Association of Patient Profile with Glycemic Control and Hypoglycemia with Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta-Analysis

ABSTRACT Aims: To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. Methods: A post hoc patient-level metaanalysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin ? oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (\65 and C 65 years), body mass index (BMI; \ 30 and C 30 kg/m2), age at onset (\40, 40–50, and [ 50 years), and diabetes duration (\ 10 and C 10 years). Results: Reduction in HbA1c was comparable between insulins, regardless of subgroup. The lower risk of C 1 nocturnal (00:00–05:59 h) confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of C 1 confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. Conclusions: Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. Funding: Sanofi. Plain Language Summary: Plain language summary available for this article. Keywords: Glycated Hemoglobin A; Hypoglycemia; Insulin Glargine; Type 2 Diabetes PLAIN LANGUAGE SUMMARY Treatments for patients with type 2 diabetes aim to reduce the levels of blood glucose and can include injections with insulin. However, care must be taken to prevent blood glucose levels falling too low (a state called hypoglycemia). Previous studies have shown that insulin glargine 300 units/mL (Gla-300) provides similar reductions in blood glucose levels as insulin glargine 100 units/mL (Gla-100) but is less likely to cause hypoglycemia. However, different patients may respond differently to treatments depending on their individual clinical and biological characteristics. The aim of this study was to evaluate how different profiles of patients with type 2 diabetes responded to Gla-300 and Gla-100 injections. Patients were grouped by different ages, weights, age at diabetes diagnosis, and number of years since diagnosis of diabetes. We found that Gla-300 and Gla-100 reduced glycated hemoglobin (HbA1c; a marker of blood glucose control over the previous 2–3 months) similarly, regardless of how patients were grouped. However, patients treated with Gla-300 were less likely to experience hypoglycemia than those treated with Gla-100, and this association was also true regardless of different patient characteristics. We therefore concluded that Gla-300 is an effective and safe treatment in patients with type 2 diabetes, regardless of their age, weight, age at diabetes diagnosis, and years since diagnosis

Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients

Background: Glucocorticoids commonly cause drug-induced diabetes. This association is well recognized but available evidence does not answer clinically relevant issues in subjects without diabetes. Methods: Thirty-five individuals without diabetes with a recent diagnosis of acute lymphoblastic leukemia or nonHodgkin’s lymphoma on high-dose glucocorticoid therapy were studied. Close systematic monitoring of fasting and postprandial glycemia and fasting insulin determinations, HOMA-insulin resistance and HOMA β-cell function were performed. The primary objective was to define the incidence of secondary diabetes in patients treated with highdose glucocorticoids. Secondary objectives were to specify the intensity, the moment it appears and the evolution of hyperglycemia, in addition to the risk factors, mechanisms and impact of continuous and cyclical glucocorticoids on the development of hyperglycemia. Results: Mean age of patients was 38.4 ± 18.7 years. The incidence of diabetes was 40.6% and was found after the first week; half the time it occurred between the second and fourth. Two-thirds spontaneously normalized by eight weeks. Continuous glucocorticoid administration had a higher incidence of fasting hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in cases of diabetes. Conclusions: High-dose prednisone for 2 to 3 months produced an elevated incidence of diabetes, usually with mild hyperglycemia occurring between the second and fourth week, normalizing spontaneously in all cases. Hyperglycemia was more frequent with continuous doses and occurred in cases with increased insulin resistance. The clinical and therapeutic characteristics of our participants, who were otherwise healthy, could represent the clinical setting of many patients with illness from other medical areas that might require high doses of GC for six to twelve weeks

Prevalencia de diabetes tipo 2 e hipertensión arterial en adultos de nivel económico bajo de Monterrey, México

Antecedentes: la hiperglucemia es signo característico de un grupo enfermedades, la diabetes tipo 2 abarca del 90 al 95% de los casos, y provoca alta morbilidad, e incapacidad e incluso muerte prematura. Objetivo: determinar la prevalencia de diabetes mellitus tipo 2, prediabetes y la de HA en adultos en área urbana de bajo nivel económico en Monterrey, México. Método: estudio de corte transversal con selección aleatoria de adultos (hombres y mujeres no embarazadas ni lactando) en una comunidad de bajo nivel económico. Se obtuvo glucemia capilar y plasmática en ayuno y 2h-poscarga oral de 75 g glucosa. Diagnósticos según criterios del American Diabetes Association 2004. Se presenta prevalencia con intervalo de confianza (IC95%) y regresión múltiple en inferencia de factores. Resultados: la prevalencia de diabetes mellitus tipo 2 fue 14.1% (9.6-18.6%), prediabetes 12.8% (8.5-17.1) y de hipertensión arterial 26.24% (20.4-32.4%). La edad, el índice de masa corporal y género justifican 38% de la variación de la hipertensión arterial (r = 0.616, todas p < 0.001); pero sólo 5% (r = 0.23) de la variación glucémica fue explicado por la edad (p < 0.01) y el índice de masa corporal (p < 0.05). Conclusiones: la prevalencia de hipertensión arterial fue la esperada, pero la de diabetes mellitus 2 sugiere ser más alta que en reportes previos. En esta población la adiposidad no justifica la alta prevalencia de diabetes mellitus 2, ni de prediabetes. ABSTRACT Background: Hyperglycemia is a characteristic sign of several diseases. In the case of type 2 diabetes, it has an effect on 90 to 95% of the patients. It produces a high morbidity, incapacity and even death. Objective: To determine the prevalence of type 2 diabetes mellitus, pre-diabetes and hypertension in a low-income urban area in Monterrey, Mexico. Method: A random, cross-sectional study was done in a low-income urban population in Monterrey, Mexico. Patients who had participated in a baseline glycemic study from 1992 to 1993 were re-examined. The concentration of capillary and plasmatic glucose on fasting and two hour post-load oral glucose (75 g) were determined. The diagnoses were established following the criteria of the American Diabetes Association 2004. Multiple regression analyses were done to infer the factors related with glycemia; the confidence interval was 95%. Results: The type 2 diabetes mellitus prevalence was 14.1%, pre-diabetes 12.8% and the one for hypertension was 26.24%. Age, body mass index and gender prognosticated in an independent manner the values of hypertension (p < 0.001). Glycemia was prognosticated based on age (p < 0.01) and body mass index (p < 0.05). Conclusions: Prevalence of type 2 diabetes was higher in low-income adult patients, but hypertension prevalence remained within normal parameters. In this population, the body mass index did not justify the high prevalence of type 2 diabetes nor that of pre-diabetes

Aptitud de los alumnos de pregrado de la carrera de Medicina ante dos modelos de evaluación: El caso de Endocrinología.

Antecedentes: La Facultad de Medicina de la UANL inició en agosto del 2006 un nuevo plan de estudios y un modelo educativo basado en el aprendizaje y en la participación más intensa del alumno. Esta modificación en la estrategia de formar a los futuros médicos requiere ser evaluada científicamente con el propósito de medir si los cambios esperados con la implementación del plan de estudios y del modelo educativo, están ocurriendo. Objetivo: Comparar la aptitud de los alumnos del curso de pregrado de endocrinología ante dos métodos de evaluación. Método: Comparación de dos exámenes como proceso de evaluación ante dos planteamientos académicos: el actual (basado en la aplicación del conocimiento, casos clínicos) y el próximo anterior (basado en la memorización de conocimientos). Se contrastó la aptitud de los alumnos del nuevo plan de estudios (n = 74) vs. los alumnos del plan anterior (n = 137), ante el mismo examen. Resultados: Los alumnos del nuevo plan de estudios tuvieron una aptitud casi idéntica al ser evaluados con el examen actual y con el aplicado en ciclos anteriores (73.4 + 7.8 vs. 72.9 + 10.7, respectivamente) p = 0.2553. El porcentaje de aprobación fue de un 71 vs. 67%. Al comparar la aptitud de los alumnos del plan actual y el anterior ante un mismo examen, la aptitud fue muy favorable en el grupo de alumnos del nuevo plan de estudios (74.7 ± 10.7 vs. 56.0 ± 9.3), p< 0.0001. Conclusiones: La combinación de un modelo educativo centrado en el aprendizaje, en una acentuada participación del alumno en la clase, en una forma de evaluación que incentiva el estudiar la clase diaria y en la aplicación de exámenes dirigidos a evaluar la aplicación del conocimiento como en la vida real de un médico, son los aspectos que debemos fortalecer en el proceso de formación de nuestros futuros médicos

The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3

Abstract Aims To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs. Methods A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, openlabel, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use. Results Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups. Conclusions Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use

Hepatogenous diabetes: Is it a neglected condition in chronic liver disease?

Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus (HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease

Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P≤0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL) (P=0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r=0.78; P≤0.001, r=0.74;  P≤0.001, and r=0.71;  P≤0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P=0.001) and free T and DHEA-S declined significantly (P=0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction

COMPARACIÓN DEL PORCENTAJE DE GRASA CORPORAL ESTIMADO POR LA FÓRMULA DE DEURENBERG Y EL OBTENIDO POR PLETISMOGRAFÍA POR DESPLAZAMIENTO DE AIRE

La pletismografía por desplazamiento de aire (BOD POD) y la fórmula de Deurenberg son dos métodos de predicción de composición corporal y de estimación de porcentaje de grasa corporal que han sido validados y utilizados en diversas poblaciones. En este estudio comparamos el porcentaje de grasa corporal estimado por ambos métodos para una población aleatoria de sujetos adultos. Doscientos noventa y seis sujetos (edad 34.73 ± 13.27 años, índice de masa corporal [IMC] 28.51 ± 5.83 kg/m2, porcentaje de grasa corporal por BOD POD 31.62 ± 12.13 %, porcentaje de grasa corporal por fórmula 33.22 ± 10.46 %, p no significativa entre ambos métodos), fueron reclutados, 31% con IMC &lt; 24.99 kg/m2 o de bajo peso, 29% con IMC entre 25 y 29.99 kg/m2 o de peso normal/sobrepeso, 35% con IMC entre 30 y 39.99 kg/m2 o con obesidad, y 3% con IMC &gt;40 kg/m2 o con obesidad mórbida. De los 97 hombres (34% del total) y 199 mujeres (66% del total), las mujeres tuvieron de forma significativa mayor edad y mayor porcentaje de grasa corporal por ambos métodos que los hombres, independientemente de su IMC. La fórmula presentó tendencia a proporcionar un mayor porcentaje de grasa corporal que el BOD POD, siendo significativo solamente en mujeres de bajo peso y obesidad mórbida, y en hombres con IMC entre 25 y 39.99 kg/m2. Abstract Air-displacement plethysmography (BOD POD) and the predictive formula proposed by Deurenberg are two of many validated methods reported for assessment of body composition and percentage of body fat calculation that have been used in diverse populations. In this study we compared the percentage of body fat calculated by both methods in a random sample of adult subjects. Two-hundred and ninety-six subjects  (age 34.73 ± 13.27 years, body mass index [BMI] 28.51 ± 5.83 kg/m2, percentage of body fat by BOD POD 31.62 ± 12.13 %, percentage of body fat by formula 33.22 ± 10.46 %, p non-significant between methods), were recruited, 31% with BMI &lt; 24.99 kg/m2 or low-weight, 29% with BMI between 25 and 29.99 kg/m2 or normal weight-overweight, 35% with BMI between 30 and 39.99 kg/m2 or obese, and 3% with BMI &gt;40 kg/m2 or severely obese. Of the 97 men (34% of the total) and 199 women (66% of the total), women were significantly older and had a significantly greater percentage of body fat by both methods compared to men, independent of their BMI. The formula tended to yield a greater percentage of body fat than the BOD POD, with significant differences in low-weight and severely obese women, and in men with BMI between 25 and 39.99 kg/m2. Palabras clave: grasa corporal, fórmula de Deurenberg, pletismografía por desplazamiento de aire, BOD POD, índice de masa corporal.

Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis

AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis. METHODS: In total, 100 patients with compensated liver cirrhosis and normal fasting plasma glucose were included. Fasting plasma insulin (FPI) levels were measured, and oral glucose tolerance test (OGTT) was performed. According to OGTT results two groups of patients were formed: those with normal glucose tolerance (NGT) and those with SAGT. Patients were followed every three months. The mean follow-up was 932 d (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and predictive factors of death were analyzed using the Cox proportional hazard regression model. RESULTS: Of the included patients, 30 showed NGT and 70 SAGT. Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs 71.6%, P = 0.02). Differences in survival were significant only after 3 years of follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for EndStage Liver Disease (MELD) scores were independent predictors of death. The causes of death in 90.3% of cases were due to complications related to liver disease. CONCLUSION: SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh and MELD scores were independent negative predictors of survival

Efecto del ejercicio cardiovascular en las mujeres con obesidad sobre las concentraciones de la adiponectina, leptina y factor de necrosis tumoral-alfa

Introducción: La relación de las hormonas adiponectina, leptina y factor de necrosis tumoralalfa del tejido adiposo sobre el proceso aterogénico es uno de los modelos más prometedores en la medicina preventiva. Los numerosos ensayos realizados para identificar el efecto del ejercicio sobre estas hormonas no han sido claros en el tipo de rutina de ejercicio y esfuerzo físico calculado que contribuya al cambio de las concentraciones plasmática en mujeres con obesidad