Use of imaging and clinical data to screen for cardiovascular disease in asymptomatic diabetics.

BACKGROUND: There is increasing evidence to suggest that not all individuals with type 2 diabetes mellitus (T2DM) have equal risk for developing cardiovascular disease. We sought to compare the yield of testing for pre-clinical atherosclerosis with various approaches. METHODS: 98 asymptomatic individuals with T2DM without known coronary artery disease (CAD) were enrolled in a prospective study and underwent carotid ultrasound, exercise treadmill testing (ETT), coronary artery calcium (CAC) scoring, and coronary computed tomography angiography (CTA). RESULTS: Of 98 subjects (average age 55 ± 6, 64 % female), 43 (44 %) had coronary plaque detectable on CTA, and 38 (39 %) had CAC score >0. By CTA, 16 (16 %) had coronary stenosis ≥50 %, including three subjects with CAC = 0. Subjects with coronary plaque had greater prevalence of carotid plaque (58 % vs. 38 %, p = 0.01) and greater carotid intima media thickness (0.80 ± 0.20 mm vs. 0.70 ± 0.11 mm, p = 0.02). Notably, 18 of 55 subjects (33 %) with normal CTA had carotid plaque. Eight subjects had a positive ETT, of whom five had ≥ 50 % coronary stenosis, two had <50 % stenosis, and one had no CAD. Among these tests, CAC scoring had the highest sensitivity and specificity for prediction of CAD. CONCLUSION: Among asymptomatic subjects with T2DM, a majority (56 %) had no CAD by CTA. When compared to CTA, CAC was the most accurate screening modality for detection of CAD, while ETT and carotid ultrasound were less sensitive and specific. However, 33 % of subjects with normal coronary CTA had carotid plaque, suggesting that screening for carotid plaque might better characterize stroke risk in such patients.

Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip syndrome.

BACKGROUND/AIMS: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism. METHODS: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles. RESULTS: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals presented high triglyceride levels, and 68.1% of patients showed high cholesterol levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPARγ2 gene was found in 86.3% of patients; the Ala/Ala variant was not observed in any patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ polymorphism of the adiponectin gene was found in 54.6% of patients. CONCLUSIONS: No association was found between lipid parameters and the relevant Pvull, Avall and Sstl polymorphisms. However, we did observe an association of the Pro12Ala and ADIPOQ polymorphisms with higher lipid levels, suggesting a close relationship between these factors.

Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class I obesity. RESEARCH DESIGN AND METHODS: Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS: Participants had severe, longstanding diabetes, with disease duration 12.5 ± 7.4 years and HbA(1c) 9.7 ± 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 ± 1.5 to 5.9 ± 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved ß-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS: This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes.

Gastric bypass surgery causes resolution of type 2 diabetes (T2DM), which has led to the hypothesis that upper gastrointestinal (UGI) tract diversion, itself, improves glycemic control. The purpose of this study was to determine whether UGI tract bypass without gastric exclusion has therapeutic effects in patients with T2DM. We performed a prospective trial to assess glucose and ß-cell response to an oral glucose load before and at 6, 9, and 12 months after duodenal-jejunal bypass (DJB) surgery. Thirty-five overweight or obese adults (BMI: 27.0 ± 4.0 kg/m(2)) with T2DM and 35 sex-, age-, race-, and BMI-matched subjects with normal glucose tolerance (NGT) were studied. Subjects lost weight after surgery, which was greatest at 3 months (6.9 ± 4.9%) with subsequent regain to 4.2 ± 5.3% weight loss at 12 months after surgery. Glycated hemoglobin (HbA(1c)) decreased from 9.3 ± 1.6% before to 7.7 ± 2.0% at 12 months after surgery (P < 0.001), in conjunction with a 20% decrease in the use of diabetes medications (P < 0.05); 7 (20%) subjects achieved remission of diabetes (no medications and HbA(1c) <6.5%). The area under the curve after glucose ingestion was ~20% lower for glucose but doubled for insulin and C-peptide at 12 months, compared with pre-surgery values (all P < 0.01). However, the ß-cell response was still 70% lower than subjects with NGT (P < 0.001). DJB surgery improves glycemic control and increases, but does not normalize the ß-cell response to glucose ingestion. These findings suggest that altering the intestinal site of delivery of ingested nutrients has moderate therapeutic effects by improving ß-cell function and glycemic control.

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

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.

Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome.

CONTEXT: Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. DESIGN: We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly. RESULTS: Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518-519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A). CONCLUSIONS: We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).

Analysis of pancreatic adenocarcinoma tumor staging and resection according to previous body mass index and diabetes duration.

BACKGROUND/AIMS: Obesity and diabetes mellitus (DM) are associated with pancreatic cancer. The present study evaluated tumor staging and resection of pancreatic adenocarcinoma (PaC) according to previous Body Mass Index (BMI), BMI on admission and DM duration. METHODS: A retrospective analysis of 151 consecutive patients with PaC was performed: 73 were evaluated according to BMI preceding tumor-related weight loss and BMI on admission; 118 according to DM diagnosis; and 38 were assessed according to DM duration (less than 1 year [recent-onset] versus more than 2 years [long-standing]). RESULTS: There was no difference in the prevalence of tumor stage III or IV between previously normal weight and overweight/obese patients (56 vs. 42%, NS). Tumor resection rate was higher in previously obese than in previously lean patients (58 vs. 24%, p < 0.05). Tumor staging and resection were similar between normal weight and overweight/obese patients considering BMI on admission and diagnosis of DM. Weight loss was more pronounced in diabetic than in non-diabetic patients (21.7 vs. 13.3%, p < 0.01). Tumor staging and resection were similar between recent-onset and long-standing diabetic patients. CONCLUSION: Tumor resection rate was lower in previously normal weight patients. Diabetics lost more weight than non-diabetic patients. Neither BMI on admission nor the presence of DM nor DM duration influenced tumor staging or resection in PaC patients.

beta-cell failure in diabetes and preservation by clinical treatment.

There is a progressive deterioration in beta-cell function and mass in type 2 diabetics. It was found that islet function was about 50% of normal at the time of diagnosis, and a reduction in beta-cell mass of about 60% was shown at necropsy. The reduction of beta-cell mass is attributable to accelerated apoptosis. The major factors for progressive loss of beta-cell function and mass are glucotoxicity, lipotoxicity, proinflammatory cytokines, leptin, and islet cell amyloid. Impaired beta-cell function and possibly beta-cell mass appear to be reversible, particularly at early stages of the disease where the limiting threshold for reversibility of decreased beta-cell mass has probably not been passed. Among the interventions to preserve or "rejuvenate" beta-cells, short-term intensive insulin therapy of newly diagnosed type 2 diabetes will improve beta-cell function, usually leading to a temporary remission time. Another intervention is the induction of beta-cell "rest" by selective activation of ATP-sensitive K+ (K(ATP)) channels, using drugs such as diazoxide. A third type of intervention is the use of antiapoptotic drugs, such as the thiazolidinediones (TZDs), and incretin mimetics and enhancers, which have demonstrated significant clinical evidence of effects on human beta-cell function. The TZDs improve insulin secretory capacity, decrease beta-cell apoptosis, and reduce islet cell amyloid with maintenance of neogenesis. The TZDs have indirect effects on beta-cells by being insulin sensitizers. The direct effects are via peroxisome proliferator-activated receptor gamma activation in pancreatic islets, with TZDs consistently improving basal beta-cell function. These beneficial effects are sustained in some individuals with time. There are several trials on prevention of diabetes with TZDs. Incretin hormones, which are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas, aid the overall maintenance of glucose homeostasis through slowing of gastric emptying, inhibition of glucagon secretion, and control of body weight. From the two major incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), only the first one or its mimetics or enhancers can be used for treatment because the diabetic beta-cell is resistant to GIP action. Because of the rapid inactivation of GLP-1 by dipeptidyl peptidase (DPP)-IV, several incretin analogs were developed: GLP-1 receptor agonists (incretin mimetics) exenatide (synthetic exendin-4) and liraglutide, by conjugation of GLP-1 to circulating albumin. The acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis and stimulation of insulin gene transcription. The chronic action is stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of beta-cell apoptosis, thus promoting expansion of beta-cell mass, as observed in rodent diabetes and in cultured beta-cells. Exenatide and liraglutide enhanced postprandial beta-cell function. The inhibition of the activity of the DPP-IV enzyme enhances endogenous GLP-1 action in vivo, mediated not only by GLP-1 but also by other mediators. In preclinical studies, oral active DPP-IV inhibitors (sitagliptin and vildagliptin) also promoted beta-cell proliferation, neogenesis, and inhibition of apoptosis in rodents. Meal tolerance tests showed improvement in postprandial beta-cell function. Obviously, it is difficult to estimate the protective effects of incretin mimetics and enhancers on beta-cells in humans, and there is no clinical evidence that these drugs really have protective effects on beta-cells.

Diabetes autoimune em adultos: características clínicas e autoanticorpos / Autoimmune diabetes in adults: clinical characteristics and antoantibody

Avaliamos a prevalência dos anticorpos anti-insulina (IAA), anti-decarboxilase do ácido glutãmico (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 (47,2ñ11,6 anos) e duração do DM de 14,3ñ8,4 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 por cento 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 (205,2ñ49,6 vs. 247,1ñ61,3mg/dl; p<0,05). Conclusão: 15,2 por cento 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.

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 / Smaller incidency of nocturnal hypoglycemia with the use of insulin lispro comparated to the regular human insulin in the treatment of diabetes mellitus type 1 patients

Insulina lispro é um análogo da insulina humana de ação e duração rápida, que mimetiza 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.

Correlaçäo da medida de espessura intra-abdominal medida pela ultra-sonografia com os fatores de risco cardiovascular / Correlation of intra-abdominal thickness measure for the ultrasound with cardiovascular risk factors

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, respecti- vamente. A GAUS é um método útil de determinar espessura visceral e parece ser capaz de predizer risco cardiovascular.

Resistência à insulina: métodos diagnóstico e fatores que influenciam a açäo da insulina / Insulin resistance: diagnostic methods and factors that influence the insulin action

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.

Etiopatogenia do diabetes mellitus do tipo 2 / Etiopathogeny of type 2 diabetes mellitus

O diabetes mellitus do tipo 2, na sua forma habitual, de início tardio, é caracterizado por resistência e deficiência insulínica, que contribuem de maneiras diferentes para a patogenia da doença. A alteração funcional da célula beta se manifesta precocemente, com aumento da relação pró-insulina/insulina. Graus variados de deficiência insulínica (absoluta ou relativa) São observados nos vários grupos étnicos estudados (caucasianos, mexicano-americanos, nipo-americanos, nipo-brasileiros, índios americanos, afro-americanos e asiáticos) onde a grande prevalência do diabetes do tipo 2 está associada à maior ingestão calórica e à redução da atividade física. A obesidade resultante tem um padrão central, visceral-abdominal. Nestas populações, a resistência insulínica é fator inicial e predominante, estanto associada à hiperinsulinemia, e à dislipidemia e ao maior risco de acometimento por doenças cardiovasculares. O papel da obesidade e dos ácidos graxos livres na produção hepática de glicose e na resistência à insulina são abordados, assim como o diagnóstico diferencial com outros tipos de diabetes.

Failure of Partial Hypophysectomy as Definitive Treatment in Cushing's Disease Owing to Nodular Corticotrope Hyperplasia: Report of Four Cases.

Nodular corticotrope hyperplasia is a rare pathology causing Cushing's syndrome owing to a primary pituitary disease or ectopic CRH production. In this study, we evaluated the laboratory and pathological findings and results of transsphenoidal pituitary surgery in four patients with Cushing's disease. Dynamic tests of pituitary-adrenal function (dexamethasone suppression, metyrapone, CRH, and DDAVP tests) were done before and after transsphenoidal pituitary surgery. Plasma and total urinary cortisol, serum 11-deoxycortisol, and plasma ACTH were determined by RIA. Hormonal dynamic tests and radiologic studies were compatible with a pituitary ACTH source. The transsphenoidal surgery revealed the presence of corticotrope hyperplasia confirmed by immunoperoxidase stain and a preserved reticulum framework in the removed pituitary tissue of these four patients. The pituitary surgery led to a short period of improvement in two of the patients (1 and 4), a 3-yr remission in one patient (patient 2), and no improvement in one (patient 3). We conclude that although our patients appear to have inadequate suppression with high-dose dexamethasone, there is no way to diagnose this pathology presurgically, and that total hypophysectomy, bilateral adrenalectomy, and irradiation are the only alternatives for definitive treatment. A CRH-secreting ectopic tumor could not be found in our patients either before or after surgery in the follow-up period.

O espectro clínico e laboratorial da forma näo clássica de hiperplasia adrenal congênita por deficiência da 21-hidroxilase / The clinical and laboratorial spectrum of the non-classic way of congenital adrenal hyperplasia by 21-hydroxilase deficiency

Foram estudadas 9 pacientes portadoras da forma nao clássica de hiperplasia adrenal congênita por deficiência de 2l-hidroxilase (2l-FNC). O diagnóstico baseou-se na resposta da 17-hidroxiprogesterona (l7-OHP) 60 minutos após estímulo com 250 ug de ACTH sintético por via EV. Em relaçao à reserva de glicocorticóide, observamos somente uma paciente com resposta deficiente de cortisol ao estímulo com ACTH. A concentraçao basal de 17-OHP foi altamente variável, tanto em relaçao a mesma paciente como entre as pacientes. Em duas delas, observamos concentraçao basal de 17-OHP normal, após estímulo com ACTH, observamos uma hiperresposta de 17-OHP, compatível com o diagnóstico de 2l-FNC. As pacientes foram subdivididas em três grupos de acordo com o diagnóstico clínico: Grupo I: Pubarca precoce (n= 1); Grupo II: Hirsutismo com ciclos menstruais regulares e ovulatórios (n= 4); e Grupo III: Hirsutismo com alteraçao menstrual (n= 3). Nao observamos qualquer diferença entre os três grupos tanto em relaçao à reserva de glicocorticóide adrenal e a concentraçao de 17-OHP, basal ou pós-estímulo, nem com relaçao à parâmetros clínicos, como obesidade, menarca ou idade de início do hirsutismo nas pacientes dos grupos II e III, sugerindo que a manifestaçao clínica da 2l -FNC esteja na dependência de fatores extra-adrenais, excetuando-se a pubarca precoce.

Estudo multicêntrico comparativo da insulina bovina com formas mais purificadas de insulina suína e humana no tratamento de diabéticos do tipo I / Multicenter studies comparative of bovine insulin with forms more purified of swine and human insulin in treatment type 1 diabetes mellitus patients

Este trabalho mostra os resultados obtidos em um estudo multicêntrico, duplo-cego e randomizado, organizado com o intuito de analisar o comportamento dos níveis de anticorpos antiinsulina e do grau de controle metabólico em diabéticos do tipo I que passaram o seu tratamento de insulina bovina para insulina suína e insulina humana mais purificadas. Foram selecionados para o estudo 28 pacientes diabéticos do tipo I e que estavam sendo tratados com insulina bovina (pró-insulina < 3.000ppm). Destes pacientes, em um protocolo de seis meses, nove permaneceram com insulina bovina, nove trocaram para insulina suína monopico (pró-insulina < 10ppm) e dez para insulina humana monocomponente (pro-insulina < 1ppm). As preparaçöes de insulina fornecidas pelo Laboratório Biobras. Os anticorpos antiinsulina (IA) foram determinados pelo método de ELISA e o metabólico foi avaliado pelos níveis de glicemia de jejum, glicosúria de 24 horas e proteína glicosilada determinada pela cromatografia de afinidade. Após a troca de insulina, ocorreu diminuiçäo dos níveis de anticorpos nos pacientes que passaram a ser tratados com as insulinas suína e humana, enquanto que, nos pacientes que permaneceram com insulina, houve subida destes valores. Quanto ao controle metabólico, verificou-se aumento significativo dos níveis glicêmicos nos pacientes que passaram a ser tratados com a insulina humana. No início do estudo, encontrou-se ainda correlaçäo significativa negativa entre os IA e a glicosúria de 24 horas (rs = -0509; p = 0,006). Concluindo, näo houve melhora do controle metabólico, apesar da diminuiçäo dos níveis de anticorpos antiinsulina, em diabéticos do tipo I que passaram a ser tratados com formas menos imunogênicas de insulina

Avaliaçäo da resposta do T3 livre, TT3 e TSH ao teste do TRH em indivíduos normais, hipotireóideos e hipertireóideos / Evaluation of the free T3, TT3 and TSH response to the TRH test in normal, hypothyroid and hyperthyroid subjects

O ensaio do T3 livre näo é influenciado pelas proteínas séricas circulantes, e sendo este o hormônio ativo, nos propusemos a estudar o T3 livre no teste do TRH em 15 indivíduos (seis normais, quatro hipertireóideos e cinco hipotireóideos), que foram submetidos à infusäo aguda de TRH (200µg EV) quantificando-se no soro, além da fraçäo livre do T3, o T3 total e o TSH. A maior variaçäo percentual de triiodotironina total nos normais ocorreu aos 180 minutos após o TRH (23,9 por cento), näo estatísticamente significativa. A maior variaçäo de FT3 ocorreu aos noventa minutos , com aumento de 88, 9 por cento (p<0,005). Os incrementos percentuais relativos (delta por cento = pico basal/basal) x 100 do T3 livre foram significativamente maiores nos indivíduos normais que nos hipertireóideos (p<0,05) e ainda significativamente menores nos hiperteireóideos (p<0,05). Em conclusäo, a utilizaçäo da determinaçäo do T3 livre nos testes de infusäo aguda de TRH nos permite a concomitante avaliaçäo da reserva pituitária de TSH e da capacidade de secreçäo tireoideana de triiodotironina na sua forma livre, podendo ser útil no diagnóstico diferencial dos distúrbios tireoideanos.