Glycemic effects of simvastatin: Where do we stand?

ABSTRACT In clinical practice, simvastatin is usually used in the treatment of dyslipidemia patients and those at risk of or with established cardiovascular disease. However, previous studies have shown that simvastatin has the potential to affect glycemic parameters as it reportedly reduced insulin secretion and sensitivity. The exact mechanism by which simvastatin affects glycemia is still unknown, but previous studies have postulated the involvement of the glucose-insulin secretion mechanism. This review focuses on the effects of simvastatin, either alone or in combination with other lipid lowering agents, antidiabetics and antihypertensives, on glucose homeostasis. Some studies have reported that simvastatin might impair the levels of glucose metabolism markers in the blood while others have reported no effect or improvement in glycemia.

A utilização de agentes hipoglicemiantes no tratamento de pacientes com síndrome dos ovários policísticos / The use of hipoglycemic agents on the treatment of patients with polycystic ovary syndrome

A síndrome dos ovários policísticos é a mais comum afecção endócrina na idade reprodutiva, acometendo 5 a 10 porcento das mulheres. Caracteriza-se por anovulação crônica, anormalidades menstruais e hiperandrogenismo laboratorial e ou clínico. O principal distúrbio na fisiopatologia ainda é desconhecido, mas há importantes evidências de que a resistência insulínica, hiperandrogenismo e alterações na liberação pulsátil das gonadotrofinas estejam envolvidos. Além das gonodatrofinas, fatores de crescimento e outros peptídeos participam da regulação do desenvolvimento folicular ovariano e da esteroidogênese e podem ter participação na SOP. Além disso, sabe-se que muitas mulheres com esta síndrome têm resistência insulínica, que pode ser corrigida pelos agentes sensibilizadores do receptor de insulina. Nesta revisão, analisou-se a ação da tiazolidinediona rosiglitazona em amenizar a sintomatologia na SOP, corrigindo a hiperinsulinemia. Sugere-se, então, que a rosiglitazona é alternativa para a correção da resistência insulínica em mulheres com a síndrome dos ovários policísticos.

The polycystic ovary syndrome is the most common endocrine-gynecological disorder of premenopausal women, affecting 5 - 10 percent of this population. It is characterized by chronic anovulation, menstrual disturbance and laboratorial and or clinic hyperandrogenism. The primary pathophysiological defect is unknown, but important characteristics include insulin resistance, androgen excess and abnormal gonadotropin dynamics. Growth factors, such as IGF-I, and other peptides have also been shown to play an important role in the regulation of ovarian follicular maturation and steroidogenesis. These factors might have important role in PCOS. Furthermore, some patients with PCOS may have insulin resistance and the insulin-sensitizing drugs may correct this condition. In this review, we analyzed the action of the thiazolidinedione rosiglitazone on decreasing SOP symptoms and regulating hyperinsulism. Our review suggests that rosiglitazone is an alternative to ameliorate insulin resistance in women with polycystic ovary syndrome.

Insulinorresistencia / Insulin resistance

La resistencia insulínica o insulinorresistencia (IR) es una disminución en la función biológica de esta hormona caracterizada por un alto nivel de la insulina plasmática que es requerido para mantener la homeostasis metabólica.Se ha estimado que aproximadamente un 25% de individuos tienen IR. Su estudio ha cobrado gran importancia en los últimos años en el ámbito médico, pues se ha demostrado que la IR conduce al desarrollo de un “síndrome de insulinorresistencia” (SIR), que comprende un conjunto de alteraciones metabólicas (hiperinsulinismo, obesidad visceral, hipertensión arterial sistólica y diastólica y dislipidemia). Todas estas alteraciones son factores de riesgo conocidos de enfermedad cardiovascular, siendo ésta una de las principales causas de morbilidad y mortalidad a nivel mundial. Fue Reaven quien en 1988 sugirió que la diabetes mellitus, la hipertensión arterial y la dislipemia eran factores que tendían a ocurrir en un mismo individuo en la forma de un síndrome, al que denominó “X”, en el que la IR constituía el mecanismo fisiopatológico básico.El incremento en la incidencia de enfermedades como la diabetes tipo 2, enfermedad cardiovascular y obesidad, es producido en muchos casos, por el aumento en la prevalencia de IR en la población, lo que podría atribuirse, en parte, a los cambios en el estilo de vida que ha experimentado la sociedad occidental a lo largo de las últimas décadas.

Insulin resistance (IR) is a decrease of the biological function of this hormone characterized by a high level of plasmic insulin which is required for the metabolic homeostasis.It is estimated that approximately 25% of people have IR. Its’ study has acquired great importance in the last years, because it has been demonstrated to lead to an insulin resistance syndrome (IRS), which includes various metabolic disorders: hiperinsulinesm, visceral obesity, systolic and diastolic hypertension, dislipidemia. All these alterations are well known to be risk factors for coronary heart disease, constituting one of the main causes of morbimortality worldwide.It was reaven who suggested in 1988, that diabetes mellitus, arterial hypertension and dislipidemia are factors which tended to occur in this the same individual as a syndrome, which he demonstrated “X”, where the IR constituted the basic fisiopathological mechanism.The increase in the incidence of diseases such as DM2, cardiovascular disease, and obesity is due mainly, to the increase in the prevalence of IR among the population, which could be attributed to the life style changes experimented by the occidental society during the last decades.

Mast cell changes in experimental diabetes: focus on attenuation of allergic events

The prevalence of atopic diseases and diabetes is increasing worldwide though the concurrence of these pathologies in individual patients is found less frequent than it would be predicted. Moreover, co-existence of diabetes and allergy is generally marked by attenuation of their respective symptoms, and effective treatment of one disease exacerbates the other. This review gives an update of the state-of-the-art concerning the intercurrence of allergy and diabetes, particularly focusing on the consequences to the allergen-evoked vascular and cellular changes. It is proposed that the reduction in mast cell numbers and reactivity may be a pivotal mechanism behind the mutual exclusion phenomenon.

Niveles plasmáticos de insulina en pacientes con cáncer de mama: su posible valor pronóstico / Insulin plasmatic level in patients with breast carcinoma, its possible pronostic value

La insulina, miembro de la familia de factores de crecimiento que incluyen al factor de crecimiento tipo insulina I (IGF-I) y II (IGF-II), presenta efectos mitogénicos sobre células epiteliales mamarias normales y malignas (Goodwin y col., 2002). Se postula que altos niveles de insulina permiten identificar mujeres con una mala evolución de su cáncer de mama, en quienes deberán aplicarse estrategias terapéuticas más efectivas. Se estudiaron 32 pacientes con cáncer de mama, de las cuales 18 presentaron carcinoma ductal invasor, incluidos 3 multifocales (56 por ciento), 6 carcinoma lobulillar infiltrante (19 por ciento), 3 carcinoma papilar (10 por ciento) y el resto otros tipos (15 por ciento). Dos pacientes (7 por ciento) presentan diabetes mellitus no-insulino dependiente. Los niveles de insulina plasmática en ayunas determinados por RIA (Insulin-CT kit) resultaron en: 18 pacientes (56 por ciento) con niveles normales (5,5 a 19,9 µUI/ml), el resto (44 por ciento) con insulinemias superiores al normal. La insulinemia plasmática en ayunas en voluntarias sanas resultó ser de 13,9ñ4,3 µUI/ml (n=10)...

Effects of insulin sensitizing agent on clomiphene induced ovulation in the polycystic ovary syndrome

This study aimed to determine whether reducing hyperinsulinaemia with metformin would increase the ovulatory response to clomiphene. The study was conducted at Al-Azhar University Hospitals between March 1999 to May 2001. One hundred women who met the PCOS eligibility criteria were included in the study and randomly assigned into 2 groups [50 patients each]. G-I received 50 mg of clomiphene twice daily starting from the third day of the cycle for 5 days plus 500mg of metformin 3 times daily for 6 months. G-II received clomiphene as in G-I plus placebo 3 times daily for 6 months. The main outcome measures included body weight, body mass index [BMI], menstrual pattern LH, FSH, LH: FSH ratio, free testosterone, sex hormone binding globulin [SHBG], fasting insulin and ovulation and pregnancy rate. It was found that the body weight and BMI were significantly reduced in group I while they were not significantly changed in group II. No significant changes were found in waist- hip ratio in both groups. Of 40 patients who completed 6 month course of treatment in G-I, 32 restored normal menstruation versus only 4.3% of women in G-II. After 6 months of therapy in GI, there was significant reduction in the levels of LH, LH: FSH ratio, free testosterone, fasting insulin and significant increase in SHBG, while no significant changes were observed in serum FSH concentration. On the other hand, there was no significant changes in the hormonal pattern in women in G-II. Women in G-I had a better ovulation and pregnancy rate [84% and 20%, respectively] than those in G-II [12% and 8%, respectively]

Resistência à insulina: métodos diagnóstico e fatores que influenciam a açäo da insulina / Insulin resistance: diagnostic methods and factors that influence the insulin action

Os autores apresentam uma definição de resistência à insulina e discutem os métodos diagnósticos desde o padrão-ouro - o "clamp" euglicêmico hiperinsulinêmico, passando pela prova de supressão da insulina, a infusão contínua de glicose, a prova de tolerância à glicose endovenosa com um modelo matemático mínimo, até o teste de tolerância à insulina. Analisam também a glicemia e insulina basais e após sobrecarga oral de glicose. Finalmente mostram fatores que influenciam a ação da insulina, como: peso corporal, condicionamento físico, pêso ao nascimento, tipo de fibra muscular predominante, hormônios, densidade capilar e fluxo no músculo esquelético, dieta, idade e hereditariedade.

Insulin resistance in essential hypertension

The study was conducted on a total number of 31 non obese adults of both sexes. They were divided into 2 groups: 21 otherwise healthy, untreated hypertensive patients and 10 normal controls. All the subjects were tested by routine investigations; including liver and kidney function tests. They were exposed to an oral glucose insulin tolerance test extended for two hours with simultaneous serum potassium assessment. We restricted our study on those with a normal glucose tolerance test. Our patients showed significant hyperinsulinemia of all the samples of the curve, and in spite of this, relative hyperglycemia. Insulin sensitivity was studied by the [A] value, the insulin area and lastly the glucose/insulin ratio. In all the patients, we found statistically significant insulin resistance as compared to the control subjects by the 3 equations, with a P value < 0.001. The degree of this resistance was not found to be in concordance with the degree of hypertension, thus pointing to other factors; e.g. dietary factors, degree of physical activity or the duration of hypertension as related to the degree of this resistance. The potassium levels were normally responsive to the released insulin thus excluding it as a parameter of insulin resistance