RESUMEN
Seventeen TM patients with impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM) and hyperinsulinism were treated for 12 months with acarbose (100 mg. orally with breakfast, lunch and evening meals). An improvement in glucose tolerance was observed in 2 out of 11 TM patients with IGT and in all TM patients with NIDDM. Acarbose does not appear to directly improve insulin resistance but may have an indirect effect delaying the absorption of glucose of complex carbohydrates and disaccharides. It may be concluded that acarbose may represent a useful first-line therapy for improving glycemic control in TM patients with abnormalities of glucose homeostasis and hyperinsulinism.
Asunto(s)
Acarbosa/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Intolerancia a la Glucosa/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Talasemia beta/tratamiento farmacológico , Adulto , Área Bajo la Curva , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Humanos , Insulina/sangre , Talasemia beta/sangre , Talasemia beta/complicacionesRESUMEN
The pathogenesis of diabetes in thalassaemia is complex and multifactorial. Understanding the sequence of abnormalities in the progression from normal glucose tolerance to impaired glucose tolerance may help in the formulation of ways to intervene in this process. In our study, we assessed the effects of acarbose, an alpha-glucosidase inhibitor, in five young adult thalassaemic patients with hyperinsulinism and normal oral glucose tolerance test (OGTT). A decrease of fasting insulin levels, insulin peak and area under the curve (AUC) after OGTT, were observed in thalassaemic patients receiving acarbose therapy. These values remained unchanged in an untreated group of eight thalassaemic patients. We believe that acarbose may have a potential role in the treatment of abnormalities of glucose homeostasis and insulin release.
Asunto(s)
Acarbosa/administración & dosificación , Glucosa/metabolismo , Hiperinsulinismo/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Talasemia beta/tratamiento farmacológico , Adulto , Área Bajo la Curva , Glucemia/metabolismo , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Hiperinsulinismo/metabolismo , Resistencia a la Insulina/fisiología , Talasemia beta/metabolismoRESUMEN
Some selected oxidative stress parameters were measured in 56 Fanconi anaemia (FA) patients (42 untransplanted and 14 transplanted), 54 FA heterozygotes (parents) and 173 controls. Untransplanted FA patients showed a highly significant increase in leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) (P = 0.00003) and a borderline increase (P = 0.076) in urinary levels of 8-OHdG versus child controls. These increases were more pronounced in female FA patients (P = 0.00005 for leukocyte 8-OHdG and P = 0.021 for urinary 8-OHdG). Female FA patients also displayed a highly significant excess of spontaneous chromosomal breaks versus male patients (P = 0.00026), in the same female:male ratio ( approximately 1.4) as detected for both leukocyte and urine 8-OHdG levels. Plasma methylglyoxal (MGlx) levels were increased in untransplanted FA patients versus child controls (P = 0.032). The increases in leukocyte and urinary 8-OHdG and in MGlx levels were detected in young FA patients (< or =15 years), whereas patients aged 16-29 years failed to display any differences versus controls in the same age group. A significant increase in oxidized:reduced glutathione (GSSG:GSH) ratio was observed (P = 0.046) in the FA patients aged < or =15 years, whereas those aged 16-29 years, both untransplanted and transplanted, displayed a decrease (P = 0.06) in the GSSG:GSH ratio versus the controls of the respective age groups. No significant changes were detected in plasma levels of vitamin C, vitamin E or uric acid. Transplanted FA patients showed lesser alterations in leukocyte 8-OHdG and in GSSG:GSH ratio versus untransplanted patients. The parents of FA patients displayed a significant increase in plasma MGlx levels (P = 0.0014) versus adult controls. The results suggest a gender- and age-related modulation of oxidative stress in FA patients. The observed increase in urinary 8-OHdG in untransplanted FA patients suggests a proficient removal of oxidized DNA bases.