RESUMEN
As part of a genetic study of type 1 diabetes in Mexican-Americans, 360 first-degree relatives of 108 type 1 diabetic probands were studied. Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD(65)), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. ICA was positive in 37% of the probands and 5.8% of the relatives. A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD(65) and was found positive. 4/14 ICA+ first-degree relatives were GAD(65) positive. Four relatives, positive for two antibodies, subsequently developed type 1 diabetes. Life-Table analysis of first-degree relatives with autoantibodies indicated an 80% disease-free survival at 3.5 yr. HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands. These results suggest that autoimmunity occurs in type 1 diabetes families of Mexican descent in similar frequencies to that of non-Hispanic, Caucasian families. The presence of autoantibodies appears to be regulated in part by HLA class II genes, even in the absence of overt diabetes.
Asunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 1/inmunología , Genes MHC Clase II , Americanos Mexicanos , Adolescente , Adulto , Alelos , Niño , Preescolar , Diabetes Mellitus Tipo 1/etnología , Diabetes Mellitus Tipo 1/genética , Femenino , Glutamato Descarboxilasa/análisis , Humanos , Insulina/inmunología , Masculino , Persona de Mediana EdadRESUMEN
The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. To determine whether HLA haplotypes differ between ethnic groups, we compared 105 HLA haplotypes from 55 Mexican-American IDDM patients with 272 haplotypes from 136 IDDM patients of non-Hispanic White descent. The accurate determination of genotypes and haplotypes requires the study of family units. Therefore, all diabetic patients in this study were from studies of families having one or more siblings with IDDM. In the Mexican-American group, HLA-DR3 and -DR4 were the most common HLA-DR alleles and were present in comparable frequencies in the non-Hispanic White group (HLA-DR3, 27% of Mexican-American and 29% of non-Hispanic White haplotypes; DR4, 46% of Mexican-American and 43% of non-Hispanic White haplotypes). However, the HLA-B/DR-containing haplotypes and haplotype frequencies differed between the two groups. Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. In contrast, uncommon haplotypes in the non-Hispanic White group comprised nearly 50% of the DR4-containing haplotypes (B35/DR4, B40/DR4, B44/DR4) in the Mexican-American group. Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles.
Asunto(s)
Diabetes Mellitus Tipo 1/inmunología , Antígenos HLA-DR/genética , Haplotipos , Hispánicos o Latinos/genética , Alelos , Diabetes Mellitus Tipo 1/genética , Humanos , Valores de Referencia , Estados Unidos , Población BlancaAsunto(s)
Diabetes Mellitus Tipo 1/prevención & control , Estado Prediabético/diagnóstico , Autoanticuerpos/análisis , Niño , Preescolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatología , Humanos , Inmunoterapia , Islotes Pancreáticos/inmunología , Estado Prediabético/terapia , Factores de RiesgoRESUMEN
We describe two brothers with small size at birth, early-onset insulin-dependent diabetes, and pancreatic exocrine insufficiency. In contrast to the findings in pancreatic aplasia, their serum C-peptide and glucagon levels were measurable. These findings, in concert with their clinical courses, are consistent with the diagnosis of congenital pancreatic hypoplasia.
Asunto(s)
Diabetes Mellitus Tipo 1/diagnóstico , Páncreas/anomalías , Adulto , Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Glucagón/sangre , Antígenos HLA/análisis , Humanos , MasculinoRESUMEN
Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.
Asunto(s)
Diabetes Mellitus Tipo 1/diagnóstico , Hipotiroidismo/diagnóstico , Hormonas Tiroideas/sangre , Adolescente , Niño , Preescolar , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Hipotiroidismo/etiología , Lactante , Masculino , Tirotropina/sangre , Hormona Liberadora de Tirotropina/sangre , Tiroxina/sangre , Triyodotironina Inversa/sangreRESUMEN
Hypoparathyroidism (hypocalcemia, hyperphosphatemia, mild hypomagnesemia, and inappropriately low serum C-terminal parathyroid hormone concentration) was found in six members of a family representing three successive generations. No patient had aortic arch or conotruncal malformations, lymphopenia, or features of type I or type II autoimmune polyglandular syndromes. Two individuals had transient neonatal seizures without further difficulties despite persistent hypocalcemia. None of the four affected adults has had major complications of hypoparathyroidism (mental retardation, cataracts, or seizures). We believe that persistence of hypoparathyroidism after resolution of neonatal hypocalcemic seizures should prompt a survey of the family for hypoparathyroidism.
Asunto(s)
Hipoparatiroidismo/genética , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Genes Dominantes , Humanos , Hipoparatiroidismo/complicaciones , Recién Nacido , Enfermedades del Recién Nacido/genética , Masculino , Persona de Mediana Edad , Linaje , Convulsiones/etiologíaRESUMEN
We report a prospective study of the recently recognized complication of limited joint mobility in childhood diabetes, summarizing data collected over the seven years after the initial description of this sign. Of 309 patients, ranging in age from 1 to 28 years, 30% had limited joint mobility. No race or sex influence on expression of limited joint mobility was found; its appearance was temporally more influenced by age than by duration of diabetes. Of 142 patients with diabetes onset before puberty and of longer than three years' duration, 74 had limited joint mobility. Disproportionate distribution of height percentiles for age characterized this entire group, but those with limited joint mobility had four times the skewing of those without (74 vs 37% below the twenty-fifth percentile). The presence or absence of thyroid microsome or islet cell antibodies did not relate significantly to limited joint mobility. Diabetes control, assessed subjectively by clinical estimation and objectively by hemoglobin A1 levels, was generally unrelated to the joint findings. For patients with diabetes duration less than five years, there was a significant association between hemoglobin A1 and limited joint mobility, but the variability in values explained by this association was small (11%).
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Trastornos del Crecimiento/fisiopatología , Artropatías/fisiopatología , Adolescente , Adulto , Factores de Edad , Peso Corporal , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inmunología , Femenino , Hemoglobina A/análisis , Humanos , Lactante , Artropatías/sangre , Masculino , Estudios ProspectivosRESUMEN
Of 771 young diabetic patients, thyroid microsomal autoantibodies occurred in 136 (17.6%) at a female/male ratio of nearly 2:1 and with a predominance of white patients (20.1%) over black patients (5.5%) (P less than 0.001). Thus, one in every four white female patients with insulin-dependent diabetes mellitus had TMA. Thyroglobulin autoantibodies were no more common in patients with IDDM than among controls. Of the 117 patients (out of the 136) with serologic evidence of chronic thyroiditis who could be studied, eight (7%) had hyperthyroidism and 45 (38%) were hypothyroid. Hyperthyroidism usually preceded or coincided with the appearance of IDDM, whereas hypothyroidism occurred with or following the onset of IDDM. Hypothyroidism appeared irreversible in most patients, but in three, periods of hypothyroidism were followed by euthyroidism, presumably explained by a compensatory hyperplasia of the thyroid gland. In the 136 patients with TMA, gastric and adrenocortical autoantibodies also occurred at relatively high frequencies (16.8% and 5.1%, respectively). On the basis of these studies, we urge that all patients with IDDM be screened for TMA and that those with positive results undergo annual thyroid function tests as well as determinations of gastric parietal and adrenocortical autoantibodies.
Asunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 1/inmunología , Glándula Tiroides/inmunología , Adolescente , Adulto , Enfermedades Autoinmunes/complicaciones , Niño , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Hipertiroidismo/complicaciones , Hipotiroidismo/complicaciones , Masculino , Microsomas/inmunología , Grupos Raciales , Razón de MasculinidadRESUMEN
Stored sera from 466 patients with insulin-dependent diabetes mellitus and from 144 controls were examined for organ-specific antibodies to human adrenal cortex. Adrenal antibodies were found in seven of the patients with IDDM (1.5%) and in one control (0.7%). None of 91 black patients with IDDM had adrenal antibodies. All of the seven patients with adrenal antibodies had other organ-specific antibodies. Three had clinical hypothyroidism and one was thyrotoxic. All of these seven patients had a HLA-B8-bearing haplotype, suggesting that the B8-bearing haplotype confers an extremely high "relative risk" for adrenal autoimmunity in IDDM. Organ-specific autoimmune disease and/or organ-specific antibodies were found in 30% of the first-degree relatives of these eight probands with the adrenal antibodies (seven with IDDM and one control). We conclude that screening patients with IDDM for adrenal antibodies of low yield (1.9% among white patients). Further, adrenal antibodies may be present for at least two years without the development of Addison disease. Antibodies reactive only to the zona glomerulosa of the adrenal cortex may be benign. Patients with IDDM and thyroid microsomal antibodies are more likely to have adrenal antibodies (6.5%), as are patients with IDDM and a B8-bearing haplotype and those with IDDM and family histories of organ-specific autoimmunity.
Asunto(s)
Enfermedad de Addison/complicaciones , Corteza Suprarrenal/inmunología , Autoanticuerpos/análisis , Complicaciones de la Diabetes , Enfermedad de Addison/genética , Enfermedad de Addison/inmunología , Diabetes Mellitus/genética , Diabetes Mellitus/inmunología , Femenino , Genotipo , Antígenos HLA/análisis , Antígenos HLA/genética , Humanos , MasculinoAsunto(s)
Hiperplasia Suprarrenal Congénita , Ginecomastia/etiología , Esteroide Hidroxilasas/deficiencia , 17-Hidroxicorticoesteroides/orina , 17-Cetosteroides/orina , Pruebas de Función de la Corteza Suprarrenal , Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológico , Aldosterona/orina , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/orina , Dexametasona , Hormona Folículo Estimulante/sangre , Ginecomastia/tratamiento farmacológico , Humanos , Hidrocortisona/orina , Lactante , Hormona Luteinizante/sangre , Masculino , Pene/anatomía & histología , Prednisona/uso terapéutico , Testosterona/sangreRESUMEN
A 3-yr-old boy was investigated for numerous episodes of fatigue, irritability, pallor, and sweating, which began at 11 mo of age, when he had an episode of symptomatic hypoglycemia with ketonuria. He had euphoria, mental confusion, drowsiness, nausea, and vomiting 1-5 hr after oral administration of glycerol in doses of 0.5-1.0gm/kg. Orally administered MCT (1 gm/kg) had similar effects. On one occasion, oral glycerol also provoked hypoglycemia, as had a 16 1/2 hr fast. Intravenously administered glycerol (0.09 gm/kg) induced an immediate loss of consciousness from which he recovered spontaneously after 30 min; there were no changes in blood glucose values. Intravenously administered fructose (0.25 gm/kg) was tolerated normally. Leukocytes showed normal activities for FDPase, glycerol kinase, and glycerol phosphate dehydrogenase. The restriction of dietary intake of fat has been associated with a marked improvement in physical and mental activities. These observations suggest a unique, yet undifined intolerance to glycerol, which suggest caution in the diagnostic use of glycerol in the investigation of hypoglycemia as well as in the therapy of increased intracranial or intraocular pressure.