OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.

Avaliamos a prevalência dos anticorpos anti-insulina (IAA), anti-decarboxilase do ácido glutâmico (anti-GAD), anti-ilhota de Langerhans (ICA) e as características clínicas e metabólicas de 66 pacientes com diabetes mellitus (DM) de início na idade adulta (47,2±11,6 anos) e duração do DM de 14,3±8,4 anos. RESULTADOS: ICA foi positivo em 10 casos (10 a 640U JDF), três deles também positivos para anti-GAD (15,6 a 113,5U/ml) e um deles para IAA (naqueles sem terapia insulínica). 15,2% dos pacientes tinham um ou mais autoanticorpos, com maior prevalência para ICA. Os pacientes com e sem autoanticorpos não diferiram quanto à apresentação clínica do DM ou à prevalência de complicações. Apenas os níveis de colesterol foram menores no grupo anticorpo positivo (205,2±49,6 vs. 247,1±61,3mg/dl; p<0,05). CONCLUSÃO: 15,2% dos pacientes com DM de início na idade adulta tinham um ou mais autoanticorpos, com maior prevalência para ICA. A determinação de autoanticorpos é necessária para o diagnóstico do DM autoimune.

The prevalence of anti-insulin (IAA), anti-glutamic acid decarboxylase 65 (anti-GAD) and anti-islet cell antibodies (ICA) and the clinical and metabolic findings of 66 patients with adult-onset diabetes mellitus (DM) manifested at 47.2±11.6 years with known duration of 14.3±8.4y were determined. RESULTS: ICA was positive in 10 cases (10 to 640 JDF U), 3 of them being also positive for anti-GAD (15.6 to 113.5 U/ml) and one for IAA (in those without previous insulin therapy). 15.2% of the patients had one or more autoantibodies, with greater prevalence for ICA. There were no differences between patients with and without autoantibodies for clinical DM presentation and prevalence of chronic complications. Only the cholesterol levels were lower in the antibody positive group (205.2±49.6 vs. 247.1±61.3mg/dl; p<0.05). CONCLUSION: 15.2% of the adult-onset DM had one or more autoantibodies, with greater prevalence for ICA. Autoantibodies determination is necessary for the diagnosis of autoimmune DM.

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.

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.

O objetivo do estudo foi determinar se a Gordura intra Abdominal medida pela Ultra-Sonografia (GAUS) em homens e mulheres tem associação com os fatores de risco cardiovascular, comparar essa medida com a circunferência abdominal e diâmetro sagital para precisar qual destes métodos é o melhor preditor de risco cardiovascular (CV), e tentar encontrar um ponto de corte para GAUS que possa definir maior risco de doença CV. Cento e noventa e um homens sadios e 231 mulheres sadias foram submetidas à medidas antropométricas, medidas de pressão arterial sistêmica e dosagens laboratoriais para colesterol, HDL, triglicerídeos e glicemia. A ultra-sonografia intra-abdominal foi realizada para medir espessura visceral. A amostra foi dividida em três grupos de acordo com a presença dos seguintes fatores de risco cardiovascular: 1) grupo de moderado risco - presença de dois ou mais dos fatores: col > 200mg/dL, HDL-colesterol < 45mg/dL, TG > 200mg/dL, Glic > 126mg/dL, PAs > 140mmHg, PAd > 90mmHg; 2) grupo de alto risco com dois ou mais dos fatores: total col > 240mg/dL, HDL-colesterol < 35mg/dL, TG > 200mg/dL +HDL < 35mg/dL, Glic > 126mg/dL, PAs > 140mmHg, PAd > 90mmHg; 3) grupo sem risco: com um ou nenhum dos fatores de risco presentes. Os resultados mostraram que a GAUS tem associação com todos os fatores de risco cardiovascular e tem melhor especificidade e acurácia que a circunferência abdominal e o diâmetro sagital. O valor de 7cm para ambos os sexos foi o ponto de corte para GAUS para predizer risco moderado; 8 e 9cm foram os pontos de cortes obtidos para GAUS para predizer alto risco CV em homens e mulheres, respectivamente. A GAUS é um método útil de determinar espessura visceral e parece ser capaz de predizer risco cardiovascular.

The objective of our study was to determine if Intra Abdominal Thickness measured by Ultrasonography (IATU) has correlation with cardiovascular risk factors, and if it is a better predictor of cardiovascular risk than waist circumference and sagittal diameter. Finally we tried to find a cut off point for abdominal thickness measured by Ultrasonography to predict cardiovascular disease (CVD). One hundred ninety one healthy men and 231 healthy women were submitted to anthropometric evaluation and blood pressure measure. Blood samples were drawn for total plasma cholesterol, HDL, triglyceride and glucose determination. Intra-abdominal Ultrasonography was performed to measure abdominal thickness. The population was divided in three groups according to the presence of CVD risk factors: 1) moderately risk group (MR) with two or more of the following: total chol > 200mg/dL, HDL-cholesterol < 45mg/dL, TRIG > 200mg/dL, Glu > 126mg/DI, SBP > 140mmHg, DBP > 90mmHg; 2) high risk group (HR) with two or more of the indicated: total chol > 240mg/dl, HDL-cholesterol < 35mg/dl, TRIG > 200mg/dl + HDL-cholesterol < 35mg/dl, Glu > 126mg/dl, SBP > 140mmHg, DBP > 90mmHg; 3) no risk group (NR) - with only one or none of the risk factors indicated in the moderate and high group. The results showed that IATU has association with all cardiovascular risk factors and has better specificity and accurately for CVD risk than waist circumference and sagittal diameter. The values of 7cm for both sexes was the cut off lengths obtained by IATU to predict moderate CV risk; 8 and 9cm were the cut off length obtained by IATU to predict high CV risk for men and for women respectively. The IATU is a useful way to determine visceral fat and seems to be predictive of cardiovascular risk.

Os autores apresentam uma definição de resistência à insulina e discutem os métodos diagnósticos desde o padrão-ouro - o "clamp" euglicêmico hiperinsulinêmico -, passando pela prova de supressão da insulina, a infusão contínua de glicose, a prova de tolerância à glicose endovenosa com um modelo matemático mínimo, até o teste de tolerância à insulina. Analisam também a glicemia e insulina basais e após sobrecarga oral de glicose. Finalmente mostram fatores que influenciam a ação da insulina, como: peso corporal, condicionamento físico, pêso ao nascimento, tipo de fibra muscular predominante, hormônios, densidade capilar e fluxo no músculo esquelético, dieta, idade e hereditariedade.

The authors define insulin resistance and discuss the diagnostic methods from the "gold-standard" - the euglycemic hyperinsulinemic clamp -, going through the insulin suppression test, the continuous glucose infusion, the intravenous glucose tolerance test with the minimal mathematical model, to the insulin tolerance test. Fasting and post-oral glucose load levels of glucose and insulin are also evaluated. Finally, factors influencing insulin action, as body weight, fitness, weight at birth, type of predominant muscle fibers, hormones, capillary density and flow through the skeletal muscle, diet, age and heredity, are indicated.