Hiperinsulinismo endógeno: dois desafios diagnósticos / Endogenous hyperinsulinism: two diagnostic challenges

A hipoglicemia em um adulto aparentemente saudável é um achado raro na prática clínica que exige uma investigação exaustiva da causa. A identificação de glicemia plasmática diminuída associada a concentrações plasmáticas de insulina e peptídeo-C não suprimidos deverá levar à exclusão de causas raras de hipoglicemia, entre elas, doença das células betapancreáticas e hipoglicemia autoimune. Neste artigo, descrevemos dois casos de hipoglicemia associada a hiperinsulinismo endógeno, cujas causas são pouco habituais na prática clínica. A propósito desses casos clínicos revemos aspectos importantes de diagnósticos e tratamento da hipoglicemia no contexto de hiperinsulinismo endógeno.

Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately high levels of insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia, including pancreatic islet-cells disease and autoimmune hypoglycemia. In this paper, we describe two cases of hypoglycemia associated with endogenous hyperinsulinism, whose causes are uncommon in clinical practice, and review important aspects of the diagnosis and treatment of hyperinsulinemic hypoglycemia.

Frequency Of Pancreatic Beta-Cell Autoimmunity Markers In Patients With Autoimmune Thyroid Disease / Frecuencia de marcadores de autoinmunidad beta pancreática en pacientes con enfermedad tiroidea autoinmune

A total of 305 ambulatory patients recruited at the Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, with autoimmune thyroid disease (AITD) were studied to search for associations between autoimmune thyroid disease and presence of serum markers of autoimmune diabetes mellitus. Screening for markers of pancreatic beta-cell autoimmunity was performed by radioligand binding assays (RBA) as follows: autoantibodies to glutamic acid decarboxylase (GADA) and proinsulin (PAA) were determined in all sera, whereas autoantibodies to protein tyrosine phosphatase (IA-2A) and insulin (IAA) were additionally measured in 200 sera randomly selected from the total collection. In addition, every GADA positive serum among the remaining 105 sera was systematically tested for the presence of IA-2A and IAA. In the cohort of 305 AITD patients 22 (7.2%) were previously diagnosed as type 1, type 2 or insulin-requiring type 2 diabetics. Ten of these patients presented serum marker positivity specific for β-cell autoantigens and 12 were marker negative. On the other hand, considering the majority of non-diabetic AITD patients (n=283), β-cell marker positivity was detected in 17 individuals (6.0%). The prevalence of autoimmune diabetes markers was much higher in the studied population than in the general population utilized as a control group, and GADA was the most frequent marker.

Se investigó la asociación entre enfermedad tiroidea autoinmune y la presencia de marcadores séricos de diabetes mellitus en 305 pacientes ambulatorios con enfermedad tiroidea autoinmune reclutados en la División Endocrinología. La búsqueda de marcadores de autoinmunidad contra las células beta pancreáticas se realizó por la técnica de unión de radioligandos (RBA) como se detalla a continuación: se determinaron autoanticuerpos contra la decarboxilasa del ácido glutámico (GADA) y proinsulina (PAA) en todos los sueros, mientras que los anticuerpos contra la proteína tirosina fosfatasa (IA-2A) e insulina (IAA) fueron medidos en 200 de estos sueros tomados al azar de la colección total. Además, en los restantes 105 pacientes, la presencia de IA-2A y IAA fue evaluada en todos los sueros positivos para GADA. Del grupo de 305 pacientes con enfermedad tiroidea autoinmune 22 (7.2%) fueron diagnosticados previamente como diabéticos tipo 1, tipo 2 o tipo 2 insulino-requirientes. Diez de ellos presentaron positividad para marcadores específicos de autoantígenos de célula β, en tanto 12 fueron negativos. Por otra parte, en 17 de los 283 pacientes (6.0%) con enfermedad tiroidea autoimmune y sin diagnóstico previo de diabetes, se detectó positividad para marcadores de célula β. La prevalencia de marcadores de autoinmunidad asociados a diabetes fue mayor en la población estudiada que en la población general usada como grupo control, siendo GADA el marcador más frecuente.

role of proinsulin in gestational diabetes mellitus

To look for any increase in proinsulin or proinsulin/insulin ratio in women suffering GDM as an additional factor to their insulin resistance state during pregnancy; and to test for its reversibility in the post partum period. The study was conducted on 30 pregnant age matched women in their second or third trimester and 10 age matched non pregnant normoglycemic women as a reference group. The pregnant women were divided into 3 groups each of ten as follow: normoglycemic women with normal OGTT as a control group, obese women with GDM and lean women with GDM. All women were subjected to full history taking and complete clinical examination. The following parameters were measured: diagnostic OGTT using 100 gm glucose, fasting serum proinsulin, fasting serum insulin, serum C-peptide, proinsulin/insulin ratio and insulin sensitivity. All these tests were repeated 4-8 weeks postpartum. The results of the study revealed that the serum levels of proinsulin and the proinsulin/insulin ratio were significantly higher in obese and lean women with GDM than the control and reference groups during pregnancy and also after delivery. The insulin sensitivity index was significantly lower and the relative resistance for insulin was significantly higher in GDM women compared with normal glucose tolerant pregnant women during pregnancy, while after delivery the sensitivity index was significantly higher than during pregnancy in GDM women as well as pregnant women with normal OGTT. The mean values of C-peptide were significantly higher in GDM patients versus control and reference groups during pregnancy. After delivery these mean values of C-peptide were significantly lower than during pregnancy in the three pregnant studied groups. Women with GOM are characterized by elevated serum proinsulin concentrations and increased proinsulin/insulin ratio which reflect beta-cell decompensation. These precursors molecules might thus serve as a marker for the disease and potentially even identify the subjects of high risk for development of type 2 diabetes. Also, it may be possible to detect such beta-cell stress earlier in pregnancy and to use this phenomena in the assistance of better prediction of GDM

Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1 percent. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95 percent CI: 1.68-2.48 and 1.09; 95 percent CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22 percent and 36 percent for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

A síndrome metabólica (SM) constitui um fator de risco independente para doenças cardiovasculares. Existem evidências de que níveis sangüíneos de proinsulina e o índice proinsulina/insulina estão associados com a presença da SM. O objetivo deste trabalho foi comparar proinsulina e insulina, índice de resistência insulínica e o fator proinsulina/insulina para predizer a presença da SM. Este é um estudo transversal envolvendo 440 homens e 556 mulheres com média de 24 anos de idade. O diagnóstico da SM foi feito de acordo com o Painel III do programa de tratamento nacional educacional de colesterol para adultos. Níveis sangüíneos de insulina e proinsulina foram medidos, o índice de resistência insulínica foi estimado através do modelo de avaliação hemostático (HOMA-IR). A prevalência da SM foi de 10 por cento. HOMA-IR demonstrou ser o melhor fator de risco da SM em homens e mulheres (OR = 2,04; 95 por cento CI: 1,68-2,48 e 1,09; 95 por cento CI: 1,05-1,13, respectivamente). HOMA-IR apresentou o melhor valor preditivo positivo para SM: 22 por cento e 36 por cento para homens e mulheres, respectivamente, e foi o melhor indicador da SM. O índice proinsulina/insulina não apresentou associação significativa com SM. HOMA-IR, proinsulina e insulina apresentaram bons valores preditivos negativos para ambos sexos, o que poderia ser usado para identificar uma população de risco.

Association of adipocytokines (leptin, adiponectin TNF-alpha), insulin and proinsulin with diabetes--the Mumbai Obesity Project [MOP].

Asian Indians have a unique phenotype characterized by increased abdominal obesity and visceral fat despite low body mass index [BMI]. Though studies have indicated some adipocytokines to be associated with diabetes and obesity in Indians, there are virtually no studies relating adipocytokines and proinsulin with diabetes and obesity in Asian Indians. In this study we looked at adipocytokines--leptin, adiponectin and tumour necrosis factor-a [TNF-alpha] and insulin and proinsulin in subjects with diabetes and obesity. Thirty five diabetic subjects and 50 healthy controls were recruited for the study. Leptin [p=0.002J and adiponectin levels [p=0.011] were lower and proinsulin values higher [p<0.001] in diabetic subjects compared to non-diabetic subjects. In addition, leptin [p<0.001] and proinsulin [p<0.001] were higher and adiponectin [p<0.001] lower, in obese subjects compared to non-obese subjects. TNF-alpha failed to show any significant difference between the study groups. Leptin and proinsulin showed a significant and positive correlation with BMI [p<0.001] and waist circumference [p<0.001]. Adiponectin showed an inverse correlation with BMI [p=0.050] and waist circumference [p=0.002]. Proinsulin showed a significant negative association with adiponectin [p=0.002]. Logistic regression analysis revealed leptin to be negatively associated [Odds ratio [OR]: 0.864, 95% confidence interval [95% CI]: 0.775 -0.963, p=0.008] and proinsulin [OR: 1.567, 95% CI: 1.246-1.971, p<0.001] to be positively associated with diabetes even after adjusting for age, gender and BMI. Leptin [OR: 1.365, 95% CI: 1.170-1.592, p<0.001] and proinsulin [OR: 1.617, 95% CI: 1.218 -2.147, p=0.001] showed a significant positive association with obesity, while adiponectin [OR: 0.927, 95% CI: 0.865 - 0.995, p=0.035] had a significant inverse association. Linear regression analysis revealed that adiponectin is inversely associated with proinsulin even after the addition of age, gender and diabetes status [beta= -0.61, p=0.033] into the model. In conclusion, in urban Asian Indians in western India, proinsulin levels showed a positive association, while leptin and adiponectin showed a negative association with diabetes. With regard to obesity, leptin and proinsulin had a positive association, while adiponectin had a negative association. Proinsulin levels showed an inverse association with adiponectin indicating a possible link between insulin secretion and insulin resistance.

Serum Insulin, Proinsulin and Proinsulin/Insulin Ratio in Type 2 Diabetic Patients: As an Index of beta-Cell Function or Insulin Resistance

BACKGROUND: Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS: We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also investigated the relationship between serum insulin, proinsulin and proinsulin/insulin ratio and several biochemical markers which represent insulin resistance or beta cell function. RESULTS: Insulin, proinsulin and proinsulin/insulin ratio were significantly higher in type 2 DM than control(p < 0.001). In diabetic patients, total insulin level was correlated with urinary albumin excretion rates(r = 0.224, p = 0.025) and body mass index(r = 0.269, p = 0.014). Proinsulin level was correlated with fasting C-peptide(r = 0.43, p = 0.002), postprandial 2 hour blood glucose(r = 0.213, p = 0.05) and triglyceride(r = 0.28, p = 0.022). Proinsulin/insulin ratio was positively correlated with fasting C-peptide(r = 0.236, p = 0.031), fasting blood glucose (r = 0.264, p = 0.015), postprandial 2 hour blood glucose(r = 0.277, p = 0.001) and triglyceride(r = 0.428, p < 0.001). In control subjects, insulin level was correlated with triglyceride(r = 0.366, p = 0.002). Proinsulin/insulin ratio was correlated with age(r = 0.241, p = 0.044). CONCLUSION: The serum levels of insulin and proinsulin seem to be associated with several markers of insulin resistance. Whereas proinsulin/insulin ratio might represent beta cell function rather than insulin resistance. But more studies are needed to clarify the mechanisms of elevated proinsulin/insulin ratio in type 2 DM.

Specific insulin and proinsulin secretion in glucokinase-deficient individuals

Glucokinase (GCK) is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY). An early onset (less than 25 years), autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA) during a 75-g oral glucose tolerance test (OGTT). Two kindreds (SA and LZ) were studied and compared to non-diabetic unrelated individuals (control group 1) matched for age and body mass index (BMI). In one kindred, some of these subjects were also obese (BMI>26 kg/m2), and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P<0.02 and P<0.01, for proinsulin and proinsulin/insulin ratio, respectively). Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindred SA is probably related to the obesity and late-onset NIDDM background present in this family.

Specific insulin and proinsulin in normal glucose tolerant first-degree relatives of NIDDM patients

In order to identify early abnormalities in non-insulin-dependent diabetes mellitus (NIDDM) we determined insulin (using an assay that does not cross-react with proinsulin) and proinsulin concentrations. The proinsulin/insulin ratio was used as an indicator of abnormal ß-cell function. The ratio of the first 30-min increase in insulin to glucose concentrations following the oral glucose tolerance test (OGTT; I30-0/G30-0) was taken as an indicator of insulin secretion. Insulin resistance (R) was evaluated by the homeostasis model assessment (HOMA) method. True insulin and proinsulin were measured during a 75-g OGTT in 35 individuals: 20 with normal glucose tolerance (NGT) and without diabetes among their first-degree relatives (FDR) served as controls, and 15 with NGT who were FDR of patients with NIDDM. The FDR group presented higher insulin (414 pmol/l vs 195 pmol/l; P = 0.04) and proinsulin levels (19.6 pmol/l vs 12.3 pmol/l; P = 0.03) post-glucose load than the control group. When these groups were stratified according to BMI, the obese FDR (N = 8) showed higher fasting and post-glucose insulin levels than the obese NGT (N = 9) (fasting: 64.8 pmol/l vs 7.8 pmol/l; P = 0.04, and 60 min post-glucose: 480.6 pmol/l vs 192 pmol/l; P = 0.01). Also, values for HOMA (R) were higher in the obese FDR compared to obese NGT (2.53 vs 0.30; P = 0.075). These results show that FDR of NIDDM patients have true hyperinsulinemia (which is not a consequence of cross-reactivity with proinsulin) and hyperproinsulinemia and no dysfunction of a qualitative nature in ß-cells

Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic Beta-cell demand in men

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0.47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m2, N = 8) and nonobese (BMI £25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand

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.

Leptinemia e secreçäo pancreática em homens / Pancreatic leptin and secretion in men

Na literatura, crescem as evidências de um possível envolvimento da insulina como reguladora da síntese adipocítica de leptina. Com o objetivo de estudar as possíveis corelações entre a leptina com a secreção das células beta-pancreáticas, em homens, estudou-se 19 indivíduos jovens (idades entre 25-33 anos), saudáveis, com tolerância normal à glicose. Os indivíduos foram avaliados por vários parâmetros de composição corporal como peso. IMC, medida da relação entre a cintura e o quadril e o percentual de gordura corporal (densitometria, LUNAR-DPX). Realizou-se dosagens com o emprego de ensaios específicos de glicose, insulina, pró-insulina, peptídeo C e leptina basais e 120 min após sobrecarga com 75 g de glicose. Encontrou-se correlações (teste de Spearman) positivas entre os níveis de leptina com todas as medidas antropométricas (todas com p < 0,0001). A leptinemia correlacionou-se positivamente com os níveis de insulina basal (r = 0,67; p < 0,05), insulina 120 min (r = 0,76; p < 0,0001), pró-insulina basal (r = 0,68; p < 0,0005), pró-insulina 120 min (r = 0,71; p < 0,0001), peptídeo C basal (r = 0,66; p < 0,005) e peptídeo C 120 min (r = 0,66; p < 0,005). Em resumo, encontramos uma associação entre os níveis circulantes de leptina com os vários produtos de secreção das células b-pancreáticas, em homens, reforçando o conceito da existência de um eixo hormonal entre o adipócito e as ilhotas pancreáticas.

Utilizaçäo da pró-insulina no diagnóstico de insulinomas: caso 01/96 (RG 921.996) e caso 02/96 (RG 891.498) - Hospital Säo Paulo/Universidade Federal de Säo Paulo/EPM / Utilization of proinsulin in the diagnosis of the insulinomas: case 01/96 (RG 921.996) and case 02/96 (RG 891.498) - Hospital Säo Paulo/Universidade Federal de Säo Paulo/EPM

Insulinomas sao tumores das células beta pancreáticas, caracterizados pela secreçao excessiva de insulina e, ocasionalmente, de outros peptídeos pancreáticos levando, na maioria dos casos, à hipoglicemia. Entretanto, o diagnóstico nao se baseia apenas no encontro de hipoglicemia laboratorial e elevaçao dos níveis de insulina, já que também ocorre aumento do peptídeo C e da pró-insulina. Com o advento das técnicas imunofluorimétricas (IFMA), utilizando-se anticorpos monocionais e técnicas de DNA recombinante, métodos sensíveis e específicos foram desenvolvidos para a dosagem da pró-insulina. Neste trabalho, descrevemos dois casos de insulinoma (um benigno e outro maligno) que apresentavam no diagnóstico níveis muito elevados de pró-insulina (IFMA) e elevaçao da relaçao pró-insulina/insulina (IFMA), demonstrando que nesta patologia a pró-insulina, ao contrário do que ocorre com a insulina, pode estar elevada mesmo fora dos episódios de hipoglicemia. Para a dosagem de insulina utilizamos também, um método específico imunofluorométrico (IFMA) que mede cerca de 50 por cento da insulina dosada por radioimunoensaio (RIE), e por esta razao consideramos como normal a relaçao insulina (IFMA)/glicemia < O, 15. Os dados sugerem que a dosagem de pró-insulina parece ser um método mais sensível, quando comparado com a dosagem de insulina, no diagnóstico de insulinoma.

A specific and highly sensitive time-resolved fluoroimmunoassay for human proinsulin

We describe a time-resolved fluoroimmunoassay specific for human proinsulin using a combination of two high-affinity monoclonal antibodies, one against insulin and the other specific for intact proinsulin and for split 65-66 and des 64-65 proinsulin forms. The assay employs only 200 micro liters of serum, with a detection limit of 0.1 pmol/l. The intra-assay variation coefficient was less than 3 percent between 3 and 1000 pmol/l. There was 0 percent cross-reaction with insulin, C-peptide, split 32-33 and des 31-32 proinsulin. Serum concentration of proinsulin was analyzed in 50 subjects during an oral glucose tolerance test (10 non-obese controls, 10 obese controls, 10 subjects with impaired glucose tolerance, 10 patients with type II diabetes meIlitus (DM) and fasting blood glucose (FBG) <140 mg/dl, and 10 patients with type II DM and FBG >150 mg/dl). Mean fasting serum proinsulin levels measured by this assay in non-obese controls (0.84 +/-0.90 pmol/l; 0.1-2.4 pmol/l) were lower than the results reported by her investigators. There was an increase of proinsulin related to obesity and increased glucose levels, suggesting that proinsulin levels increase with insulin resistance.

Influência da obesidade e da glicemia nos níveis de pró-insulina durante o teste oral de tolerância à glicose / Influence of the obesity and the blood glucose in the proinsulin levels during the glucose tolerance oral test

A insulina provém da conversao da pró-insulina intacta que é submetida a uma série de clivagens insimáticas até a remoçao do peptídeo C. Neste trabalho determinamos os níveis séricos de pró-insulina por ensaio imunofluorimétrico específico durante a realizaçao de um teste oral de tolerância à glicose (TOTG) em cinco grupos de dez indivíduos: I) indivíduos normais com índice de massa corporal (IMC) < 25 Kg/m2, II) indivíduos com sobrepeso, III) tolerância diminuída à glicose (TDG) IV) diabetes mellítus tipo 2 (DM II) com glicemia de jejum < 140 mg/dl e, V) DM II com glicemia de jejum > 140 mg/dl. Os resultados mostraram um aumento significante da pró-insulina de jejum nos grupos II, III, IV e V em comparaçao ao grupo I (p<0,002). As concentraçoes de pró-insulina durante a realizaçao do TOTG, avaliado pela área sob a curva (ASC), foram significantemente maiores nos grupos II, III e V em comparaçao grupo I (p<0,004). Nos grupos III,IV e V verificamos uma correlaçao positiva entre a glicemia de jejum e pró-insulina de jejum (r=0,53; p=0,002). As concentraçoes crescentes de pró-insulina com a obesidade e a piora da tolerância à glicose sugerem que a sua dosagem possa ser um indicador precoce de disfunçao da célula beta.

Associaçäo entre auto-anticorpos anti-pro-insulina e anti-insulina com diabetes mellitus do tipo I / The association between insulin and proinsulin autoantibodies with tipe I Diabetes Mellitus

O presente trabalho compara a incidência de auto-anticorpos anti-insulina (IAA) e anti-pró-insulina (PAA) em diabéticos do tipo I de início recente e em seus parentes de primeiro grau. Foram estudados 33 indivíduos normais (grupo I), 16 diabéticos do tipo I de início recente (grupo II) e 141 parentes em primeiro grau de diabéticos do tipo I (grupo III). Os IAA e PAA foram determinados pelo método de radioensaio, sendo considerados anormais níveis de IAA acima de 0,584 pmol/L e de PAA acima de 0,441 pmol/L. Näo foram observadas diferenças significantes quanto a idade e sexo entre os 3 grupos. Nos indivíduos normais os níveis de PAA foram significantemente menores do que os de IAA. Entre os diabéticos de início recente foi encontrada uma incidência de IAA de 37,5 por cento e de PAA de 25,0 por cento, näo ocorrendo, entretanto, diferenças significantes entre os níveis destes dois anticorpos. Entre os parentes em primeiro grau a incidência de IAA foi de 3,5 por cento e de PAA de 7,8 por cento, näo ocorrendo também diferenças entre os dois testes. Houve uma correlaçäo significante entre os níveis dos IAA e dos PAA no grupo de diabéticos de início recente (r=0,64; p < 0,05). Os IAA e PAA parecem estar dirigidos contra o mesmo determinante antigênico e, portanto, têm o mesmo valor preditivo para o DM tipo I