[Presence of markers predictive of type I pre-diabetes mellitus status in relatives of patients with type I diabetes mellitus]. / Presencia de marcadores predictivos del estado de prediabetes mellitus tipo I en familiares de pacientes con diabetes mellitus tipo I.

BACKGROUND: The aim of this study was to analyze the predictive factors of IDDM in first degree relatives of IDDM patients. SUBJECTS AND METHODS: From 1992 to 1994, 1,053 first degree relatives were screened for measuring islet cell antibodies (ICA) by indirect immunofluorescence (iFl). In all ICA positive subjects, beta cell function was analyzed by intravenous glucose tolerance test (IVGTT) and other immunologic parameters were also studied: anti-insulin antibodies (IAA) by radiobinding and antibodies to glutamic acid decarboxylase (GADAb) by ELISA methods. RESULTS: ICA were found in 3.1% of the first degree relatives. IVGTT showed a significant decrease in acute first phase of insulin response to glucose (IRI 1 minute + 3 minute) in those with ICA > or = 20 JDF units. In patients with ICA > or = 20 JDF units, 20% were found to be positive for IAA and 40% were positive for GAdAb. Thirty-one percent (10/32) of ICA positive first degree relatives fulfilled prediabetes criteria. During follow-up, 40% (4/10) of these prediabetic patients developed IDDM. CONCLUSION: This study confirms the possibility of identifying among first degree relatives of IDDM patients the subgroup with high risk of developing IDDM thus allowing the initiation of therapy for preventing or delaying IDDM onset.

Correlation between residual beta-cell function and islet cell antibodies in newly diagnosed type I diabetes. Follow-up study.

To establish whether there is a correlation between the autoimmune response to the islets and beta-cell function during the initial stages of type I (insulin-dependent) diabetes, and islet cell antibody (ICA) titer and C-peptide levels (fasting and glucagon stimulated) were determined in 39 newly diagnosed patients at onset of diabetes and every 3-6 mo for 2 yr. ICAs were detected in 74% of the patients, and beta-cell function was detected in 84% of the patients at onset. The ICA+ and ICA- groups had similar C-peptide values at diagnosis and at 3 mo, but from 6 mo on, the ICA+ group consistently showed a tendency to lose C-peptide secretory capacity more quickly when assessed by fasting and glucagon-stimulated C-peptide levels (ICA+ vs. ICA- fasting C-peptide levels at 18 and 24 mo, P = .013 and .017, respectively; ICA+ vs. ICA- glucagon-stimulated C-peptide levels at 6, 18, and 24 mo, P = .023, .007, and .028, respectively). The initial ICA titer had the highest predictive value on the outcome of beta-cell function (P = .04), and patients with complement-fixing ICAs did not behave differently from the general ICA+ group. This correlation between beta-cell function and ICA titer supports the role of autoimmunity in the pathogenesis of type I diabetes and has important implications for the design of immunotherapy trials.

Presence of insulin autoantibodies at clinical diagnosis of diabetes mellitus type I predicts loss of beta cell function.

Recently the spontaneous development of insulin autoantibodies (IAA) has been detected in patients at diagnosis of Type I diabetes mellitus before the beginning of insulin treatment. The present study was undertaken to investigate if the presence of IAA at clinical onset of IDDM may act as a new marker of the beta cell function. The results obtained showed that IAA were present in 44% of newly diagnosed diabetic patients before therapy. Patients without IAA displayed a higher C-peptide secretion than those with IAA, at six months (12.11 +/- 5.08 versus 5.88 +/- 3.25 ng/ml/10 min.)(X +/- SD) and at twelve months (10.45 +/- 3.05 versus 4.90 +/- 5.25 ng/ml/10 min)(X +/- SD) of the follow up period. HbA1 levels, and insulin requirements were similar in both groups (IAA+ and IAA-). We conclude that the presence of insulin autoantibodies at clinical diagnosis, before initiating insulin treatment, may well predict the loss of the beta cell function.

17-ketosteroid reductase deficiency in an adult patient without gynaecomastia but with female psychosexual orientation.

A 24 years old male with pseudohermaphroditism due to a deficiency in 17-ketosteroid reductase activity is described. Plasma delta 4 is 21 times higher than normal for an adult male, delta 4/T is greater than 6, both E1 and F2 are elevated and E1/E2 = 3. There is very slight modification of delta 4 on administration of ACTH, dexamethasone, hCG and fluoxymesterone. Steroid concentrations in the spermatic veins and arteries confirm the testicular origin of the increased secretion of delta 4 and E1 and show a lower secretion by the cryptorchidic testis. In vitro testicular tissue incubation and fibroblast studies confirm the 17-ketosteroid reductase deficiency and rule out any other anomaly as the cause of the ambiguous genitalia. Psychologically the patient seemed to be identified with a female social and sexual role in spite of her advanced degree of virilization.

[Glycosylated hemoglobin as an index of diabetes mellitus control (author's transl)]. / Hemoglobina glucosilada como índice de control de la diabetes mellitus.

Glycosylated hemoglobin ((HbA1c) is formed by structural modification of HbA in a slow and irreversible non-enzymatic reaction. Its concentration is proportional to mean blood glucose levels during approximately four weeks, being therefore a useful index of diabetes mellitus control. The introduction of a microcolumn chromatographic method that measures together the subfractions HbA1a + b + c (fast Hb) and is well correlated to HbA1c has permitted the routine clinical measurement of this parameter. The authors used this method to study the levels of glycosylated hemoglobin in normal subjects, acutely decompensated diabetics, and diabetic outpatients classified according to their degree of control. The highest levels were detected in acutely decompensated patients and in those with chronic poor compensation. It is concluded that HbA1 constitutes a good index of compensation in diabetes, and that it may in the future unify existing criteria on the disease, contributing to clarify the problems about the correlation between the degree of compensation of diabetes and the incidence and evolution of its specific complications.