RESUMO
AIM: The aim of this trial was to obtain further data on the efficacy and safety of benfluorex as an add-on therapy in type 2 diabetic patients insufficiently controlled by sulfonylurea monotherapy who had a limitation for the use of metformin during a 4-month extension period following a 4-month double-blind trial. METHODS: Patients who completed the 18-week double-blind period entered the 16-week extension period. Patients in the benfluorex group during the double-blind period continued benfluorex 450 mg/day (B-B group), whilst patients in the placebo group switched to benfluorex 450 mg/day (P-B group). The main efficacy criterion was HbA(1c), analyzed as the change from week 18 (W18) to the end of treatment using a two-sided Student paired t-test. Secondary criteria were fasting plasma glucose (FPG), insulin resistance and lipids. RESULTS: Between W18 and the end of treatment, HbA(1c) decreased in the P-B group from 8.53+/-1.37% to 7.49+/-1.04% (P<0.001) and remained stable in the B-B group from 7.52+/-1.07% to 7.53+/-1.14% (NS). In the P-B group, parameters of glycemic control showed improvements from W18 to week 34 (W34) which were similar to those observed from baseline to W18 in the B-B group. Overall, the target HbA(1c) (Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico
, Fenfluramina/análogos & derivados
, Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
, Compostos de Sulfonilureia/uso terapêutico
, Adolescente
, Adulto
, Idoso
, Glicemia/análise
, Método Duplo-Cego
, Feminino
, Fenfluramina/uso terapêutico
, Hemoglobinas Glicadas/análise
, Humanos
, Hipoglicemiantes/uso terapêutico
, Masculino
, Pessoa de Meia-Idade
, Placebos
, Segurança
, Adulto Jovem
RESUMO
OBJECTIVE: To study the tolerability and efficacy of acipimox on hyperlipidemia and diabetes compensation in patients with NIDDM under conditions of a routine clinical practice. RESEARCH DESIGN AND METHODS: We recruited 121 patients (60 men and 61 women) from 10 participating clinical centers. They were randomly divided into two groups and treated for 3 mo either with acipimox (250 mg three times a day) or placebo, using an open study design. RESULTS: Acipimox treatment led to a significant drop in fasting serum total triglyceride levels (by 28%) after 1 mo of drug administration. This decrease prevailed up to the end of the 3-mo study. Serum total cholesterol levels declined by 14%, and high-density lipoprotein tended to rise in acipimox-treated patients. These changes in lipid metabolism were not accompanied by any adverse effects of acipimox on glucose metabolism as judged by HbA1c measurements and the oral glucose tolerance test. Eight patients (out of 82 treated with acipimox) reported moderate adverse events of transient character, such as skin reactions and gastric disturbances. CONCLUSIONS: Acipimox seems to be a useful agent for treatment of diabetic dyslipidemia and does not deteriorate glycemic control.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hiperlipoproteinemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Lipoproteínas/sangue , Pirazinas/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Triglicerídeos/sangueRESUMO
OBJECTIVES: The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity. METHODS: 36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test. RESULTS: The subjects with I degree of obesity demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity (p<0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p<0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity receptors (p<0.001) per cell as well as an increase (p<0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p<0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p<0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed. CONCLUSION: We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.
Assuntos
Glicemia/metabolismo , Resistência à Insulina , Insulina/metabolismo , Obesidade/fisiopatologia , Receptor de Insulina/metabolismo , Área Sob a Curva , Peso Corporal , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/sangue , Insulina/sangue , Insulina/farmacologia , Secreção de Insulina , Obesidade/sangue , Obesidade/classificação , Valores de ReferênciaRESUMO
The study was designed to evaluate the pattern of insulin secretion and the presence of anti-GAD65 antibodies as beta-cell autoimmune marker in subjects with impaired glucose tolerance (IGT) and their impact on the further development of glucose intolerance. 29 subjects with IGT, of mean BMI 24.7 +/- 2.4 kg/m(2) and mean age 37.7 +/- 7.0 years were enrolled in the study. They were followed-up once yearly for three years. A group of 59 age- and weight-matched subjects with normal glucose tolerance (NGT) served as a control group. 42 newly-diagnosed diabetic patients, of mean BMI 24.4 +/- 2.7 kg/m(2) and mean age 37.2 +/- 6.9 years were also studied. According to their response during IVGTT the subjects with IGT were divided into two groups. The first group (n = 11)(IGT-I) showed reduced FPIS (34.0 +/- 8.9 mU/l vs 114.4 +/- 41.2, p < 0.001), SPIS being within normal values, and reduced AUC for total insulin secretion (1554.1 +/- 496.3 vs 2323.6 +/- 804.5 mU/l x 60 min, p < 0.001); the difference with type 1 diabetic patients being significant (p < 0.001), the pattern of insulin secretion being quite similar to that of type 2 diabetic patients. The other group (n = 18) (IGT-II) demonstrated normal insulin secretion (FPIS, SPIS, AUC for insulin secretion), not differing from that of the controls with NGT. Anti-GAD65 were present in 3.3% of subjects with NGT, in 73.7% of patients with type 1 diabetes and in none of type 2 diabetic patients. 18% from the group with IGT-I were anti-GAD65 positive, and 22% - from IGT-II. 5 of the subjects with IGT-I developed diabetes during the follow-up period - 2 at the 1st year, 1 at the 2nd year and 2 - at the third year. One of these patients was anti-GAD65 positive (having the highest anti-GAD65 level amongst the others with IGT - 15.2 U/ml), showing pattern of insulin secretion similar to that of type 1 diabetic patients. 3 of the subjects with IGT-II reverted to NGT within the first year and 2 - at the second year, none of them being anti-GAD65 positive. The anti-GAD65 positive patients from this group remained with IGT, and none progressed to diabetes mellitus. We consider that IVGTT allows precise assessment of the phases of insulin secretion and in combination with the study of anti-GAD65 antibodies helps to identify the subjects with IGT at risk of developing diabetes mellitus. As far as the decrease in the FPIS is considered it could be proposed that such subjects are assigned to certain protective measures - diet, physical activity and some drugs affecting postprandial glucose levels.
Assuntos
Anticorpos/sangue , Intolerância à Glucose/fisiopatologia , Glutamato Descarboxilase/imunologia , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Isoenzimas/imunologia , Adulto , Área Sob a Curva , Autoimunidade , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/imunologia , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Insulina/imunologia , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
Obesity is considered a chronic disease requiring treatment. The effect of sibutramine combined with hypocaloric diet and exercise on body weight, body fat mass, lipids, glycemic control, insulin secretion and insulin resistance was evaluated in a randomized, controlled, open-label study. A total of 44 obese type 2 diabetic patients (aged 45.2+/-5.2 years, BMI 33.62+/-2.2 kg/m(2)) and 49 obese nondiabetic subjects (aged 41.9+/-5.7 years, BMI 34.3+/-2.6 kg/m(2)) were treated with sibutramine for 3 months. Moreover, 39 age-matched obese type 2 diabetic patients and 41 obese nondiabetic subjects only on hypocaloric diet and exercise served as control groups. Insulin secretion was estimated during intravenous glucose tolerance test; insulin resistance was assessed by the HOMA index. There was a significant reduction in body weight in both sibutramine-treated diabetic patients (7.1%) and nondiabetic subjects (9.1%), accompanied by a significant reduction in body fat mass. HbA1c decreased significantly in the diabetic patients after sibutramine treatment. There was a significant improvement of lipid parameters in the two groups. Insulin resistance decreased by 21.9% in the sibutramine-treated diabetic patients and by 38.5% in the nondiabetic group. Weight loss was accompanied by an increase of 43.8% in first phase insulin secretion in the sibutramine-treated diabetic group; in the treated nondiabetic subjects there was a decrease in first and second phase insulin secretion and the area under the curve for total insulin secretion. In conclusion, sibutramine leads to a significant reduction in body weight, body fat mass and waist and hip circumferences; it improves insulin sensitivity, insulin secretion, glycaemic control and lipid parameters in both diabetic and nondiabetic obese subjects.
Assuntos
Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Obesidade/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Adulto , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/fisiopatologia , Relação Cintura-QuadrilRESUMO
201 insulin-treated diabetic patients were followed upto 6 months and 1 year after a 5-day structured teaching program. There was a significant increase in overall quality of life (score 51+/-5.7 after 1 year versus 41+/-6.1 before education, P<0.01), due to reduction in depression (P<0.01) and anxiety (P<0.001) and increase in well-being (P<0.05). The metabolic control improved significantly - HbA(1c) fell from 9.1+/-1.5 to 8.0+/-1.1 and 7.8+/-1.3% after 6 months and 1 year, respectively, P<0.05. The rate of severe hypoglycaemia decreased from 0.15 to 0.06cas/pat/year after 1 year (P<0.01). The incidence of diabetic ketoacidosis decreased from 0.30 to 0.14cas/pat/year (P<0.01). These results demonstrate that structured patient education improves the quality of life of diabetic patients and their metabolic control and significantly reduces the rate of acute complications.
Assuntos
Diabetes Mellitus/terapia , Educação de Pacientes como Assunto , Autocuidado , Adulto , Análise de Variância , Glicemia , Bulgária , Diabetes Mellitus/sangue , Diabetes Mellitus/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Estudos ProspectivosRESUMO
In a previous paper we demonstrated a link between growth hormone releasing hormone (GHRH) and prostaglandin E2 (PGE2) in their action on growth hormone (GH) in normal subjects. However, in diabetes mellitus various disturbances of GH and PGE2 secretion have been reported. In the present study the response of GH, PGE2 and insulin to GHRH (1 microgram/kg b.w.) intravenously was investigated in 12 poorly controlled non-insulin-dependent diabetic patients (8 males and 4 females) and 10 normal volunteers (5 males and 5 females). After GHRH injection, GH increased in diabetic patients from 2.28 +/- 0.52 mU/l to 14.76 +/- 1.29 mU/l at 30 min (p < 0.001). This response was not statistically different compared to the control subjects. The basal values of plasma PGE2 were significantly lower in diabetic patients than in control subjects. GHRH induced a slight but significant increase of PGE2 in normal subjects (9.80 +/- 0.44 pg/ml at 0 min; 14.50 +/- 1.30 pg/ml at 90 min, p < 0.05) and did not have any effect on PGE2 in diabetic patients. Serum insulin decreased significantly after GHRH in both normal subjects and diabetic patients at 60 min. We conclude that GH response to GHRH is not significantly impaired in poorly controlled non-insulin-dependent diabetic patients. The lack of an effect of GHRH on PGE2 in diabetic subjects provides further evidence of abnormal PGE2 synthesis or metabolism in this disorder. The physiological significance of the GHRH suppressive effect on serum insulin remains to be explained.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Dinoprostona/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Insulina/sangue , Adulto , Idoso , Análise de Variância , Feminino , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
The effects of 5 days sodium-free diet associated with furosemide administration were studied in 12 diabetic patients with insulin-dependent diabetes mellitus and 12 healthy control subjects. Plasma renin activity was significantly lower in diabetics compared with that of normal subjects. Plasma aldosterone was similar in both groups. Urinary excretion of prostaglandin E2 was significantly lower in diabetics before and after sodium depletion in comparison with normal subjects. Urinary excretion of 6-keto prostaglandin F1 alpha and thromboxane B2 was similar in both groups. It is concluded that the lower excretion of prostaglandin E2 in diabetics is related to the decreased activity of renin-angiotensin system. Decreased production of prostaglandin E2 may contribute to the development of arterial hypertension in the diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Dieta Hipossódica/efeitos adversos , Prostaglandinas/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Furosemida/farmacologia , Humanos , Hiponatremia/sangue , Hiponatremia/fisiopatologia , MasculinoRESUMO
The effect of captopril on the response of plasma aldosterone (PA) and plasma renin activity (PRA) to 10 mg metoclopramide i.v. was studied in 9 normal subjects. In the same conditions the prolactine response was studied in 6 healthy males. Metoclopramide induced a significant increase of PA during control study, as well as after treatment with captopril. The maximal increase of PA was of similar magnitude and occurred 15 mn after injection of metoclopramide on both occasions. PRA did not change appreciably after metoclopramide neither during control study nor during captopril. The prolactin response to metoclopramide was blunted by treatment with captopril. In conclusion, captopril did not alter the aldosterone response to metoclopramide, which suggests that dopaminergic control of aldosterone secretion is independent of modifications in the renin-angiotensin system.
Assuntos
Aldosterona/sangue , Captopril/farmacologia , Metoclopramida/farmacologia , Adulto , Feminino , Humanos , Masculino , Prolactina/sangue , Valores de Referência , Renina/sangueRESUMO
Menopause is associated with two main risk factors for the development of type 2 diabetes mellitus--impaired beta-cell insulin secretion and insulin resistance. Physiologically estrogens improve carbohydrate metabolism, but this is not the case with different progestogens. The aim of the present study was to evaluate the effect of Cyproterone acetate (a progestogen with antiandrogenic activity) on insulin secretion, peripheral insulin sensitivity, lipid parameters and parameters of oxidative stress. Seven type 2 diabetic females, of mean age 55.4 +/- 4.7 years and mean BMI 30.8 +/- 9.39 kg/m2, in menopause for average 5 years, in good borderline glycaemic control (mean HbAic 7.8%), with dyslipidaemia, normal parameters of calcium and phosphate metabolism and with osteopenia (T-score < 88%) were enrolled in the study. They were treated with Estradiol valerate + Cyproterone acetate (Climen, Schering) for three months. Phases of insulin secretion--first phase (FPIS), second phase (SPIS) and AUC for FPIS and SPIS were assessed during IVGTT. Insulin sensitivity was determined with the manual method of euglycaemic hyperinsulinaemic clamp technique. The postmenopausal diabetic women in the present study were with overweight and obesity; they did not increase their body weight during HRT and even decreased it by mean 0.7%. Insulin secretion improved after Climen--FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 15%; triglycerides decreased by 16% and HDL-cholesterol increased by 27%. Total antioxidant capacity of the serum (TAOK) increased by 7%. The favourable effect on the pathophysiological mechanisms improved metabolic control--HbAic was reduced by mean 3% after 3 months. In conclusion, our results suggest that HRT with the progestogen Cyproterone acetate (Climen) should be preferred in postmenopausal type 2 diabetic females with predominant beta-cell insulin secretion defect.
Assuntos
Acetato de Ciproterona/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Terapia de Reposição de Estrogênios , Ilhotas Pancreáticas/efeitos dos fármacos , Pós-Menopausa , Glicemia/análise , Densidade Óssea/fisiologia , Acetato de Ciproterona/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Pessoa de Meia-IdadeRESUMO
Twenty-three diabetic patients -- 16 men and seven women (mean age: 50.7 +/- 17.4 years; mean duration of diabetes: 13.6 +/- 6.9 years) -- with diabetic mononeuropathy of the cranial nerves participated in the study. Four of them were with mononeuropathia multiplex and total ophthalmoplegia, affecting the oculomotor, trochlear and abducent nerves; 12 with paresis of the oculomotor nerve, one -- of the trochlear nerve and six -- of the abducent nerve. They were treated with alpha-lipoic acid (600 mg) for 10 days daily intravenously, thereafter one film tablet of 600 mg daily for 60 days. On the 10th day, we found significant improvement in the clinical signs of diabetic mononeuropathy - double vision, motility and position of the eyeball, ptosis of the upper eyelid and mydriasis. The mean period of oral treatment was 69.1 +/- 23.8 days, following the 10-day intravenous application of alpha-lipoic acid, and full recovery of the diabetic mononeuropathy was achieved with this therapeutic approach. Peripheral neuropathy was present in 17 patients (74%). On the 10th day, we established a decrease in total symptom score by an average of 2.7 +/- 1.4 points and by the end of the treatment period it was improved by 5.9 +/- 1.9 points (p = 0.04). On the 10th day, we found a decrease of 33% in foot pain and by the end of the second month, it fell by 65.5% (p < 0.0001). Vibration perception threshold was reduced in these patients at entry -- mean: 2.42 +/- 1.8 at the great toe, 2.89 +/- 1.8 at the first metatarsal and 3.65 +/- 1.7 at the medial malleolus. By the end of the second month, it reached mean 4.7 +/- 1.8 (p < 0.002) at the great toe, 4.92 +/- 2.1 (p = 0.004) at the first metatarsal and 5.3 +/- 1.4 (p < 0.01) at the medial malleolus. Cardiovascular autonomic neuropathy was present in two of the patients and there was improvement after treatment in the Ewing's tests -- Valsalva manoeuvre, deep-breathing test and lying-to-standing test. The results of our study demonstrate that alpha-lipoic acid appears to be an effective drug in the treatment for not only peripheral and autonomic diabetic neuropathy, but also diabetic mononeuropathy of the cranial nerves leading to full recovery of the patients.
Assuntos
Antioxidantes/uso terapêutico , Doenças dos Nervos Cranianos/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Administração Oral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.
Assuntos
Envelhecimento/metabolismo , Insulina/metabolismo , Caracteres Sexuais , Adulto , Análise de Variância , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/fisiologia , Secreção de Insulina , Masculino , Receptor de Insulina/metabolismoRESUMO
A study was made of the blood plasma renin activity in 63 patients suffering from thyrotoxicosis before the treatment and in 42 healthy individuals. In comparison with the healthy, renin activity was increased in patients with thyrotoxicosis and displayed a positive correlation with the severity of the disease the level of protein-bound iodine, tachycardia and the degree of loss of weight. Stimulation of the renin-angiotensin system by the salt-free diet, hydrochlorthiazide and by placing the body into orthostatic position caused a relatively weaker increase in the renin activity in comparison with such in healthy individuals. Following successful treatment and the occurrence of an euthyroidal state renin activity proved to fall to the normal level. An increased renin activity was combined with increased urinary aldosterone excretion with a normal serum electrolyte level. Such combination pointed to the secondary character of aldosteronism. Block of the alpha- and beta-adrenergic receptors led to reduction in the level of renin activity. Despite the frequent affection of hepatic function there was revealed no correlation between the increase in the renin activity and the pathological results of hepatic tests. Plasma renin activity was reduced in 8 patients with myxedema. It is supposed that the principal factors causing activation of the renin-angiotensin system in thyrotoxicosis were the loss of water and electrolytes by the organism and the appearance of oversensitivity to adrenergic receptors.
Assuntos
Angiotensina II/sangue , Hiperaldosteronismo/etiologia , Hipertireoidismo/fisiopatologia , Renina/metabolismo , Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Aldosterona/urina , Peso Corporal , Dieta Hipossódica , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Hipertireoidismo/enzimologia , Hipertireoidismo/terapia , Testes de Função Hepática , Masculino , Mixedema/complicações , Mixedema/metabolismo , Postura , Receptores Adrenérgicos , Taquicardia/etiologia , Testes de Função Tireóidea , Equilíbrio HidroeletrolíticoRESUMO
Plasma renin activity (PRA) in 40 diabetic patients and 42 healthy controls was investigated using the method of Pickens in modification of Serebrovskaja et al. (1967). PRA was slightly lower in the whole group of diabetes but the difference was not significant. The subgroup of 20 maturity-onset diabetics had significantly lower PRA in comparison with 22 controls of similar age, while PRA in juvenile diabetics did not differ significantly from matched controls. In patients without clinical signs and symptoms of microangiopathy PRA was as high as in the controls. In diabetics with microangiopathy PRA was significantly lower. PRA was also lower in patients with longer duration of the disease. The stimulation of juxtaglomerular apparatus with sodium free diet and diuretic drugs resulted in an increase of PRA both in controls and diabetics. This suggests a functional depression of PRA in diabetic patients. In diabetics with ketoacidosis PRA was higher than in control subjects and decreased after disappearance of ketoacidosis. A high level was recorded in a patient with hyperosmolar coma and a very low level in a patient with polyneuropathy and severe orthostatic hypotension. The possible mechanisms involved in the changes of PRA in diabetic patients are discussed.
Assuntos
Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus/enzimologia , Renina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Angiopatias Diabéticas/enzimologia , Cetoacidose Diabética/enzimologia , Retinopatia Diabética/enzimologia , Dieta Hipossódica , Diuréticos/farmacologia , Feminino , Humanos , Sistema Justaglomerular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The fibrin split products, soluble fibrin monomer complexes and other coagulation indices were studied in 38 diabetic patients. In these patients there is a tendency towards hypercoagulation. The patients with retinopathy show higher values of fibrin split products and soluble fibrin monomer complexes than the patients without retinopathy. In 24 diabetic patients with ketoacidosis the follow up showed significant increase of the indices studied and correlation of fibrin split products with blood pH. In patients with severe ketoacidosis and diabetic coma disseminated intravasal coagulopathy was found. The early prophylactic treatment of these complications with antiaggregants and anticoagulants is discussed and recommended.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Testes de Coagulação Sanguínea , Angiopatias Diabéticas/sangue , Cetoacidose Diabética/sangue , Retinopatia Diabética/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A woman of 30 with Simmonds--Sheehan syndrome is described that developed after delivery by vacuum-extraction of the fetus, due to powerless labour. The clinical picture was dominated by suprarenal cortical insufficiency, manifested with pains in the abdomen, vomiting, hypotonia and severe asthenic-adynamic syndrome. The substitutional hormonal treatment completely restored the general state and the working capacity of the patient.
Assuntos
Hipopituitarismo , Adulto , Feminino , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Gravidez , Hormônios Tireóideos/uso terapêuticoRESUMO
A 16 years old male is described who was taken ill by diabetes mellitus at the age of 8, treated with insulin, 36 U daily, but with constant poor control of the diabetes. His soft tissues of hands and fingers got thickened in the course of the last several years, with restriction of articular movements and impossible full extent of active and passive extension. No clinical and laboratory data about inflammatory articular process were established. The necessity of a strict control of diabetes is stressed upon, both for the prophylaxis and treatment of juvenile diabetic cheiroarthropathy.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Deformidades Adquiridas da Mão/etiologia , Adolescente , Doença Crônica , Diabetes Mellitus Tipo 1/fisiopatologia , Articulações dos Dedos/fisiopatologia , Deformidades Adquiridas da Mão/fisiopatologia , Humanos , Artropatias/etiologia , Artropatias/fisiopatologia , MasculinoRESUMO
The effect of captopril on urinary excretion of prostaglandin E2, 6-keto prostaglandin F1 alpha, thromboxane B2 and renin-angiotensin-aldosterone system was studied in 13 healthy volunteers during normal and low sodium diet. Angiotensin converting enzyme inhibition led to marked increase in plasma renin activity during both dietary periods without significant modification of plasma aldosterone during normal sodium diet. Prostaglandin E2 significantly increased after captopril during both sodium intakes. Captopril did not change significantly urinary excretion of 6-keto prostaglandin F1 alpha and thromboxane B2. The results indicate that the hypotensive response to captopril in normal subjects is related to the state of sodium balance. Although renin-angiotensin-aldosterone system is the major contributor to this response, it is possible that prostaglandin E2 mediates at least partly the hypotensive and diuretic response to captopril.
Assuntos
Captopril/farmacologia , Prostaglandinas/urina , Sistema Renina-Angiotensina/efeitos dos fármacos , 6-Cetoprostaglandina F1 alfa/metabolismo , Adulto , Pressão Sanguínea/efeitos dos fármacos , Dieta Hipossódica , Dinoprostona/sangue , Feminino , Humanos , Masculino , Concentração Osmolar , Renina/sangue , Tromboxano B2/metabolismoRESUMO
Twelve well-controlled, type II diabetic patients without hypertension and advanced diabetic complications and 12 age-matched healthy control subjects were treated for 4 days with captopril 25 mg three times daily. The pretreatment values of plasma renin activity, plasma aldosterone, urinary 6-keto prostaglandin F1 alpha and thromboxane B2 were similar in both groups. Urinary prostaglandin E2 was significantly reduced in diabetics. After captopril plasma renin activity increased significantly in the diabetics and control subjects. Plasma aldosterone was not significantly decreased in both groups. Urinary prostaglandin E2 increased significantly in both diabetic and control groups. Other measured prostaglandins remained unchanged. After captopril systolic blood pressure decreased significantly in diabetics and not significantly in the control group. The results indicate that captopril was an effective drug for lowering blood pressure in diabetic patients, too. It is possible that the antihypertensive effect of captopril in diabetics could be due at least partly to prostaglandin E2.
Assuntos
6-Cetoprostaglandina F1 alfa/urina , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Dinoprostona/urina , Renina/sangue , Tromboxano B2/urina , Aldosterona/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
AIM: to evaluate the effect of alpha-lipoic acid in autonomic diabetic neuropathy in a controlled, randomized, open-label study. MATERIAL AND METHODS: 46 patients with type 1 diabetes and different forms of autonomic neuropathy, of mean age 38.1 +/- 12.5 years and mean duration of diabetes 16.8 +/- 8.9 years were treated with alpha-lipoic acid for 10 days 600mg daily iv, thereafter one film tablet of 600mg daily for 50 days. 29 type 1 diabetic patients with autonomic diabetic neuropathy, of mean age 40.2 +/- 9.3 years and mean duration of diabetes 15.4 +/- 7.9 years served as a control group. We have followed-up patients' complaints, Ewing's tests, laboratory parameters of oxidative stress. RESULTS: There was a significant improvement after treatment in the score for severity of cardiovascular autonomic neuropathy--from 6.43 +/- 0.9 to 4.24 +/- 1.8 (p<0.001), while in the control group it worsened from 6.18 +/- 1.3 to 6.52 +/- 0.9 (p>0.1). We found improvement in the Valsalva manoeuvre after treatment - from 1.05 +/- 0.04 to 1.13 +/- 0.08 (p<0.001); in the deep-breathing test -from 3.4 +/- 2.8 to 10.4 +/- 5.7 (p<0.001); and in the lying-to-standing test--from 0.99 +/- 0.01 to 1.01 +/- 0.02 (p>0.1), while in the control group there was no improvement. There was a beneficial effect of treatment on the change of systolic blood pressure at the lying-to-standing test--from 22.7 +/- 11.5 to 9.8 +/- 7.9 (p<0.001), while in the control group the change was 20.5 +/- 11.1 mmHg and 19.7 +/- 12.9 mmHg (p>0.1), respectively. We found improvement in diabetic enteropathy in six patients; in the complaints of dizziness, instability upon standing in six patients; in neuropathic edema of the lower extremities in four patients and in erectile dysfunction in four patients after treatment, while in the control group no change was reported in the symptoms and signs of autonomic neuropathy by the end of the follow-up period. There were changes in the laboratory parameters of oxidative stress after therapy--total serum antioxidant capacity increased from 20.42 +/- 1.8 to 22.96 +/- 2.3 microgH2O2/ml/min (p<0.05), serum SOD activity - from 269.8 +/- 31.1 to 319.8 +/- 29.IU/l (p=0.02) and erythrocyte SOD--from 0.89 +/- 0.10 to 1.11 +/- 0.09 U/gHb (p=0.04). CONCLUSION: Our results demonstrate that alpha-lipoic acid (Thiogamma) appears to be an effective drug in the treatment of the different forms of autonomic diabetic neuropathy.