RESUMEN
Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT.
Asunto(s)
Amiloide/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Insulina/metabolismo , Adulto , Amiloide/sangre , Biomarcadores/sangre , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Secreción de Insulina , Polipéptido Amiloide de los Islotes Pancreáticos , Cinética , Obesidad/sangre , Estado Prediabético/sangre , Radioinmunoensayo , Valores de Referencia , Factores de TiempoRESUMEN
Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.
Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares/fisiopatología , Ritmo Circadiano/fisiología , Glucosa/metabolismo , Hipopituitarismo/fisiopatología , Adenoma/complicaciones , Adenoma/terapia , Neoplasias Encefálicas , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Prueba de Tolerancia a la Glucosa , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Humanos , Hipopituitarismo/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
Miglitol (BAYm 1099), an alpha-glucosidase inhibitor, reduces the postprandial increase of blood glucose and serum insulin levels in type II (non-insulin-dependent) diabetes mellitus, as shown in short-term studies. In this study, the effects of long-term miglitol treatment on metabolic control, C-peptide secretion, hepatic glucose output, and peripheral insulin sensitivity (euglycemic clamp) were tested in 15 type II diabetic patients (8 receiving insulin, 7 receiving oral hypoglycemic agents). For 8 wk they received either miglitol (300 mg/day) or placebo with a double-blind crossover design that had a 4-wk washout period between treatments. Miglitol therapy induced a reduction of postprandial blood glucose levels (miglitol compared with placebo; areas under the curve; P less than .002), whereas fasting blood glucose levels were not influenced. Miglitol caused a slight reduction of glycosylated hemoglobin levels (mean +/- SE miglitol and placebo 9.50 +/- 0.3 and 10.0 +/- 0.4%, respectively; P less than .05), which was more pronounced in insulin-treated patients. Miglitol caused a reduction of postprandial C-peptide increase (P less than .03). Hepatic glucose output (both in the basal state and during euglycemic clamp conditions) and peripheral insulin sensitivity were not influenced by miglitol therapy. Specific side effects were observed in 11 patients; in 6 patients only to a moderate degree. Long-term miglitol treatment induces a persistent reduction of postprandial blood glucose increase. This effect is more pronounced in type II diabetic patients on insulin therapy, which can cause a moderate improvement of overall metabolic control.
Asunto(s)
Glucemia/análisis , Péptido C/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inhibidores de Glicósido Hidrolasas , Insulina/sangre , Hígado/metabolismo , 1-Desoxinojirimicina/análogos & derivados , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Glucosamina/efectos adversos , Glucosamina/análogos & derivados , Glucosamina/farmacología , Glucosamina/uso terapéutico , Humanos , Iminopiranosas , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the effects of long-term high-dose oral magnesium (Mg) therapy (30 mmol/day) in patients with type II diabetes. Low plasma magnesium levels have been reported in type II diabetes and are associated with insulin resistance and diabetic late complications. RESEARCH DESIGN AND METHODS: Forty patients with type II diabetes and hypomagnesemia were observed in a randomized double-blind placebo-controlled trial for 3 months (body mass index: 28 +/- 4 kg/m2; HbA1c: 7.4 +/- 0.8%). Plasma and urine magnesium and metabolic control parameters were determined, and side effects were considered, especially with regard to patients' compliance. RESULTS: A significant increase in plasma magnesium levels was observed after 3 months of treatment (Mg: 0.73 +/- 0.8 vs. 0.81 +/- 0.1 mmol/l), reaching magnesium levels of the control group (0.88 +/- 0.8 mmol/l; NS); metabolic control, however, was not altered (HbA1c: 7.2 +/- 0.7 vs. 7.4 +/- 0.9%). Six months after the end of the trial, plasma magnesium declined to pretreatment levels (Mg: 0.73 +/- 0.07 mmol/l). The prevalence of side effects was high at the beginning and was reduced significantly during treatment. CONCLUSIONS: We conclude that oral magnesium replacement therapy corrects hypomagnesemia after a minimum treatment period of 3 months. These observations might be important for the prevention of diabetic late complications.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/tratamiento farmacológico , Magnesio/uso terapéutico , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Método Doble Ciego , Hemoglobina Glucada/análisis , Humanos , Magnesio/sangre , Magnesio/orina , Deficiencia de Magnesio/metabolismo , Persona de Mediana Edad , Factores de Tiempo , Triglicéridos/sangreRESUMEN
GH and/or growth factors are thought to play a role in the pathogenesis of diabetic retinopathy. In addition, the occurence of retinal changes mimicking diabetic retinopathy in two GH-deficient (GHD) patients receiving GH replacement therapy (GHRT) has recently been reported. The present study was performed to evaluate whether this was a coincidence or whether GHRT might regularly induce retinal changes. Sixty-one GHD patients on GHRT with a mean age of 42.5 +/-17.3 yr were examined by one ophthalmologist (AR). The mean duration of GHRT was 8.4 +/- 3.7 yr in childhood onset and 3.5 +/- 2.1yr in adult onset patients. Plasma insulin-like growth factor I concentrations were 76.4 +/- 49.6 ng/mL before GHRT and 244.3 +/- 119.2 ng/mL while receiving GHRT with a dose of 1.7 +/- 0.7 IU/day. After pupil dilatation with tropicamide, fundus examinations of both eyes were performed using a Volk 90 diopter fundus lens with a slit lamp (Haag Streit, Bern, Switzerland). In none of the patients were vascular or retinal changes like macular edema, microaneurysms, hemorrhages, hard exsudates, cotton wool spots, preproliferative signs, or proliferations found. The optic discs were also normal in all patients. We conclude, therefore, that long-term GHRT can be administered safely in GHD patients without an increased risk of retinal changes.
Asunto(s)
Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/uso terapéutico , Terapia de Reemplazo de Hormonas , Retina/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127 +/- 3 versus 139 +/- 6 mm Hg and 129 +/- 4 versus 142 +/- 4, respectively; p less than 0.05). Fasting blood glucose (190 +/- 21 versus 152 +/- 15 mg/dl; p less than 0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Hidroclorotiazida/farmacología , Piridinas/farmacología , Adulto , Glucemia/análisis , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Isradipino , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To investigate whether serum levels of lipid peroxides measured as thiobarbituric-acid-reactive substances (TBARS) differ in type I and type II diabetic patients, whether serum levels correlate with late sequelae of diabetes, and whether serum levels of free vitamin E correlate with levels of lipid peroxidation by-products. PATIENTS AND METHODS: The relationship among lipids, glycosylated hemoglobin A1c (HbA1c), lipid peroxides measured as TBARS, and free vitamin E was determined in 158 patients. Fifteen of the 77 patients with type I diabetes and 39 of the 81 patients with type II diabetes had clinically apparent peripheral vascular disease or coronary artery disease, or both. RESULTS: Compared with control subjects, serum levels of TBARS were found to be significantly elevated (P < 0.001) in diabetic patients, and type II diabetic patients had significantly higher levels (P < 0.001) than type I patients. Both type I and type II diabetic patients with good metabolic control (HbA1c < 6.5%) had significantly lower (P < 0.005) TBARS levels than patients with poor metabolic control, but all groups had higher levels than the control group. Type II patients with angiopathy had significantly higher levels of TBARS than patients without angiopathy. Free vitamin E levels in control subjects and diabetic patients did not differ statistically. CONCLUSION: Serum levels of TBARS were significantly increased in all patients suffering from diabetes mellitus, whereby TBARS levels did not depend on the total amount of circulating lipids. It can be suggested that the enhanced lipidperoxidation is contributed to an increased formation of free radicals in diabetes mellitus.
Asunto(s)
Diabetes Mellitus/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Adulto , Anciano , Complicaciones de la Diabetes , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Peroxidación de Lípido/fisiología , Masculino , Persona de Mediana Edad , Ácido Úrico/sangre , Vitamina E/sangreRESUMEN
Diabetes mellitus is associated with disturbances of the hemostatic system, which might contribute to the development of diabetic vascular disease. We investigated the effect of metabolic improvement by insulin therapy on the haemostatic system in 61 patients with type 2 diabetes mellitus and secondary sulfonylurea failure compared with 45 healthy control subjects matched for age, sex and BMI. Median age was 65, median diabetes duration 10 years. Median HbA1c (10%) and fructosamine (4.0 mM) levels were elevated before induction of therapy and decreased significantly within 6 months of insulin treatment to 7.5% and 3.0 mM, respectively (p < 0.0001). Compared with control subjects, median plasma levels of fibrinogen (317 vs 286 mg/dl), coagulation factor VII activity (1.1 vs 0.89 U/l), von Willebrand factor (1.6 vs 1.3 U/l), D-dimer (105 vs 86 micrograms/l), protein C:Ag (1.24 vs 0.95 U/l), total protein S:Ag (1.15 vs 0.91 U/l), and antithrombin III activity (1.17 vs 1.08 U/l) were significantly elevated. Levels of free protein S were not different from control values. No significant decline of coagulation parameters could be recorded during insulin therapy. Patients with diabetic vasculopathy had higher levels of D-dimer than those without (133 vs 76 micrograms/l before, 109 vs 88 micrograms/l during therapy), whereas the other haemostatic parameters were not different. Our data indicate a significant activation of the coagulation system in diabetic patients with secondary failure to sulfonylurea drugs, with signs of a prethrombotic state and endothelial cell disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemostasis/fisiología , Insulina/uso terapéutico , Anciano , Peso Corporal/fisiología , Estudios de Casos y Controles , Femenino , Hemostasis/efectos de los fármacos , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos de Sulfonilurea/uso terapéutico , Resultado del TratamientoRESUMEN
Beside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/uso terapéutico , Inhibidor 1 de Activador Plasminogénico/sangre , Activador de Tejido Plasminógeno/sangre , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Compuestos de Sulfonilurea/uso terapéutico , Factores de TiempoRESUMEN
Although cardiovascular and cerebrovascular morbidity and mortality in type 2 diabetic patients is closely related to urinary albumin excretion rate (UAER), the causative mechanisms are not yet identified. The aim of our study was to define the circadian variation of blood pressure (BP) in 72 type 2 diabetic patients (mean age 60 years, mean diabetes mellitus duration: 12 years) in comparison with 41 nondiabetic controls with essential hypertension (mean age 58 years) by using ambulatory blood pressure measurement. Thirty diabetic patients had normal UAER (< 30 mg/24 h), 27 had microalbuminuria (30 to 300 mg/24 h), and 15 had persistent proteinuria (> 300 mg/24 h). Systolic blood pressure during both nighttime and daytime was significantly elevated in type 2 diabetic patients with macroalbuminuria compared to controls and patients with normal UAER. During nighttime even type 2 diabetic patients with microalbuminuria had significantly elevated systolic blood pressure compared to controls with essential hypertension. We also observed a correlation of nocturnal blood pressure to UAER (systolic: r = 0.32, P < .007 and diastolic: r = 0.24, P < .04). Nondipping (defined as a reduction of nocturnal BP < 10%) was observed in 80% of the macroalbuminuric, 74% of the microalbuminuric, but only in 43% of the normoalbuminuric type 2 diabetic patients and in 37% of the controls (P < .04). Since a loss of circadian variation of BP is closely related to vascular complications in nondiabetics, our findings may indicate an important relationship between nondipping of BP and the high morbidity and mortality rate in diabetic patients with increased UAER.
Asunto(s)
Albuminuria/fisiopatología , Presión Sanguínea , Ritmo Circadiano , Diabetes Mellitus Tipo 2/fisiopatología , Albuminuria/complicaciones , Monitoreo Ambulatorio de la Presión Arterial , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Frecuencia Cardíaca , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
In 97 patients with type I diabetes mellitus, 155 patients with type II diabetes mellitus, and two matched control groups, serum concentrations of laminin P1, a non-collagenous component of basement membranes, were determined by radioimmunoassay to see whether laminin P1 might be a valuable indicator of microangiopathic complications in diabetics. Independent of the type of diabetes, serum laminin concentrations in patients without nephropathy or with early renal damage as assessed by microalbuminuria were comparable with those of the control subjects. Patients with macroproteinuria or with renal insufficiency had significantly increased serum laminin P1 concentrations. Diabetic retinopathy was not found to influence serum laminin P1 concentrations. These data indicate that serum laminin P1 concentrations are increased in advanced diabetic nephropathy.
Asunto(s)
Nefropatías Diabéticas/sangre , Laminina/sangre , Fragmentos de Péptidos/sangre , Adulto , Anciano , Albuminuria/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Humanos , Persona de Mediana EdadRESUMEN
Persistent increased urinary albumin excretion rate (UAER) is associated with increased cardiovascular mortality in type-2 diabetes, however, there are no conclusive data about the progression of advanced UAER in these patients. The present study has investigated the effect of metabolic intervention on the progression in UAER in relation to initial UAER levels. A total of 20 patients with type-2 diabetes and secondary failure to sulfonylurea were observed during 1 year (age, 60 +/- 8 years; HbA1c, 10.8 +/- 1.4%; and duration of diabetes, 17 +/- 10 years) and divided into two groups: group 1 (n = 10; UAER: 51 +/- 35 mg/24 h); and group 2 (n = 10; UAER: 191 +/- 175 mg/24 h). Despite a significant improvement of metabolic control by insulin treatment in both groups (HbA1c: group 1: 11 +/- 1.5 vs. 7.9 +/- 1.2%; group 2: 10.6 +/- 0.9 vs. 9.1 +/- 1.3%, P < 0.001), a progression of UAER was observed in group 2 (191 +/- 175 vs. 331 +/- 237 mg/24 h, P < 0.02), but not in group 1 (51 +/- 35 vs. 41 +/- 24 mg/24 h). Still serum creatinine levels remained normal in all patients during the observation period. The 24 h blood pressure (RR) values in the two groups remained normal under antihypertensive therapy throughout the study (group 1: RR syst: 130 vs. 136 mmHg; RR diast: 80 vs. 81 mmHg, mean arterial pressure (MAD): 89 vs. 93 mmHg; group 2: RR syst: 139 vs. 134 mmHg; RR diast: 78 vs. 75 mmHg, MAD: 97 vs. 90 mmHg). The data shows that in type-2 diabetic patients with normotensive blood pressure values the initial urinary albumin excretion levels determine the progression of UAER. When metabolic control is improved incipient UAER remains constant, but advanced UAER shows progression.
Asunto(s)
Albuminuria/orina , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Anciano , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Lípidos/sangre , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n = 8; dosage 30 mg/day) or placebo (n = 7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q1/Q3 in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90), P < 0.02; 12 months 39 (15/79), P < 0.05). GFR was significantly decreased by nifedipine treatment (baseline 157 +/- 15, 6 months 122 +/- 8, 12 months 111 +/- 47 ml/min; P < 0.05, mean +/- SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121 +/- 7, 12 months 124 +/- 2 mmHg, mean +/- SEM) or diastolic (baseline 72 +/- 2, 12 months 74 +/- 3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Albuminuria/tratamiento farmacológico , Albuminuria/etiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Nifedipino/uso terapéutico , Adulto , Análisis Químico de la Sangre , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 1/fisiopatología , Método Doble Ciego , Humanos , Insulina/uso terapéutico , Nifedipino/administración & dosificación , Flujo Plasmático Renal/efectos de los fármacos , Factores de TiempoRESUMEN
Increased serum levels of lipoprotein (a) have been found to be an independent risk factor for coronary heart disease. The major protein constituents of lipoprotein (a) are apolipoprotein B 100 und apolipoprotein (a) (apo(a)). We determined the serum levels of apo(a) and several lipid (cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A, A1 and B) and glycaemic (HbA1c, fasting blood glucose) parameters in 40 patients with type 1 diabetes mellitus and in 103 age- and sex-matched control subjects. The median serum levels of apo(a) were significantly increased in the type 1 diabetic patients (142.7 vs. 80.0 U/L; P = 0.03), whilst HDL, LDL-cholesterol, and apolipoprotein A, A1 and B levels were lower (P < 0.01). No significant correlation was found between parameters of metabolic control and apo(a) levels. After subdivision of the diabetic patients according to different stages of diabetic nephropathy (DN), determined by urinary albumin excretion, significant relationships were found between DN and triglycerides (P = 0.04), LDL (P = 0.03) and apolipoprotein B (P = 0.008, Kruskal-Wallis test) levels. Apo(a) levels were significantly higher than normal values in patients without DN (P < 0.05), but unrelated to the degree of DN. Patients with diabetic macroangiopathy had significant higher levels of cholesterol (P = 0.0001), triglycerides (P = 0.026), LDL (P = 0.0003), and apoB (P = 0.002) than patients without. Apo(a) levels were unrelated to diabetic macroangiopathy. The significantly elevated levels of apo(a) even in patients without DN or macroangiopathy are noteworthy.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Apolipoproteínas A/sangre , Diabetes Mellitus Tipo 1/sangre , Angiopatías Diabéticas/sangre , Adulto , Glucemia/metabolismo , Enfermedad Coronaria/sangre , Enfermedad Coronaria/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/administración & dosificación , Lípidos/sangre , Masculino , Valores de Referencia , Factores de RiesgoRESUMEN
In spite of the availability and widespread use of a number of effective medications, the frequency of severe attacks of asthma bronchiale including those with fatal outcome has not decreased. One possible reason for this is the delay in therapeutic intervention of up to 30 minutes resulting either from transport time to a hospital or from the response time of mobile ambulance services. Treatment delays are also frequent co-factors for decreased well-being in non-emergency cases. Prompt initiation of countermeasures, regardless of time or place, can only be guaranteed when the patient himself is capable of carrying them out with the same expertise as his attending physician. Toward this end, a model patient-training program was investigated. The didactic goal of the training was to make the patient an expert in his chronic disease. The medical goal of the training was to improve the quality of a complex long-term therapy and with it, the patient's well-being and quality of life. The content of the training corresponded largely to that contained in a lecture series for medical students or physicians on the same subject. Style and choice of words (avoidance or explanation of medical terminology) was of course adapted to the lay-status of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedades Pulmonares Obstructivas/rehabilitación , Educación del Paciente como Asunto/métodos , Autocuidado/métodos , Rol del Enfermo , Adaptación Psicológica , Adulto , Anciano , Asma/fisiopatología , Asma/psicología , Asma/rehabilitación , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Humanos , Enfermedades Pulmonares Obstructivas/fisiopatología , Enfermedades Pulmonares Obstructivas/psicología , Masculino , Persona de Mediana Edad , Autocuidado/psicología , Capacidad Vital/fisiologíaRESUMEN
OBJECTIVE: DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. METHODS: Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. RESULTS: Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (ß-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. CONCLUSIONS: Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/enzimología , Quitinasas/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Daño del ADN/fisiología , Demencia/líquido cefalorraquídeo , Demencia/diagnóstico , Demencia/enzimología , Diagnóstico Diferencial , Femenino , Hexosaminidasas/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Factor 1 de Elongación Peptídica/líquido cefalorraquídeo , Estatmina/líquido cefalorraquídeo , Telómero/fisiologíaRESUMEN
Aggregation of alpha-synuclein may contribute to neuropathology in Parkinson's disease patients and in transgenic animal models. Natively unfolded alpha-synuclein binds to various proteins and conformational changes due to alpha-synuclein misfolding may alter physiological interactions. In the present study, we used protein arrays spotted with 5000 recombinant human proteins for a large scale interaction analysis of monomeric versus oligomeric alpha-synuclein. Monomeric alpha-synuclein bound to arrayed cAMP regulated phosphoprotein 19 and binding appears to be disrupted by alpha-synuclein oligomerization. Incubation with recombinant alpha-synuclein oligomers lead to the identification of several GTPase activating proteins and Cdc42 effector proteins as binding partners. Protein database searches revealed a Cdc42/Rac interactive binding domain in some interactors. To demonstrate in vivo relevance, we analyzed brainstem protein extracts from alpha-synuclein(A30P) transgenic mice. Pull-down assays using beads conjugated with a Cdc42/Rac interactive binding domain lead to an enrichment of endogenous alpha-synuclein oligomers. Cdc42 effector proteins were also co-immunoprecipitated with alpha-synuclein from brainstem lysates and were colocalized with alpha-synuclein aggregates in brain sections by double immunostaining. By two-dimensional gel electrophoretic analysis of synaptosomal fractions from transgenic mouse brains we detected additional isoforms of septin 6, a downstream target of Cdc42 effector proteins. Small GTPases have recently been identified in a genetic modifier screen to suppress alpha-synuclein toxicity in yeast. Our data indicate that components of small GTPase signal transduction pathways may be directly targeted by alpha-synuclein oligomers which potentially leads to signaling deficits and neurodegeneration.
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Encéfalo/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Animales , Western Blotting , Encéfalo/patología , Electroforesis en Gel Bidimensional , Humanos , Inmunohistoquímica , Inmunoprecipitación , Ratones , Ratones Transgénicos , Microscopía de Fuerza Atómica , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Análisis por Matrices de Proteínas , Conformación Proteica , Pliegue de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteína de Unión al GTP cdc42/químicaRESUMEN
AIMS/HYPOTHESIS: Pregnancy is characterised by temporarily increased insulin resistance. Gestational diabetes occurs when pancreatic beta cell function is unable to compensate for this insulin resistance. Retinol-binding protein 4 (RBP4) could be related to insulin resistance. We hypothesised that RBP4 is elevated in gestational diabetes. METHODS: Serum RBP4, transthyretin and retinol were cross-sectionally measured in 42 women with gestational diabetes and 45 pregnant controls. Of these, 20 women with and 22 without gestational diabetes were included in an additional longitudinal study. RBP4 was determined by enzyme immunometric assay (EIA) and western blot. RESULTS: Women with gestational diabetes had lower RBP4 EIA and western blot levels than controls (median 6.8 [interquartile range, 3.9-14.3] vs 11.3 [7.8-19.9] microg/ml, p < 0.001 and 25.1 [21.7-29.6] vs 26.6 [23.5-32.2] microg/ml, p = 0.026). Transthyretin and the RBP4:transthyretin molar ratio were comparable between the groups. Serum retinol was lower (p < 0.001) and the RBP4 Western blot level: retinol molar ratio was higher in women with gestational diabetes (p = 0.044). RBP4 was not associated with the glucose or homeostasis model assessment of insulin resistance (HOMA-IR), but in gestational diabetes the RBP4:retinol molar ratio correlated with blood glucose and negatively with 2 h post-load insulin. The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls. In women with gestational diabetes RBP4 EIA and western blot levels increased after delivery. Retinol increased in both groups, while transthyretin and the RBP4:transthyretin ratio were not altered after parturition. CONCLUSIONS/INTERPRETATION: RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes. Thus, the RBP4:retinol ratio and the RBP4:transthyretin ratio are more informative than RBP4 levels alone when assessing insulin-glucose homeostasis during pregnancy.
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Diabetes Gestacional/sangre , Homeostasis/fisiología , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Adulto , Glucemia/metabolismo , Western Blotting , Estudios Transversales , Femenino , Humanos , Técnicas para Inmunoenzimas , Insulina/sangre , Resistencia a la Insulina , Estudios Longitudinales , Prealbúmina/metabolismo , Embarazo , Vitamina A/sangreRESUMEN
BACKGROUND: Cardiovascular mortality is increased in patients with hypopituitarism. Elevated concentrations of the endogenous NO synthase antagonist asymmetrical dimethylarginine (ADMA) may be related to the development of atherosclerosis and are associated with cardiovascular risk. We studied the concentrations of ADMA in hypopituitary patients with and without growth hormone deficiency (GHD) and in healthy subjects. MATERIALS AND METHODS: Plasma from 44 patients with hypopituitarism with (n = 30) and without GHD (n = 14) and from 25 age- and sex-matched healthy controls was taken for analysis of L-arginine, ADMA, symmetrical dimethylarginine (SDMA) and clinical parameters. Further plasma from 10 hypopituitary patients was examined before and after treatment with 9 g of oral L-arginine for 14 days. RESULTS: Asymmetrical dimethylarginine was significantly higher in the hypopituitary patients than in the controls (0.63 +/- 0.12 vs. 0.51 +/- 0.15 micromol L(-1); P < 0.005). L-arginine and the L-arginine/ADMA ratios were lower in the subjects with hypopituitarism (53 +/- 18 vs. 90 +/- 29 micromol L(-1) and 87 +/- 31 vs. 185 +/- 59; both P < 0.0001). Symmetrical dimethylarginine was comparable between the patients and the controls. L-arginine and dimethylarginines were associated with 2-h stimulated glucose levels in a glucose tolerance test (r = 0.33; P < 0.05), but not other cardiovascular risk factors. Oral L-arginine supplementation normalized the reduced L-arginine/ADMA ratio in the hypopituitary patients. CONCLUSION: Asymmetrical dimethylarginine is elevated in patients with hypopituitarism independent of GHD and traditional risk factors. This might contribute to the increased cardiovascular morbidity in hypopituitary patients.