RESUMEN
UNLABELLED: In order to examine the significance of differences in the triiodothyronine/thyroxine (T3/T4) ratio in the achievement of euthyroidism and in different thyroidal diseases, we studied 1050 subjects: 233 were euthyroid (Eu), 239 hypothyroid (Hypo) with initial TSH levels >15 mU/L, 273 hypothyroid on substitution therapy with L-thyroxine alone and TSH values of 0.35-3.5 mU/L, (hypoRx), 236 hyperthyroid (hyper) and 69 in the acute phase of subacute thyroiditis De Quervain's (DQ). The ratio of T3/T4 was calculated using the conventional values. RESULTS: The values of T3/T4 ratio in the various categories were: Eu= 15.89, Hypo= 24.12, hyper= 19.57, hypoRx= 13.42, DQ= 15.16. The T3/T4 ratio was lower in the hypoRx group than in the EU group (P <0.001), although neither TSH values nor T3 values showed any differences between these two groups, whereas T4 levels were significantly higher in the hypoRx group (Eu= 7.99+/-1.46, hypoRx = 9.11+/-1.58, P< 0.001). The T3/T4 ratio in the DQ group was comparable to that of the Eu group, but significantly lower than the hyper group (P=0.95 between Eu and DQ, P<0.001 between DQ and hyper). CONCLUSIONS: These findings indicate that in hypothyroid patients, L-T4-replacement that is sufficient to maintain a normal serum TSH is accompanied by a serum T4 that is higher than in normal individuals and may not result in an appropriately normal serum T3 concentration. In Thyrotoxicosis, a ratio of total T3/T4 >18.9 suggests Graves' disease or toxic multinodular goiter whereas T3/T4 <16 suggests thyroiditis (subacute or silent).
RESUMEN
The lipid domains of the cell membrane are believed to be one of the sites where biguanides exert their antihyperglycemic effect. We have examined the effects of metformin on the membrane fluidity of intact erythrocytes in vivo and in vitro. Membrane fluidity was measured by monitoring changes in the anisotropy of the fluorescent probe 6-antroyloxystearic acid (6-AS). The erythrocyte membranes from patients with non-insulin dependent diabetes mellitus treated with metformin were more fluid than those from non-insulin dependent diabetes mellitus patients treated by diet or healthy controls. There was no correlation between membrane fluidity and the plasma lipids or the parameters of metabolic control, suggesting that the high fluidity is an effect of metformin itself. Incubation of erythrocytes from healthy controls and diabetic patients treated by diet or glibenclamide with metformin in vitro confirmed that metformin increases the fluidity of erythrocyte membranes. In vitro metformin did not alter the fluidity of membranes from diabetic patients treated with metformin, perhaps because the basal high fluidity due to their in vivo interaction with plasma metformin could be increased no further. Since insulin appears to be required for the antihyperglycemic effect of metformin, the effect of insulin on membrane fluidity was also evaluated. Insulin generally had a small fluidizing effect on erythrocytes in vitro. The fluidizing action of both insulin and metformin could represent a membrane event common to the hormone and drug leading to additive or synergistic effects in vivo.
Asunto(s)
Membrana Eritrocítica/efectos de los fármacos , Hipoglucemiantes/farmacología , Metformina/farmacología , Adulto , Diabetes Mellitus Tipo 2/sangre , Colorantes Fluorescentes , Gliburida/farmacología , Humanos , Técnicas In Vitro , Masculino , Fluidez de la Membrana/efectos de los fármacosRESUMEN
It has been suggested that changes in the properties of cell membranes are involved in an altered insulin action. However, the influence of changes in the distribution of phospholipid classes has not been explored. We investigated 69 obese nondiabetic normoglycemic women (17 patients with impaired glucose tolerance) with varying degrees of insulin sensitivity to determine the phospholipid composition and fluid state of their erythrocyte plasma membranes. The fasting plasma insulin, the homeostasis model analysis of insulin resistance (HOMA), and the integrated area under the insulin curve (AUC-I) after an oral glucose challenge were used as markers of insulin resistance. Results were divided into normal glucose tolerance (NGT) and impaired glucose tolerance. There was a positive correlation in NGT group between the membrane sphingomyelin (SM) content and the fasting plasma insulin (r = 0.523; P < 0.0001), HOMA value (r = 0.483; P < 0.0005), and AUC-I (r = 0.352; P < 0.05) and negative correlations between membrane fluidity determined with two fluorescent probes and plasma fasting insulin (r = 0.320; r = -0.365; P < 0.05) and HOMA value (r = 0.321; r = -0.382; P < 0.05). There were also correlations between SM and the three markers of insulin resistance in the impaired glucose tolerance group. There was no correlation between insulin resistance and other membrane components. Stepwise multiple regression analysis in the NGT group confirmed that the membrane SM content was an independent predictor of plasma fasting insulin, HOMA values, and AUC-I variations. Sphingomyelin could be one of the membrane parameters contributing to insulin resistance.
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Membrana Eritrocítica/metabolismo , Eritrocitos/metabolismo , Hiperinsulinismo/sangre , Fluidez de la Membrana , Obesidad/sangre , Fosfolípidos/metabolismo , Administración Oral , Adulto , Ayuno , Femenino , Glucosa/farmacología , Homeostasis , Humanos , Insulina/sangre , Resistencia a la Insulina , Persona de Mediana Edad , Modelos Biológicos , Obesidad/fisiopatología , Análisis de Regresión , Esfingomielinas/sangreRESUMEN
The increased erythrocyte aggregation observed in diabetes mellitus is mainly due to changes in the balance between aggregating factors and anti-aggregating ones, like albumin. Since chronic hyperglycaemia results in protein glycation, we examined the effect of in vitro glycation of albumin on its anti-aggregating role with blood from 29 Type 1 diabetic patients and 29 healthy controls. After the addition of glycated and unglycated albumin, samples had a glycation level of 24% for healthy controls and 28% for diabetic patients. Erythrocyte aggregation was determined by the analysis of the light backscattered by a blood suspension. Erythrocytes from healthy controls suspended in glycated albumin had significantly higher rates of rouleaux formation (p < 0.01) than in unglycated albumin and increased cohesion of rouleaux (p < 0.05). The erythrocyte aggregation in diabetic patients underwent similar changes (p < 0.01). The time-resolved fluorescence of the single tryptophan residue was monitored to describe the changes in the conformational equilibrium of albumin. The lifetime data showed that the increases in the two lifetime components and in the relative proportion of the major lifetime are in agreement with a conformational change in albumin after glycation. Thus, the changes in albumin conformation could be responsible for the smaller hypoaggregating effect of glycated albumin.
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Diabetes Mellitus Tipo 1/sangre , Agregación Eritrocitaria , Productos Finales de Glicación Avanzada/sangre , Albúmina Sérica/química , Adulto , Femenino , Fluorescencia , Glucosa/química , Productos Finales de Glicación Avanzada/química , Glicosilación , Humanos , Masculino , Conformación Proteica , Triptófano/químicaRESUMEN
OBJECTIVE: To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 +/- 0.60% [mean +/- SD]), 10 with poor BG control (HbA1C 9.48 +/- 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 +/-2.25%, strongly positive ketonuria 3+ and elevated plasma beta-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS: Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS: The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.
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Diabetes Mellitus Tipo 1/sangre , Cetoacidosis Diabética/sangre , Eritrocitos/metabolismo , Fluidez de la Membrana/fisiología , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Cetoacidosis Diabética/etiología , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Factores de RiesgoRESUMEN
Lp(a) has atherogenic and thrombotic properties and is considered to be a major risk factor for the development of atherosclerotic disease. The risk of cardiovascular disease is increased in both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), and Lp(a) has attracted attention as a potential risk factor in diabetic patients. Lp(a) levels are "probably" elevated in IDDM patients and related to altered metabolic control and increased urinary albumin excretion rate or renal insufficiency, although results are controversial. There appears to be a real difference between the Lp(a) of patients with proliferative diabetic retinopathy and those with or without background retinopathy. The plasma Lp(a) level may therefore be associated with microangiopathy in some IDDM patients. However, data relating Lp(a) to complications of diabetes are limited, and the literature is conflicting. The few available data suggest that Lp(a) is not elevated in NIDDM patients and that there is no strong link between blood glucose control and plasma Lp(a). There is no clear evidence as to whether Lp(a) is related to microalbuminuria in NIDDM patients. There is little evidence for a correlation between increased risk of cardiovascular disease and plasma Lp(a) among diabetic patients. However, some diabetic patients with coronary heart disease have elevated plasma Lp(a), which seems to be correlated with genetic factors (especially the isoforms of apolipoprotein a) rather than to diabetes per se. Lp(a) synthesis and catabolism could be influenced by insulin or by diabetes and its metabolic concomitants. The atherogenic and thrombogenic potential of Lp(a) could also be increased in diabetic patients. Plasma Lp(a) should be measured for both IDDM and NIDDM patients. If the Lp(a) level is elevated, it seems reasonable to check the other major vascular risk factors.
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Enfermedades Cardiovasculares/etiología , Diabetes Mellitus/sangre , Angiopatías Diabéticas/etiología , Lipoproteína(a)/sangre , Complicaciones de la Diabetes , Angiopatías Diabéticas/sangre , Humanos , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the prevalence of lower-extremity arterial disease and the sites of arterial obstruction in patients with pancreatic diabetes. PATIENTS AND METHODS: The retrospective study included 83 patients with diabetes due to chronic pancreatitis (age [m +/- SD] 54.5 +/- 9.5 yr, diabetes duration 9.7 +/- 7.4 yr) and 83 patients with idiopathic diabetes were carefully matched for sex, age, diabetes duration and treatment. They were screened for arteriopathy by segmental blood pressures and Doppler ultrasound, and for cardiovascular risk factors. The arterial lesions were classified as proximal (above-knee), distal (below-knee), and combined (both above- and below-knee). RESULTS: Lower extremity arterial disease occurred in 25.3% of pancreatitis patients and in 14.5% of idiopathic diabetes patients (p = 0.08). The sites of obstruction in both groups were similar; proximal obstruction: 4 vs 4 cases; distal: 10 vs 5 cases, combined: 7 vs 3 cases. The prevalence of arteriopathy increased with age and diabetes duration in both groups (p < 0.01). Total cholesterol, LDL cholesterol and apolipoprotein B were lower in the pancreatitis patients (p < 0.01); 92% of these were smokers vs 62% of idiopathic diabetes patients (p < 0.001). CONCLUSIONS: Arteriopathy, assessed by non-invasive tests, has the same prevalence and distribution in chronic pancreatitis and idiopathic diabetes patients, despite their different vascular risk factor profiles. This emphasizes the role of chronic hyperglycaemia and its duration in the pathogenesis of macroangiopathy in diabetic patients.
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Arteriopatías Oclusivas/etiología , Angiopatías Diabéticas/etiología , Pierna/irrigación sanguínea , Pancreatitis/complicaciones , Anciano , Arteriopatías Oclusivas/diagnóstico por imagen , Enfermedad Crónica , Angiopatías Diabéticas/diagnóstico por imagen , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Ultrasonografía DopplerRESUMEN
Red blood cell aggregation in vitro (kinetics and shear resistance) was studied in 13 healthy controls and 13 type I (insulin-dependent) diabetic patients free of severe degenerative complications who were matched for age, sex, and body mass index. Measurements were performed with a device that analyzes the laser light backscattered by a blood suspension. Both the velocity of rouleau formation and the cohesion of the rouleau network were significantly increased in diabetic patients. Plasma viscosity and whole-blood viscosity measured at low shear rate (0.95 s-1) were also significantly elevated in the diabetic group. Multivariate analyses of the whole population sample and the diabetic patients confirmed the influence of plasma proteins on the kinetics of aggregation. Fibrinogen levels, which were close to normal, affected mainly the shear resistance of the aggregates. Triglyceride and apolipoprotein (apo) B levels and indexes of metabolic control or protein glycation (fasting blood glucose and fructosamine) also appeared to influence markedly both the kinetics of rouleau formation and the cohesion of the rouleau networks. These rheological abnormalities occurred in diabetic patients before the appearance of any severe degenerative complications. We suggest that these rheological abnormalities are linked to plasma or erythrocyte factors, and are not due to angiopathy.
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Circulación Sanguínea , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Agregación Eritrocitaria , Adulto , Proteínas Sanguíneas/análisis , Viscosidad Sanguínea , Femenino , Humanos , Lípidos/sangre , Masculino , Análisis Multivariante , Estrés MecánicoAsunto(s)
Diabetes Mellitus Tipo 2/terapia , Glucemia/metabolismo , Colesterol/sangre , HDL-Colesterol/sangre , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Hemoglobina Glucada/análisis , Humanos , Insulina/uso terapéutico , Resistencia a la Insulina , Obesidad , Examen Físico , Negativa del Paciente al Tratamiento , Triglicéridos/sangreRESUMEN
Authors report an original case of mental neuropathy which reveal prolymphocytoid transformation of Chronic lymphocytic leukaemia. They discuss various pathogenic hypotheses which can join these two events; these are evolutive markers of bad prognosis concerning this hemopathy. Clinical, etiopathological and prognostic features of mental neuropathy associated with hemopathies are studied through this case.
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Mentón/inervación , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Prolinfocítica/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Anciano , Humanos , Masculino , PronósticoRESUMEN
Junction scotoma is a classic field defect initially described by Traquair in 1917. Sparse cases have been reported until today. The authors report a silent pituitary adenoma in a 58 year-old female revealed by a junction scotoma. The field defects secondary to insult of chiasma from pituitary tumors besides usual bitemporal hemianopsia are reviewed by the authors. The possibility of minor ophthalmologic symptoms despite voluminous tumor has to be emphasized.