Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment

Background\ud Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels.\ud \ud Methods\ud Sixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with 14C-cholesteryl ester and 3H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro.\ud \ud Results\ud LDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal.\ud \ud Conclusion\ud T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.This study was supported by Fundação do Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil. Dr. Maranhão has a Research Award from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Brasília, Brazil

Menor incidência de hipoglicemia noturna com o uso de insulina lispro comparada à insulina humana regular no tratamento de pacientes com diabetes do tipo 1

Insulin lispro is a human insulin analog of rapid onset of action and duration, which mimics the physiological insulin profile after a meal. We have evaluated the safety and efficacy of lispro insulin in comparison with human regular insulin in a crossover, multicenter, randomized trial in 25 type 1 diabetic patients in use of human NPH and regular insulin (median age = 16 years). After administration of lispro or regular insulin for 2 months, the patients were transferred for the other insulin for two more months, maintaining the basal NPH insulin regimen. There was no difference in the postprandial glucose excursion and glycated hemoglobin A1c comparing the 2 groups (lispro and regular). The relative percentage decrease in glycemia was significantly greater with lispro insulin after lunch, in the first phase of the study (p<0.02). The total number of hypo-glycemic episodes was not different comparing both groups. However, there was a significant difference in the nocturnal hypoglycemia incidence with initial administration of lispro (p<0.05). With initial administration of regular insulin, there was an increase in the incidence of nocturnal hypoglycemia (p=0.038), with a subsequent reduction of hypoglycemia with insulin lispro (p=0.04). In the end of the study, 68% of the patients referred preference and better feeling with lispro, compared to regular insulin. Insulin lispro was a safe and efficacious option, with lower incidence of nocturnal hypoglycemia in type 1 diabetics. An optimization of the basal insulin regimen is necessary to improve glucose control with the use of rapid-action insulin.Insulina lispro é um análogo da insulina humana de ação e duração rápida, que mimeíiza o perfil fisiológico da insulina após uma refeição. Avaliamos a segurança e eficácia da insulina lispro em comparação com a insulina humana regular em um estudo multicêntrico, randomizado e cruzado em 27 diabéticos tipo 1 em uso de insulina humana NPH e regular (idade mediana = 16 anos). Após uso de insulina lispro ou regular por 2 meses, fez-se a transferência para a outra insulina por mais 2 meses mantendo-se a insulina NPH basal. Não houve diferença em relação à excursão prandial da glicemia da hemoglobina glicosilada A1C, comparando-se os 2 grupos (lispro e regular). O decréscimo percentual relativo da glicemia foi significantemente maior com insulina lispro no período do almoço, na primeira fase do estudo (p<0,02). O número total de episódios hipoglicêmicos não foi diferente, comparando os 2 grupos. Houve, porém, uma redução significante na incidência de hipoglicemia noturna e na madrugada com o uso inicial de lispro (p<0,05). Com o uso inicial de insulina regular, houve incremento na incidência de hipoglicemia noturna (p=0,038), com redução posterior na incidência da hipoglicemia com insulina lispro (p=0,04). Ao final do estudo, 68% dos pacientes referiram preferência e maior comodidade com insulina lispro em relação à insulina regular. A insulina lispro se mostrou uma opção segura e eficaz, com menor incidência de hipoglicemia noturna em diabéticos tipo 1. Uma otimização do regime de insulina basal é necessária para melhora do controle glicêmico, quando em uso de uma insulina de ação rápida.Universidade Federal do CearáUniversidade de São Paulo Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP)Laboratório Eli Lilly do BrasilUNIFESPSciEL

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing

The prevalence of diabetes and stress hyperglycemia in the acute myocardial infarction patients

OBJETIVOS: Determinar a prevalência do diabetes melito (DM) e da hiperglicemia de estresse (HE) em pacientes com infarto agudo do miocárdio (IAM) admitidos em unidade de emergência cardiológica. MÉTODOS: Análise retrospectiva de 2.262 pacientes com IAM, avaliando, além da prevalência de diabetes referido, o diagnosticado e a hiperglicemia de estresse. RESULTADOS: Apesar de referido em 12,1% dos pacientes (H: 10,7%, M: 15,8%), o DM ocorria efetivamente em 24,8% (H: 22,9%, M: 29,7%) e a HE em 13,6% (H: 14,3%, M: 11,7%) dos indivíduos dessa população. Portanto, alterações glicêmicas ocorreram em 37,4% dos indivíduos com IAM (H: 37,2%, M: 41,4%). Nos pacientes com DM, observou-se maior precocidade etária do IAM, maior prevalência de óbitos (DM: 20,7%, ND:13,8%, HE: 13,4%) e de procedimentos cirúrgicos (ND: 33,8%, HE: 18,0%, DM: 21,7%). CONCLUSÃO: A elevada prevalência de DM e hiperglicemia de estresse observada em nosso estudo indica que as alterações glicêmicas constituem um dos mais importantes fatores de risco para o IAM.OBJECTIVES: To evaluate in our population the real prevalence of diabetes (DM) and stress hyperglycemia (HE) in patients with myocardial infarction (IAM) admitted in a cardiologic emergency unit. METHODS: A retrospective analysis of 2262 patients with AMI evaluating the prevalence of DM (referred and diagnosed) and stress hyperglycemia. RESULTS: Besides 12,1% of subjects were previously referred to be diabetic (men: 10.7% and women: 15.8%), diabetes was effectively diagnosed in 24,8% (M: 22,9%, W: 29,7%) and stress hyperglycemia in 13,6% HE of the patients (M: 14,3%, W: 11,7%) indicating that glycemic alterations were effectively observed in 37.2.% of the patients with IAM (M: 37,2%, W: 41,4%). In DM subjects IAM events occurred earlier, total intra-hospital mortality was higher (DM: 20.7%, ND: 13,8%, HE: 13,4%) and less surgical procedures were performed (ND 33.8%, DM: 21.7%, HE: 18.0%). CONCLUSION: The elevated DM and stress hyperglycemia prevalence observed in our study indicates that glycemic alterations is one of the most important risk factors for IAM

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

EVALUATION OF THE GONADOTROPHIC RESPONSIVENESS OF THE PITUITARY TO ACUTE AND PROLONGED ADMINISTRATION OF LH/FSH-RELEASING HORMONE (LH-RH) IN NORMAL FEMALES AND MALES

ABSTRACT In normal females, the injection of 25 μg of LH-RH (acute test) induced a greater LH and FSH release from the pituitary in the mid-luteal than in the mid-follicular phase of the menstrual cycle. In normal males, the responsiveness to 25 μg LH-RH was greater than that in females at mid-follicular but not at the luteal stage. The pituitary response to the prolonged LH-RH infusion (0.21 μg/min/8 h) was similar in both phases of the cycle of the females with a decline in serum gonadotrophins after the 4th hour and was paralleled by a significant increase of plasma oestradiol levels. In males the LH, but not the FSH secretion was lower as compared to female subjects, and gonadotrophin levels did not show a fall during the infusion. The acute injection of 25 μg LH-RH at the end of a prolonged infusion induced the same response in the female subjects in both phases of the cycle. In males, the acute test following prolonged infusion produced a similar LH secretion, but a lower FSH response than in females. The comparison of the acute test alone and that preceded by a prolonged LH-RH infusion, demonstrated that, in females, the only significant differences consisted of a greater LH secretion in the former test in the mid-luteal phase. In males there was greater FSH secretion in the acute isolated test than when this test was given after the prolonged infusion