa EDITION evaluó la eficacia y seguridad de glargina U300 vs. glargina U100 en pacientes con diabetes tipo 1 y 2, en distintas etapas de la enfermedad. Glargina U300 es una nueva formulación de insulina glargina con perfil farmacocinético y farmacodinámico más estable y prolongado que glargina U100. Glargina U300 demostró eficacia y tolerabilidad comparable a glargina U100, con descenso significativo del riesgo de hipoglucemias nocturnas y en 24 horas, aportando mayor flexibilidad en el horario de inyección, con una ventana de 6 horas. Además, no se observó mayor aumento de peso que con glargina U100. El estudio Bright (2018) comparó glargina U300 vs. degludec U100, demostrando mayor beneficio en relación al riesgo de hipoglucemia con Gla-300 durante el período de titulación. Gla-300 es una insulina basal de última generación, disponible para mejorar el control metabólico, con menor riesgo de hipoglucemia.

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.

Inercia clínica en el tratamiento con insulina en el primer nivel de atención / Clinical inertia in insulin treatment at the primary care level

Resumen Introducción: Poco se ha evaluado el rechazo de los médicos a prescribir insulina a sus pacientes; el retraso en intensificar el tratamiento impide una atención adecuada y de calidad. Objetivo: Identificar la percepción de los médicos acerca de las barreras para iniciar la insulina en los pacientes con diabetes. Método: Por Índice Smith y análisis multivariado, en 81 médicos familiares se evaluó la relevancia y agrupación de los conceptos relacionados con las barreras para la prescripción de insulina. Resultados: 35.8 % de los médicos mostró confianza en prescribir insulina; casi la mitad calificó la intensificación del tratamiento entre moderadamente y poco importante (39.5 y 6.2 %). Las barreras se relacionaron con el médico (39.5 %), el paciente (37 %), el tratamiento con insulina (11.1 %) y la institución (6.2 %); 6.2 % de los médicos no percibió ninguna barrera. Las barreras se agruparon en cinco factores, que explicaron 62.48 % de la varianza: cultura de los pacientes, falta de habilidades, miedo a los eventos adversos, inseguridad y falta de capacitación. Conclusión: La inercia clínica no resultó de una condición clínica compleja o comorbilidades del paciente, sino de la percepción del médico y de su confianza en sus habilidades clínicas y comunicativas.

Abstract Introduction: Refusal of physicians to prescribe insulin to their patients has been scarcely evaluated; the delay in treatment intensification hinders adequate and quality care. Objective: To identify the perception of primary care physicians about barriers to initiate insulin treatment in patients with diabetes. Method: Using the Smith Index and multivariate analysis, the relevance and grouping of concepts related to barriers to insulin prescription were assessed in 81 family doctors. Results: Only 35.8% of physicians showed confidence for prescribing insulin; almost half of them rated treatment intensification between moderately and little important (39.5% and 6.2%). Barriers were related to the physician (39.5%), the patient (37%), insulin treatment (11.1%) and the institution (6.2%); 6.2 % of physicians did not perceive any barrier. The barriers were grouped in 5 factors that explained 62.48% of the variance: patient cultural level, lack of medical skills, fear of adverse events, insecurity and lack of training. Conclusion: Clinical inertia was not the result of a complex medical condition or patient comorbidities, but of doctor’s perception and confidence in his/her clinical and communication skills.

Fatores associados ao controle glicêmico de pessoas com diabetes mellitus / Factors associated with glycemic control in people with diabetes mellitus

Resumo Investigar os fatores associados ao controle glicêmico de pessoas com diabetes mellitus (DM). Estudo transversal realizado com 746 pessoas com DM tipo 2 e 40 anos ou mais de idade. Elegeu-se as seguintes variáveis: socioeconômicas, dados clínicos, estilo de vida e o risco para o desenvolvimento de úlceras nos pés. A coleta dos dados ocorreu por meio de entrevista, análise do prontuário e exame clínico dos membros inferiores. Utilizou-se o modelo de regressão múltipla de Poisson para determinação das razões de prevalência (RP) brutas e ajustadas da alteração do exame de hemoglobina glicada (HbA1c), considerada como variável dependente desta pesquisa, sendo esta classificada como elevada quando o valor apresentava resultado superior a 7%. Identificou-se a elevação da HbA1c em 68,9% dos participantes e foi mais prevalente em indivíduos com idade entre 50 e 69 anos (RP = 1,38/IC95% = 1,09-1,75), os que faziam uso de insulina (RP = 1,35/IC95% = 1,24-1,47), obesos (RP = 1,14/IC95% = 1,03-1,25) e naqueles que possuíam risco de ulceração nos pés (RP = 1,14/IC95% = 1,09-1,28). Os indivíduos na faixa etária entre 50 e 69 anos, os que faziam uso de insulina, os obesos e os que possuíam risco de ulceração nos pés apresentaram maiores taxas de prevalência de alteração na hemoglobina glicada.

Abstract Investigate the factors associated with the glycemic control in people with diabetes mellitus (DM). Cross-sectional study with 746 people with type-2 DM of age 40 or older. The following variables were selected: socioeconomic, clinical data, lifestyle and the risk of developing foot ulcers. Data collection occurred through interviews, medical record analysis and clinical examination of the lower limbs. We used the Poisson multiple regression model to determine the crude and adjusted prevalence ratios (PR) of the glycemic alteration. The alteration in the glycated hemoglobin (HbA1c) test was considered as a dependent variable in this study, which has been classified as high when the result was higher than 7%. The alteration in HbA1c was present in 68.9% of the participants and was more prevalent in individuals aged between 50 and 69 (PR = 1.38/IC95% = 1.09-1.75), who were taking insulin (PR = 1.35/IC95% = 1.24-1.47), obese (PR = 1.14/IC95% = 1.03-1.25) and who had foot ulceration risk (PR = 1.14/IC95% = 1.09-1.28). Individuals aged between 50 and 69; the ones who used insulin; the obese ones; and those who had a risk of foot ulceration, presented higher prevalence rates of alteration in the glycated hemoglobin.

The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.

The characteristics of blood glucose fluctuations in patients with fulminant type 1 diabetes mellitus in the stable stage

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.