RESUMEN
The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case-control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3-43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Neuropatías Diabéticas/complicaciones , Enfermedades del Pie/complicaciones , Anciano , Estudios de Casos y Controles , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/etiología , Neuropatías Diabéticas/diagnóstico por imagen , Neuropatías Diabéticas/patología , Femenino , Enfermedades del Pie/diagnóstico por imagen , Enfermedades del Pie/patología , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica , PronósticoRESUMEN
AIMS: Decreased chemosensitivity to hypercapnia, a common finding in Type 1 diabetes mellitus, seems related to autonomic neuropathy. We proposed to verify whether simple neuroautonomic cardiovascular tests or indexes of severity of diabetes and respiratory impairment can identify patients with such a dysfunction, but no clinical evidence of autonomic neuropathy. METHODS: Forty patients with Type 1 diabetes, 20 with autonomic neuropathy according to the results of a standardized test battery, were studied and compared with 40 normal subjects matched by age and sex. Spirometry and pulmonary diffusing capacity for carbon monoxide were performed. The chemosensitivity to hypercapnia was tested by the rebreathing method. RESULTS: There was no significant difference between patients with and without autonomic neuropathy in chemosensitivity to hypercapnia, as expressed by the ventilation response to increasing end-tidal pressure of carbon dioxide; however, it was lower in the whole group of patients with diabetes than in control subjects (1.71 ± 0.80 vs. 2.45 ± 1.11 l⻹ min⻹ mmHg, respectively, P=0.002). No significant correlation was found between ventilation response to increasing end-tidal pressure of carbon dioxide and the results of autonomic tests. In patients with diabetes mellitus, the ventilatory response to hypercapnia significantly correlated with pulmonary diffusing capacity for carbon monoxide (Spearman's rho=0.387, P=0.013) and this was the only variable significantly associated with ventilation response to increasing end-tidal pressure of carbon dioxide in a multiple regression model. CONCLUSIONS: Chemosensitivity to hypercapnia was depressed in patients with diabetes mellitus, irrespective of autonomic neuropathy, in comparison with control subjects. The correlation with pulmonary diffusing capacity for carbon monoxide suggests that microcirculatory damage might contribute to depress the central chemosensitivity.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/metabolismo , Monóxido de Carbono/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Neuropatías Diabéticas/metabolismo , Hipercapnia/metabolismo , Capacidad de Difusión Pulmonar , Adulto , Enfermedades del Sistema Nervioso Autónomo/etiología , Monóxido de Carbono/efectos adversos , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/etiología , Femenino , Humanos , Hipercapnia/complicaciones , Masculino , Persona de Mediana Edad , Ventilación Pulmonar , Pruebas de Función RespiratoriaAsunto(s)
Alendronato/uso terapéutico , Artropatía Neurógena/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Resorción Ósea/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Enfermedad Aguda , Artropatía Neurógena/metabolismo , Neuropatías Diabéticas/metabolismo , Humanos , InflamaciónRESUMEN
Although thyroid disorders related to the end-stage renal disease (ESRD) are well known, there are discordant data on the function and morphology of the thyroid gland after renal transplantation (RT). The objective of this cross-sectional, case-control study was to investigate the prevalence and risk factors for disorders in the thyroid function and morphology after a successful RT. Fifty consecutive patients (25 females, 25 males) with fully functioning allograft were enrolled. Their age at transplant ranged from 23 to 44 yr (median, 38) and their post-RT follow-up lasted 15-86 months (median, 23). One hundred healthy subjects matched for sex, age and body mass index (BMI) were included as controls. Serum free thyroid hormones, TSH, thyroglobulin, thyroid hormone-binding globulin (TBG) and iodine urinary excretion were determined; ultrasonographic exam of the thyroid gland was performed in all subjects. Age, gender, time elapsed from RT, dialysis duration, kidney function, type of immunosuppression and corticosteroid dose were considered as possible influencing factors for the thyroid function. Hypothyroidism was found in 6% of patients, "low T3 syndrome" in 52%, while another 26% had free T3 (FT3), free T4 (FT4) and TSH in the lowest third of the normal range, suggesting inhibition of the whole hypothalamic-pituitary-thyroid (HPT) axis. Iodine excretion and prevalence of anti-thyroid antibodies were similar in both patients and controls. There was no significant difference in the thyroid function according to different immunosuppressive regimens. In patients, an ultrasonographic exam revealed a very variable thyroid volume ranging from 7.2 to 24.8 ml. Solid nodules were detected in 12 (24%) cases and cystic lesions in another four (8%); they were proven negative at cytological examination. Dialysis duration was longer in patients with thyroid nodules than in those without (p<0.05). Inhomogeneous hypoechoic pattern typical for chronic thyroiditis was more frequent than its biochemical expression. In conclusion, a high prevalence of abnormal thyroid morphology was found in patients after a successful RT, being partly related to a previous uremia. Abnormalities in the thyroid function are likely an expression of the post-transplant general and immunological conditions. Endocrinological follow-up is advisable in patients after RT, in order to discriminate thyroid dysfunctions which need specific treatments from those that can only be followed-up, avoiding inappropriate treatments of biochemical abnormalities.
Asunto(s)
Trasplante de Riñón , Glándula Tiroides/anatomía & histología , Glándula Tiroides/fisiología , Adulto , Autoanticuerpos/sangre , Autoantígenos/inmunología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inmunosupresores/farmacología , Yoduro Peroxidasa/inmunología , Yodo/orina , Proteínas de Unión a Hierro/inmunología , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Caracteres Sexuales , Tiroglobulina/sangre , Tiroglobulina/inmunología , Enfermedades de la Tiroides/diagnóstico por imagen , Enfermedades de la Tiroides/epidemiología , Pruebas de Función de la Tiroides , Glándula Tiroides/diagnóstico por imagen , Hormonas Tiroideas/sangre , Tirotropina/sangre , UltrasonografíaRESUMEN
Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and vitamin D alone, group 2 received the same treatment in combination with hormone replacement therapy (HRT), group 3 received risedronate (35 mg weekly, orally for 1 year) and group 4 zoledronic acid (3 monthly doses of 4 mg (intravenous)). All groups were similar for age, body mass index, underlying disease and time elapsed from transplant. Lumbar and femoral bone mineral density (BMD) were measured at baseline and after 12 months, together with serum osteocalcin and urinary hydroxyproline. At 12 months, a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2. Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck. Zoledronic acid increased significantly both lumbar and femoral BMD. In groups 3 and 4 the hydroxyproline excretion was significantly reduced, while osteocalcin mildly increased only in group 4. In conclusion, bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Hipogonadismo , Osteoporosis/tratamiento farmacológico , Trasplante de Células Madre , Adolescente , Adulto , Anemia Aplásica/complicaciones , Anemia Aplásica/terapia , Anemia Aplásica/orina , Densidad Ósea/efectos de los fármacos , Femenino , Terapia de Reemplazo de Hormonas/métodos , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/orina , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/terapia , Trastornos Linfoproliferativos/orina , Osteoporosis/etiología , Osteoporosis/orina , Trasplante HomólogoRESUMEN
To investigate the relationships between the GH-IGF-I axis and the atherosclerotic profile, we designed this open, observational, prospective study. Peak GH after GHRH+arginine (ARG) test, serum IGF-I and IGF binding protein-3 (IGFBP-3), lipid profile, homeostasis model assessment (HOMA) index and intima-media thickness (IMT) at common carotid arteries were measured in 174 healthy individuals (92 women, 82 men, aged 18-80 yr). Exclusion criteria for this study were: 1) body mass index (BMI) > or = 30 kg/m2; 2) personal history of cardiovascular diseases; 3) previous or current treatments of diabetes or hypertension; 4) previous corticosteroids treatment for longer than 2 weeks or estrogens for longer than 3 months; 5) smoking of more than 15 cigarettes/day and alcohol abuse. Subjects were divided according to age in decade groups from < 20 to > 70 yr. BMI increased with age, as did systolic and diastolic blood pressures, although they remained in the normal range. The GH peak after GHRH+ARG test was significantly higher in the subjects aged < 20 yr than in all the other groups (p < 0.01), but was similar in the remaining groups. An inverse correlation was found between the IGF-I z-score and total/HDL-cholesterol ratio (p = 0.02) and mean IMT (p = 0.0009); IGFBP-3 z-score and mean IMT (p = 0.043); IGF: IGFBP-3 molar ratio and total/HDL-cholesterol ratio (p < 0.0001) and mean IMT (p < 0.0001). Atherosclerotic plaques were found in 7 out of 12 subjects (53.8%) with a z-IGF-I score from < or = -2 to -1, in 4 out of 63 (6.3%) with a z-IGF-I score from -0.99 to 0.1 out of 66 (1.5%) with a z-IGF-I score from 0.1 to 1 and none of the 33 subjects with an IGF-I z-score >1 (p = 0.006). At multi-step regression analysis, age was the best predictor of HDL-cholesterol levels and mean IMT, IGF-I level was the best predictor of total cholesterol and total/HDL-cholesterol ratio, the IGF-I/IGFBP-3 molar ratio was the best predictor of triglycerides levels. The z-scores of IGF-I and IGFBP-3 were the second best predictors of mean IMT after age. In conclusion, IGF-I and IGFBP-3 were negatively correlated with common cardiovascular risk factors, studied as total/HDL-cholesterol ratio, and/or early atherosclerosis, studied as IMT at common carotid arteries. The prevalence of atherosclerotic plaques, though not hemodinamically significant, was higher in the subjects having a z-score of IGF-I of < or = -2 to -1. Our results support a role of the IGF/IGFBP-3 axis in the pathogenesis of atherosclerosis.
Asunto(s)
Arteriosclerosis/fisiopatología , Biomarcadores/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arterias Carótidas/anatomía & histología , Homeostasis , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/fisiología , Lípidos/sangre , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Valores de Referencia , Túnica Íntima/anatomía & histologíaRESUMEN
Osteoporosis is a common disorder, especially among elderly post-menopausal women. Elderly women are often affected by co-morbidities, impaired gastrointestinal function and reduced mobility; therefore, the treatment strategy for their osteoporosis can be difficult. In this randomized pilot study, we have investigated the effects of a 12-month treatment with neridronate on bone mineral density (BMD), bone turnover markers and quality of life (QoL). The study included 40 women (age, 65-80 yr; post-menopausal period, >15yr) from a single osteoporosis centre. Twenty women received a monthly im injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone. Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free-deoxypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin levels were determined. For the QoL assessment, the Italian version of the SF-36 test was administrated. Spine and hip BMD rose by 6.6 +/- 3 and 4.2 +/- 2.3%, respectively (p < 0.05), after 12 months of neridronate treatment. Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months. The mean decrease at 12 months ranged from 38 +/- 11% for sCTX to 25.2 +/- 15% for ufDPD (p < 0.001, all). The mean improvement in QoL in the treated group was 45.7% for bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for emotional role functioning and 12% for physical role functioning. The changes observed in BMD, turnover markers and QoL in the untreated group were ns. The intermittent neridronate administration was easily manageable and well tolerated. In conclusion, neridronate currently represents a valid option for the treatment of osteoporosis, since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective.
Asunto(s)
Difosfonatos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Densidad Ósea/efectos de los fármacos , Difosfonatos/efectos adversos , Femenino , Humanos , Masculino , Osteoporosis/psicología , Proyectos Piloto , Calidad de VidaRESUMEN
The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Early changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass and strength, reduced exercise tolerance, thinned skin, decreased strength and impaired quality of life. These observations led to hypothesize that the elderly could be GH deficient and would benefit from GH treatment. However, the effects of GH treatment in healthy elderly subjects by randomized and controlled studies are less promising than initially hypothesized. The etiopathology of age-related bone loss is multifactorial including menopause, andropause, somatopause and secondary hyperparathyroidism. GH has multiple effects on bone, either direct or mediated by IGF-I, stimulating osteoblast proliferation as well as osteoclast differentiation. Consequently, decline in GH secretion reduces bone turnover that causes osteopenia in young adults, but it has been hypothesized that it could protect against fractures in elderly subjects. The increase of bone remodeling achieved by GH therapy may be helpful in elderly men and women who have severely decreased bone turnover and impaired osteoblastic function. In conclusion, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism. However, GH plays a role in metabolism and bone physiology throughout the human life span, although there is insufficient evidence for a clear therapeutic role of rhGH in aging. Thus, more data are needed to define the effects of somatopause to identify who could potentially benefit from the effects of somatotropic treatment.